FOS (Protein c-Fos) variants and mutations
FOS (also known as Protein c-Fos) is a human protein-coding gene encoding a protein c-Fos protein. Together with JUN-family proteins, it forms AP-1 transcriptional complexes that rapidly convert growth-factor and stress signals into gene-expression changes. Abnormal AP-1 activity can promote proliferation, inflammation, and tumor progression, and recurrent FOS rearrangements occur in certain bone tumors. This analysis covers 660 FOS variants and mutations. Of these, 83% have computational variant effect predictions. Disease context includes Crohn disease, inflammatory bowel disease, and smoking initiation. Example FOS variants include M2V, M2K, and S4*.
Variant analysis overview
- Gene: FOS
- Protein: Protein c-Fos
- UniProt accession: P01100
- Organism: Homo sapiens
- Variants analyzed: 660
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 385 unspecified-consequence records; 166 missense variants; 72 synonymous variants; 4 in-frame deletions; 14 frameshift variants; 7 stop-gained variants; 2 splice-region variants; 2 stop lost; 1 splice acceptor variant; 1 stop retained variant; 6 substitution
- Prediction scores: 545 variants have prediction scores (83% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Crohn disease, inflammatory bowel disease, smoking initiation, psoriasis, ulcerative colitis, neurodegenerative disease, osteopetrosis, ankylosing spondylitis, sclerosing cholangitis, alcohol drinking, seasonal allergic rhinitis, ocular hypotension.
Protein structure and variant hotspots
- Protein features: 1 domains; 7 post-translational modification sites.
- Structural context: 141 variants have structural context.
- PTM context: 8 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable FOS variants
Examples include M2V, M2K, S4*, S4L, S4S, G5D, G5S, G5V. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M2V (p.Met2Val), gnomAD 14-75278986-A-G, REVEL 0.40, MetaLR 0.49
- M2K (p.Met2Lys), gnomAD 14-75278987-T-A, REVEL 0.46, MetaLR 0.49
- S4* (p.Ser4Ter), TOPMed rs1359533864, gnomAD rs1359533864, CADD 37.00
- S4L (p.Ser4Leu), rs1359533864, NCI-TCGA Cosmic COSV1003, cosmic curated COSV10033, TOPMed rs1359533864, REVEL 0.06, MetaLR 0.15, Variant assessed as somatic; moderate impact.
- S4S (p.Ser4Ser), rs745318617, gnomAD 14-75278994-G-C, CADD 8.20
- G5D (p.Gly5Asp), Ensembl rs1478792356, REVEL 0.14, MetaLR 0.27
- G5S (p.Gly5Ser), gnomAD rs1299824967, REVEL 0.07, MetaLR 0.17
- G5V (p.Gly5Val), gnomAD 14-75278996-G-T, REVEL 0.15, MetaLR 0.29
- N7S (p.Asn7Ser), TOPMed rs1341043635, gnomAD rs1341043635, REVEL 0.05, MetaLR 0.12
- N7N (p.Asn7Asn), rs775518430, gnomAD 14-75279003-C-T, CADD 15.00
- N7K (p.Asn7Lys), gnomAD 14-75279003-C-G, REVEL 0.09, MetaLR 0.25
- A8E (p.Ala8Glu), gnomAD rs1283649601, REVEL 0.16, MetaLR 0.23
- A8S (p.Ala8Ser), gnomAD 14-75279004-G-T, REVEL 0.03, MetaLR 0.13
- A8A (p.Ala8Ala), rs1594901393, gnomAD 14-75279006-A-G, CADD 14.40
- D9D (p.Asp9Asp), rs1376999049, gnomAD 14-75279009-C-T, CADD 15.40
- D9E (p.Asp9Glu), gnomAD 14-75279009-C-A, REVEL 0.10, MetaLR 0.11
- E11Q (p.Glu11Gln), gnomAD 14-75279013-G-C, REVEL 0.14, MetaLR 0.27
- E11K (p.Glu11Lys), gnomAD 14-75279013-G-A, REVEL 0.18, MetaLR 0.21
- E11E (p.Glu11Glu), rs1566699923, gnomAD 14-75279015-G-A, CADD 14.90
- E54del (p.Glu54del), rs1357628386, gnomAD 14-75280567-CAGA-, CADD 24.40
- A12E (p.Ala12Glu), ExAC rs749267828, TOPMed rs749267828, gnomAD rs749267828, REVEL 0.23, MetaLR 0.40
- A12V (p.Ala12Val), ExAC rs749267828, TOPMed rs749267828, gnomAD rs749267828, REVEL 0.15, MetaLR 0.40
- A12G (p.Ala12Gly), gnomAD 14-75279017-C-G, REVEL 0.14, MetaLR 0.40
- S13L (p.Ser13Leu), ExAC rs768537632, gnomAD rs768537632, REVEL 0.14, MetaLR 0.32
- S13P (p.Ser13Pro), gnomAD 14-75279019-T-C, REVEL 0.15, MetaLR 0.20
- S14F (p.Ser14Phe), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10033, Variant assessed as somatic; moderate impact.
