In support of the preadaptation model, an analysis of ISD in mice and yeast found that young genes have higher ISD than old genes, while random non-genic sequences tend to show the lowest levels of ISD. [ 110 ]  Although the observed trend may have partly resulted from a subset of young genes derived by overprinting, [ 142 ]  higher ISD in young genes is also seen among overlapping viral gene pairs. [ 143 ]  With respect to other predicted structural features such as β-strand content and aggregation propensity, the peptides encoded by proto-genes are similar to non-genic sequences and categorically distinct from canonical genes. [ 144 ]


This proto-gene model agrees with the preadaptation model about the importance of pervasive expression, and refers to the set of pervasively expressed sequences that do not meet all definitions of a gene as “proto-genes”. [ 59 ]  In contrast to the preadaptation model, the proto-gene model, suggests newborn genes have features intermediate between old genes and non-genes. [ 110 ]   Specifically this model envisages a more gradual process under selection from non-genic to genic state, rejecting the binary classification of gene and non-gene.


In an extension of the proto-gene model, it has been proposed that as proto-genes become more gene-like, their potential for adaptive change gives way to selected effects; thus, the predicted impact of mutations on fitness is dependent on the evolutionary status of the ORF. [ 105 ]   This notion is supported by the fact that overexpression of established ORFs in S. cerevisiae tends to be less beneficial (and more harmful) than does overexpression of emerging ORFs. [ 105 ]


Several features of ORFs correlate with ORF age as determined by phylostratigraphic analysis, with young ORFs having properties intermediate between old ORFs and non-genes; this has been taken as evidence in favor of the proto-gene model, in which proto-gene state is a continuum . [ 59 ]  This evidence has been criticized, because the same apparent trends are also expected under a model in which identity as a gene is a binary. Under this model, when each age group contains a different ratio of genes vs. non-genes,  Simpson's paradox  can generate correlations in the wrong direction. [ 110 ]


The “grow slow and moult” model describes a potential mechanism of  de novo  gene birth, particular to protein-coding genes. In this scenario, existing protein-coding ORFs expand at their ends, especially their 3’ ends, leading to the creation of novel N- and C-terminal domains. [ 145 ] [ 146 ] [ 147 ] [ 148 ] [ 149 ]  Novel C-terminal domains may first evolve under weak selection via occasional expression through read-through translation, as in the preadaptation model, only later becoming constitutively expressed through a mutation that disrupts the stop codon. [ 140 ] [ 146 ]  Genes experiencing high translational readthrough tend to have intrinsically disordered C-termini. [ 150 ]  Furthermore, existing genes are often close to repetitive sequences that encode disordered domains. These novel, disordered domains may initially confer some non-specific binding capability that becomes gradually refined by selection. Sequences encoding these novel domains may occasionally separate from their parent ORF, leading or contributing to the creation of a  de novo  gene. [ 146 ]  Interestingly, an analysis of 32 insect genomes found that novel domains (i.e. those unique to insects) tend to evolve fairly neutrally, with only a few sites under positive selection, while their host proteins remain under purifying selection, suggesting that new functional domains emerge gradually and somewhat stochastically. [ 151 ]


The evolutionary model escape from adaptive conflict (EAC) proposes a possible way for new gene duplication to be fixed: conflict due to contrasting function within a single gene drives the fixation of new duplication. [ 152 ] [ 153 ]


The 'pleiotropy-barrier' model suggests that newly evolved genes, including de novo genes and duplication-related genes, could facilitate evolutionary innovation or evolution of specific functions due to their low (or no)  pleiotropic effect , when facing new selective force, based on observations from human gene-disease data.


In addition to its significance for the field of evolutionary biology,  de novo  gene birth has implications for human health. It has been speculated that novel genes, including  de novo  genes, may play an outsized role in species-specific traits; [ 6 ] [ 10 ] [ 32 ] [ 154 ]  however, many species-specific genes lack functional annotation. [ 136 ]  Nevertheless, there is evidence to suggest that human-specific  de novo  genes are involved in diseases such as cancer.  NYCM , a  de novo  gene unique to humans and chimpanzees, regulates the pathogenesis of neuroblastomas in mouse models, [ 155 ]  and the primate-specific  PART1 , an lncRNA gene, has been identified as both a tumor suppressor and an oncogene in different contexts. [ 37 ] [ 156 ]  Several other human- or primate-specific  de novo  genes, including  PBOV1 , [ 157 ]   GR6 , [ 158 ] [ 159 ]   MYEOV , [ 160 ]   ELFN1-AS1 , [ 161 ]  and  CLLU1 , [ 38 ]  are also linked to cancer. Some have even suggested considering tumor-specifically expressed, evolutionary novel genes as their own class of genetic elements, noting that many such genes are under positive selection and may be neofunctionalized in the context of tumors. [ 161 ]


The specific expression of many  de novo  genes in the human brain [ 57 ]  also raises the intriguing possibility that  de novo  genes influence human cognitive traits. One such example is  FLJ33706 , a  de novo  gene that was identified in  GWAS  and linkage analyses for nicotine addiction and shows elevated expression in the brains of Alzheimer's patients. [ 162 ]  Generally speaking, expression of young, primate-specific genes is enriched in the fetal human brain relative to the expression of similarly young genes in the mouse brain. [ 163 ]  Most of these young genes, several of which originated  de novo , are expressed in the neocortex, which is thought to be responsible for many aspects of human-specific cognition. Many of these young genes show signatures of positive selection, and functional annotations indicate that they are involved in diverse molecular processes, but are enriched for transcription factors. [ 163 ]


In addition to their roles in cancer processes,  de novo  originated human genes have been implicated in the maintenance of pluripotency [ 164 ]  and in immune function. [ 37 ] [ 136 ] [ 165 ]  The preferential expression of  de novo  genes in the testes is also suggestive of a role in reproduction. Given that the function of many  de novo  human genes remains uncharacterized, it seems likely that an appreciation of their contribution to human health and development will continue to grow.


In vivo translation assay for subset (45) of translated iORFS


Note: For purposes of this table, genes are defined as orphan genes (when species-specific) or TRGs (when limited to a closely related group of species) when the mechanism of origination has not been investigated, and as  de novo  genes when  de novo  origination has been inferred, irrespective of method of inference. The designation of  de novo  genes as “candidates” or “proto-genes” reflects the language used by the authors of the respective studies.


This article was adapted from the following source under a  CC BY 4.0  license ( 2019 ) ( reviewer reports ):
 Stephen Branden Van Oss; Anne-Ruxandra Carvunis (23 May 2019).  "De novo gene birth" .  PLOS Genetics .  15  (5): e1008160.  doi : 10.1371/JOURNAL.PGEN.1008160 .  ISSN   1553-7390 .  PMC   6542195 .  PMID   31120894 .  Wikidata   Q86320144 .


NM_001171002 NM_027299


NP_001164473 NP_081575


Delta(4)-desaturase, sphingolipid 2  is a  protein  that in humans is encoded by the DEGS2  gene . [ 5 ]


This gene encodes a bifunctional enzyme that is involved in the  biosynthesis  of  sphingolipids  in human skin and in other phytosphingolipid-containing tissues. This enzyme can act as a sphingolipid delta(4)- desaturase , and also as a sphingolipid C4- hydroxylase .


This article on a  gene  on human  chromosome 14  is a  stub . You can help Wikipedia by  expanding it .


Chromosome 16p12.2-p11.2 deletion syndrome  is a gene deletion syndrome in the position  16p12.2-p11.2  of the human genome.
 [ 1 ]


This article on a  gene  on human  chromosome 16  is a  stub . You can help Wikipedia by  expanding it .


Deafness, Y-linked 1  ( DFNY1 ) is a  protein  that in humans is encoded by the  DFNY1   gene . Y-linked hearing impairment (DFNY1, MIM 400043) is one of the few  Mendelian disorders  showing  Y-linkage  in humans. [ 2 ]


ENSG00000157379 ENSG00000284868


NM_001136050 NM_138452


NP_001129522 NP_612461


Dehydrogenase/reductase SDR family member 1 , also known as  Short chain dehydrogenase/reductase family 19C member 1  is an  enzyme  that in humans is encoded by the  DHRS1   gene  located on  chromosome 14 . [ 5 ] [ 6 ] [ 7 ]


The DHRS1 gene is located on the chromosome 14q21.3 region and contains 9  exons . It encodes a 314-amino-acid, 33-kDa protein that is thought to be located to the  endoplasmic reticulum  and the  mitochondrial inner membrane  inside the cell.


The DHRS1 protein is thought to have  oxidoreductase  activity based on sequence similarity and conserved  catalytic sites  with other short-chain oxidoreductase enzymes. The enzyme is found to be expressed in the fetal  brain . [ 8 ]


The DHRS1 protein is thought to interact with the protein phospholipid scrambase 1 ( PLSCR1 ). [ 9 ]


Transmembrane protein 261  is a  protein  that in humans is encoded by the  TMEM261   gene  located on  chromosome 9 . [ 2 ]  TMEM261 is also known as  C9ORF123  and  DMAC1 , Chromosome 9 Open Reading Frame 123 and  Transmembrane  Protein C9orf123 [ 3 ]  and Distal membrane-arm assembly complex protein 1. [ 4 ]


TMEM261 is located at 9p24.1, its length is 91,891  base pairs  (bp) on the reverse strand. [ 3 ]  Its neighbouring gene is  PTPRD  located at 9p23-p24.3 also on the reverse strand and encodes  protein tyrosine phosphatase  receptor type delta. [ 2 ] [ 3 ]
 TMEM261  has 2  exons  and 1  intron , and 6  primary transcript  variants; the largest mRNA transcript variant consisting of 742bp with a protein 129  amino acids  (aa) in length and 13,500  daltons  (Da) in size, and the smallest coding transcript variant being 381bp with a protein 69aa long and 6,100 Da in size. [ 5 ] [ 6 ]


TMEM261 is a protein consisting out of 112 amino acids, with a  molecular weight  of 11.8 kDa. [ 7 ]  The  isoelectric point  is predicted to be 10.2, [ 8 ]  whilst its  posttranslational modification  value is 9.9. [ 6 ]


TMEM261 contains a  domain of unknown function , DUF4536 (pfam15055), predicted as a helical membrane spanning domain about 45aa ( Cys  47-  Ser  92) in length with no known domain relationships. [ 9 ] [ 10 ]  Two further transmembrane helical domains are predicted of lengths 18aa ( Val  52- Ala  69) and 23aa ( Pro  81- Ala  102]). [ 11 ] [ 12 ]  There is also a low complexity region spanning 25aa ( Thr  14- Ala  39). [ 13 ]  The  tertiary structure  for TMEM261 has not yet been determined. However, its  protein secondary structure  is mostly composed of  coiled-coil  regions with  beta strands  and  alpha helices  found within the  transmembrane  and  domain of unknown function  regions. The N-terminal region of TMEM261 is composed of a disordered region [ 14 ] [ 15 ]  which contains the low complexity region [ 13 ]   that is not highly conserved amongst orthologues. [ 16 ] [ 17 ]


A N-myristoylation domain is shown to be present in most TMEM261 protein variants. [ 6 ]  Post-translational modifications include  myristoylation  of the  N-terminal   Glycine  residue ( Gly 2) [ 6 ] [ 18 ]  of the TMEM261 protein as well as  phosphorylation  of  Threonine  31. [ 19 ]


