FGFR4 (P22455) variants and mutations
FGFR4 (also known as P22455) is a human protein-coding gene encoding a fibroblast growth factor receptor 4 protein. It transmits fibroblast-growth-factor signals involved in metabolism, tissue repair, development, and cell proliferation, with FGF19 as an important metabolic ligand. Aberrant signaling can support tumor growth, and activating alterations are therapeutic targets in selected cancers. This analysis covers 2,024 FGFR4 variants and mutations. Of these, 53% have computational variant effect predictions. Disease context includes cancer, urothelial carcinoma, and rhabdomyosarcoma. Example FGFR4 variants include R2Q, R2W, and R2R.
Variant analysis overview
- Gene: FGFR4
- Protein: P22455
- UniProt accession: P22455
- Organism: Homo sapiens
- Variants analyzed: 2024
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 1,824 unspecified-consequence records; 74 synonymous variants; 1 in-frame deletions; 108 missense variants; 4 frameshift variants; 1 splice-region variants; 11 stop-gained variants; 4 substitution
- Prediction scores: 1,069 variants have prediction scores (53% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: cancer, urothelial carcinoma, rhabdomyosarcoma, idiopathic pulmonary fibrosis, neoplasm, cholangiocarcinoma, non-small cell lung carcinoma, Abnormality of the skeletal system, bone development disease, type 2 diabetes mellitus, interstitial lung disease, breast carcinoma.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 4 domains; 2 binding sites; 10 post-translational modification sites.
- Structural context: 1,480 variants have structural context.
- PTM context: 23 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, MaveDB, LitVar.
Notable FGFR4 variants
Examples include R2Q, R2W, R2R, R2L, L3V, L3M, L3L, p.Leu5del. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- R2Q (p.Arg2Gln), cosmic curated COSV10941, ESP rs141355998, ExAC rs141355998, TOPMed rs141355998, REVEL 0.23, CADD 1.02
- R2W (p.Arg2Trp), rs545721160, TOPMed rs545721160, gnomAD rs545721160, REVEL 0.30, CADD 14.20, Variant assessed as somatic; moderate impact.
- R2R (p.Arg2Arg), rs545721160, gnomAD 5-177089606-C-A, CADD 3.34
- R2L (p.Arg2Leu), gnomAD 5-177089607-G-T, REVEL 0.22, CADD 1.58
- L3V (p.Leu3Val), Ensembl rs2149729643
- L3M (p.Leu3Met), gnomAD 5-177089609-C-A, REVEL 0.19, CADD 22.50
- L3L (p.Leu3Leu), rs1784278395, gnomAD 5-177089611-G-T, CADD 6.35
- L5del (p.Leu5del), rs2149729637, gnomAD 5-177089607-GGCT-, CADD 15.10
- L5L (p.Leu5Leu), rs778479517, gnomAD 5-177089615-C-T, CADD 2.23
- A6D (p.Ala6Asp), Ensembl rs2149729654
- A6T (p.Ala6Thr), gnomAD rs1169827041
- A6V (p.Ala6Val), Ensembl rs2149729654, REVEL 0.13, CADD 2.57
- L7M (p.Leu7Met), ExAC rs745509807, TOPMed rs745509807, gnomAD rs745509807, REVEL 0.29, CADD 8.74
- L7L (p.Leu7Leu), gnomAD 5-177089623-G-T, CADD 0.08
- L8L (p.Leu8Leu), gnomAD 5-177089624-T-C, CADD 0.64
- L8S (p.Leu8Ser), gnomAD 5-177089625-T-C, REVEL 0.38, CADD 20.20
- G9R (p.Gly9Arg), cosmic curated COSV10462, Ensembl rs1352897988
- V10F (p.Val10Phe), 1000Genomes rs1966265, ESP rs1966265, ExAC rs1966265, TOPMed rs1966265, Benign
- V10G (p.Val10Gly), NCI-TCGA TCGA novel, gnomAD rs1400416973, REVEL 0.39, CADD 22.10, Variant assessed as somatic; high impact.