- S14S (p.Ser14Ser), rs1353278087, gnomAD 14-75279024-C-T, CADD 12.20
- S15F (p.Ser15Phe), gnomAD 14-75279026-C-T, REVEL 0.20, MetaLR 0.51
- S15S (p.Ser15Ser), gnomAD 14-75279027-C-T, CADD 15.40
- R16H (p.Arg16His), Ensembl rs1897195014, REVEL 0.34, MetaLR 0.53
- R16S (p.Arg16Ser), ExAC rs774334267, gnomAD rs774334267, REVEL 0.27, MetaLR 0.45
- C17G (p.Cys17Gly), ExAC rs202084337, gnomAD rs202084337
- C17Y (p.Cys17Tyr), gnomAD rs1448048786
- C17C (p.Cys17Cys), rs1897195121, gnomAD 14-75279033-C-T, CADD 16.10
- S19R (p.Ser19Arg), TOPMed rs1187522995, gnomAD rs1187522995
- S19S (p.Ser19Ser), rs1187522995, gnomAD 14-75279039-C-T, CADD 15.20
- A20P (p.Ala20Pro), ESP rs139508491, ExAC rs139508491, TOPMed rs139508491, gnomAD rs139508491, REVEL 0.24, MetaLR 0.41
- A20T (p.Ala20Thr), ESP rs139508491, ExAC rs139508491, TOPMed rs139508491, gnomAD rs139508491, REVEL 0.27, MetaLR 0.44
- A20S (p.Ala20Ser), gnomAD 14-75279040-G-T, REVEL 0.21, MetaLR 0.37
- A20V (p.Ala20Val), gnomAD 14-75279041-C-T, REVEL 0.21, MetaLR 0.44
- A20A (p.Ala20Ala), rs773306716, gnomAD 14-75279042-G-C, CADD 13.00
- S21Y (p.Ser21Tyr), gnomAD 14-75279044-C-A, REVEL 0.46, MetaLR 0.62
- S21S (p.Ser21Ser), rs1487435024, gnomAD 14-75279045-C-T, CADD 14.10
- P22L (p.Pro22Leu), ExAC rs760763610, TOPMed rs760763610, gnomAD rs760763610, REVEL 0.50, MetaLR 0.67
- P22Q (p.Pro22Gln), ExAC rs760763610, TOPMed rs760763610, gnomAD rs760763610
- P22P (p.Pro22Pro), rs1253018666, gnomAD 14-75279048-G-A, CADD 13.30
- A23S (p.Ala23Ser), gnomAD 14-75279049-G-T, REVEL 0.13, MetaLR 0.24
- A23A (p.Ala23Ala), rs1181947073, gnomAD 14-75279051-C-T, CADD 15.40
- G24E (p.Gly24Glu), Ensembl rs992850455
- G24R (p.Gly24Arg), Ensembl rs960012786, REVEL 0.34, MetaLR 0.46
- p.Gly24 Ala34del, rs1566699946, gnomAD 14-75279042-GTCCC, CADD 22.50
- G24A (p.Gly24Ala), gnomAD 14-75279051-CGGGG, CADD 32.00
- G24G (p.Gly24Gly), rs1379247271, gnomAD 14-75279054-G-T, CADD 13.50
- D25V (p.Asp25Val), Ensembl rs78326384
- D25G (p.Asp25Gly), gnomAD 14-75279056-A-G, REVEL 0.29, MetaLR 0.44
