FOXP1 (Forkhead box protein P1) variants and mutations
FOXP1 (also known as Forkhead box protein P1) is a human protein-coding gene encoding a forkhead box protein P1 protein. It regulates transcriptional programs in brain, heart, lung, and immune development and is especially important for neuronal differentiation and language-related circuits. Haploinsufficiency causes a neurodevelopmental syndrome with intellectual disability, speech and language impairment, and frequent autism-related features. This analysis covers 1,544 FOXP1 variants and mutations. Of these, 49% have computational variant effect predictions. Disease context includes intellectual disability-severe speech delay-mild dysmorphism syndrome, intellectual disability with language impairment, and hereditary disease. Example FOXP1 variants include M1?, M2I, and M2K.
Variant analysis overview
- Gene: FOXP1
- Protein: Forkhead box protein P1
- UniProt accession: Q9H334
- Organism: Homo sapiens
- Variants analyzed: 1544
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 1,406 unspecified-consequence records; 1 stop retained variant; 63 synonymous variants; 56 missense variants; 3 in-frame deletions; 2 splice-region variants; 3 stop-gained variants; 9 frameshift variants; 1 in-frame insertions
- Prediction scores: 762 variants have prediction scores (49% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: intellectual disability-severe speech delay-mild dysmorphism syndrome, intellectual disability with language impairment, hereditary disease, Intellectual disability, basal cell carcinoma, skin cancer, intelligence, skin neoplasm, arthropathy, attention deficit-hyperactivity disorder, nasal cavity polyp, neurodegenerative disease.
Protein structure and variant hotspots
- Protein features: 1 domains; 3 post-translational modification sites.
- Structural context: 47 variants have structural context.
- PTM context: 5 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable FOXP1 variants
Examples include M1?, M2I, M2K, M2L, Q3*, Q3E, Q3H, Q3L. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, NCI-TCGA Cosmic COSV5952, cosmic curated COSV59526, Variant assessed as somatic; high impact.
- M2I (p.Met2Ile), Ensembl rs2108382769, Likely benign, not specified
- M2K (p.Met2Lys), Ensembl rs2108382790
- M2L (p.Met2Leu), Ensembl rs2108382806
- Q3* (p.Gln3Ter), Ensembl rs2108382754
- Q3E (p.Gln3Glu), Ensembl rs2108382754
- Q3H (p.Gln3His), ExAC rs763607334, gnomAD rs763607334
- Q3L (p.Gln3Leu), cosmic curated COSV59523, gnomAD rs898658081, Likely benign
- Q3R (p.Gln3Arg), rs898658081, ClinGen CA77135960, ClinVar RCV001265466, ClinVar RCV003770379, CADD 24.90, PolyPhen-2 0.00, Conflicting interpretations, Inborn genetic diseases; not provided
- E4* (p.Glu4Ter), cosmic curated COSV10589, Ensembl rs2108382698