Proteins shown to interact with TMEM261 include  NAAA  ( protein-protein interaction ),  QTRT1  ( RNA-protein interaction ), ZC4H2 ( DNA-protein interaction ) [ 20 ]  and  ZNF454 (DNA-protein interaction). [ 21 ] [ 22 ]  It has also shown to interact with  APP (protein-protein interaction), [ 23 ]   ARHGEF38 (protein-protein interaction) [ 24 ]  and  HNRNPD ( RNA-protein interaction ). [ 25 ] [ 26 ]


Additional  transcription factor  binding sites (DNA-protein interaction) predicted include one binding site for  MEF2C  a  monocyte -specific  enhancement factor  that is involved in  muscle-cell  regulation particularly in the  cardiovascular system [ 3 ] [ 28 ]  and two binding sites for  GATA1  which is a globin transcription factor 1 involved in  erythroblast  development regulation. [ 29 ] [ 30 ] [ 31 ]


TMEM261  shows ubiquitous expression in humans and is detected in almost all tissue types. [ 32 ] [ 33 ]  It shows  tissue-enriched gene  (TEG) expression when compared to  housekeeping gene  (HKG) expression. [ 27 ]  Its highest expression is seen in the  heart  (overall relative expression 94%) particularly in heart  fibroblast  cells,  thymus  (overall relative expression 90%), and  thyroid  (overall relative expression 93%) particularly in thyroid  glandular  cells. [ 27 ] [ 32 ]  Staining intensity of  cancer  cells showed intermediate to high expression in  breast ,  colorectal ,  ovarian ,  skin ,  urothelial ,  head  and  neck  cells. [ 32 ]


Currently the function for TMEM261 is unknown. [ 34 ]  However,  gene amplification  and rearrangements of its locus have been associated with various cancers including  colorectal cancer , [ 35 ]
 breast cancer [ 36 ]  and  lymphomas . [ 37 ] [ 38 ]


The  orthologues  and  homologues  of TMEM261 are limited to  vertebrates , its oldest homologue dates to that of the  cartilaginous fishes [ 39 ]  which diverged from  Homo sapiens  462.5  million years ago. [ 40 ]   The  protein primary structure  of TMEM261 shows higher overall conservation in  mammals , however high conservation of the  domain of unknown function  (DUF4536) to the  C-terminus  region is seen in all orthologues, including distant homologues. The  protein structure  of TMEM261 shows conservation across most orthologues. [ 16 ] [ 17 ]


TMEM261 has no known paralogs. [ 39 ]


Q92782 Q6PJ73


NM_001135155 NM_001135156 NM_001289978 NM_004647 NM_001363579


NM_013874 NM_001368371


NP_001390137 NP_001390138 NP_001390140 NP_001390141 NP_001390143 NP_001390144 NP_001390145 NP_001390146 NP_001390147 NP_001390148 NP_001390149 NP_001390139


D4, zinc and double PHD fingers family 1  is a  protein  that in humans is encoded by the DPF1  gene .
 [ 5 ]


This article on a  gene  on human  chromosome 19  is a  stub . You can help Wikipedia by  expanding it .


ENSG00000260596 ENSG00000283949


NM_001205218 NM_001278056 NM_001293798 NM_001306068 NM_001363820


NP_001280727 NP_001292997 NP_001350749


Double homeobox, 4  also known as  DUX4  is a  protein  which in humans is encoded by the  DUX4   gene . [ 3 ]  Its misexpression is the cause of  facioscapulohumeral muscular dystrophy  (FSHD).


This gene is located within a D4Z4  macrosatellite  repeat array in the  subtelomeric region  of  chromosome 4q35 . The D4Z4 repeat array contains 11-150 D4Z4 repeats in the general population; a highly  homologous  D4Z4 repeat array has been identified on chromosome 10. The gene consists of three  exons . Exons 1 and 2 are present in each D4Z4 repeat. Only one copy of exon 3 is present, telomeric to the D4Z4 repeat array. [ 4 ]  The  open reading frame  (ORF) is entirely contained within exon 1 and contains two  homeoboxes . [ 4 ]  Exons 2 and 3 encode for the  three prime untranslated region  (3′-UTR). [ 4 ]  In certain haplotypes, exon 3 contains a  polyadenylation  signal. [ 4 ]  There was no evidence for transcription from standard  cDNA libraries  however  RT-PCR  and in-vitro expression experiments indicate that the ORF is transcribed. [ 5 ]


The repeat-array and ORF are conserved in other mammals.


DUX4 protein is 424  amino acids  long. [ 4 ]  Two homeodomains are situated at the  N-terminus . A  transcription-activating domain (TAD)  and  p300 -binding domain are situated at the  C-terminus . The TAD encompasses a potential nine amino acid TAD (9aaTAD). [ 4 ]


The two homeodomains and TAD have well-defined tertiary structure. [ 4 ]  The region between the second homeodomain and TAD is predicted to be disordered. [ 4 ]


DUX4  transcripts can be spliced to produce either  DUX4-S  (short) or  DUX4-FL  (full length) mRNAs.  DUX4-FL  mRNA encodes for the entire DUX4 protein.  DUX4-S  mRNA encodes for a partial DUX4 protein, which lacks the transcription-activating domain. [ 4 ]


DUX4 protein a transcriptional activator of many genes, one example being paired-like homeodomain transcription factor 1 ( PITX1 ). [ 5 ]  It likely stimulates  zygotic genome activation . [ citation needed ]


The two homeodomains allow DUX4 protein to bind to DNA. [ 4 ]  The C-terminal domain is involved in target gene activation. [ 4 ]


DUX is normally expressed in the  testes ,  thymus , and  cleavage -stage  embryos . [ 6 ]


Inappropriate expression of DUX4 in  muscle cells  is the cause of  facioscapulohumeral muscular dystrophy  (FSHD). [ 7 ] [ 8 ]


Overexpression of DUX4 due to  translocations  can cause  B-cell leukemia . [ 6 ]  A translocation that merges DUX4 with  CIC  can cause an aggressive type of  sarcoma . [ 9 ]


This article on a  gene  on human  chromosome 4  is a  stub . You can help Wikipedia by  expanding it .


NM_033148 NM_183360 NM_183361 NM_001320932 NM_001320933 NM_001320934 NM_001320935 NM_001320936 NM_001320937 NM_001351381 NM_001351382 NM_001351383 NM_001351384 NM_001351385 NM_001351386 NM_001351387 NM_001351388 NM_001351389 NM_001351390 NM_001351391 NM_001351392 NM_001351393 NM_001351394 NM_001351395 NM_001394686


NM_001162465 NM_007886 NM_001355528 NM_001374710


NP_001307863 NP_001307864 NP_001307865 NP_001307866 NP_068707 NP_149159 NP_149160 NP_899204 NP_899205 NP_001338310 NP_001338311 NP_001338312 NP_001338313 NP_001338314 NP_001338315 NP_001338316 NP_001338317 NP_001338318 NP_001338319 NP_001338320 NP_001338321 NP_001338322 NP_001338323 NP_001338324


NP_001155937 NP_031912 NP_001342457 NP_001361639


Dystrobrevin beta  is a  protein  which in humans is encoded by the  DTNB   gene . [ 5 ]


This gene encodes dystrobrevin beta, a component of the  dystrophin -associated protein complex ( DPC ). The DPC consists of dystrophin and several integral and peripheral membrane proteins, including  dystroglycans ,  sarcoglycans ,  syntrophins  and  dystrobrevin  alpha and beta. The DPC localizes to the sarcolemma and its disruption is associated with various forms of muscular dystrophy. Dystrobrevin beta is thought to interact with syntrophin and the DP71 short form of dystrophin.  Alternatively spliced  transcript variants encoding different isoforms have been identified. [ 6 ]


NM_001297554 NM_001399422


NP_001284483 NP_001386351


ELABELA  (ELA, Apela, Toddler) is a  hormonal peptide  that in humans is encoded by the  APELA   gene . Elabela is one of two endogenous  ligands  for the  G-protein -coupled  APLNR receptor . [ 5 ]


Ela is secreted by certain  cell  types including human  embryonic stem cells . [ 6 ]  It is widely expressed in various developing organs such as the  blastocyst , [ 7 ]   placenta , [ 8 ]  heart, [ 9 ]   kidney , [ 10 ]   endothelium , and is circulating in human  plasma .


Elabela is a  micropeptide  that was identified in 2013 by Professor  Bruno Reversade's  team. [ 7 ]


Elabela gene encodes a pre-proprotein of 54 amino acids, with a  signal peptide  in the  N-terminal  region. After translocation into the  endoplasmic reticulum  and cleavage of the signal peptide, the proprotein of 32 amino acids may generate several active fragments. [ 11 ]


The sites of  APLNR  receptor expression are linked to the different functions played by Elabela in the organism. Despite that, Elabela is capable of signaling independently of  APLNR  in human  embryonic stem cells [ 6 ]  and certain cancer cell lines including OVISE. [ 12 ]


The Elabela protein is synthesized, processed and secreted by undifferentiated human  embryonic stem cells   [ 7 ]  but not mouse embryonic stem cells. In humans it is under the direct regulation of  POU5F1  (a.k.a.  OCT4 ) and  NANOG .


Through  autocrine  and  paracrine  signalling, endogenous Elabela entrains the  PI3K/AKT/mTOR pathway  to maintain  pluripotency  and  self-renewal . [ 6 ]


Elabela is expressed by midline tissues (such as  the notochord  in  zebrafish  and  neural tube  in mammals) during  organogenesis .


There it serves as a  chemoattractant  to  angioblasts  expressing  APLNR  at their cell surface. [ 13 ]  This participates in the formation of the first and secondary vessels of the vascular system. [ 14 ]


The ELABELA -APLNR signaling axis is required for formation of the coronary vessels of the heart in mice through the sinus venosus progenitors. [ 15 ]


ELA is a secreted into the  bloodstream  by the developing  placenta .  Pregnant  mice lacking Ela, [ 16 ]  exhibit  pre-eclampsia -like symptoms, characterized by  proteinuria  and  gestational hypertension . [ 8 ]


Infusion of exogenous ELA normalizes  blood pressure  and prevents  intrauterine growth retardation  in pups born to Ela  knockout  mothers. ELA increases the invasiveness of  trophoblast -like cells, suggesting that it may enhance placental development to prevent  eclampsia . [ 17 ]


Several mimetics of ELA have been developed for  therapeutic  purposes.  Amgen  has created a camel  antibody [ 18 ]  and a  small molecule [ 19 ]  agonist capable of mimicking the function of ELA  towards it cognate receptor APLNR.


The latter has entered phase 1 clinical trials for  heart failure  and  acute kidney disease .  Bristol Myers Squibb  has also created its own small molecule agonist of APLNR. [ 20 ]


An opinion published in  the Lancet  in 2019 suggested that ELABELA could be used to treat   intrauterine growth restriction  and maternal  morbidity  linked to  eclampsia . [ 21 ]


HERV-K_19q12 provirus ancestral Pol protein  is a  protein  that in humans is encoded by the  ERVK6   gene . [ 2 ] [ 3 ] [ 4 ]


This  protein -related article is a  stub . You can help Wikipedia by  expanding it .


NM_014297 NM_001320867 NM_001320868 NM_001320869


NM_023154 NM_001364014


NP_001307796 NP_001307797 NP_001307798 NP_055112


NP_075643 NP_001350943


Protein ETHE1, mitochondrial , also known as "ethylmalonic encephalopathy 1 protein" and "per sulfide dioxygenase", is a  protein  that in humans is encoded by the  ETHE1   gene  located on chromosome 19. [ 5 ]


The human ETHE1  gene  consists of 7 exons and encodes for a protein that is approximately 27 kDa in size.