- D25D (p.Asp25Asp), rs766480635, gnomAD 14-75279057-T-C, CADD 14.40
- S26S (p.Ser26Ser), rs754314937, gnomAD 14-75279060-C-T, CADD 6.56
- L27V (p.Leu27Val), gnomAD 14-75279061-C-G, REVEL 0.13, MetaLR 0.31
- L27L (p.Leu27Leu), rs1594901431, gnomAD 14-75279063-C-T, CADD 12.70
- S28F (p.Ser28Phe), 1000Genomes rs563193220, ExAC rs563193220, TOPMed rs563193220, gnomAD rs563193220, REVEL 0.10, MetaLR 0.30
- S28P (p.Ser28Pro), gnomAD 14-75279064-T-C, REVEL 0.07, MetaLR 0.18
- Y29C (p.Tyr29Cys), ExAC rs765575516, TOPMed rs765575516, gnomAD rs765575516, REVEL 0.41, MetaLR 0.44
- Y29H (p.Tyr29His), TOPMed rs1297123496, REVEL 0.23, MetaLR 0.44
- Y29L (p.Tyr29Leu), rs1341280530, gnomAD 14-75279065-CTT-C, CADD 27.00
- Y29Y (p.Tyr29Tyr), rs1332061712, gnomAD 14-75279069-C-T, CADD 13.40
- Y30H (p.Tyr30His), gnomAD rs1360829507, REVEL 0.19, MetaLR 0.50
- Y30* (p.Tyr30Ter), gnomAD 14-75279072-C-G, CADD 36.00
- H31Q (p.His31Gln), TOPMed rs1257579493, gnomAD rs1257579493
- H31N (p.His31Asn), gnomAD 14-75279073-C-A, REVEL 0.11, MetaLR 0.12
- H31R (p.His31Arg), gnomAD 14-75279074-A-G, REVEL 0.09, MetaLR 0.14
- H31H (p.His31His), rs1257579493, gnomAD 14-75279075-C-T, CADD 7.67
- S32L (p.Ser32Leu), Ensembl rs1897196338
- P33S (p.Pro33Ser), gnomAD 14-75279079-C-T, REVEL 0.19, MetaLR 0.22
- P33P (p.Pro33Pro), rs753174473, gnomAD 14-75279081-C-T, CADD 7.69
- A34S (p.Ala34Ser), gnomAD 14-75279082-G-T, REVEL 0.16, MetaLR 0.36
- A34A (p.Ala34Ala), gnomAD 14-75279084-A-G, CADD 7.81
- S36S (p.Ser36Ser), rs1376432483, gnomAD 14-75279090-C-T, CADD 14.30
- F37del (p.Phe37del), rs1315892643, gnomAD 14-75279089-CCTT-, CADD 21.30
- S38S (p.Ser38Ser), rs1897196564, gnomAD 14-75279096-C-T, CADD 15.50
- S39T (p.Ser39Thr), TOPMed rs1473426535, gnomAD rs1473426535, REVEL 0.24, MetaLR 0.38
- S39G (p.Ser39Gly), gnomAD 14-75279097-A-G, REVEL 0.23, MetaLR 0.36
- M40L (p.Met40Leu), ExAC rs758695063, gnomAD rs758695063, REVEL 0.14, MetaLR 0.08
- M40T (p.Met40Thr), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10033, Variant assessed as somatic; moderate impact.
