WT1 (Wilms tumor protein) variants and mutations
WT1 (also known as Wilms tumor protein) is a human protein-coding gene encoding a wilms tumor protein. It controls transcriptional programs required for kidney and gonadal development and also restrains or promotes cell growth in a context-dependent manner. Germline pathogenic variants cause Wilms-tumor predisposition and Denys-Drash or Frasier syndromes, while somatic alterations occur in some leukemias. This analysis covers 104 WT1 variants and mutations. Of these, 84% have computational variant effect predictions. Disease context includes Denys-Drash syndrome, Wilms tumor 1, and Frasier syndrome. Example WT1 variants include D7A, A131T, and R145S.
Variant analysis overview
- Gene: WT1
- Protein: Wilms tumor protein
- UniProt accession: P19544
- Organism: Homo sapiens
- Variants analyzed: 104
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 40 unspecified-consequence records; 1 stop retained variant; 23 missense variants; 15 synonymous variants; 3 in-frame deletions; 12 frameshift variants; 4 stop-gained variants; 1 in-frame insertions; 1 splice-region variants; 4 substitution
- Prediction scores: 87 variants have prediction scores (84% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Denys-Drash syndrome, Wilms tumor 1, Frasier syndrome, nephrotic syndrome, type 4, Meacham syndrome, malignant mesothelioma, Nephroblastoma, familial idiopathic steroid-resistant nephrotic syndrome, Wilms tumor, WAGR syndrome, neurodegenerative disease, acute myeloid leukemia.
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, ClinGen, MaveDB, LitVar.
Notable WT1 variants
Examples include D7A, A131T, R145S, P181S, S223N, G253A, S273G, L281P. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- D7A (p.Asp7Ala), rs997104313, Uncertain significance
- A131T (p.Ala131Thr), UniProt VAR 043798, Uncertain significance, Inborn genetic diseases
- R145S (p.Arg145Ser), rs908414065, []
- P181S (p.Pro181Ser), rs2234584, UniProt VAR 007739, AlphaMissense 0.10, MetaLR 0.36, Pathogenic, in WT1
- S223N (p.Ser223Asn), UniProt VAR 007740, MetaLR 0.41, MetaSVM -0.28, Pathogenic, in WT1
- G253A (p.Gly253Ala), UniProt VAR 007741, MetaLR 0.51, MetaSVM 0.07, Uncertain significance, Wilms tumor 1
- S273G (p.Ser273Gly), rs121907908, UniProt VAR 007742, AlphaMissense 0.14, MetaLR 0.47, Uncertain significance, Drash syndrome; Meacham syndrome; Mesothelioma, malignant
- L281P (p.Leu281Pro), UniProt VAR 058021, MetaLR 0.64, MetaSVM 0.37, Uncertain significance, in RNA edited version
- R312Q (p.Arg312Gln), UniProt VAR 015053, MetaLR 0.69, MetaSVM 0.46, Pathogenic, in NPHS4
- C330Y (p.Cys330Tyr), UniProt VAR 007743, Pathogenic, in DDS
- M342R (p.Met342Arg), UniProt VAR 015054, MetaLR 0.43, MetaSVM -0.48, Pathogenic, in DDS