This gene encodes a protein that is expressed mainly in the gastrointestinal tract, but also in several other tissues such as the liver and the thyroid. [ 5 ]


The ETHE1 protein is thought to localize primarily to the  mitochondrial matrix [ 6 ] [ 7 ]  and functions as a  sulfur dioxygenase .  Sulfur deoxygenates are proteins that function in  sulfur metabolism . The ETHE1 protein is thought to catalyze the following reaction:


and requires  iron [ 8 ]  and possibly  glutathione [ 8 ]  as  cofactors . The physiological  substrate  of ETHE1 is thought to be  glutathione persulfide , [ 8 ]  an intermediate  metabolite  involved in  hydrogen sulfide  degradation.


Mutations in ETHE1  gene   are thought to cause  ethylmalonic encephalopathy , [ 7 ] [ 9 ]  a rare  inborn error of metabolism . Patients carrying ETHE1 mutations have been found to exhibit lower activity of ETHE1 and affinity for the ETHE1 substrate. [ 8 ]  Mouse models of Ethe1 genetic ablation likewise exhibited reduced sulfide dioxygenase catabolism and cranial features of ethylmalonic encephalopathy. [ 6 ]  Decrease in sulfide dioxygenase activity results in abnormal  catabolism  of  hydrogen sulfide , a gas-phase signaling molecule in the central nervous system, [ 8 ]  whose accumulation is thought to inhibit  cytochrome c oxidase  activity in the  respiratory chain  of the  mitochondrion . [ 6 ]  However, other metabolic pathways may also be involved that could exert a modulatory effect on  hydrogen sulfide  toxicity. [ 10 ]


ETHE1 has been shown to  interact  with  RELA . [ 11 ]


Evx1  is a mammalian gene located downstream of the HoxA cluster, which encodes for a homeobox transcription factor. Evx1 is a homolog of even-skipped (eve), which is a  pair-rule gene  that regulates body segmentation in Drosophila. [ 1 ] [ 2 ]  The expression of Evx1 is developmentally regulated, displaying a biphasic expression pattern with peak expression in the  primitive streak  during  gastrulation  and in interneurons during neural development. [ 3 ] [ 4 ]  Evx1 has been shown to regulate anterior-posterior patterning during gastrulation by acting as a downstream effector of the  Wnt  and BMP signalling pathways. [ 4 ] [ 5 ]  It is also a critical regulator of  interneuron  identity. [ 6 ]


Despite a regulatory role in both of these processes, the Evx1 KO mouse is viable and displays no overt phenotype after birth. [ 4 ] [ 6 ]


A divergent  long non-coding RNA  (Evx1as) is also expressed from the locus, which is temporally and spatially co-expressed with Evx1. [ 3 ] [ 4 ] [ 7 ]  Evx1as does not have a function beyond that of Evx1 (in trans); [ 4 ]  however, it has been shown to regulate Evx1 at the locus (in cis). [ 7 ]


Fatty acid binding protein 9, testis  is a  protein  that in  humans  is encoded by the FABP9  gene . [ 5 ]


This article on a  gene  on human  chromosome 8  is a  stub . You can help Wikipedia by  expanding it .


NM_031208 NM_001018104 NM_001142398


NP_001018114 NP_001135870 NP_112485


Fumarylacetoacetate hydrolase domain-containing protein 1 , also known as FLJ36880 protein, is an  enzyme  that in humans is encoded by the  FAHD1   gene  on  chromosome 16 . [ 4 ]


The FAHD1 gene encodes for a 24-kDa protein that is localized to the  mitochondrion  and belongs to the  fumarylacetoacetate hydrolase  family of proteins. [ 5 ]  The structure of FAHD1 has been resolved using  X-ray crystallography  at 2.2-Å resolution. The overall structure is similar to the C-terminal domain of the bifunctional enzyme HpcE from Escherichia coli C, fumarylacetoacetate hydrolase from Mus musculus and to YcgM (Apc5008) from E. coli 1262. [ 5 ]  A number of conserved amino acids including Asp-102 and Arg-106 of FAHD1 appear to be important for its catalytic activity. [ 6 ]


The FAHD1 protein has been shown to function as an  oxaloacetate   decarboxylase  in  eukaryotes . [ 7 ]  The FAHD1 protein probably also functions as an  acylpyruvase , having been shown to catalyze the  hydrolysis  of  acetylpyruvate  and  fumarylpyruvate  in in vitro experiments. [ 5 ]   Mg(2+)  was required for maximal enzyme activity. [ 6 ]


Family with sequence similarity 3, member D  is a  protein  that in humans is encoded by the FAM3D  gene .
 [ 1 ]


This article on a  gene  on human  chromosome 3  is a  stub . You can help Wikipedia by  expanding it .


NM_001347843 NM_001347844 NM_001347845 NM_001347846 NM_001347847 NM_001347848 NM_001347849 NM_001347850 NM_001347851 NM_001347852 NM_198215


NM_001143776 NM_001143777 NM_024244 NM_001359551


NP_001334772 NP_001334773 NP_001334774 NP_001334775 NP_001334776 NP_001334777 NP_001334778 NP_001334779 NP_001334780 NP_001334781 NP_937858


NP_001137248 NP_001137249 NP_077206 NP_001346480


Family with sequence similarity 13, member C  is a  protein  that in humans is encoded by the FAM13C  gene . [ 5 ]


FAM63B  is a  protein  which in humans is encoded by the  gene  FAM63B. This gene is highly expressed in humans. The FAM63B gene is also highly conserved throughout evolutionary history. The discovered function of FAM63B is an interaction with the kinesin-1 light chain and the transportation of  vaccinia virus  from the nucleus to the cell periphery.


FAM63B is located at 15q21.3-q22.1, [ 1 ]  spanning 90,707 base pairs on  chromosome 15 . [ 2 ]


The full name of FAM63B is family with sequence similarity 63, member B. [ 3 ]  FAM63B is also listed by its alias, KIAA1164, in some publications. [ 4 ]


The FAM63B gene encodes a primary transcript that can be alternatively spliced into 9 protein variants. FAM63B variant a is the most common isoform found in humans. [ 2 ]


FAM63B is a member of the  Pfam  super family, and contains a domain of unknown function (DUF544) that is homologous within the protein family. [ 2 ]  FAM63B protein variant an also contains a  bipartite  tryptophan binding motif from W476 to W533. [ 6 ]  Variant a of the protein also contains a hydrophobic stretch of alanine from 567 to 574 and a mixed charge sequence from residue 598 to 617. [ 5 ]  FAM63B protein may contain a signal sequence specifying return to the endoplasmic reticulum (KDEL) from residue 607 to 621 in variant a.


The secondary structure of FAM63B is a combination of coils, some  α-helices , and few  β-sheets . [ 5 ] [ 7 ] [ 8 ]  The Phyre 2 program predicts α-helices in 23% of the protein, β-strands in 9% of the protein, and the remaining 59% of the protein as disordered. [ 7 ]  The disordered regions coincide with the coiled regions predicted by other programs, and this results in the long stretch of coiled protein beginning at the N-terminus. According to the SOUSI program, there is a 16-amino acid-long span from residues 265 to 280 of FAM63B that could be a transmembrane sequence. [ 9 ]  However, transmembrane sequences generally need to be at least 20 amino acids long in order to be stable in the membrane, so a transmembrane sequence is unlikely. Therefore, FAM63B is not fixed in the membrane of any organelle and is free to move through the cell and between organelles.


Not much is known about the tertiary structure of FAM63B. A predicted folding is shown.


Post-translational modifications of the FAM63B protein. [ 9 ]


FAM63B has predicted NES ( nuclear export signals ) at Val274 and Leu277. [ 10 ]  Also, a NLS ( nuclear localization signal ) is predicted for FAM63B at RKRK at residue 599. [ 9 ]  In agreement, Reinhardt's method for cytoplasmic/nuclear discrimination predicts FAM63B to be located in the nucleus with a reliability of 76.7%. The presence of both NLS and NES signals and  O-GlcNAc  post-translational modification of FAM63B supports the protein's location in both the nucleus and cytoplasm and the discovered protein function as a shuttle for vaccinia virus between the nucleus and the cell periphery.


FAM63B has moderately-high to high expression and is constitutively expressed. FAM63B is likely  ubiquitously  expressed in humans. [ 11 ]


Expression of FAM63B is high in the embryonic stem cells and differentiated tissues but low or off in  embryoid bodies  and other  progenitor  cells, such as the  multipotent   mesenchymal stem cells . It is likely that FAM63B is expressed during  pluripotency  and  unipotency  but is not important for differentiation, as is occurring in embryoid bodies, mesenchymal stem cells, and other progenitor cells.


The promoter of FAM63B is GXP_5885, located on the positive strand of chromosome 15 from (58770692, 58771462) and is 711 base pairs long. [ 12 ]


FAM63B is shown to interact with one protein,  KLC-1 . [ 13 ]  KLC-1, kinesin light chain 1, is a protein which recruits kinesin-1 via its cargo binding light chain and contains a bipartite tryptophan binding motif. [ 13 ]  This motif is present in a vaccinia virus integral membrane protein, A36, that is required for transport of the virus from the perinuclear space to the cell periphery. [ 13 ]  In the absence of A36, proteins with a bipartite tryptophan binding motif can interact with the kinesin light chain, recruit KLC-1, and promote virus transport from the nucleus to the cytoplasm. [ 13 ]


The discovered function of FAM63B protein is a transporter of vaccinia virus in the human genome. FAM63B contains a bipartite tryptophan binding motif between W476 and W533. [ 13 ]  The motif also contains a  Q residue  at the +2 position, which was found to be a frequent occurrence in proteins that bind KLC-1 or KLC-2. [ 13 ]  FAM63B is among proteins studied that can rescue virus transport to the cell periphery when expressed in A36-deficient cells, successfully replacing the cytoplasmic domain A36 of vaccinia. [ 13 ]


The specific pathology of FAM63B is unknown.


FAM63B is part of four networks regulated by miRNA, three of which are linked to neuronal differentiation and  dopaminergic  gene expression. [ 14 ]  These findings indicate that FAM63B could be used as a biomarker for the detection and treatment of  schizophrenia . [ 14 ]  Furthermore, aberrant methylation of FAM63B may play a role in the development of schizophrenia. [ 14 ]  FAM63B has also been ranked 13 of 25 on a list of associated genes relevant to  arthritis . [ 15 ]


FAM63B has one paralog,  FAM63A , which is a gene of unknown function. FAM63A gene encodes a protein that is 469 amino acids long and 76% similar to FAM63B. [ 16 ]


FAM63B has been found in all multicellular and unicellular eukaryotes, including plants but excluding protists and fungi. The gene has also been found in archaea but not bacteria. [ 17 ]


The most distant homolog of FAM63B is found in  Thermoplasmatales archaeon , an  archaea  that diverged from the human gene 4.25 billion years ago. [ 17 ] [ 18 ]


FAM63B is a member of the Pfam super family, and contains a domain of unknown function (DUF544) homologous within the protein family. [ 17 ]  This region of the protein is highly conserved through FAM63B homologs, as is the bipartite tryptophan binding motif of FAM63B and the C-terminus signal sequence.


The phylogenetic tree below shows a time calibration for the evolution of FAM63B.