- M40R (p.Met40Arg), gnomAD 14-75279101-T-G, REVEL 0.19, MetaLR 0.18
- G41C (p.Gly41Cys), ExAC rs780840095, gnomAD rs780840095, REVEL 0.51, MetaLR 0.48
- G41S (p.Gly41Ser), gnomAD 14-75279103-G-A, REVEL 0.30, MetaLR 0.46
- G41V (p.Gly41Val), gnomAD 14-75279104-G-T, REVEL 0.46, MetaLR 0.48
- G41R (p.Gly41Arg), rs2139936568, gnomAD 14-75279948-G-A, CADD 8.67, SIFT 0.07
- S42L (p.Ser42Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S42S (p.Ser42Ser), rs750065249, gnomAD 14-75279108-G-A, CADD 3.80
- P43S (p.Pro43Ser), ExAC rs779749255, TOPMed rs779749255, gnomAD rs779749255, REVEL 0.26, MetaLR 0.42
- P43L (p.Pro43Leu), gnomAD 14-75279110-C-T, REVEL 0.31, MetaLR 0.48
- P43P (p.Pro43Pro), rs1277044696, gnomAD 14-75279111-T-A, CADD 3.17
- N45S (p.Asn45Ser), ExAC rs749214376, gnomAD rs749214376, REVEL 0.09, MetaLR 0.05, Uncertain significance, not specified
- A46V (p.Ala46Val), gnomAD rs1203741003, REVEL 0.04, MetaLR 0.08
- A46T (p.Ala46Thr), gnomAD 14-75279118-G-A, REVEL 0.07, MetaLR 0.04
- A46S (p.Ala46Ser), gnomAD 14-75279118-G-T, REVEL 0.10, MetaLR 0.03
- A46G (p.Ala46Gly), gnomAD 14-75279119-C-G, REVEL 0.05, MetaLR 0.08
- A46A (p.Ala46Ala), gnomAD 14-75279120-G-A, CADD 9.53
- Q47R (p.Gln47Arg), Ensembl rs1023466184
- Q47Q (p.Gln47Gln), rs768770253, gnomAD 14-75279123-G-A, CADD 23.10
- Q47E (p.Gln47Glu), rs1159087315, gnomAD 14-75279909-C-G, CADD 15.20, SIFT 0.03
- Q47* (p.Gln47Ter), rs1159087315, gnomAD 14-75279909-C-T, CADD 15.60
- D48E (p.Asp48Glu), gnomAD rs1169737592, REVEL 0.03, MetaLR 0.08
- D48H (p.Asp48His), Ensembl rs1897206168
- F49L (p.Phe49Leu), gnomAD rs1397471123, REVEL 0.14, MetaLR 0.09
- F49S (p.Phe49Ser), TOPMed rs1897206245
- C50R (p.Cys50Arg), gnomAD rs1386493581, REVEL 0.22, MetaLR 0.11
- T51R (p.Thr51Arg), gnomAD 14-75279887-C-G, REVEL 0.12, MetaLR 0.18
- T51M (p.Thr51Met), gnomAD 14-75279887-C-T, REVEL 0.14, MetaLR 0.19
- T51T (p.Thr51Thr), rs200415205, gnomAD 14-75279888-G-A, CADD 8.94
- D52E (p.Asp52Glu), gnomAD rs1897206461, REVEL 0.07, MetaLR 0.12
- D52N (p.Asp52Asn), Ensembl rs761521741
- L53P (p.Leu53Pro), gnomAD 14-75279893-T-C, REVEL 0.58, MetaLR 0.40
- L53L (p.Leu53Leu), rs144239514, gnomAD 14-75279894-G-A, CADD 15.00
- L53F (p.Leu53Phe), rs747221475, gnomAD 14-75279936-C-T, CADD 13.90, SIFT 1.00
- A54T (p.Ala54Thr), Ensembl rs150228591
- A54V (p.Ala54Val), NCI-TCGA TCGA novel, REVEL 0.04, MetaLR 0.10, Variant assessed as somatic; moderate impact.