- C355G (p.Cys355Gly), UniProt VAR 043799, Pathogenic, in WT1
- C355Y (p.Cys355Tyr), UniProt VAR 015055, MetaLR 0.66, MetaSVM 0.37, Pathogenic, in DDS
- C360G (p.Cys360Gly), UniProt VAR 007744, Pathogenic, in DDS
- C360Y (p.Cys360Tyr), UniProt VAR 043800, MetaLR 0.64, MetaSVM 0.29, Pathogenic, in DDS
- F364L (p.Phe364Leu), UniProt VAR 043801, MetaLR 0.80, MetaSVM 0.59, Pathogenic, in NPHS4
- R366C (p.Arg366Cys), UniProt VAR 007745, Pathogenic, Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome
- R366H (p.Arg366His), UniProt VAR 007746, Pathogenic, Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome
- R366L (p.Arg366Leu), UniProt VAR 043802, Pathogenic, in DDS
- Q369P (p.Gln369Pro), UniProt VAR 043803, MetaLR 0.77, MetaSVM 0.61, Uncertain significance, Inborn genetic diseases; Wilms tumor 1; 11p partial monosomy syndrome
- H373Q (p.His373Gln), UniProt VAR 007747, Pathogenic, in DDS and WT1
- H373Y (p.His373Tyr), UniProt VAR 015056, Pathogenic, in DDS
- H377R (p.His377Arg), UniProt VAR 015057, Pathogenic, in DDS
- H377Y (p.His377Tyr), UniProt VAR 007748, Pathogenic, in NPHS4
- G379C (p.Gly379Cys), UniProt VAR 043804, Pathogenic, in NPHS4
- F383L (p.Phe383Leu), UniProt VAR 007749, MetaLR 0.04, MetaSVM -1.07, Pathogenic, in NPHS4
- C385R (p.Cys385Arg), UniProt VAR 015058, Pathogenic, Wilms tumor 1; 11p partial monosomy syndrome; Drash syndrome
- C388F (p.Cys388Phe), UniProt VAR 015059, Pathogenic, in DDS
- C388R (p.Cys388Arg), UniProt VAR 043805, Likely pathogenic, WT1-related disorder
- C388Y (p.Cys388Tyr), UniProt VAR 043806, MetaLR 0.70, MetaSVM 0.43, Pathogenic, in DDS
- F392L (p.Phe392Leu), UniProt VAR 015060, Pathogenic, in FS
- R394L (p.Arg394Leu), UniProt VAR 043807, Uncertain significance, Wilms tumor 1; Meacham syndrome; Nephrotic syndrome, type 4
- R394P (p.Arg394Pro), UniProt VAR 043808, Pathogenic, WT1-related disorder
- R394Q (p.Arg394Gln), UniProt VAR 015061, Pathogenic/Likely pathogenic, WT1-related Wilms tumor; Kidney disorder; Frasier syndrome
- R394W (p.Arg394Trp), UniProt VAR 007750, MetaLR 0.33, MetaSVM -0.59, Pathogenic/Likely pathogenic, WT1-related disorder; Kidney disorder; Frasier syndrome
- D396G (p.Asp396Gly), UniProt VAR 007752, Likely pathogenic, Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome
- D396N (p.Asp396Asn), UniProt VAR 007751, Pathogenic/Likely pathogenic, Wilms tumor 1; 11p partial monosomy syndrome; Frasier syndrome
- D396Y (p.Asp396Tyr), UniProt VAR 043809, Pathogenic, in DDS
- H397P (p.His397Pro), UniProt VAR 043810, MetaLR 0.11, MetaSVM -0.86, Pathogenic, in NPHS4
- L398P (p.Leu398Pro), UniProt VAR 015062, MetaLR 0.60, MetaSVM 0.40, Pathogenic, in DDS
- H401Y (p.His401Tyr), UniProt VAR 043811, Likely pathogenic, not provided