- E4K (p.Glu4Lys), Ensembl rs2108382698
- E4Q (p.Glu4Gln), Ensembl rs2108382698
- E4V (p.Glu4Val), Ensembl rs2108382677
- S5C (p.Ser5Cys), Ensembl rs2063433476
- S5F (p.Ser5Phe), cosmic curated COSV10644, Ensembl rs2063433476
- S5P (p.Ser5Pro), rs762898505, ClinGen CA205696, ClinVar RCV000192698, ClinVar RCV000880214, CADD 28.50, PolyPhen-2 0.91, Conflicting interpretations, FOXP1-related disorder; not specified; not provided
- S5T (p.Ser5Thr), ExAC rs762898505, gnomAD rs762898505, Uncertain significance
- S5Y (p.Ser5Tyr), cosmic curated COSV59524, Uncertain significance, Intellectual disability-severe speech delay-mild dysmorphism syndrome
- G6E (p.Gly6Glu), Ensembl rs2108382577
- G6K (p.Gly6Lys), cosmic curated COSV59524
- G6R (p.Gly6Arg), Ensembl rs2108382600
- G6V (p.Gly6Val), Ensembl rs2108382577
- G6W (p.Gly6Trp), Ensembl rs2108382600
- T7I (p.Thr7Ile), Ensembl rs867123824, CADD 23.80, PolyPhen-2 0.01
- T7S (p.Thr7Ser), Ensembl rs867123824
- E8D (p.Glu8Asp), gnomAD rs1429864752
- E8G (p.Glu8Gly), Ensembl rs2108382515
- E8Q (p.Glu8Gln), rs2546770800, ClinGen CA353565294, ClinVar RCV004394414, Uncertain significance, Inborn genetic diseases
- E8V (p.Glu8Val), Ensembl rs2108382515
- T9A (p.Thr9Ala), gnomAD rs1192817397, CADD 20.50, PolyPhen-2 0.00
- T9I (p.Thr9Ile), Ensembl rs2108382467
- T9K (p.Thr9Lys), cosmic curated COSV59529, Uncertain significance, not provided
- T9R (p.Thr9Arg), Ensembl rs2108382467, CADD 24.20, PolyPhen-2 0.22
- T9S (p.Thr9Ser), gnomAD rs1192817397
- K10Q (p.Lys10Gln), NCI-TCGA TCGA novel, Uncertain significance, not provided
- K10R (p.Lys10Arg), rs1476826805, ClinGen CA353565277, ClinVar RCV002623149, gnomAD rs1476826805, CADD 23.70, PolyPhen-2 0.00, Likely benign, not provided
- S11G (p.Ser11Gly), rs775317391, ClinGen CA2491473, ClinVar RCV001092350, ExAC rs775317391, CADD 23.10, PolyPhen-2 0.00, Uncertain significance, not provided
- S11N (p.Ser11Asn), gnomAD rs1188423211, CADD 18.50, PolyPhen-2 0.07
- S11R (p.Ser11Arg), TOPMed rs1486275946, gnomAD rs1486275946, CADD 22.60, PolyPhen-2 0.28
- N12D (p.Asn12Asp), Ensembl rs2108382372, CADD 27.10, PolyPhen-2 0.90, Uncertain significance
- N12H (p.Asn12His), Ensembl rs2108382372, Uncertain significance
- N12I (p.Asn12Ile), Ensembl rs2108382357
- N12K (p.Asn12Lys), ExAC rs759226701, gnomAD rs759226701, CADD 25.10, PolyPhen-2 0.96
- N12Y (p.Asn12Tyr), rs2108382372, ClinGen CA353565264, ClinVar RCV001420541, Ensembl rs2108382372, CADD 27.30, PolyPhen-2 0.98, Uncertain significance, Intellectual disability-severe speech delay-mild dysmorphism syndrome
- G13A (p.Gly13Ala), Ensembl rs2108382290, Uncertain significance
- G13C (p.Gly13Cys), TOPMed rs1202112901, gnomAD rs1202112901, Uncertain significance
- G13D (p.Gly13Asp), NCI-TCGA Cosmic COSV5952, cosmic curated COSV59526, Ensembl rs2108382290, Uncertain significance