Family with sequence similarity 151 member A  (abbreviated  FAM151A ) is a  protein  that in humans is encoded by the FAM151A  gene .  The protein is a  transmembrane protein  expressed in the  kidney tubules , and is an  ortholog  of menorin, a protein involved in  neuron  development in  nematodes . [ 5 ] [ 6 ]


The FAM151A gene contains 8  exons  and is located on the minus strand of  chromosome 1  at 1p32.3, spanning approximately 14 kbp. [ 7 ] [ 8 ]  The last exon contains approximately half of the  coding sequence , and overlaps with the  3' UTR  of gene  ACOT11 . [ 9 ]  No  alternative splicings  of FAM151A are known.


The  mRNA  transcript of FAM151A is expressed in the  kidney ,  small intestine , and  liver , while the FAM151A protein is only expressed in kidney tubules. [ 10 ]


The FAM151A protein contains three known  domains , one  transmembrane domain  and two  domains of unknown function  DUF2181. [ 11 ]  DUF2181 is a member of the GDPD/PLCD  superfamily , which are known to  hydrolyze glycerophosphodiester bonds . [ 12 ]  The second DUF2181 of FAM151A is hypothesized to be nonfunctional through  homology  analysis. The  molecular weight  of FAM151A is known to be approximately 95  kDa . [ 13 ]


FAM151A has direct orthologs in  chimpanzee , [ 14 ]   mouse , [ 15 ]   zebrafish , [ 16 ]  and other members of the clade  Eumetazoa  that diverged from humans up to around 700 million years ago. [ 17 ] [ 18 ]  However, FAM151A does not have any known orthologs in  birds .


FAM151A has one known  paralog  in humans, FAM151B, which contains only the first DUF2181 and no transmembrane region. [ 19 ]  In mammals, both FAM151A and FAM151B are homologs of the  C. elegans  menorin gene, involved in  dendrite  branching. [ 12 ] [ 6 ]


FAM151A contains an  SNP , rs11206394, that is a significant predictor of  colorectal cancer . The SNP is a  missense mutation  that occurs in the region of the second DUF2181 of FAM151A that overlaps with the 3' UTR of ACOT11. Individuals with both copies of the minor  allele  have been observed to have the odds of cancer decreased between 11% and 59%. [ 20 ]


Human growth and transformation-dependent protein  (HGTD-P), also called E2-induced gene 5 protein (E2IG5), is a  protein  that in humans is encoded by the  FAM162A   gene  on chromosome 3. [ 5 ] [ 6 ]  This protein promotes intrinsic  apoptosis  in response to  hypoxia  via interactions with hypoxia-inducible factor-1α ( HIF-1α ). [ 5 ] [ 7 ] [ 8 ] [ 9 ] [ 10 ]  As a result, it has been associated with cerebral  ischemia ,  myocardial infarction , and various  cancers . [ 8 ] [ 11 ] [ 12 ]


HGTD-P contains two transmembrane domains that are required for its localization to the mitochondria and induction of cell death. [ 8 ]


HGTD-P localizes to the mitochondria, where it participates in regulation of apoptosis. [ 5 ] [ 8 ]  This localization is aided by the chaperone  Hsp90 , which is required to stabilize the protein during the transit. [ 7 ] [ 9 ]  HGTD-P primarily acts in response to hypoxia by interacting with HIF-1α, which then triggers apoptotic cascades that result in the release of cytochrome C, induction of mitochondrial permeability transition, and activation of caspase-9 and 3. [ 5 ] [ 7 ] [ 8 ] [ 9 ] [ 10 ]  In neuronal cells, it additionally stimulates mitochondrial release of  AIFM1 , which then translocates to the nucleus to effect apoptosis, which indicates that it may participate in the  caspase -independent apoptotic pathway depending on cell type or organism. [ 5 ] [ 9 ]


Human growth and transformation-dependent protein (HGTD-P) is involved in intrinsic  apoptosis . Apoptosis, an ancient Greek word used to describe the "falling off" of petals from flowers or leaves from trees, is a highly regulated, evolutionarily conserved, and energy-requiring process by which activation of specific signaling cascades ultimately leads to cell death. An apoptotic cell undergoes structural changes including cell shrinkage, plasma membrane blebbing, nuclear condensation, and fragmentation of the  DNA  and  nucleus . This is followed by fragmentation into apoptotic bodies that are quickly removed by  phagocytes , thereby preventing an  inflammatory  response. [ 13 ]  It is a mode of cell death defined by characteristic  morphological ,  biochemical  and  molecular  changes. It was first described as a "shrinkage  necrosis ", and then this term was replaced by apoptosis to emphasize its role opposite  mitosis  in tissue kinetics. During apoptosis the cell decrease in size, loose contact with neighboring cells, and loose specialized surface elements such as microvilli and cell-cell junctions. A shift of fluid out of the cells causes cytoplasm condensation, which is followed by convolution of the nuclear and cellular outlines. In later stages of apoptosis the entire cell becomes fragmented, forming a number of plasma membrane-bounded apoptotic bodies which contain  nuclear  and or  cytoplasmic  elements. The ultrastructural appearance of necrosis is quite different, the main features being mitochondrial swelling, plasma membrane breakdown and cellular disintegration. Apoptosis occurs in many  physiological  and  pathological  processes. It plays an important role during  embryonal  development as programmed cell death and accompanies a variety of normal involutional processes in which it serves as a mechanism to remove "unwanted" cells.


Due to its involvement in  hypoxia , HGTD-P has been implicated in cerebral ischemia and myocardial infarction, as well as numerous cancers, including cervical cancer and gastric cancer. [ 8 ] [ 11 ] [ 12 ]  In the case of cervical cancer, HGTD-P is expressed in the early developmental stages and, thus, may prove useful as a diagnostic marker to control the spread of the cancer. Despite its proapoptotic function, HGTD-P has been observed to coordinate with HIF-1α to promote cell growth and proliferation under hypoxic conditions in cervical cancer. [ 11 ]  In the case of hypoxia-ischemia brain damage, the  microRNA  agomir, miR-139-5p, attenuates HGTD-P expression and brain damage, and has the therapeutic potential to treat hypoxia-ischemia brain damage. [ 10 ]


HGTD-P has been shown to  interact  with  Hsp90 [ 7 ]  and  VDAC . [ 8 ]


Family with sequence similarity 180  is a  Homo sapiens  protein that is encoded by the FAM180b gene also known as LOC399888. [ 1 ]  It is located on the positive DNA strand in Chromosome 11p11.2 (47,586,651 – 47,589,194) and is 1403 nucleotides long. The gene also has 3 exons. [ 2 ]


The  isoelectric point  of FAM180b is 4.74 and has a molecular weight of 20KDa. [ 3 ]  The protein lacks any prominent amino acids, but does have an increase in acidity due to the negatively charged KR-ED. [ 4 ]


FAM180A is the only paralog to FAM180b. The four different isoforms of FAM180b are listed below. [ 5 ]


FAM180b is found in Primates, Mammalians, and Fungi. But there are no  orthologs  in plants. [ 6 ]


A table indicating the various orthologs:


FAM180b is composed of 63%  alpha-helixes  and 54.1%  beta sheets . [ 8 ]  Certain amino acids have an overlap in both, hence the percentage exceeding 100% when totaled. The predicted tertiary structure obtained from  Phyre 2 [ permanent dead link  ]  can be seen in  Figure 3.  on the right. [ 9 ]


FAM180b has a  CpG island  associated with its promoter, and has a CpG count of 150. FAM180b also has relatively low levels of  H3K4me1 ,  H3K4me3  and  H3K27Ac  amongst the cell types, MADD, ARFGAP2, FNBP4, C1QTNF4, AGBL2, and PTPRJ. [ 10 ]


The FAM180b protein is predicted to be located in the  extracellular region , with a reliability score of 55.6%. [ 11 ]  The protein contains a  signal peptide , which has a cleavage site between 23 and 24 aa. However, FAM180b does not have any ER retention motif in the C-terminus, nor cleavage sites for  mitochondria . [ 12 ]


FAM180b has two cysteine residues located at amino acid (aa) 10 and 16, that are predicted to be palmitoylation sites. [ 13 ]  FAM180b also has three Threonine residues positioned in aa 4, 22, and 23, and one Glycine residue located in aa 19 that are all predicted to be phosphorylation sites. [ 14 ]  O-GlcNacylation sites are present in serine residues located in 35 aa, 171 aa and in Threonine residue located in 36 aa.
 [ 15 ]


FAM180b has one domain listed as Big-1 (bacterial IG-like domain 1) domain at position 1–8. It has an e-value of 1.6 + 0.3. As for the motif, there is an amidation site at  position 78–81. [ 16 ]


In human fetal tissues, FAM180b is expressed in the lungs and stomach at 10 weeks. It's also highly expressed in the intestine at 11 weeks. Amongst various different RNA sequenced tissues, FAM180b is highly expressed in fat, skin, and thyroid. [ 17 ]


Currently there are no clinical significances associated with protein FAM180b  [ 18 ]


Strausberg, Robert L et al. “Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.” Proceedings of the National Academy of Sciences of the United States of America vol. 99,26 (2002): 16899–903. doi:10.1073/pnas.242603899


ENSG00000140067 ENSG00000273533


NM_001207071 NM_001207072 NM_001207073 NM_001207074 NM_138344


NP_001194000 NP_001194001 NP_001194002 NP_001194003 NP_612353


Family with sequence similarity 181, member A  is a  protein  that in humans is encoded by the FAM181A  gene .
 [ 5 ]


FAM210B  is a gene that which in  Homo sapiens  encodes the protein FAM210B. It has been conserved throughout evolutionary history, and is highly expressed in multiple tissues within the human body. FAM210B's primary location is the  endoplasmic reticulum .


FAM210B is found on the plus strand of  chromosome 20 , precisely at 20q13.2. This gene is 9,749 bases in length, corresponding to a 192  amino acid  protein. [ 5 ]


Alternative names include C20orf108, Hypothetical protein LOC116151, DJ116H4.1, and 5A3. [ 5 ]


FAM210B has 2 known splice variants, formally known as FAM210B-001 an FAM210B-002. FAM210B-001 is 3 exons in length, whereas FAM210B-002 is 2 exons. [ 6 ]


The longest  precursor protein  is 192 amino acids in length. The  molecular weight  is 20.4 kdal, and  isoelectric point  is 10.8. [ 7 ]


There is 1 positive charge run of 4 residues at position 79, EEKK. A high scoring transmembrane sequence is present at positions 99–123, VGVSLHIGISLISLGIFYM
VVSSGV. An endoplasmic reticulum retention signal (PAAK) is present at positions 187–191. [ 7 ]


The majority of the structure is composed of alpha helices. As predicted my Phyre 2, 61% of the protein forms alpha helices, and 28% forms transmembrane segments. A detailed map of the transmembrane topology is shown below. [ 8 ]


I-Tasser predicted the folding of FAM210B to be as shown below.


The primary location of the FAM210B protein is the endoplasmic reticulum. The amino acid sequence contains the endoplasmic retention signal PAAK near the C-terminus. There are 2 transmembrane domains, which have been determined and reaffirmed by multiple methods. They are highlighted in the post-translational modification image below. [ 9 ]


The following conceptual translation presents expected post-translational modifications. The modifications were predicted by MotifScan, and then searched in greater detail in Expasy [ 10 ]
Modifications found include propeptide cleavage sites, C-mannosylation sites, GalNAc O-glycosylation sites, lysine glycation sites, phosphorylation sites, a Coronavirus 3C-like proteinase cleavage site, and a GPI modification site.


