FOS
protein-codingFos proto-oncogene, AP-1 transcription factor subunit, the group of Fos transcription factor family|Basic leucine zipper proteins
Gene summary
The Fos gene family consists of 4 members: FOS, FOSB, FOSL1, and FOSL2. These genes encode leucine zipper proteins that can dimerize with proteins of the JUN family, thereby forming the transcription factor complex AP-1. As such, the FOS proteins have been implicated as regulators of cell proliferation, differentiation, and transformation. In some cases, expression of the FOS gene has also been associated with apoptotic cell death. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0018883
Submitter: Orphanet
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to FOS variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005252.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 6 | 3 | 11 | ||
| missense | 1 | 31 | 3 | 35 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 1 | 34 | 9 | 3 | 47 |
Highest pathogenic variant AF is 6.8406473e-7
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005243.1 | 4 | MANE Select | |
| Ensembl | ENSP00000306245.4 | 4 | MANE Select | |
| Ensembl | ENSP00000442268.1 | 3 | Standard | |
| Ensembl | ENSP00000442268.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Relaxin signaling pathway - Homo sapiens (human)
- Oxytocin signaling pathway - Homo sapiens (human)
- T cell receptor signaling pathway - Homo sapiens (human)
- B cell receptor signaling pathway - Homo sapiens (human)
- Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)
Biological Process
- conditioned taste aversion
- DNA methylation
- regulation of transcription by RNA polymerase II
- transcription by RNA polymerase II
- inflammatory response
Molecular Function
- RNA polymerase II proximal promoter sequence-specific DNA binding
- RNA polymerase II core promoter sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- RNA polymerase II activating transcription factor binding
- DNA-binding transcription activator activity, RNA polymerase II-specific
Cellular Component
- nucleus
- nucleoplasm
- endoplasmic reticulum
- cytosol
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000303562
- Coding exons
- 4
- Length
- 3457
- Individuals with no LoFs
- 125743
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125748
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.08 | 170 | 215 | 0.792 | 0.0000112 | 2446 |
| Missense (PolyPhen) | 63 | 84.127 | 0.74887 | 923 | ||
| Synonymous | -0.0530 | 95 | 94.3 | 1.01 | 0.00000514 | 820 |
| Loss of Function | 2.41 | 3 | 12.0 | 0.249 | 6.06e-7 | 137 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000036 | 0.000035 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Nuclear phosphoprotein which forms a tight but non- covalently linked complex with the JUN/AP-1 transcription factor. In the heterodimer, FOS and JUN/AP-1 basic regions each seems to interact with symmetrical DNA half sites. On TGF-beta activation, forms a multimeric SMAD3/SMAD4/JUN/FOS complex at the AP1/SMAD- binding site to regulate TGF-beta-mediated signaling. Has a critical function in regulating the development of cells destined to form and maintain the skeleton. It is thought to have an important role in signal transduction, cell proliferation and differentiation. In growing cells, activates phospholipid synthesis, possibly by activating CDS1 and PI4K2A. This activity requires Tyr-dephosphorylation and association with the endoplasmic reticulum. {ECO:0000269|PubMed:16055710, ECO:0000269|PubMed:17160021, ECO:0000269|PubMed:22105363, ECO:0000269|PubMed:7588633, ECO:0000269|PubMed:9732876}.;
Recessive Scores
- pRec
- 0.967
Intolerance Scores
- LoFtool
- 0.255
- RVIS EVS
- -0.05
- RVIS percentile EVS
- 50.01
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |