FOXA1 (P55317) variants and mutations
FOXA1 (also known as P55317) is a human protein-coding gene encoding a hepatocyte nuclear factor 3-alpha protein. It acts as a pioneer transcription factor that opens compacted chromatin and helps steroid receptors access lineage-specific regulatory regions. Alterations can reprogram androgen- or estrogen-receptor signaling and are important drivers of prostate and breast cancer. This analysis covers 1,966 FOXA1 variants and mutations. Of these, 56% have computational variant effect predictions. Disease context includes prostate adenocarcinoma, breast adenocarcinoma, and prostate carcinoma. Example FOXA1 variants include L2F, L2S, and G3A.
Variant analysis overview
- Gene: FOXA1
- Protein: P55317
- UniProt accession: P55317
- Organism: Homo sapiens
- Variants analyzed: 1966
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 1,612 unspecified-consequence records; 191 synonymous variants; 127 missense variants; 7 stop-gained variants; 18 frameshift variants; 1 in-frame insertions; 7 in-frame deletions; 3 substitution
- Prediction scores: 1,094 variants have prediction scores (56% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: prostate adenocarcinoma, breast adenocarcinoma, prostate carcinoma, prostate small cell carcinoma, breast ductal adenocarcinoma, breast lobular carcinoma, mixed lobular and ductal breast carcinoma, breast carcinoma by gene expression profile, breast carcinoma, colorectal adenocarcinoma, hepatocellular carcinoma, non-small cell lung carcinoma.
Protein structure and variant hotspots
- Protein features: 2 post-translational modification sites.
- PTM context: 12 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 FOXA1 variants
Examples include L2F, L2S, G3A, G3E, G3R, T4N, V5G, V5M. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- L2F (p.Leu2Phe), 1000Genomes rs2139188245, REVEL 0.64, MetaLR 0.92
- L2S (p.Leu2Ser), ExAC rs749317547, gnomAD rs749317547, REVEL 0.70, MetaLR 0.92
- G3A (p.Gly3Ala), TOPMed rs1406059545, gnomAD rs1406059545, REVEL 0.31, MetaLR 0.67
- G3E (p.Gly3Glu), TOPMed rs1406059545, gnomAD rs1406059545, REVEL 0.32, MetaLR 0.65
- G3R (p.Gly3Arg), TOPMed rs1382070601, gnomAD rs1382070601, REVEL 0.32, MetaLR 0.68
- T4N (p.Thr4Asn), TOPMed rs2095600743, gnomAD rs2095600743, REVEL 0.33, MetaLR 0.45
- V5G (p.Val5Gly), Ensembl rs2139188200
- V5M (p.Val5Met), TOPMed rs1007881450, REVEL 0.64, MetaLR 0.91
- K6N (p.Lys6Asn), TOPMed rs2095600728, REVEL 0.40, MetaLR 0.71
- M7T (p.Met7Thr), gnomAD rs1166386427, REVEL 0.76, MetaLR 0.85
- E8K (p.Glu8Lys), NCI-TCGA Cosmic COSV9916, REVEL 0.73, MetaLR 0.91, Variant assessed as somatic; moderate impact.
- G9R (p.Gly9Arg), TOPMed rs1382142512, gnomAD rs1382142512, REVEL 0.75, MetaLR 0.80
- G9V (p.Gly9Val), NCI-TCGA TCGA novel, REVEL 0.76, MetaLR 0.78, Variant assessed as somatic; moderate impact.
- H10N (p.His10Asn), TOPMed rs2095600712, REVEL 0.68, MetaLR 0.87
- E11K (p.Glu11Lys), NCI-TCGA Cosmic COSV9916, REVEL 0.73, MetaLR 0.77, Variant assessed as somatic; moderate impact.