- A54D (p.Ala54Asp), gnomAD 14-75279896-C-A, REVEL 0.06, MetaLR 0.11
- A54A (p.Ala54Ala), gnomAD 14-75279897-C-T, CADD 9.31
- V55A (p.Val55Ala), TOPMed rs1897206646, REVEL 0.04, MetaLR 0.06
- V55I (p.Val55Ile), cosmic curated COSV57840, gnomAD rs1405963852, REVEL 0.07, MetaLR 0.12
- V55V (p.Val55Val), gnomAD 14-75279900-C-G, CADD 13.50
- S56S (p.Ser56Ser), gnomAD 14-75279903-C-T, CADD 14.50
- S57I (p.Ser57Ile), TOPMed rs1897206682
- S57V (p.Ser57Val), gnomAD 14-75279901-TC-T, CADD 31.00
- A58P (p.Ala58Pro), gnomAD 14-75279906-T-TCC, CADD 25.10
- N59K (p.Asn59Lys), TOPMed rs1897206777, REVEL 0.05, MetaLR 0.08, Uncertain significance, not specified
- N59S (p.Asn59Ser), gnomAD 14-75279911-A-G, REVEL 0.13, MetaLR 0.04
- F60L (p.Phe60Leu), gnomAD 14-75279915-C-A, REVEL 0.37, MetaLR 0.33
- I61M (p.Ile61Met), ExAC rs778847921, gnomAD rs778847921, REVEL 0.21, MetaLR 0.19
- I61V (p.Ile61Val), TOPMed rs926276216, gnomAD rs926276216, REVEL 0.08, MetaLR 0.04
- I61T (p.Ile61Thr), gnomAD 14-75279917-T-C, REVEL 0.27, MetaLR 0.18
- P62S (p.Pro62Ser), TOPMed rs1897206923, REVEL 0.56, MetaLR 0.46
- P62A (p.Pro62Ala), gnomAD 14-75279919-C-G, REVEL 0.60, MetaLR 0.46
- T63A (p.Thr63Ala), ESP rs374460026, ExAC rs374460026, gnomAD rs374460026
- T63M (p.Thr63Met), ExAC rs771873149, gnomAD rs771873149, REVEL 0.49, MetaLR 0.43
- T63R (p.Thr63Arg), rs1278046677, gnomAD 14-75279916-AT-A, CADD 29.90
- T63K (p.Thr63Lys), gnomAD 14-75279923-C-A, REVEL 0.49, MetaLR 0.43
- V64A (p.Val64Ala), gnomAD 14-75279926-T-C, REVEL 0.42, MetaLR 0.31
- V64M (p.Val64Met), gnomAD 14-75279957-G-A, CADD 12.40, SIFT 0.00
- I67V (p.Ile67Val), gnomAD rs1207749111, REVEL 0.18, MetaLR 0.16
- S68W (p.Ser68Trp), Ensembl rs1044633931
- T69I (p.Thr69Ile), TOPMed rs1472232276, gnomAD rs1472232276, REVEL 0.31, MetaLR 0.41
- T69N (p.Thr69Asn), gnomAD 14-75279941-C-A, REVEL 0.26, MetaLR 0.41
- S70I (p.Ser70Ile), Ensembl rs2139936550, REVEL 0.36, MetaLR 0.44
- P71R (p.Pro71Arg), TOPMed rs1000193997, gnomAD rs1000193997, REVEL 0.34, MetaLR 0.39, Uncertain significance, not specified
- P71T (p.Pro71Thr), 1000Genomes rs148786753, ESP rs148786753, ExAC rs148786753, TOPMed rs148786753, REVEL 0.27, MetaLR 0.51
- P71S (p.Pro71Ser), gnomAD 14-75279946-C-T, REVEL 0.26, MetaLR 0.51
- P71L (p.Pro71Leu), gnomAD 14-75279947-C-T, REVEL 0.32, MetaLR 0.35
- D72E (p.Asp72Glu), gnomAD 14-75279951-C-G, REVEL 0.36, MetaLR 0.33