- G13R (p.Gly13Arg), TOPMed rs1202112901, gnomAD rs1202112901, CADD 24.80, PolyPhen-2 0.20, Uncertain significance
- G13S (p.Gly13Ser), rs1202112901, ClinGen CA353565258, ClinVar RCV002591932, TOPMed rs1202112901, CADD 18.10, PolyPhen-2 0.00, Uncertain significance, not provided
- G13V (p.Gly13Val), rs2108382290, ClinGen CA353565254, ClinVar RCV002266746, Ensembl rs2108382290, CADD 23.70, PolyPhen-2 0.06, Uncertain significance, Intellectual disability-severe speech delay-mild dysmorphism syndrome
- S14* (p.Ser14Ter), Ensembl rs2108382243
- S14A (p.Ser14Ala), TOPMed rs1272223678, gnomAD rs1272223678, CADD 19.30, PolyPhen-2 0.00
- S14L (p.Ser14Leu), Ensembl rs2108382243
- S14P (p.Ser14Pro), TOPMed rs1272223678, gnomAD rs1272223678
- S14T (p.Ser14Thr), TOPMed rs1272223678, gnomAD rs1272223678
- A15D (p.Ala15Asp), ExAC rs532329866, gnomAD rs532329866, Likely pathogenic
- A15P (p.Ala15Pro), Ensembl rs2108382208
- A15T (p.Ala15Thr), Ensembl rs2108382208
- A15V (p.Ala15Val), rs532329866, ClinGen CA208669, cosmic curated COSV10056, ClinVar RCV000194481, CADD 25.00, PolyPhen-2 0.00, Conflicting interpretations, Inborn genetic diseases; not specified; not provided
- I16F (p.Ile16Phe), Ensembl rs2108382176
- I16L (p.Ile16Leu), cosmic curated COSV59523, Ensembl rs2108382176
- I16M (p.Ile16Met), Ensembl rs2108382147
- I16N (p.Ile16Asn), Ensembl rs2108382162
- I16S (p.Ile16Ser), Ensembl rs2108382162
- Q17* (p.Gln17Ter), cosmic curated COSV10738, Ensembl rs2108382136
- Q17H (p.Gln17His), ESP rs368833720, TOPMed rs368833720, CADD 33.00, PolyPhen-2 0.12, Likely benign
- N18I (p.Asn18Ile), Ensembl rs2108382109
- N18K (p.Asn18Lys), gnomAD rs1264184449
- N18S (p.Asn18Ser), cosmic curated COSV59529, Ensembl rs2108382109
- G19A (p.Gly19Ala), TOPMed rs913995844, gnomAD rs913995844, CADD 24.90, Uncertain significance, not provided
- G19E (p.Gly19Glu), TOPMed rs913995844, gnomAD rs913995844, Uncertain significance
- G19R (p.Gly19Arg), gnomAD rs2063430712
- G19V (p.Gly19Val), TOPMed rs913995844, gnomAD rs913995844, Uncertain significance
- G19W (p.Gly19Trp), gnomAD rs2063430712, CADD 28.30
- S20A (p.Ser20Ala), Ensembl rs2108382004
- S20L (p.Ser20Leu), rs1348187295, ClinGen CA353565211, NCI-TCGA Cosmic COSV5951, cosmic curated COSV59519, CADD 23.10, PolyPhen-2 0.01, Uncertain significance, Intellectual disability-severe speech delay-mild dysmorphism syndrome
- S20P (p.Ser20Pro), Ensembl rs2108382004
- S20T (p.Ser20Thr), Ensembl rs2108382004
- S20W (p.Ser20Trp), TOPMed rs1348187295, gnomAD rs1348187295, CADD 29.00, Uncertain significance
- G21A (p.Gly21Ala), Ensembl rs2108381929
- G21C (p.Gly21Cys), cosmic curated COSV59517, Ensembl rs2108381948
- G21D (p.Gly21Asp), NCI-TCGA TCGA novel, CADD 23.00, PolyPhen-2 0.01, Variant assessed as somatic; moderate impact.