An important paralog for FAM210B is FAM210A. Orthologs and distant homologs have been found throughout mammalia, reptiles, birds, invertebrates, fish, amphibian, trichoplax, and fungi. [ 11 ]


The size of the gene family is two, and includes FAM210A and FAM210B. Gene duplication seems to have occurred when plants diverged from protists. The most distant ortholog found was Populus trichocarpa, also known as the black cottonwood tree. [ 12 ]  The unrooted phylogenetic tree below demonstrates this divergence. [ 13 ]  All of the organisms in the tree can also be found in the ortholog table above.


FAM210B is ubiquitously expressed in  Homo sapiens . [ 14 ]  It is expressed in each stage of development, and in many compromised health states including breast, cervical, liver, lung, ovarian, and pancreatic tumors. [ 15 ]


These images were taken from  Allen Brain Atlas  and demonstrate expression of FAM210B in the mouse brain.
The images compare the expression of FAM210B (left) to  dopamine beta hydroxylase  (right) in a  sagittal  cut of the  cerebellum . [ 16 ]


The following image contains the gene expression of FAM210B in patients with  dengue fever  or those who are  convalescent . As seen by the blue dots, there is decreased rank of FAM210B in patients experiencing  hemorrhagic fever  and fever as compared to the healthy controls. [ 17 ]


The following image contains the gene expression of FAM210B in patients with severe  bacterial pneumonia , severe  influenza , and those who received the  influenza vaccine . As seen in the image, FAM210B is lower in rank in the patients with severe bacterial pneumonia and are even lower in those with severe influenza, as compared to those who received the influenza vaccine. [ 18 ]


The following proteins were determined to interact with FAM210B. Their interaction was determined by affinity capture and  mass spectrometric  methods. [ 19 ]  By analyzing the function of these proteins, more insight can be given into the function of FAM210B.


FAM237A  is a  protein  coding  gene  which encodes a protein of the same name. [ 1 ]  Within  Homo sapiens ,  FAM237A is believed to be primarily expressed within the  brain , with moderate  heart  and lesser  testes  expression [ 1 ] , . [ 2 ]  FAM237A is hypothesized to act as a specific activator of receptor GPR83. [ 3 ]


FAM237A is alternatively known as HCG1657980 and LOC200726. [ 2 ] [ 4 ]   Homo sapiens  FAM237A's sequence resides on  chromosome 2 ’s + strand, and extends from  bases  207486904 to 207514174. [ 2 ]   Homo sapiens  FAM237A sequence contains 13  exons  unspliced. [ 2 ]


Homo sapiens  FAM237A is predicted to produce six unique transcripts, of which four are spliced. [ 2 ]


Homo sapiens  FAM237A is associated with three unnamed  protein isoforms . [ 2 ]  FAM237A's most-researched isoform is 181  amino acids  long, and is predicted to contain a  transmembrane domain . [ 2 ]  FAM237A's second protein isoform is predicted to be 417 amino acids long; it contains a transmembrane domain and an  upstream open reading frame . [ 2 ]  The last protein isoform of FAM237A is made up of 158 amino acids and contains a transmembrane domain; this isoform is predicted to localize within the membrane. [ 2 ]  Several databases, including  NCBI , only recognize FAM237A's 181 amino acid isoform. [ 1 ]  Given the relative abundance of literature surrounding it, the remainder of this page's findings only discuss FAM237A's 181 amino acid isoform.


The theoretical molecular weight of this isoform is 20.56  kDA . [ 5 ] [ 6 ] [ 7 ]  Its theoretical isoelectric point is 8.96. [ 5 ] [ 6 ] [ 7 ]   Homo sapiens  FAM237A amino acid composition is predicted to be relatively standard. [ 8 ]  It notably contains a repeat LFWD motif at amino acids 90 and 97. [ 8 ]


FAM237A's transmembrane domain is generally predicted to reside on amino acids 14-32 within the protein. [ 8 ] [ 9 ]  However, structure prediction tool  Phyre2  predicts that the protein's transmembrane domain resides on amino acids 91–106. [ 10 ]


Three  promoters  of  Homo sapiens  FAM237A are predicted: GXP_8991091, GXP_7539237, and GXP_8991092. [ 11 ]  Of these, GXP_8991091 has the  greatest predicted tissue expression levels. [ 11 ]


AceView predicts that  Homo sapiens  FAM237A is localized to membranes. [ 2 ]  However, this is disputed, with protein localization prediction resource Hum-mPLoc predicting that  Homo sapiens  FAM237A is expressed within the nucleus and resource PSORT II predicting ER localization, with lesser chances of expression within the  mitochondria  and  Golgi apparatus . [ 12 ] [ 13 ] [ 14 ] [ 15 ] [ 16 ] [ 17 ]


An abundance of predicted  phosphorylation sites  reside on  Homo sapiens  FAM237A's sequence. [ 18 ] [ 19 ] [ 20 ] [ 21 ]   Homo sapiens  FAM237A contains two predicted fatty acid addition sites at amino acids 18 and 26; these sites overlap with one of the FAM237A's predicted transmembrane sequences. [ 22 ] [ 23 ]   Homo sapiens  FAM237A is additionally predicted to contain two sites of  ubiquitination  at amino acids 179 and 181 on its sequence. [ 24 ] [ 25 ]  These ubiquitination sites are predicted to perfectly overlap two  acetylation  sites. [ 26 ] [ 27 ]


Homo sapiens  FAM237A has one predicted paralog: FAM237B. [ 4 ]  FAM237B has 21.6% predicted identity with FAM237A [ 28 ]


FAM237A has orthologs in a broad range of  vertebrate  organisms, including other  Mammals ,  Reptilia ,  Actinopterygii , and  Aves . [ 29 ]  The gene is not found in  invertebrates . Based upon  BLAST  analysis, FAM237A is not found in  invertebrates . [ 29 ]  The only reptiles which FAM237A is found in are predicted to be of the suborder  Cryptodira , based upon BLAST searches. [ 29 ]


Information regarding FAM237A's function is limited; however, FAM237A is predicted to be a specific activator of GPR83, which is implicated in energy metabolism, dietary patterns, and reward signaling. [ 3 ] [ 30 ]  GPR83 is additionally suspected to be correlated to immune system function [ 30 ]


NM_027123 NM_001330423


NP_001317352 NP_081399


FAST kinase domain-containing protein 3  (FASTKD3) is a  protein  that in humans is encoded by the  FASTKD3   gene  on chromosome 5. [ 5 ] [ 6 ]  This protein is part of the Fas-activated serine/threonine kinase domain (FASTKD) containing protein family, which is known for regulating the energy balance of mitochondria under stress. [ 7 ] [ 8 ]


FASTKD3 shares structural characteristics of the FASTKD family, including an  N-terminal   mitochondrial  targeting domain and three  C-terminal  domains: two FAST kinase-like domains (FAST_1 and FAST_2) and a RNA-binding domain (RAP). [ 7 ] [ 8 ]  The mitochondrial  targeting domain directs FASTKD3 to be imported into the mitochondria. Though the functions of the C-terminal domains are unknown, RAP possibly binds RNA during trans-splicing. [ 7 ]


As a member of the FASTKD family, FASTKD3 localizes to the mitochondria to modulate their energy balance, especially under conditions of stress. Though ubiquitously expressed in all tissues, FASTKD3 appears more abundantly in skeletal muscle, heart muscle, and other tissues enriched in mitochondria. FASTKD3 has been proposed to regulate energy production by serving as a scaffold protein that brings together RNA processing/translation and respiratory components. [ 7 ]


Currently, FASTKD3 has not been linked to any disease. (Dated: September 17, 2015)


FASTKD3 has been shown to  interact  with:


This article on a  gene  on human  chromosome 5  is a  stub . You can help Wikipedia by  expanding it .


FLS  genes have been discovered to be involved in  flagellin  reception of bacteria. FLS1 was the original  gene  discovered shown to correspond with a specific ecotype within  Arabidopsis thaliana . Even so, further studies have shown a second FLS gene known as  FLS2  that is also associated with flagellin reception.  FLS2  and FLS1 are different genes with different responsibilities, but are related genetically.  FLS2  has a specific focus in plant defense and is involved in promoting the  MAP kinase cascade . Mutations in the  FLS2  gene can cause bacterial infection by lack of response to flg22. Therefore,  FLS2 ’s primary focus is association with flg22 while its secondary focus is the involvement of promoting the MAP kinase cascade in plant defense. [ 2 ]


FLS2  is considered a  receptor-like kinase  (RLK). RLKs are essentially  tyrosine kinases  fused to an N-terminal  leucine-rich repeat  domain, which controls its function. Although tyrosine kinases are widespread and present in mammals, this type of fusion is only found in plants. RLKs are  transmembrane proteins  that consists of inner, outer, and central membrane regions. [ clarification needed ]  RLKs play an important role in plant reception which will be shown through  FLS2 . [ 3 ]   BRASSINOSTEROID INSENSITIVE 1  (BRI1) is another important RLK with a lot of similarities to FLS2. Despite sharing many of the same signalling components, FLS2 and BRI1 have very different effects on the cell. [ 4 ]


FLS2  consists of 3 domains: an extracellular, a transmembrane, and an intracellular. The extracellular domain is known as the  Leucine-rich repeat  (LRR) domain. It is in this region, which is the amino-terminus, where it is said to have direct interaction with flagellin initiating the response of  FLS2  to flg22. The transmembrane domain is where proteins transition from extracellular to intracellular. This region is usually very thermodynamically stable and occurs only in the  phospholipid membrane  between cells. The intracellular domain is the serine/threonine kinase domain. In this domain, phosphorylation catalyzes a protein kinase cascade leading to a response. [ 5 ]  In  FLS2 , this response elicits changes in growth and plant defenses. [ 6 ]


One experiment performed to show involvement of  FLS2  in flagellin perception was an  ectopic expression  of  FLS2  using the CaMV 35S  gene promoter  in one wild type  Arabidopsis thaliana  plant and two supposed mutant  Arabidopsis thaliana  plants. The wild type  Arabidopsis  plant was indicated by Col-0 and the two mutants were indicated by 35S:: FLS2 - col2  and 35S:: FLS2 - col4 . In this experiment, callose deposition and production of active oxygen species were the variables considered to show flagellin perception after treatment of flg22 as indicated by previous research (Gomez-Gomez, et al. 1999). Results for this study showed a few things. The first thing it showed was a response in callose deposition 12 hours after treatment in only one plant type which was the mutant 35S:: FLS2 - col2 . In the wild type and mutant 35S:: FLS2 - col4 , no callose deposition was detected in plants that exhibited reduced levels of  FLS2 . In direct correlation to the callose deposition response, the second thing observed was a luminol-based assay to show oxidative burst in leaf tissues of the three plants types. The luminol-based assay showed a rapid and strong  oxidative response  in mutant 35S:: FLS2 - col2  with treatment of 10nM flg22, whereas a 10nM treatment of flg22 in the mutant 35S:: FLS2 - col4  was unable to induce any oxidative response that would occur naturally in the wild type  Arabidopsis  plant. Even so, higher treatment levels of flg22 would elicit an oxidative response but not significant compared to the wild type. The last thing observed in this experiment was treatment of flg22 in regards to growth inhibition to T2 seedlings. Growth inhibition in 35S:: FLS2 - col2  was greater than the wild type under flg22 treatment, whereas 35S:: FLS2 - col4  showed a reduced growth inhibition compared to wild type plants under flg22 treatment which is inverse of the oxidative response in these two mutants relative to the wild type. [ 2 ]