- L73M (p.Leu73Met), TOPMed rs1209982378
- L73V (p.Leu73Val), gnomAD 14-75279981-C-G, CADD 11.50, SIFT 0.09
- L73F (p.Leu73Phe), rs1212518561, gnomAD 14-75279981-C-T, CADD 11.90, SIFT 0.20
- Q74K (p.Gln74Lys), gnomAD rs1897207496, REVEL 0.41, MetaLR 0.39
- W75C (p.Trp75Cys), Ensembl rs1897207533, REVEL 0.60, MetaLR 0.53
- L76P (p.Leu76Pro), gnomAD 14-75279962-T-C, REVEL 0.54, MetaLR 0.37
- V77G (p.Val77Gly), cosmic curated COSV57840, ExAC rs74685695, gnomAD rs74685695, REVEL 0.63, MetaLR 0.40
- V77M (p.Val77Met), TOPMed rs1267404934
- Q78E (p.Gln78Glu), ExAC rs759555917, gnomAD rs759555917, REVEL 0.40, MetaLR 0.43
- Q78R (p.Gln78Arg), ExAC rs769885316, gnomAD rs769885316, REVEL 0.52, MetaLR 0.41
- Q78A (p.Gln78Ala), rs1478797379, gnomAD 14-75279964-G-GT, CADD 32.00
- Q78K (p.Gln78Lys), gnomAD 14-75279967-C-A, REVEL 0.39, MetaLR 0.43
- P79S (p.Pro79Ser), TOPMed rs1345359778, gnomAD rs1345359778, REVEL 0.37, MetaLR 0.48
- P79T (p.Pro79Thr), gnomAD 14-75279970-C-A, REVEL 0.52, MetaLR 0.53
- A80P (p.Ala80Pro), 1000Genomes rs200973067, ExAC rs200973067, TOPMed rs200973067, gnomAD rs200973067, REVEL 0.10, MetaLR 0.11
- A80S (p.Ala80Ser), 1000Genomes rs200973067, ExAC rs200973067, TOPMed rs200973067, gnomAD rs200973067, REVEL 0.05, MetaLR 0.08
- A80T (p.Ala80Thr), rs766059225, gnomAD 14-75279999-G-A, CADD 12.40, SIFT 0.12
- L81R (p.Leu81Arg), Ensembl rs1171330070, REVEL 0.53, MetaLR 0.40
- L81V (p.Leu81Val), gnomAD 14-75280038-C-G, CADD 8.24, SIFT 0.68
- L81F (p.Leu81Phe), rs1240933856, gnomAD 14-75280053-C-T, CADD 9.57, SIFT 0.19
- V82G (p.Val82Gly), Ensembl rs2139936628
- V82I (p.Val82Ile), gnomAD 14-75279979-G-A, REVEL 0.11, MetaLR 0.04
- S84T (p.Ser84Thr), gnomAD 14-75280014-T-A, CADD 9.18, SIFT 0.13
- V85L (p.Val85Leu), ExAC rs774634258, gnomAD rs774634258, REVEL 0.21, MetaLR 0.40
- V85F (p.Val85Phe), rs774634258, []
- A86V (p.Ala86Val), rs1295646143, NCI-TCGA Cosmic COSV1003, cosmic curated COSV10033, gnomAD rs1295646143, REVEL 0.31, MetaLR 0.45, Variant assessed as somatic; moderate impact.
- P87R (p.Pro87Arg), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10033, Variant assessed as somatic; moderate impact.
- P87S (p.Pro87Ser), TOPMed rs1897208308, REVEL 0.32, MetaLR 0.42
- P87T (p.Pro87Thr), gnomAD 14-75279994-C-A, REVEL 0.40, MetaLR 0.50
Public FOS analysis runs
- FOS analysis run — FOS (660 variants) — completed 2026-08-19