- S13R (p.Ser13Arg), gnomAD rs1249735550, REVEL 0.29, MetaLR 0.54
- D14E (p.Asp14Glu), Ensembl rs2139188147, REVEL 0.25, MetaLR 0.49
- D14G (p.Asp14Gly), TOPMed rs1188937831, gnomAD rs1188937831, REVEL 0.72, MetaLR 0.69
- D14H (p.Asp14His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- W15* (p.Trp15Ter), TOPMed rs1157025978, gnomAD rs1157025978, CADD 35.00
- W15C (p.Trp15Cys), TOPMed rs1157025978, gnomAD rs1157025978, REVEL 0.88, MetaLR 0.90
- W15G (p.Trp15Gly), TOPMed rs1404986030, gnomAD rs1404986030, REVEL 0.87, MetaLR 0.90
- Y18N (p.Tyr18Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- Y19C (p.Tyr19Cys), ExAC rs751532891, gnomAD rs751532891, REVEL 0.40, MetaLR 0.19
- Y19H (p.Tyr19His), ExAC rs754806369, gnomAD rs754806369, REVEL 0.37, MetaLR 0.21
- A20S (p.Ala20Ser), Ensembl rs2095600683, REVEL 0.03, MetaLR 0.02
- A20T (p.Ala20Thr), Ensembl rs2095600683, REVEL 0.04, MetaLR 0.02
- Q23H (p.Gln23His), 1000Genomes rs139801655, ESP rs139801655, ExAC rs139801655, TOPMed rs139801655, REVEL 0.13, MetaLR 0.08
- E24K (p.Glu24Lys), NCI-TCGA Cosmic COSV5164, Ensembl rs1566826601, Variant assessed as somatic; moderate impact.
- E24Q (p.Glu24Gln), Ensembl rs1566826601
- A25V (p.Ala25Val), Ensembl rs2139184300
- Y26C (p.Tyr26Cys), ExAC rs771360009, TOPMed rs771360009, gnomAD rs771360009, REVEL 0.39, MetaLR 0.18
- S27A (p.Ser27Ala), ExAC rs763040361, TOPMed rs763040361, gnomAD rs763040361, REVEL 0.13, MetaLR 0.08, Uncertain significance, not specified
- S27F (p.Ser27Phe), gnomAD rs1303594032, REVEL 0.32, MetaLR 0.16
- S28P (p.Ser28Pro), NCI-TCGA Cosmic COSV5164, Variant assessed as somatic; moderate impact.
- V29A (p.Val29Ala), Ensembl rs2139184278
- V29F (p.Val29Phe), TOPMed rs2095597293
- V29I (p.Val29Ile), NCI-TCGA Cosmic COSV5164, TOPMed rs2095597293, REVEL 0.12, MetaLR 0.08, Variant assessed as somatic; moderate impact.
- V29L (p.Val29Leu), TOPMed rs2095597293
- P30L (p.Pro30Leu), Ensembl rs2095597279, REVEL 0.08, MetaLR 0.04
- P30R (p.Pro30Arg), Ensembl rs2095597279, REVEL 0.09, MetaLR 0.05
- P30S (p.Pro30Ser), gnomAD rs1344315520, REVEL 0.16, MetaLR 0.04
- V31D (p.Val31Asp), Ensembl rs2139184256
- V31G (p.Val31Gly), Ensembl rs2139184256
- V31L (p.Val31Leu), Ensembl rs2139184258
- S32C (p.Ser32Cys), TOPMed rs2095597271
- S32N (p.Ser32Asn), gnomAD rs1458740505, REVEL 0.12, MetaLR 0.08
- M34I (p.Met34Ile), TOPMed rs1375221568, gnomAD rs1375221568, REVEL 0.77, MetaLR 0.77
- M34K (p.Met34Lys), ExAC rs770046064, TOPMed rs770046064, gnomAD rs770046064
- M34L (p.Met34Leu), gnomAD rs2095597259, REVEL 0.54, MetaLR 0.63
- M34Q (p.Met34Gln), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- M34R (p.Met34Arg), ExAC rs770046064, TOPMed rs770046064, gnomAD rs770046064
- M34T (p.Met34Thr), ExAC rs770046064, TOPMed rs770046064, gnomAD rs770046064, REVEL 0.81, MetaLR 0.83
- N35H (p.Asn35His), TOPMed rs1450673506, gnomAD rs1450673506, REVEL 0.60, MetaLR 0.83
- N35K (p.Asn35Lys), 1000Genomes rs533636044, ExAC rs533636044, gnomAD rs533636044, REVEL 0.46, MetaLR 0.73
- N35Y (p.Asn35Tyr), NCI-TCGA Cosmic COSV5164, Variant assessed as somatic; moderate impact.