- V10I (p.Val10Ile), rs1966265, ClinGen CA3575785, cosmic curated COSV52803, ClinVar RCV001713551, REVEL 0.26, CADD 0.49, Benign, not provided
- V10L (p.Val10Leu), 1000Genomes rs1966265, ESP rs1966265, ExAC rs1966265, TOPMed rs1966265, Benign
- V10A (p.Val10Ala), gnomAD 5-177089630-GT-G, CADD 23.00
- V10D (p.Val10Asp), gnomAD 5-177089630-G-GA, CADD 23.40
- V10V (p.Val10Val), rs1229801039, gnomAD 5-177089632-C-T, CADD 5.50
- L11A (p.Leu11Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- L11C (p.Leu11Cys), gnomAD 5-177089631-TC-T, CADD 21.40
- L12M (p.Leu12Met), TOPMed rs1784279793, REVEL 0.19, CADD 11.70
- L12P (p.Leu12Pro), Ensembl rs1379659427
- S13G (p.Ser13Gly), ExAC rs746965870, TOPMed rs746965870, gnomAD rs746965870, REVEL 0.16, CADD 9.55
- V14M (p.Val14Met), ExAC rs768529489, gnomAD rs768529489, REVEL 0.12, CADD 9.97
- V14A (p.Val14Ala), gnomAD 5-177089643-T-C, REVEL 0.23, CADD 3.52
- V14V (p.Val14Val), gnomAD 5-177089644-G-T, CADD 0.72
- P15R (p.Pro15Arg), rs747930223, ClinGen CA3575789, ClinVar RCV004278437, ExAC rs747930223, REVEL 0.22, CADD 9.14, Uncertain significance, not specified
- P15S (p.Pro15Ser), cosmic curated COSV52811, ExAC rs776518605, TOPMed rs776518605, gnomAD rs776518605, REVEL 0.12, CADD 9.10
- G16V (p.Gly16Val), TOPMed rs1784280548, gnomAD rs1784280548, REVEL 0.17, CADD 6.42
- G16G (p.Gly16Gly), rs1313569494, gnomAD 5-177089650-G-T, CADD 5.82
- P17L (p.Pro17Leu), 1000Genomes rs200148492, ExAC rs200148492, gnomAD rs200148492, REVEL 0.13, CADD 13.00
- P17S (p.Pro17Ser), NCI-TCGA Cosmic COSV9944, cosmic curated COSV99448, Variant assessed as somatic; moderate impact.
- P17R (p.Pro17Arg), gnomAD 5-177089652-C-G, REVEL 0.09, CADD 11.20
- P17H (p.Pro17His), gnomAD 5-177089652-C-A, REVEL 0.12, CADD 13.30
- P17P (p.Pro17Pro), gnomAD 5-177089653-T-A, CADD 7.15
- P18L (p.Pro18Leu), Ensembl rs2149729712, REVEL 0.16, CADD 19.30
- P18P (p.Pro18Pro), rs369319378, gnomAD 5-177089656-A-G, CADD 8.24
- L20S (p.Leu20Ser), Ensembl rs2149729716
- L20F (p.Leu20Phe), gnomAD 5-177089662-G-C, REVEL 0.18, CADD 17.90
- L22L (p.Leu22Leu), rs1021400810, gnomAD 5-177089666-C-T, CADD 6.65
- L22R (p.Leu22Arg), gnomAD 5-177089667-T-G, REVEL 0.27, CADD 19.30
- E23A (p.Glu23Ala), gnomAD 5-177089670-A-C, REVEL 0.27, CADD 18.60