- G21R (p.Gly21Arg), Ensembl rs2108381948
- G21S (p.Gly21Ser), Ensembl rs2108381948, Uncertain significance, not provided
- G21V (p.Gly21Val), Ensembl rs2108381929
- G22A (p.Gly22Ala), gnomAD rs1382312066
- G22D (p.Gly22Asp), gnomAD rs1382312066, CADD 19.40, PolyPhen-2 0.01
- G22R (p.Gly22Arg), cosmic curated COSV59525, TOPMed rs794727811, gnomAD rs794727811, Uncertain significance
- G22S (p.Gly22Ser), rs794727811, ClinGen CA246831, cosmic curated COSV59523, ClinVar RCV000179547, CADD 0.03, PolyPhen-2 0.00, Uncertain significance, not provided
- G22V (p.Gly22Val), gnomAD rs1382312066, CADD 19.80, PolyPhen-2 0.02
- S23C (p.Ser23Cys), gnomAD rs2063429307
- S23G (p.Ser23Gly), gnomAD rs2063429307, CADD 12.70
- S23N (p.Ser23Asn), Ensembl rs2108381825
- S23T (p.Ser23Thr), Ensembl rs2108381825
- N24D (p.Asn24Asp), cosmic curated COSV59529
- N24H (p.Asn24His), ExAC rs748388342, gnomAD rs748388342, CADD 23.40, PolyPhen-2 0.35
- N24I (p.Asn24Ile), ESP rs372024541, TOPMed rs372024541, gnomAD rs372024541, Uncertain significance
- N24K (p.Asn24Lys), Ensembl rs2108381785
- N24S (p.Asn24Ser), ESP rs372024541, TOPMed rs372024541, gnomAD rs372024541, Uncertain significance
- N24T (p.Asn24Thr), rs372024541, ClinGen CA77135956, ClinVar RCV003707040, ESP rs372024541, CADD 18.40, PolyPhen-2 0.04, Uncertain significance, not provided
- N24Y (p.Asn24Tyr), ExAC rs748388342, gnomAD rs748388342, CADD 25.20, PolyPhen-2 0.45
- H25L (p.His25Leu), Ensembl rs2108381766
- H25N (p.His25Asn), cosmic curated COSV10589
- H25P (p.His25Pro), Ensembl rs2108381766
- H25Q (p.His25Gln), Ensembl rs2108381753
- H25R (p.His25Arg), cosmic curated COSV59526, CADD 23.20, PolyPhen-2 0.84
- L26* (p.Leu26Ter), Ensembl rs2108381712
- L26I (p.Leu26Ile), rs533097431, ClinGen CA353565175, ClinVar RCV002296579, 1000Genomes rs533097431, CADD 20.60, PolyPhen-2 0.07, Uncertain significance, not provided
- L26V (p.Leu26Val), 1000Genomes rs533097431, ExAC rs533097431, gnomAD rs533097431, CADD 19.60, PolyPhen-2 0.04, Uncertain significance
- L27P (p.Leu27Pro), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E28* (p.Glu28Ter), TOPMed rs2063428325
- E28D (p.Glu28Asp), TOPMed rs933638471, gnomAD rs933638471, CADD 17.10, PolyPhen-2 0.02
- E28G (p.Glu28Gly), Ensembl rs2108381662, CADD 22.30, PolyPhen-2 0.00
- E28K (p.Glu28Lys), TOPMed rs2063428325, CADD 19.20, PolyPhen-2 0.01
- E28Q (p.Glu28Gln), TOPMed rs2063428325, CADD 17.70, PolyPhen-2 0.03
- C29S (p.Cys29Ser), gnomAD rs2063427946, CADD 22.90
- C29W (p.Cys29Trp), 1000Genomes rs550457312, ExAC rs550457312, TOPMed rs550457312, gnomAD rs550457312, Likely benign
- G30A (p.Gly30Ala), TOPMed rs1429222088, gnomAD rs1429222088
- G30C (p.Gly30Cys), NCI-TCGA Cosmic COSV1005, cosmic curated COSV10056, TOPMed rs913003790, gnomAD rs913003790, Uncertain significance
- G30D (p.Gly30Asp), TOPMed rs1429222088, gnomAD rs1429222088, CADD 13.30, PolyPhen-2 0.01
- G30R (p.Gly30Arg), TOPMed rs913003790, gnomAD rs913003790, CADD 13.20, PolyPhen-2 0.06, Uncertain significance