- S36T (p.Ser36Thr), Ensembl rs2139184222
- G37A (p.Gly37Ala), Ensembl rs80196093
- G37V (p.Gly37Val), Ensembl rs80196093
- G39D (p.Gly39Asp), Ensembl rs2139184204, REVEL 0.32, MetaLR 0.09
- G39R (p.Gly39Arg), Ensembl rs2139184210
- G39S (p.Gly39Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G39V (p.Gly39Val), Ensembl rs2139184204
- S40C (p.Ser40Cys), ESP rs372790088, ExAC rs372790088, TOPMed rs372790088, gnomAD rs372790088, REVEL 0.17, MetaLR 0.08
- M41I (p.Met41Ile), NCI-TCGA Cosmic COSV5164, REVEL 0.29, MetaLR 0.11, Variant assessed as somatic; moderate impact.
- M41R (p.Met41Arg), 1000Genomes rs571158363, ExAC rs571158363, TOPMed rs571158363, gnomAD rs571158363
- M41T (p.Met41Thr), 1000Genomes rs571158363, ExAC rs571158363, TOPMed rs571158363, gnomAD rs571158363, REVEL 0.34, MetaLR 0.14
- N42Y (p.Asn42Tyr), Ensembl rs2139184187
- S43C (p.Ser43Cys), ExAC rs757052588, gnomAD rs757052588, REVEL 0.25, MetaLR 0.14
- S43F (p.Ser43Phe), ExAC rs757052588, gnomAD rs757052588
- S43P (p.Ser43Pro), ExAC rs778522379, TOPMed rs778522379, gnomAD rs778522379, REVEL 0.24, MetaLR 0.06, Uncertain significance, not specified
- M44I (p.Met44Ile), NCI-TCGA TCGA novel, Ensembl rs2139184162, REVEL 0.28, MetaLR 0.21, Variant assessed as somatic; high impact.
- M44R (p.Met44Arg), ExAC rs777563544, TOPMed rs777563544, gnomAD rs777563544, REVEL 0.55, MetaLR 0.23
- M44T (p.Met44Thr), ExAC rs777563544, TOPMed rs777563544, gnomAD rs777563544, REVEL 0.39, MetaLR 0.23
- M44V (p.Met44Val), ExAC rs753616150, TOPMed rs753616150, gnomAD rs753616150, REVEL 0.32, MetaLR 0.23
- T46I (p.Thr46Ile), NCI-TCGA Cosmic COSV5164, TOPMed rs2095597209, Variant assessed as somatic; moderate impact.