- A24D (p.Ala24Asp), ExAC rs759833131, TOPMed rs759833131, gnomAD rs759833131
- A24T (p.Ala24Thr), TOPMed rs1784281289
- A24V (p.Ala24Val), cosmic curated COSV52801, ExAC rs759833131, TOPMed rs759833131, gnomAD rs759833131, REVEL 0.14, CADD 18.70
- A24A (p.Ala24Ala), rs772280627, gnomAD 5-177089674-C-T, CADD 10.90
- S25C (p.Ser25Cys), Ensembl rs2149729734
- S25P (p.Ser25Pro), TOPMed rs968495498, gnomAD rs968495498
- S25T (p.Ser25Thr), TOPMed rs968495498, gnomAD rs968495498, REVEL 0.29, CADD 23.00
- S25F (p.Ser25Phe), gnomAD 5-177089676-C-T, REVEL 0.45, CADD 24.50
- E27E (p.Glu27Glu), rs1317488441, gnomAD 5-177089683-A-G, CADD 11.10
- V28L (p.Val28Leu), TOPMed rs979979470, gnomAD rs979979470, REVEL 0.10, CADD 12.00
- V28M (p.Val28Met), TOPMed rs979979470, gnomAD rs979979470, REVEL 0.15, CADD 13.40
- E29K (p.Glu29Lys), gnomAD 5-177089687-G-A, REVEL 0.26, CADD 20.50
- E31D (p.Glu31Asp), gnomAD rs1400592724, REVEL 0.28, CADD 24.10
- E31G (p.Glu31Gly), Ensembl rs2149730629
- E31V (p.Glu31Val), Ensembl rs2149730629
- E31Q (p.Glu31Gln), gnomAD 5-177089693-G-C, REVEL 0.30, CADD 35.00
- E31E (p.Glu31Glu), gnomAD 5-177090391-G-A, CADD 14.80
- P32S (p.Pro32Ser), rs762859761, ClinGen CA3575908, ClinVar RCV004089999, ExAC rs762859761, REVEL 0.31, CADD 23.00, Uncertain significance, not specified
- P32T (p.Pro32Thr), ExAC rs762859761, TOPMed rs762859761, gnomAD rs762859761, Uncertain significance
- P32H (p.Pro32His), gnomAD 5-177090393-C-A, REVEL 0.37, CADD 23.20
- P32P (p.Pro32Pro), gnomAD 5-177090394-C-A, CADD 12.60
- C33F (p.Cys33Phe), gnomAD 5-177090396-G-T, REVEL 0.45, CADD 22.10
- C33Y (p.Cys33Tyr), gnomAD 5-177090396-G-A, REVEL 0.44, CADD 21.30
- C33S (p.Cys33Ser), gnomAD 5-177090396-G-C, REVEL 0.46, CADD 20.40
- C33C (p.Cys33Cys), rs1359204737, gnomAD 5-177090397-C-T, CADD 12.80
- L34P (p.Leu34Pro), ExAC rs766080164, TOPMed rs766080164, gnomAD rs766080164, REVEL 0.24, CADD 18.10, Uncertain significance, not specified
- L34V (p.Leu34Val), TOPMed rs922358662, gnomAD rs922358662, REVEL 0.20, CADD 12.60
- L34Q (p.Leu34Gln), gnomAD 5-177090399-T-A, REVEL 0.22, CADD 16.20
- L34L (p.Leu34Leu), rs752966003, gnomAD 5-177090400-G-T, CADD 7.43
- A35V (p.Ala35Val), cosmic curated COSV52807, REVEL 0.20, CADD 16.80