- G30S (p.Gly30Ser), rs913003790, ClinGen CA77135954, ClinVar RCV001318134, TOPMed rs913003790, CADD 4.26, PolyPhen-2 0.00, Uncertain significance, not provided
- G30V (p.Gly30Val), cosmic curated COSV59527, TOPMed rs1429222088, gnomAD rs1429222088
- G31A (p.Gly31Ala), Ensembl rs2108381524
- G31C (p.Gly31Cys), ExAC rs750746668, gnomAD rs750746668, CADD 16.20, PolyPhen-2 0.26
- G31D (p.Gly31Asp), cosmic curated COSV59527, Ensembl rs2108381524, CADD 17.40, PolyPhen-2 0.02
- G31R (p.Gly31Arg), ExAC rs750746668, gnomAD rs750746668, CADD 10.70, PolyPhen-2 0.00
- G31S (p.Gly31Ser), cosmic curated COSV10056, ExAC rs750746668, gnomAD rs750746668, CADD 1.66, PolyPhen-2 0.00
- G31V (p.Gly31Val), Ensembl rs2108381524
- L32F (p.Leu32Phe), Ensembl rs2063426502
- L32H (p.Leu32His), Ensembl rs2108381480
- L32I (p.Leu32Ile), rs2063426502, ClinGen CA353565138, ClinVar RCV003148111, AlphaMissense 0.06, MetaLR 0.71, Uncertain significance, Intellectual disability-severe speech delay-mild dysmorphism syndrome
- L32P (p.Leu32Pro), Ensembl rs2108381480
- L32V (p.Leu32Val), Ensembl rs2063426502
- R33G (p.Arg33Gly), TOPMed rs1358353721, gnomAD rs1358353721
- R33L (p.Arg33Leu), ExAC rs587780339, TOPMed rs587780339, gnomAD rs587780339, CADD 27.10, PolyPhen-2 0.00, Likely benign
- R33P (p.Arg33Pro), rs587780339, ClinGen CA152900, ClinVar RCV000117092, ExAC rs587780339, CADD 27.60, PolyPhen-2 0.10, Likely benign, not specified
- R33Q (p.Arg33Gln), rs587780339, ClinGen CA2491462, ClinVar RCV001906888, ExAC rs587780339, CADD 27.60, PolyPhen-2 0.01, Uncertain significance, not provided
- R33W (p.Arg33Trp), rs1358353721, NCI-TCGA Cosmic COSV5952, cosmic curated COSV59520, TOPMed rs1358353721, CADD 32.00, PolyPhen-2 0.17, Uncertain significance, not provided
- E34* (p.Glu34Ter), Ensembl rs2108381359
- E34D (p.Glu34Asp), ExAC rs751234324, TOPMed rs751234324, gnomAD rs751234324
- E34G (p.Glu34Gly), Ensembl rs2108381344
- E34K (p.Glu34Lys), cosmic curated COSV59525, Ensembl rs2108381359
- E34Q (p.Glu34Gln), Ensembl rs2108381359
- E34V (p.Glu34Val), cosmic curated COSV59521, Ensembl rs2108381344
- G35A (p.Gly35Ala), rs969304991, ClinGen CA77135953, ClinVar RCV003032913, ClinVar RCV006377866, CADD 16.50, PolyPhen-2 0.00, Conflicting interpretations, not provided; Inborn genetic diseases
- G35E (p.Gly35Glu), TOPMed rs969304991, gnomAD rs969304991, CADD 22.50, PolyPhen-2 0.02, Uncertain significance
- G35R (p.Gly35Arg), TOPMed rs1337954936, gnomAD rs1337954936, CADD 23.40
- G35W (p.Gly35Trp), TOPMed rs1337954936, gnomAD rs1337954936, CADD 25.60, PolyPhen-2 0.22
- R36G (p.Arg36Gly), TOPMed rs935869094, gnomAD rs935869094, CADD 24.10, PolyPhen-2 0.93
- R36L (p.Arg36Leu), 1000Genomes rs200643313, ExAC rs200643313, TOPMed rs200643313, gnomAD rs200643313, Benign
- R36Q (p.Arg36Gln), rs200643313, ClinGen CA2491458, ClinVar RCV001816771, ClinVar RCV002067041, CADD 26.30, PolyPhen-2 0.89, Conflicting interpretations, Inborn genetic diseases; not specified; not provided
- R36W (p.Arg36Trp), rs935869094, NCI-TCGA Cosmic COSV5951, cosmic curated COSV59516, TOPMed rs935869094, CADD 28.20, PolyPhen-2 0.97, Variant assessed as somatic; moderate impact.