- T46S (p.Thr46Ser), Ensembl rs2139184150
- Y47H (p.Tyr47His), Ensembl rs1432467776
- Y47N (p.Tyr47Asn), Ensembl rs1432467776
- M48I (p.Met48Ile), Ensembl rs2139184133, REVEL 0.28, MetaLR 0.08
- M50I (p.Met50Ile), ExAC rs752132466, gnomAD rs752132466, REVEL 0.12, MetaLR 0.08
- M50K (p.Met50Lys), ExAC rs760082238, TOPMed rs760082238, gnomAD rs760082238, Uncertain significance
- M50L (p.Met50Leu), ESP rs140306561, ExAC rs140306561, TOPMed rs140306561, gnomAD rs140306561, REVEL 0.18, MetaLR 0.04, Uncertain significance
- M50R (p.Met50Arg), rs760082238, ClinGen CA7160214, ClinVar RCV004228129, ExAC rs760082238, REVEL 0.32, MetaLR 0.13, Uncertain significance, not specified
- M50V (p.Met50Val), rs140306561, ClinGen CA7160215, ClinVar RCV004167642, ESP rs140306561, REVEL 0.20, MetaLR 0.07, Uncertain significance, not specified
- N51K (p.Asn51Lys), Ensembl rs2139184110
- N51Y (p.Asn51Tyr), Ensembl rs2139184114
- T52I (p.Thr52Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- T52N (p.Thr52Asn), TOPMed rs906738343
- T52P (p.Thr52Pro), ExAC rs766847827, TOPMed rs766847827, gnomAD rs766847827, REVEL 0.15, MetaLR 0.03
- T52S (p.Thr52Ser), ExAC rs766847827, TOPMed rs766847827, gnomAD rs766847827, REVEL 0.09, MetaLR 0.04
- M53I (p.Met53Ile), Ensembl rs2139184093
- M53R (p.Met53Arg), Ensembl rs2095597177
- M53T (p.Met53Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- M53V (p.Met53Val), TOPMed rs1360932810
- T54A (p.Thr54Ala), TOPMed rs2095597171, REVEL 0.08, MetaLR 0.04
- T54I (p.Thr54Ile), ExAC rs763349376, gnomAD rs763349376, REVEL 0.10, MetaLR 0.05
- T54S (p.Thr54Ser), ExAC rs763349376, gnomAD rs763349376, REVEL 0.09, MetaLR 0.02
- T55K (p.Thr55Lys), TOPMed rs1019690230, gnomAD rs1019690230, REVEL 0.08, MetaLR 0.05, Uncertain significance, not specified
- T55M (p.Thr55Met), rs1019690230, NCI-TCGA Cosmic COSV9916, TOPMed rs1019690230, gnomAD rs1019690230, REVEL 0.06, MetaLR 0.04, Variant assessed as somatic; moderate impact.
- S56G (p.Ser56Gly), Ensembl rs2139184076
- S56R (p.Ser56Arg), TOPMed rs1566824925, REVEL 0.31, MetaLR 0.10
- G57C (p.Gly57Cys), ExAC rs769942089, TOPMed rs769942089, gnomAD rs769942089, REVEL 0.23, MetaLR 0.08
- G57D (p.Gly57Asp), Ensembl rs2139184063, REVEL 0.20, MetaLR 0.10
- G57R (p.Gly57Arg), ExAC rs769942089, TOPMed rs769942089, gnomAD rs769942089, REVEL 0.23, MetaLR 0.09
- G57S (p.Gly57Ser), ExAC rs769942089, TOPMed rs769942089, gnomAD rs769942089, REVEL 0.05, MetaLR 0.04
- N58K (p.Asn58Lys), Ensembl rs2095597155, REVEL 0.18, MetaLR 0.11
- N58S (p.Asn58Ser), TOPMed rs1353832949, gnomAD rs1353832949, REVEL 0.10, MetaLR 0.04
- M59I (p.Met59Ile), rs1165110401, gnomAD rs1165110401, NCI-TCGA Cosmic COSV5164, AlphaMissense 0.43, MetaLR 0.73, Variant assessed as somatic; moderate impact.
- M59K (p.Met59Lys), TOPMed rs887208594, gnomAD rs887208594, REVEL 0.76, MetaLR 0.77
- M59T (p.Met59Thr), TOPMed rs887208594, gnomAD rs887208594, REVEL 0.50, MetaLR 0.68
- M59V (p.Met59Val), TOPMed rs1208394972, gnomAD rs1208394972, REVEL 0.31, MetaLR 0.67, Uncertain significance, not specified
- T60I (p.Thr60Ile), TOPMed rs2095597141, REVEL 0.55, MetaLR 0.81
- P61L (p.Pro61Leu), ExAC rs201436632, gnomAD rs201436632, REVEL 0.24, MetaLR 0.64, Uncertain significance, not specified
- P61R (p.Pro61Arg), ExAC rs201436632, gnomAD rs201436632
- P61S (p.Pro61Ser), Ensembl rs898912091, REVEL 0.25, MetaLR 0.39
- A62P (p.Ala62Pro), Ensembl rs2139184029
- A62V (p.Ala62Val), rs186148706, 1000Genomes rs186148706, ExAC rs186148706, gnomAD rs186148706, REVEL 0.06, MetaLR 0.03, Variant assessed as somatic; moderate impact.