- A35S (p.Ala35Ser), gnomAD 5-177090401-G-T, REVEL 0.20, CADD 14.20
- A35T (p.Ala35Thr), gnomAD 5-177090401-G-A, REVEL 0.21, CADD 15.40
- A35D (p.Ala35Asp), gnomAD 5-177090402-C-A, REVEL 0.28, CADD 16.30
- A35A (p.Ala35Ala), rs373784652, gnomAD 5-177090403-T-C, CADD 11.90
- P36T (p.Pro36Thr), gnomAD 5-177090404-C-A, REVEL 0.36, CADD 23.20
- P36L (p.Pro36Leu), gnomAD 5-177090405-C-T, REVEL 0.51, CADD 23.60
- S37R (p.Ser37Arg), Ensembl rs2149730657, REVEL 0.16, CADD 16.30
- S37I (p.Ser37Ile), gnomAD 5-177090408-G-T, REVEL 0.10, CADD 14.70
- S37N (p.Ser37Asn), gnomAD 5-177090408-G-A, REVEL 0.14, CADD 12.70
- S37S (p.Ser37Ser), rs2149730660, gnomAD 5-177090409-C-T, CADD 10.00
- L38L (p.Leu38Leu), rs757295817, gnomAD 5-177090412-G-A, CADD 2.92
- E39K (p.Glu39Lys), gnomAD rs1217937501, REVEL 0.28, CADD 22.30
- E39Q (p.Glu39Gln), gnomAD rs1217937501, REVEL 0.20, CADD 21.40
- E39W (p.Glu39Trp), rs1278695971, gnomAD 5-177090409-C-CCT, CADD 23.80
- E39* (p.Glu39Ter), gnomAD 5-177090413-G-T, CADD 38.00
- E39E (p.Glu39Glu), rs1353646935, gnomAD 5-177090415-G-A, CADD 8.84
- E39D (p.Glu39Asp), gnomAD 5-177090415-G-T, REVEL 0.20, CADD 16.50
- Q40* (p.Gln40Ter), Ensembl rs2149730679
- Q40P (p.Gln40Pro), gnomAD 5-177090417-A-C, REVEL 0.22, CADD 17.40
- Q40H (p.Gln40His), gnomAD 5-177090418-G-T, REVEL 0.18, CADD 21.30
- Q41* (p.Gln41Ter), Ensembl rs2149730689, CADD 37.00
- Q41K (p.Gln41Lys), rs2149730689, ClinGen CA362285724, ClinVar RCV004394143, REVEL 0.14, CADD 15.30, Uncertain significance, not specified
- Q41L (p.Gln41Leu), NCI-TCGA Cosmic COSV5280, cosmic curated COSV52806, Variant assessed as somatic; moderate impact.
- E42K (p.Glu42Lys), 1000Genomes rs528745108, ExAC rs528745108, gnomAD rs528745108, REVEL 0.22, CADD 19.80
- E42Q (p.Glu42Gln), gnomAD 5-177090422-G-C, REVEL 0.14, CADD 17.90
- E42* (p.Glu42Ter), gnomAD 5-177090422-G-T, CADD 37.00
- E42D (p.Glu42Asp), gnomAD 5-177090424-G-T, REVEL 0.12, CADD 11.50
- E42E (p.Glu42Glu), gnomAD 5-177090424-G-A, CADD 6.85
- Q43K (p.Gln43Lys), gnomAD 5-177090425-C-A, REVEL 0.11, CADD 17.60
- E44D (p.Glu44Asp), NCI-TCGA Cosmic COSV5281, cosmic curated COSV52810, REVEL 0.17, CADD 9.45, Variant assessed as somatic; moderate impact.