In the same way that mammals and insects have an innate immunity response to pathogens, plants have a defense system that is similar yet modified. The biggest difference between plants, mammals, and insects is that mammals and insects are not stationary like plants, therefore a plant's defense system is more complex and more reliant of signaling pathways to notify the plant of what could be potentially attacking. With that in mind, it is important that all gram positive and gram negative bacteria share flagellin. With plants being stationary, a specific molecular pattern of flagellin can be recognized by plants to determine phytopathogenic bacteria in plant defense. As discovered by the ectopic expression of  FLS2  study, [ 2 ]   FLS2  is directed related to flagellin perception, so by discovery and by natural way of the plant,  FLS2  is the gene responsible for perception of flagellin which signals a plant defense response. Things are not all settled here because, as mentioned earlier, gram positive and gram negative bacteria share flagellin which means that plants cannot distinguish between avirulent and virulent bacteria. This could provide extremely useful when an abundance of pathogenic bacteria are present, however this can also prove inefficient when plant defense response is occurring due to flagellin perception of avirulent bacteria, or so one would think. In actuality, avirulent bacteria defense responses are higher than virulent bacteria defense response due to the presence of multiple specific elicitors. Hutcheson (1997) [ 7 ]  found that the tertiary and quaternary structures of protein elicitors are dependent on elicitor activity. Even so, resistant gene products are commonly found in Leucine rich repeat domains which is the extracellular domain of  FLS2 , and  hrp  genes are directly related to disease incitement and hypersensitive response to resistant plants. In short, the more elicitors that are present within flagellin perception, the more plant defense response will occur regardless of virulence. It is just more common for avirulent pathogen to produce more elicitors. [ 2 ]


The design of this experiment is similar to previous literature from [ 2 ]  and [ 8 ]  but unlike those two publications, in this publication, [ 3 ]  the promoter used was the 35S  cauliflower mosaic virus  promoter used to express  FLS2  coding sequences fused to a triple c-myc tag. What happens to a  FLS2  gene in  Arabidopsis  is known but this study looks at how the  FLS2  gene in  Arabidopsis  may affect a plant that contains a  FLS2  gene that does not respond similarly to  Arabidopsis . Figure 1 in [ 3 ]  shows how tomato cells with no introduction to an  Arabidopsis FLS2  gene show no response to the perception of either flg15 or flg22. However, when viewing the  Arabidopsis   FLS2  gene and the tomato cells with the  Arabidopsis FLS2  gene added, it is clear that the responses are similar due to the presence of the  Arabidopsis   FLS2  gene. [ 3 ]


Alkalinization has been used to show ion fluxes across membranes in previous literature. [ 9 ] [ 10 ] [ 11 ]  In this study, alkalinization induced by the flagellin derivative flg22-ΔA 16/17  in tomato plants expressing the  Arabidopsis FLS2  gene. Extracellular alkalinization was used to elicit a response in these type plants. Alkalinization had no effect on non-treated tomato plants, but increased binding activity to  FLS2  was shown with no increase in sensitivity toward flg22 in the tomato plants expressing the  Arabidopsis   FLS2  gene. This lack of increase in sensitivity could be attributed to a number of factors that are unknown, yet hypothesized. Even so, the binding of tomato plants expressing  Arabidopsis   FLS2  gene showed similar sensitivity of flg15 to that of normal tomato plants. This indicates that both the  Arabidopsis FLS2  gene and the tomato plant  FLS2  gene are both working in tomato plants expressing  Arabidopsis   FLS2  gene. The  Arabidopsis FLS2  gene responds to flg22 and the natural tomato  FLS2  gene responds to flg15. Furthermore, the tomato  FLS2  gene was analyzed for any derivatives that might be responsible for gene expression. Although less active than flg22, its derivative flg22-ΔA 16/17  was found to elicit a medium alkalinization response in  Arabidopsis FLS2  gene in both  Arabipdopsis  and tomato plants expressing  Arabidopsis   FLS2  gene. Essentially, the majority of flagellin perception occurring in tomato plants expressing  Arabidopsis   FLS2  gene is occurring because of the  Arabidopsis   FLS2  gene while a minor portion of flagellin perception can be attributed to the tomato  FLS2  gene. [ 3 ]


FOXC2 antisense RNA 1  is a  protein  that in humans is encoded by the FOXC2-AS1  gene .
 [ 2 ]


Forkead box I3  (FOXI3) is a  protein  that in humans is encoded by the  FOXI3  gene. FOXI3 is a  forkhead box   transcription factor  that is expressed in the development of hair and teeth. One of its mutations is a  dominant allele  responsible for the  heterozygous  Hh hairless trait in dogs. It was identified in 2008. [ 5 ]


Forkhead box Q1  is a  protein  that in humans is encoded by the FOXQ1  gene .
 [ 5 ]


FOXQ1 is a member of the FOX gene family, which is characterized by a conserved 110-amino acid DNA-binding motif called the forkhead or winged helix domain. FOX genes are involved in embryonic development, cell cycle regulation, tissue-specific gene expression, cell signaling, and tumorigenesis (Bieller et al., 2001 [PubMed 11747606]).


This article on a  gene  on human  chromosome 6  is a  stub . You can help Wikipedia by  expanding it .


Fragile site, aphidicolin type, common, fra(3)(p24.2)  is a  protein  that in humans is encoded by the FRA3A  gene .
 [ 2 ]


Fibrous sheath CABYR binding protein  is a  protein  that in humans is encoded by the FSCB  gene , which is found on  chromosome 14 . [ 1 ]   It is found in  Homo sapiens , and has the following lineage:  Eukaryota ;  Metazoa ;  Chordata ;  Craniata ;  Vertebrata ;  Euteleostomi ;  Mammalia ;  Eutheria ;  Euarchontoglires ;  Primates ;  Haplorrhini ;  Catarrhini ;  Hominidae ;  Homo .
 [ 2 ] [ 3 ]  The sub-cellular function of the protein is to localize to the cortex of the fibrous sheath, including the surface of the longitudinal columns and ribs of the main part of  sperm   flagella . [ 1 ]


Gene conversion  is the process by which one  DNA  sequence replaces a  homologous sequence  such that the sequences become identical after the conversion. [ 1 ]  Gene conversion can be either  allelic , meaning that one  allele  of the same gene replaces another allele, or  ectopic , meaning that one  paralogous DNA sequence  converts another. [ 2 ]


Allelic gene conversion  occurs during  meiosis  when  homologous recombination  between  heterozygotic  sites results in a mismatch in base pairing. This mismatch is then recognized and corrected by the cellular machinery causing one of the alleles to be converted to the other. This can cause  non-Mendelian  segregation of alleles in germ cells. [ 3 ]


Recombination occurs not only during meiosis, but also as a mechanism for repair of double-strand breaks (DSBs) caused by DNA damage. These DSBs are usually repaired using the sister  chromatid  of the broken duplex and not the homologous chromosome, so they would not result in allelic conversion. Recombination also occurs between homologous sequences present at different genomic loci (paralogous sequences) which have resulted from previous gene duplications. Gene conversion occurring between paralogous sequences ( ectopic gene conversion ) is conjectured to be responsible for  concerted evolution  of gene families. [ 3 ] [ 4 ] [ 5 ]


Conversion of one allele to the other is often due to base mismatch repair during  homologous recombination : if one of the four chromatids during meiosis pairs up with another chromatid, as can occur because of sequence  homology , DNA strand transfer can occur followed by mismatch repair.  This can alter the sequence of one of the chromosomes, so that it is identical to the other.


Meiotic recombination is initiated through formation of a double-strand break (DSB). The 5’ ends of the break are then degraded, leaving long 3’ overhangs of several hundred nucleotides. One of these 3’ single stranded DNA segments then invades a homologous sequence on the homologous chromosome, forming an intermediate which can be repaired through different pathways resulting either in crossovers (CO) or noncrossovers (NCO). At various steps of the recombination process, heteroduplex DNA (double-stranded DNA consisting of single strands from each of the two homologous chromosomes which may or may not be perfectly complementary) is formed. When mismatches occur in heteroduplex DNA, the sequence of one strand will be repaired to bind the other strand with perfect complementarity, leading to the conversion of one sequence to another. This repair process can follow either of two alternative pathways as illustrated in the Figure.  By one pathway, a structure called a double  Holliday junction  (DHJ) is formed, leading to the exchange of DNA strands. By the other pathway, referred to as Synthesis Dependent Strand Annealing (SDSA), there is information exchange but not physical exchange. Gene conversion will occur during SDSA if the two DNA molecules are heterozygous at the site of the recombinational repair.  Gene conversion may also occur during recombinational repair involving a DHJ, and this gene conversion may be associated with physical recombination of the DNA duplexes on the two sides of the DHJ.


Biased gene conversion (BGC) occurs when one allele has a higher probability of being the donor than the other in a gene conversion event. For example, when a T:G mismatch occurs, it would be more or less likely to be corrected to a C:G pair than a T:A pair. This gives that allele a higher probability of transmission to the next generation. Unbiased gene conversion means that both possibilities occur with equal probability.


GC-biased gene conversion (gBGC) is the process by which the GC content of DNA increases due to gene conversion during recombination. [ 4 ]  Evidence for gBGC exists for yeasts and humans and the theory has more recently been tested in other eukaryotic lineages. [ 6 ]  In analyzed human DNA sequences, crossover rate has been found to correlate positively with GC-content. [ 4 ]  The  pseudoautosomal regions  (PAR) of the X and Y chromosomes in humans, which are known to have high recombination rates also have high GC contents. [ 3 ]  Certain mammalian genes undergoing concerted evolution (for example, ribosomal operons, tRNAs, and histone genes) are very GC-rich. [ 3 ]  It has been shown that GC content is higher in paralogous human and mouse histone genes that are members of large subfamilies (presumably undergoing concerted evolution) than in paralogous histone genes with relatively unique sequences. [ 7 ]
There is also evidence for GC bias in the mismatch repair process. [ 3 ]  It is thought that this may be an adaptation to the high rate of methyl-cytosine deamination which can lead to C→T transitions.


The Fxy or Mid1 gene in some mammals closely related to house mice (humans, rats, and other Mus species) is located in the sex-linked region of the X chromosome. However, in  Mus musculus , it has recently translocated such that the 3’ end of the gene overlaps with the PAR region of the X-chromosome, which is known to be a recombination hotspot. This portion of the gene has experienced a dramatic increase in GC content and substitution rate at the 3rd codon position as well as in introns but the 5’ region of the gene, which is X-linked, has not. Because this effect is present only in the region of the gene experiencing increased recombination rate, it must be due to biased gene conversion and not selective pressure. [ 4 ]


GC content varies widely in the human genome (40–80%), but there seem to be large sections of the genome where GC content is, on average, higher or lower than in other regions. [ 3 ]  These regions, although not always showing clear boundaries, are known as isochores. One possible explanation for the presence of GC-rich isochores is that they evolved due to GC-biased gene conversion in regions with high levels of recombination.