- S63C (p.Ser63Cys), Ensembl rs2139184022
- S63Y (p.Ser63Tyr), Ensembl rs2139184022
- F64I (p.Phe64Ile), ExAC rs747106044, gnomAD rs747106044, REVEL 0.15, MetaLR 0.09
- F64L (p.Phe64Leu), ExAC rs747106044, gnomAD rs747106044, REVEL 0.17, MetaLR 0.08
- N65S (p.Asn65Ser), rs200438155, ClinGen CA7160204, ClinVar RCV004392106, 1000Genomes rs200438155, REVEL 0.16, MetaLR 0.08, Uncertain significance, not specified
- M66I (p.Met66Ile), gnomAD rs1489514341, REVEL 0.38, MetaLR 0.20
- M66T (p.Met66Thr), ExAC rs749094950, gnomAD rs749094950, REVEL 0.39, MetaLR 0.18
- M66V (p.Met66Val), ExAC rs770840380, gnomAD rs770840380
- S67T (p.Ser67Thr), Ensembl rs2139184003
- Y68F (p.Tyr68Phe), Ensembl rs2139183999
- Y68H (p.Tyr68His), gnomAD rs2095597116, REVEL 0.39, MetaLR 0.13
- A69P (p.Ala69Pro), Ensembl rs2139183997
- A69S (p.Ala69Ser), Ensembl rs2139183997
- A69T (p.Ala69Thr), Ensembl rs2139183997
- A69V (p.Ala69Val), TOPMed rs1266097110, gnomAD rs1266097110
- N70I (p.Asn70Ile), TOPMed rs943056111
- N70T (p.Asn70Thr), TOPMed rs943056111
- P71R (p.Pro71Arg), Ensembl rs2139183974
- P71T (p.Pro71Thr), ExAC rs777725133, TOPMed rs777725133, gnomAD rs777725133, REVEL 0.10, MetaLR 0.03
- G72A (p.Gly72Ala), UniProt VAR 015183
- G72C (p.Gly72Cys), ExAC rs755762174, gnomAD rs755762174, REVEL 0.33, MetaLR 0.13
- G72S (p.Gly72Ser), ExAC rs755762174, gnomAD rs755762174, REVEL 0.22, MetaLR 0.09
- G72V (p.Gly72Val), Ensembl rs2139183966
- L73R (p.Leu73Arg), rs2548700257, ClinGen CA389515358, ClinVar RCV004095079, Uncertain significance, not specified
- G74R (p.Gly74Arg), Ensembl rs77215770, REVEL 0.23, MetaLR 0.11
- A75G (p.Ala75Gly), ExAC rs780802269, gnomAD rs780802269
- A75V (p.Ala75Val), ExAC rs780802269, gnomAD rs780802269, REVEL 0.11, MetaLR 0.08
- G76A (p.Gly76Ala), Ensembl rs2095597078
- G76C (p.Gly76Cys), ESP rs368989227, ExAC rs368989227, TOPMed rs368989227, gnomAD rs368989227, REVEL 0.24, MetaLR 0.16, Uncertain significance
- G76D (p.Gly76Asp), Ensembl rs2095597078
- G76R (p.Gly76Arg), rs368989227, ClinGen CA7160196, ClinVar RCV004187931, ESP rs368989227, REVEL 0.31, MetaLR 0.15, Uncertain significance, not specified
- G76S (p.Gly76Ser), ESP rs368989227, ExAC rs368989227, TOPMed rs368989227, gnomAD rs368989227, Uncertain significance
- S78G (p.Ser78Gly), Ensembl rs2139183921
- P79L (p.Pro79Leu), NCI-TCGA TCGA novel, gnomAD rs1387961059, REVEL 0.20, MetaLR 0.06, Variant assessed as somatic; moderate impact.