- E44K (p.Glu44Lys), Ensembl rs2149730693
- E44V (p.Glu44Val), gnomAD rs1484903613, REVEL 0.19, CADD 21.70
- E44* (p.Glu44Ter), gnomAD 5-177090428-G-T, CADD 36.00
- E44Q (p.Glu44Gln), gnomAD 5-177090428-G-C, REVEL 0.09, CADD 16.90
- E44E (p.Glu44Glu), gnomAD 5-177090430-G-A, CADD 4.71
- L45L (p.Leu45Leu), rs138373273, gnomAD 5-177090431-C-T, CADD 5.03
- L45M (p.Leu45Met), gnomAD 5-177090431-C-A, REVEL 0.29, CADD 20.50
- L45P (p.Leu45Pro), gnomAD 5-177090432-T-C, REVEL 0.63, CADD 24.80
- T46I (p.Thr46Ile), ExAC rs746357877, TOPMed rs746357877, gnomAD rs746357877, REVEL 0.29, CADD 8.12
- T46K (p.Thr46Lys), ExAC rs746357877, TOPMed rs746357877, gnomAD rs746357877
- T46R (p.Thr46Arg), gnomAD 5-177090435-C-G, REVEL 0.39, CADD 10.20
- T46T (p.Thr46Thr), rs1455792482, gnomAD 5-177090436-A-G, CADD 0.24
- V47G (p.Val47Gly), Ensembl rs2149730721, REVEL 0.50, CADD 23.80
- V47I (p.Val47Ile), Ensembl rs2149730716, REVEL 0.04, CADD 5.58
- V47L (p.Val47Leu), gnomAD 5-177090437-G-T, REVEL 0.10, CADD 3.77
- A48D (p.Ala48Asp), 1000Genomes rs201142834, ExAC rs201142834, gnomAD rs201142834, REVEL 0.12, CADD 9.71
- A48V (p.Ala48Val), 1000Genomes rs201142834, ExAC rs201142834, gnomAD rs201142834, REVEL 0.06, CADD 11.50
- A48S (p.Ala48Ser), gnomAD 5-177090440-G-T, REVEL 0.17, CADD 14.40
- A48A (p.Ala48Ala), gnomAD 5-177090442-C-A, CADD 8.38
- L49F (p.Leu49Phe), TOPMed rs987602724, gnomAD rs987602724, REVEL 0.19, CADD 16.00
- L49H (p.Leu49His), 1000Genomes rs780226734, ExAC rs780226734, gnomAD rs780226734, REVEL 0.30, CADD 22.40
- L49I (p.Leu49Ile), TOPMed rs987602724, gnomAD rs987602724, REVEL 0.10, CADD 12.20
- L49P (p.Leu49Pro), 1000Genomes rs780226734, ExAC rs780226734, gnomAD rs780226734, REVEL 0.20, CADD 15.20
- L49R (p.Leu49Arg), 1000Genomes rs780226734, ExAC rs780226734, gnomAD rs780226734, REVEL 0.32, CADD 22.30
- L49V (p.Leu49Val), gnomAD 5-177090443-C-G, REVEL 0.09, CADD 7.95
- G50V (p.Gly50Val), Ensembl rs2149730737, REVEL 0.74, CADD 26.00
- G50W (p.Gly50Trp), gnomAD 5-177090446-G-T, REVEL 0.58, CADD 27.70
- G50R (p.Gly50Arg), gnomAD 5-177090446-G-A, REVEL 0.53, CADD 26.60
- G50G (p.Gly50Gly), gnomAD 5-177090448-G-T, CADD 9.80
- Q51* (p.Gln51Ter), Ensembl rs2149730743, CADD 37.00
- Q51K (p.Gln51Lys), Ensembl rs2149730743, REVEL 0.28, CADD 19.60
- Q51L (p.Gln51Leu), gnomAD rs1161701931
- Q51R (p.Gln51Arg), gnomAD rs1161701931, REVEL 0.21, CADD 22.80
- Q51H (p.Gln51His), gnomAD 5-177090451-G-T, REVEL 0.23, CADD 19.40
- Q51Q (p.Gln51Gln), rs1393115813, gnomAD 5-177090451-G-A, CADD 9.12
- P52L (p.Pro52Leu), gnomAD rs1429405481, REVEL 0.22, CADD 17.00
- P52T (p.Pro52Thr), Ensembl rs2149730753, REVEL 0.11, CADD 8.76
- P52A (p.Pro52Ala), gnomAD 5-177090452-C-G, REVEL 0.14, CADD 9.73
- P52S (p.Pro52Ser), gnomAD 5-177090452-C-T, REVEL 0.10, CADD 10.80
- P52H (p.Pro52His), gnomAD 5-177090453-C-A, REVEL 0.25, CADD 21.60
- P52P (p.Pro52Pro), rs1784321004, gnomAD 5-177090454-T-C, CADD 9.45
- V53E (p.Val53Glu), gnomAD rs916468815, REVEL 0.67, CADD 26.00
- V53G (p.Val53Gly), gnomAD rs916468815
- V53L (p.Val53Leu), gnomAD 5-177090455-G-T, REVEL 0.15, CADD 10.30
- V53M (p.Val53Met), gnomAD 5-177090455-G-A, REVEL 0.33, CADD 17.00
- V53V (p.Val53Val), gnomAD 5-177090457-G-T, CADD 6.51
- R54C (p.Arg54Cys), rs572098218, NCI-TCGA Cosmic COSV9944, cosmic curated COSV99449, ExAC rs572098218, REVEL 0.46, CADD 23.50, Variant assessed as somatic; moderate impact.