Studies of gene conversion have contributed to our understanding of the adaptive function of meiotic recombination.  The ordinary segregation pattern of an allele pair (Aa) among the 4 products of meiosis is 2A:2a.  Detection of infrequent gene conversion events (e.g. 3:1 or 1:3 segregation patterns during individual meioses) provides insight into the alternate pathways of recombination leading either to crossover or non-crossover chromosomes.  Gene conversion events are thought to arise where the "A" and "a" alleles happen to be near the exact location of a molecular recombination event. Thus, it is possible to measure the frequency with which gene conversion events are associated with crossover or non-crossover of chromosomal regions adjacent to, but outside, the immediate conversion event.  Numerous studies of gene conversion in various fungi (which are especially suited for such studies) have been carried out, and the findings of these studies have been reviewed by Whitehouse. [ 8 ]   It is clear from this review that most gene conversion events are not associated with outside marker exchange.  Thus, most gene conversion events in the several different fungi studied are associated with non-crossover of outside markers.  Non-crossover gene conversion events are mainly produced by Synthesis Dependent Strand Annealing (SDSA). [ 9 ]   This process involves limited informational exchange, but not physical exchange of DNA, between the two participating homologous chromosomes at the site of the conversion event, and little genetic variation is produced.  Thus, explanations for the adaptive function of meiotic recombination that focus exclusively on the adaptive benefit of producing new genetic variation or physical exchange seem inadequate to explain the majority of recombination events during meiosis.  However, the majority of meiotic recombination events can be explained by the proposal that they are an adaptation for repair of damage in the DNA that is to be passed on to gametes. [ 10 ]


Of particular interest, from the point of view that recombination is an adaptation for DNA repair, are the studies in yeast showing that gene conversion in mitotic cells is increased by UV [ 11 ] [ 12 ]  and ionizing radiation [ 13 ]


In the discussions of  genetic diseases  in humans,  pseudogene  mediated gene conversions that introduce pathogenic  mutations  into functional genes is a well known mechanism of mutation. In contrast, it is possible that pseudogenes could serve as templates. During the course of evolution, functional source genes which are potentially advantageous have been derived from multiple copies in their single source gene. The pseudogene-templated changes might eventually become fixed as long as they did not possess deleterious effects. [ 14 ]  So, in fact, pseudogenes can act as sources of sequence variants which can be transferred to functional genes in novel combinations and can be acted upon by  selection .  Lectin  11 ( SIGLEC 11), a human immunoglobulin that binds to sialic acid, can be considered an example of such a gene conversion event which has played a significant role in evolution. While comparing the homologous genes of  human  SIGLEC11 and its pseudogene in the  chimpanzee ,  gorilla  and  orangutan , it appears that there was gene conversion of the sequence of 5’ upstream regions and the exons that encode the sialic acid recognition domain, approximately 2kbp from the closely flanking hSIGLECP16 pseudogene (Hayakawa et al., 2005). The three pieces of evidence concerning this event have together suggested this as an adaptive change which is very evolutionarily important in  genus   Homo . Those includes that only in human lineage this gene conversion happened, the brain cortex has acquired an important expression of SIGLEC11 specifically in human lineage and the exhibition of  a change in substrate binding in human lineage when compared to that of its counterpart in chimpanzees. Of course the frequency of the contribution of this pseudogene-mediated gene conversion mechanism to functional and adaptive changes in evolution of human is still unknown and so far it has been scarcely explored. [ 15 ]  In spite of that, the introduction of positively selective genetic changes by such mechanism can be put forward for consideration by the example of SIGLEC11. Sometimes due to interference of  transposable elements  in to some members of a gene family, it causes a variation among them and finally it may also cease the rate of gene conversion due to lack of sequence similarity which leads to  divergent evolution .


From various genome analyses, it was concluded that the double-strand breaks (DSB) can be repaired via  homologous recombination  by at least two different but related pathways. [ 14 ]  In case of major pathway, homologous sequences on both sides of the DSB will be employed which seems to be analogous to the conservative DSB repair model  [ 16 ]  that was originally proposed for meiotic recombination in yeast. [ 17 ]  where as the minor pathway is restricted to only one side of the DSB as postulated by nonconservative one-sided invasion model. [ 18 ]  However, in both cases the sequence of the recombination partners will be absolutely conserved. By virtue of their high degree of homology, the new gene copies that came into existence following the gene duplication naturally tend to either unequal crossover or unidirectional gene conversion events. In the latter process, there exists the acceptor and donor sequences and the acceptor sequence will be replaced by a sequence copied from the donor, while the sequence of the donor remains unchanged. [ 15 ]


The effective homology between the interacting sequences makes the gene conversion event successful. Additionally, the frequency of gene conversion is inversely proportional to the distance between the interacting sequences in cis, [ 19 ] [ 14 ]   and the rate of gene conversion is usually directly proportional to the length of uninterrupted sequence tract in the assumed converted region. It seems that conversion tracts accompanying crossover are longer (mean length = ~460 bp) than conversion tracts without crossover (mean length = 55–290 bp). [ 20 ]  In the studies of human globulin genes, it has long been supported that the gene conversion event or branch migration events can either be promoted or inhibited by the specific motifs that exist in the vicinity of the DNA sequence. [ 21 ] [ 14 ]  Another basic classification of gene conversion events is the interlocus (also called nonallelic) and interallelic gene conversions. The cis or trans nonallelic or interlocus gene conversion events occur between nonallelic gene copies residing on sister chromatids or homologous chromosomes, and, in case of interallelic, the gene conversion events take place between alleles residing on homologous chromosomes. [ 15 ] [ 14 ]  If the interlocus gene conversion events are compared, it will be frequently revealed that they exhibit biased directionality. Sometimes, such as in case of human globin genes, [ 21 ] [ 14 ]  the gene conversion direction correlates with the relative expression levels of the genes that participate in the event, with the gene expressed at higher level, called the 'master' gene, converting that with lower expression, called the 'slave' gene. Originally formulated in an evolutionary context, the 'master/slave gene' rule should be explained with caution. In fact, the increase in gene transcription exhibits not only the increase in likelihood of it to be used as a donor but also as an acceptor. [ 14 ] [ 22 ]


Normally, an organism that has inherited different copies of a gene from each of its parents is called heterozygous. This is generically represented as genotype: Aa (i.e. one copy of variant ( allele ) 'A', and one copy of allele 'a'). When a heterozygote creates gametes by  meiosis , the alleles normally duplicate and end up in a 2:2 ratio in the resulting 4 cells that are the direct products of meiosis. However, in gene conversion, a ratio other than the expected 2A:2a is observed, in which A and a are the two alleles. Examples are 3A:1a and 1A:3a. In other words, there can, for example, be three times as many A alleles as a alleles expressed in the daughter cells, as is the case in 3A:1a.


Gene conversion resulting in mutation of the  CYP21A2  gene is a common underlying genetic cause of  congenital adrenal hyperplasia . Somatic gene conversion is one of the mechanisms that can result in familial  retinoblastoma , a congenital cancer of the  retina , and it is theorized that gene conversion may play a role in the development of  Huntington's disease .


In  genetics , the  gene density  of an organism's  genome  is the ratio of the number of  genes  per number of  base pairs , usually written in terms of a million base pairs, or  megabase  (Mb). The  human genome  has a gene density of 11-15 genes/Mb, while the genome of the  C. elegans  roundworm is estimated to have 200. [ 1 ]


Seemingly simple organisms, such as  bacteria  and  amoebas , have a much higher gene density than humans. Bacterial  DNA  has a gene density on the order of 500-1000 genes/Mb. This is due several factors, including that the fact that bacterial DNA has no  introns . There are also fewer  codons  in bacterial genes. [ 2 ]


Gene count is calculated by the number of gene flags in the latest version of a given species gtf annotation file. Bear in mind that well studied organisms will probably have higher gene counts because these species have better annotation, therefore these numbers are estimates for comparison.


Gene dosage  is the number of copies of a particular  gene  present in a  genome . [ 1 ]  Gene dosage is related to the amount of  gene product  (proteins or functional RNAs) the cell is able to express. Since a gene acts as a template, the number of templates in the cell contributes to the amount of gene product able to be produced. However, the amount of gene product produced in a cell is more commonly dependent on  regulation of gene expression . [ 2 ]  The normal gene dosage is dependent on the species; humans generally have two doses -- one copy from the mother and one from the father. Changes in gene dosage can be a result of  copy number variation  (gene insertions or gene deletions), or  aneuploidy  (chromosome number abnormalities). These changes can have significant phenotypic consequences. [ 1 ]


Ploidy  refers to the number of complete sets of chromosomes in a cell.


Humans typically have a gene dosage of two. Because they are diploid, they have two sets of 23 different chromosomes. The number of copies of chromosomes generally correlates to the number of copies of a gene present in the genome. For example, the gene that codes for the beta-subunit of hemoglobin (HBB) is located on chromosome 11. Humans have 2 copies of chromosome 11, so they have 2 copies of the HBB gene. [ 3 ]


If an individual has an abnormal number of chromosomes, then it is called aneuploidy. Aneuploidy is very common in humans, with around 20-40% of all conceptions making a embryo displaying aneuploidy. [ 4 ]  Most aneuploidy events are fatal and lead to miscarriage. However, there are a few exceptions, including Down Syndrome and intersex conditions. Down Syndrome is caused by trisomy 21, which means having three copies of chromosome 21. Thus gene dosage is increased by 50% for the genes on that chromosome. Though not fully understood, it is thought that the increased expression of genes on chromosome 21 is the cause of some of the characteristic traits of  Down syndrome . The intersex condition,  Turner syndrome , occurs when a female only has one X chromosome, so she has one sex chromosome.  Klinefelter syndrome  is another intersex condition where a male has two X chromosomes and one Y chromosome, and so three sex chromosomes. All of these syndromes have characteristic changes in either appearance and/or behavior.


Not all species are diploid like humans [see  Polyploidy ]. For example, some species of strawberries are octoploid. Those species have eight copies of each chromosome, so they would have eight copies of each gene if that gene has only one copy per chromosome. Some species of wheat are hexaploid, and some species of watermelon are triploid.


Prokaryotes  reproduce through  asexual reproduction , usually by  binary fission . The bacterial chromosome is present only in one copy per cell. However, there still can be variation in gene dosage due to  DNA replication , which starts at the  origin of replication  and ends at the termination site. The genes that are closer to the origin site are replicated first and are consequently present in two copies in the cell for a longer time than the genes that are closer to the termination site. These slight gene dosage differences are responsible for variation in gene expression depending on their position on the chromosome. [ 5 ]


Copy number variation


Some genes have more than one copy on a chromosome; sometimes this is normal, and sometimes it is abnormal.


Gene nomenclature  is the scientific  naming  of  genes , the units of  heredity  in living organisms. It is also closely associated with  protein  nomenclature, as genes and the proteins they code for usually have similar nomenclature. An international committee published recommendations for genetic symbols and nomenclature in 1957. [ 1 ]  The need to develop formal guidelines for human gene names and symbols was recognized in the 1960s and full guidelines were issued in 1979 (Edinburgh Human Genome Meeting). [ 2 ]  Several other  genus -specific research communities (e.g.,  Drosophila  fruit flies,  Mus  mice) have adopted nomenclature standards, as well, and have published them on the relevant  model organism  websites and in scientific journals, including the  Trends in Genetics  Genetic Nomenclature Guide. [ 3 ] [ 4 ]  Scientists familiar with a particular  gene family  may work together to revise the nomenclature for the entire set of genes when new information becomes available. [ 5 ]  For many genes and their corresponding proteins, an assortment of alternate names is in use across the scientific literature and public  biological databases , posing a challenge to effective organization and exchange of biological information. [ 6 ]   Standardization  of nomenclature thus tries to achieve the benefits of  vocabulary control  and  bibliographic control , although adherence is voluntary. The advent of the  information age  has brought  gene ontology , which in some ways is a next step of gene nomenclature, because it aims to unify the representation of gene and gene product attributes across all species.