- P79R (p.Pro79Arg), gnomAD rs1387961059, REVEL 0.26, MetaLR 0.11
- P79S (p.Pro79Ser), ExAC rs763380198, TOPMed rs763380198, gnomAD rs763380198, REVEL 0.12, MetaLR 0.06
- G80A (p.Gly80Ala), Ensembl rs2139183891, REVEL 0.10, MetaLR 0.04
- G80C (p.Gly80Cys), ExAC rs761971884, TOPMed rs761971884, gnomAD rs761971884
- G80R (p.Gly80Arg), ExAC rs761971884, TOPMed rs761971884, gnomAD rs761971884, REVEL 0.14, MetaLR 0.07
- G80S (p.Gly80Ser), ExAC rs761971884, TOPMed rs761971884, gnomAD rs761971884, REVEL 0.06, MetaLR 0.02
- A81E (p.Ala81Glu), NCI-TCGA Cosmic COSV5164, Variant assessed as somatic; moderate impact.
- A81S (p.Ala81Ser), Ensembl rs2139183884, REVEL 0.03, MetaLR 0.02
- A81T (p.Ala81Thr), Ensembl rs2139183884, REVEL 0.02, MetaLR 0.02
- V82A (p.Val82Ala), gnomAD rs1197445288, REVEL 0.12, MetaLR 0.04
- V82G (p.Val82Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- V82I (p.Val82Ile), ExAC rs776810070, gnomAD rs776810070, REVEL 0.05, MetaLR 0.04
- A83D (p.Ala83Asp), TOPMed rs1206030230, gnomAD rs1206030230, REVEL 0.06, MetaLR 0.05
- A83P (p.Ala83Pro), 1000Genomes rs7144658, ESP rs7144658, ExAC rs7144658, TOPMed rs7144658, REVEL 0.05, MetaLR 0.05
- A83T (p.Ala83Thr), rs7144658, UniProt VAR 013457, 1000Genomes rs7144658, ESP rs7144658, REVEL 0.03, MetaLR 0.00
- A83V (p.Ala83Val), TOPMed rs1206030230, gnomAD rs1206030230, REVEL 0.09, MetaLR 0.06
- G84D (p.Gly84Asp), Ensembl rs2139183828
- G84R (p.Gly84Arg), 1000Genomes rs201324809, ExAC rs201324809, TOPMed rs201324809, gnomAD rs201324809, REVEL 0.24, MetaLR 0.13
- G84S (p.Gly84Ser), 1000Genomes rs201324809, ExAC rs201324809, TOPMed rs201324809, gnomAD rs201324809
- M85I (p.Met85Ile), ExAC rs775489171, TOPMed rs775489171, gnomAD rs775489171, REVEL 0.26, MetaLR 0.14
- M85L (p.Met85Leu), TOPMed rs2095597034, gnomAD rs2095597034, REVEL 0.24, MetaLR 0.09
- M85V (p.Met85Val), TOPMed rs2095597034, gnomAD rs2095597034, REVEL 0.28, MetaLR 0.13
- P86A (p.Pro86Ala), Ensembl rs2139183809
- P86L (p.Pro86Leu), Ensembl rs2139183802
- P86R (p.Pro86Arg), Ensembl rs2139183802, REVEL 0.12, MetaLR 0.07
- P86S (p.Pro86Ser), NCI-TCGA Cosmic COSV5164, Ensembl rs2139183809, Variant assessed as somatic; moderate impact.
- G87E (p.Gly87Glu), rs35220193, UniProt VAR 055835, ExAC rs35220193, gnomAD rs35220193, REVEL 0.05, MetaLR 0.04
- G87R (p.Gly87Arg), ExAC rs770844920, TOPMed rs770844920, gnomAD rs770844920, REVEL 0.06, MetaLR 0.03
Public FOXA1 analysis runs
- FOXA1 analysis run — FOXA1 (1,966 variants) — completed 2026-08-19