- R54H (p.Arg54His), rs776394759, ExAC rs776394759, TOPMed rs776394759, gnomAD rs776394759, REVEL 0.33, CADD 22.00, Uncertain significance, not specified
- R54S (p.Arg54Ser), ExAC rs572098218, gnomAD rs572098218, REVEL 0.42, CADD 17.30
- R54W (p.Arg54Trp), cosmic curated COSV10641
- R54G (p.Arg54Gly), gnomAD 5-177090458-C-G, REVEL 0.43, CADD 20.70
- R54L (p.Arg54Leu), gnomAD 5-177090459-G-T, REVEL 0.38, CADD 17.40
- R54R (p.Arg54Arg), rs446382, gnomAD 5-177090460-T-A, CADD 9.73
- L55M (p.Leu55Met), gnomAD 5-177090461-C-A, REVEL 0.45, CADD 23.30
- L55L (p.Leu55Leu), gnomAD 5-177090461-C-T, CADD 9.37
- C56S (p.Cys56Ser), cosmic curated COSV52804, ESP rs150191035, ExAC rs150191035, TOPMed rs150191035, REVEL 0.41, CADD 19.80
- C56W (p.Cys56Trp), ExAC rs762728948, gnomAD rs762728948, REVEL 0.60, CADD 23.00
- C56Y (p.Cys56Tyr), ESP rs150191035, ExAC rs150191035, TOPMed rs150191035, gnomAD rs150191035
- C56F (p.Cys56Phe), gnomAD 5-177090465-G-T, REVEL 0.43, CADD 21.10
- C56C (p.Cys56Cys), rs762728948, gnomAD 5-177090466-C-T, CADD 13.10
- C56* (p.Cys56Ter), gnomAD 5-177090466-C-A, CADD 37.00
- C57R (p.Cys57Arg), Ensembl rs2149730795, REVEL 0.88, CADD 26.60
- C57F (p.Cys57Phe), gnomAD 5-177090468-G-T, REVEL 0.89, CADD 26.60
- C57* (p.Cys57Ter), gnomAD 5-177090469-T-A, CADD 36.00
- G58R (p.Gly58Arg), gnomAD rs1315733816
- G58W (p.Gly58Trp), gnomAD rs1315733816, REVEL 0.48, CADD 24.70
- G58V (p.Gly58Val), gnomAD 5-177090471-G-T, REVEL 0.41, CADD 22.20
- G58G (p.Gly58Gly), rs1215145722, gnomAD 5-177090472-G-T, CADD 8.70
- R59G (p.Arg59Gly), cosmic curated COSV52810, 1000Genomes rs200344385, ESP rs200344385, ExAC rs200344385, REVEL 0.28, CADD 14.30
- R59L (p.Arg59Leu), ExAC rs751304047, TOPMed rs751304047, gnomAD rs751304047, REVEL 0.23, CADD 15.80
- R59Q (p.Arg59Gln), cosmic curated COSV52806, ExAC rs751304047, TOPMed rs751304047, gnomAD rs751304047, REVEL 0.17, CADD 14.90, Uncertain significance, not specified
- R59W (p.Arg59Trp), cosmic curated COSV52800, 1000Genomes rs200344385, ESP rs200344385, ExAC rs200344385, REVEL 0.42, CADD 21.20
Public FGFR4 analysis runs
- FGFR4 analysis run — FGFR4 (2,024 variants) — completed 2026-08-21