Gene nomenclature and  protein nomenclature  are not separate endeavors; they are aspects of the same whole. Any name or symbol used for a protein can potentially also be used for the gene that encodes it, and vice versa. [ citation needed ]  But owing to the nature of how science has developed (with knowledge being uncovered bit by bit over decades), proteins and their corresponding genes have not always been discovered simultaneously (and not always physiologically understood when discovered), which is the largest reason why protein and gene names do not always match, or why scientists tend to favor one symbol or name for the protein and another for the gene. [ citation needed ]  Another reason is that many of the mechanisms of life are the same or very similar across  species , genera, orders, and phyla (through  homology, analogy, or some of both ), so that a given protein may be produced in many kinds of organisms; and thus scientists naturally often use the same symbol and name for a given protein in one species (for example, mice) as in another species (for example, humans). Regarding the first duality (same symbol and name for gene or protein), the context usually makes the sense clear to scientific readers, and the nomenclatural systems also provide for some specificity by using  italic  for a symbol when the gene is meant and plain (roman) for when the protein is meant. [ citation needed ]  Regarding the second duality (a given protein is  endogenous  in many kinds of organisms), the nomenclatural systems also provide for at least human-versus-nonhuman specificity by using different  capitalization , [ citation needed ]  although scientists often ignore this distinction, given that it is often biologically irrelevant. [ citation needed ]


Also owing to the nature of how scientific knowledge has unfolded, proteins and their corresponding genes often have several names and symbols that are  synonymous . Some of the earlier ones may be  deprecated  in favor of newer ones, although such deprecation is voluntary. Some older names and symbols live on simply because they have been widely used in the  scientific literature  (including before the newer ones were coined) and are well established among users. For example,  mentions of  HER2  and  ERBB2  are synonymous .


Lastly, the correlation between genes and proteins is not always  one-to-one  (in either direction); in some cases it is several-to-one or one-to-several, and the names and symbols may then be gene-specific or protein-specific to some degree, or overlapping in usage:


The  HUGO Gene Nomenclature Committee  is responsible for providing human gene naming guidelines and approving new, unique human gene names and symbols (short  identifiers  typically created by abbreviating). For some nonhuman species, model organism databases serve as central repositories of guidelines and help resources, including advice from  curators  and nomenclature committees. In addition to species-specific databases, approved gene names and symbols for many species can be located in the  National Center for Biotechnology Information's   "Entrez Gene" [ 7 ]  database.


There are generally accepted rules and conventions used for naming  genes  in  bacteria . Standards were proposed in 1966 by Demerec et al. [ 8 ]


Each bacterial gene is denoted by a  mnemonic  of three lower case letters which indicate the pathway or process in which the gene-product is involved, followed by a capital letter signifying the actual gene. In some cases, the gene letter may be followed by an  allele  number. All letters and numbers are underlined or italicised.  For example,  leuA  is one of the genes of the  leucine  biosynthetic pathway, and  leuA273  is a particular allele of this gene.


Where the actual protein coded by the gene is known then it may become part of the basis of the mnemonic, thus:


Some gene designations refer to a known general function:


In a 1998 analysis of the  E. coli  genome, a large number of genes with unknown function were designated names beginning with the letter  y , followed by sequentially generated letters without a mnemonic meaning (e.g.,  ydiO  and  ydbK ). [ 9 ]  Since being designated, some  y-genes  have been confirmed to have a function, [ 10 ]  and assigned a synonym (alternative) name in recognition of this. However, as y-genes are not always re-named after being further characterised, this designation is not a reliable indicator of a gene's significance. [ 10 ]


Loss of gene activity leads to a nutritional requirement ( auxotrophy ) not exhibited by the  wildtype  ( prototrophy ).


Amino acids:


Some pathways produce metabolites that are precursors of more than one pathway. Hence, loss of one of these enzymes will lead to a requirement for more than one amino acid. For example:


Nucleotides:


Vitamins:


Loss of gene activity leads to loss of the ability to catabolise (use) the compound.


If the gene in question is the wildtype a superscript '+' sign is used:


If a gene is mutant, it is signified by a superscript '-':


By convention, if neither is used, it is considered to be mutant.


There are additional superscripts and subscripts which provide more information about the mutation:


Other modifiers:


When referring to the genotype (the gene) the mnemonic is italicized and not capitalised. When referring to the gene product or phenotype, the mnemonic is first-letter capitalised and not italicized ( e.g.  DnaA – the protein produced by the  dnaA  gene; LeuA −  – the phenotype of a  leuA  mutant; Amp R  – the ampicillin-resistance phenotype of the β-lactamase gene  bla ).


Protein names are generally the same as the gene names, but the protein names are not italicized, and the first letter is upper-case. E.g. the name of  R NA  po lymerase is RpoB, and this protein is encoded by  rpoB  gene. [ 11 ]


The research communities of  vertebrate  model organisms have adopted guidelines whereby genes in these species are given, whenever possible, the same names as their human  orthologs . The use of prefixes on gene symbols to indicate species (e.g., "Z" for zebrafish) is discouraged. The recommended formatting of printed gene and protein symbols varies between species.


Vertebrate genes and proteins have names (typically strings of words) and symbols, which are short  identifiers  (typically 3 to 8 characters). For example, the gene  cytotoxic T-lymphocyte-associated protein 4  has the HGNC symbol  CTLA4 . These symbols are usually, but not always, coined by  contraction  or  acronymic  abbreviation of the name. They are  pseudo-acronyms , however, in the sense that they are complete identifiers by themselves—short names, essentially. They are synonymous with (rather than standing for) the gene/protein name (or any of its aliases), regardless of whether the initial letters "match". For example, the symbol for the gene v-akt murine thymoma viral oncogene homolog 1, which is  AKT1 , cannot be said to be an acronym for the name, and neither can any of its various synonyms, which include  AKT ,  PKB ,  PRKBA , and  RAC . Thus, the relationship of a gene symbol to the gene name is functionally the relationship of a  nickname  to a formal name (both are complete  identifiers )—it is not the relationship of an acronym to its expansion. In this sense they are similar to the symbols for  units of measurement  in the SI system (such as km for the  kilometre ), in that they can be viewed as true  logograms  rather than just abbreviations. Sometimes the distinction is academic, but not always. Although it is not wrong to say that "VEGFA" is an acronym standing for " vascular endothelial growth factor A ", just as it is not wrong that "km" is an abbreviation for "kilometre", there is more to the formality of symbols than those statements capture.


The  root  portion of the symbols for a  gene family  (such as the " SERPIN " root in  SERPIN1 ,  SERPIN2 ,  SERPIN3 , and so on) is called a root symbol. [ 12 ]


The  HUGO Gene Nomenclature Committee  is responsible for providing human gene naming guidelines and approving new, unique human gene names and symbols (short  identifiers  typically created by abbreviating). All human gene names and symbols can be searched online at the HGNC [ 13 ]  website, and the guidelines for their formation are available there. [ 14 ]  The guidelines for humans fit logically into the larger scope of  vertebrates  in general, and the HGNC's remit has recently expanded to assigning symbols to all vertebrate species without an existing nomenclature committee, to ensure that vertebrate genes are named in line with their human orthologs/paralogs. Human gene symbols generally are italicised, with all letters in uppercase (e.g.,  SHH , for  sonic hedgehog ). Italics are not necessary in gene catalogs. Protein designations are the same as the gene symbol except that they are not italicised. Like the gene symbol, they are in  all caps  because human (human-specific or human homolog). mRNAs and cDNAs use the same formatting conventions as the gene symbol. [ 5 ]  For naming  families of genes , the HGNC recommends using a "root symbol" [ 15 ]  as the root for the various gene symbols. For example, for the  peroxiredoxin  family,  PRDX  is the root symbol, and the family members are  PRDX1 ,  PRDX2 ,  PRDX3 ,  PRDX4 ,  PRDX5 , and  PRDX6 .


Gene symbols generally are italicised, with only the first letter in uppercase and the remaining letters in lowercase ( Shh ). Italics are not required on web pages. Protein designations are the same as the gene symbol, but are not italicised and all are upper case (SHH). [ 16 ]


Nomenclature generally follows the conventions of human nomenclature. Gene symbols generally are italicised, with all letters in uppercase (e.g.,  NLGN1 , for neuroligin1). Protein designations are the same as the gene symbol, but are not italicised; all letters are in uppercase (NLGN1). mRNAs and cDNAs use the same formatting conventions as the gene symbol. [ 17 ]


Gene symbols are italicised and all letters are in lowercase ( shh ). Protein designations are different from their gene symbol; they are not italicised, and all letters are in uppercase (SHH). [ 18 ]


Gene symbols are italicised and all letters are in lowercase ( shh ). Protein designations are the same as the gene symbol, but are not italicised; the first letter is in uppercase and the remaining letters are in lowercase (Shh). [ 19 ]


Gene symbols are italicised, with all letters in lowercase ( shh ). Protein designations are the same as the gene symbol, but are not italicised; the first letter is in uppercase and the remaining letters are in lowercase (Shh). [ 20 ]


A nearly universal rule in copyediting of articles for  medical journals  and other health science publications is that abbreviations and acronyms must be  expanded  at first use, to provide a  glossing  type of explanation. Typically no exceptions are permitted except for small lists of especially well known terms (such as  DNA  or  HIV ). Although readers with high  subject-matter expertise  do not need most of these expansions, those with intermediate or (especially) low expertise are appropriately served by them.


One complication that gene and protein symbols bring to this general rule is that they are not, accurately speaking, abbreviations or acronyms, despite the fact that many were originally coined via abbreviating or acronymic etymology. They are  pseudoacronyms  (as  SAT  and  KFC  also are) because they do not "stand for" any expansion. Rather, the relationship of a gene symbol to the gene name is functionally the relationship of a  nickname  to a formal name (both are complete  identifiers )—it is not the relationship of an acronym to its expansion. In fact, many official gene symbol–gene name pairs do not even share their initial-letter sequences (although some do). Nevertheless, gene and protein symbols "look just like" abbreviations and acronyms, which presents the problem that "failing" to "expand" them (even though it is not actually a failure and there are no true expansions) creates the appearance of violating the spell-out-all-acronyms rule.


One common way of reconciling these two opposing forces is simply to exempt all gene and protein symbols from the glossing rule. This is certainly fast and easy to do, and in highly specialized journals, it is also justified because the entire target  readership  has high subject matter expertise. (Experts are not confused by the presence of symbols (whether known or novel) and they know where to look them up online for further details if needed.) But for journals with broader and more general target readerships, this action leaves the readers without any  explanatory annotation  and can leave them wondering what the apparent-abbreviation stands for and why it was not explained. Therefore, a good alternative solution is simply to put either the official gene name or a suitable short description (gene alias/other designation) in parentheses after the first use of the official gene/protein symbol. This meets both the formal requirement (the presence of a gloss) and the functional requirement (helping the reader to know what the symbol refers to). The same guideline applies to shorthand names for sequence variations;  AMA  says, "In general medical publications, textual explanations should accompany the shorthand terms at first mention." [ 21 ]  Thus "188del11" is glossed as "an 11-bp deletion at nucleotide 188." This corollary rule (which forms an adjunct to the spell-everything-out rule) often also follows the "abbreviation-leading" style of expansion that is becoming more prevalent in recent years. Traditionally, the abbreviation always followed the fully expanded form in parentheses at first use. This is still the general rule. But for certain classes of abbreviations or acronyms (such as  clinical trial  acronyms [e.g.,  ECOG ] or standardized polychemotherapy regimens [e.g.,  CHOP ]), this pattern may be reversed, because the short form is more widely used and the expansion is merely parenthetical to the discussion at hand. The same is true of gene/protein symbols.