- S37A (p.Ser37Ala), TOPMed rs1247696224, gnomAD rs1247696224
- S37C (p.Ser37Cys), rs1383155725, ClinGen CA353565109, ClinVar RCV001816362, TOPMed rs1383155725, CADD 28.20, PolyPhen-2 0.11, Uncertain significance, not provided
- S37F (p.Ser37Phe), TOPMed rs1383155725, gnomAD rs1383155725, CADD 28.60, PolyPhen-2 0.09, Uncertain significance
- S37P (p.Ser37Pro), TOPMed rs1247696224, gnomAD rs1247696224, CADD 21.60, PolyPhen-2 0.00
- S37T (p.Ser37Thr), TOPMed rs1247696224, gnomAD rs1247696224, CADD 14.90, PolyPhen-2 0.01, Uncertain significance, not provided
- N38D (p.Asn38Asp), gnomAD rs2063423709, CADD 27.00, PolyPhen-2 0.03, Uncertain significance, not provided; Inborn genetic diseases
- N38I (p.Asn38Ile), gnomAD rs1330345201, Likely benign
- N38K (p.Asn38Lys), TOPMed rs1560102007, Likely benign
- N38S (p.Asn38Ser), rs1330345201, ClinGen CA353565103, ClinVar RCV003277257, gnomAD rs1330345201, CADD 23.50, PolyPhen-2 0.03, Likely benign, Inborn genetic diseases
- N38T (p.Asn38Thr), gnomAD rs1330345201, Likely benign
- G39* (p.Gly39Ter), cosmic curated COSV10644, ExAC rs752297898, gnomAD rs752297898, Uncertain significance
- G39A (p.Gly39Ala), rs2108381045, ClinGen CA353565096, ClinVar RCV002510725, ClinVar RCV006559505, AlphaMissense 0.21, MetaLR 0.82, Uncertain significance, Intellectual disability-severe speech delay-mild dysmorphism syndrome; not provi
- G39E (p.Gly39Glu), cosmic curated COSV59526, Ensembl rs2108381045, Uncertain significance
- G39R (p.Gly39Arg), rs752297898, ExAC rs752297898, gnomAD rs752297898, ClinGen CA2491457, CADD 28.30, PolyPhen-2 0.54, Uncertain significance, not provided
- E40D (p.Glu40Asp), Ensembl rs2108380980
- E40K (p.Glu40Lys), gnomAD rs1398482259
- E40Q (p.Glu40Gln), gnomAD rs1398482259, CADD 26.20, PolyPhen-2 0.00
- E40V (p.Glu40Val), rs765070623, ClinGen CA2491456, ClinVar RCV001196089, ClinVar RCV001251757, CADD 29.30, PolyPhen-2 0.00, Conflicting interpretations, Inborn genetic diseases; not provided; Intellectual disability-severe speech del
- T41A (p.Thr41Ala), rs2063422516, ClinGen CA353565086, ClinVar RCV002731600, Ensembl rs2063422516, CADD 19.00, PolyPhen-2 0.00, Uncertain significance, not provided
- T41M (p.Thr41Met), rs756099573, ClinGen CA2491455, cosmic curated COSV59518, ClinVar RCV002369208, CADD 25.00, PolyPhen-2 0.54, Conflicting interpretations, Inborn genetic diseases; not provided
- T41P (p.Thr41Pro), Ensembl rs2063422516, Uncertain significance
- T41R (p.Thr41Arg), ExAC rs756099573, TOPMed rs756099573, gnomAD rs756099573, CADD 27.00, PolyPhen-2 0.33, Likely benign
- T41S (p.Thr41Ser), Ensembl rs2063422516, Uncertain significance
- P42A (p.Pro42Ala), cosmic curated COSV59520, Ensembl rs2108380921
- P42L (p.Pro42Leu), rs766294895, ClinGen CA2491453, ClinVar RCV002962014, ExAC rs766294895, CADD 26.60, PolyPhen-2 0.98, Uncertain significance, not provided
- P42Q (p.Pro42Gln), ExAC rs766294895, TOPMed rs766294895, gnomAD rs766294895, CADD 26.00, PolyPhen-2 0.99, Uncertain significance
- P42R (p.Pro42Arg), ExAC rs766294895, TOPMed rs766294895, gnomAD rs766294895, Uncertain significance
Public FOXP1 analysis runs
- FOXP1 analysis run — FOXP1 (1,544 variants) — completed 2026-08-19