- H405R (p.His405Arg), UniProt VAR 043812, MetaLR 0.19, MetaSVM -0.84, Likely pathogenic, Wilms tumor 1; Meacham syndrome; Nephrotic syndrome, type 4
- G407G (p.Gly407Gly), gnomAD 11-32392754-A-C, CADD 16.40, SIFT 0.13
- P419P (p.Pro419Pro), gnomAD 11-32392745-T-G, CADD 6.36, SIFT 0.12
- C421C (p.Cys421Cys), gnomAD 11-32392036-A-G, CADD 13.00
- Q422Q (p.Gln422Gln), rs774650640, gnomAD 11-32392739-C-T, CADD 8.61, SIFT 0.20
- Q422H (p.Gln422His), rs774650640, gnomAD 11-32392739-C-G, REVEL 0.17, MetaLR 0.10
- Q422P (p.Gln422Pro), rs1358408901, gnomAD 11-32392740-T-G, REVEL 0.35, MetaLR 0.08
- F425S (p.Phe425Ser), gnomAD 11-32392020-GGGAG, CADD 33.00
- F425L (p.Phe425Leu), rs1430665640, gnomAD 11-32392024-G-T, REVEL 0.64, MetaLR 0.42
- F425F (p.Phe425Phe), rs1430665640, gnomAD 11-32392024-G-A, CADD 11.60
- F425I (p.Phe425Ile), rs28941779, gnomAD 11-32392026-A-T, REVEL 0.68, MetaLR 0.53
- S428S (p.Ser428Ser), gnomAD 11-32392015-G-T, CADD 7.88
- S428R (p.Ser428Arg), rs1554939078, gnomAD 11-32392015-GGA-G, CADD 34.00
- S428G (p.Ser428Gly), gnomAD 11-32392019-CGGGA, CADD 34.00
- S466del (p.Ser466del), rs1199306379, gnomAD 11-32392020-GGGA-, CADD 21.40
- S428F (p.Ser428Phe), rs1421664466, gnomAD 11-32392022-G-A, REVEL 0.40, MetaLR 0.14
- S428L (p.Ser428Leu), gnomAD 11-32392022-G-GTA, CADD 34.00
- S428* (p.Ser428Ter), gnomAD 11-32392022-G-GTA, CADD 35.00
- S428N (p.Ser428Asn), gnomAD 11-32392024-G-GTA, CADD 33.00
- p.Asp469 Lys472delinsGlu, gnomAD 11-32392003-CTTCA, CADD 20.90
- D429E (p.Asp429Glu), gnomAD 11-32392012-G-T, REVEL 0.70, MetaLR 0.11
- D429N (p.Asp429Asn), rs28941778, gnomAD 11-32392014-C-T, REVEL 0.32, MetaLR 0.29
- D429D (p.Asp429Asp), rs2132920169, gnomAD 11-32392697-G-A, CADD 10.80, SIFT 0.26
- D429Y (p.Asp429Tyr), rs771494968, gnomAD 11-32392735-C-A, REVEL 0.49, MetaLR 0.16
- E430* (p.Glu430Ter), gnomAD 11-32392720-C-A, CADD 42.00
- E430E (p.Glu430Glu), rs767850636, gnomAD 11-32392751-C-T, CADD 9.43, SIFT 0.16
- V432V (p.Val432Val), rs2132915368, gnomAD 11-32392060-C-G, CADD 11.10
- R433S (p.Arg433Ser), rs1851852809, gnomAD 11-32392712-C-A, REVEL 0.27, MetaLR 0.02
- R433R (p.Arg433Arg), gnomAD 11-32392714-T-G, CADD 13.20, SIFT 0.25
- R433Q (p.Arg433Gln), rs144788858, gnomAD 11-32392716-C-T, REVEL 0.35, MetaLR 0.03
- H438H (p.His438His), rs761414130, gnomAD 11-32391985-A-G, CADD 10.50
- H438Y (p.His438Tyr), rs1250438314, gnomAD 11-32391999-G-A, REVEL 0.89, MetaLR 0.54
- Q439H (p.Gln439His), rs2132920088, gnomAD 11-32392694-C-G, REVEL 0.27, MetaLR 0.07
- R440Q (p.Arg440Gln), rs139893274, gnomAD 11-32389158-C-T, REVEL 0.33, MetaLR 0.15
- R440P (p.Arg440Pro), rs139893274, gnomAD 11-32389158-C-G, REVEL 0.53, MetaLR 0.12
- R440W (p.Arg440Trp), rs1315549918, gnomAD 11-32389159-G-A, REVEL 0.48, MetaLR 0.29
- R440R (p.Arg440Arg), rs2132913818, gnomAD 11-32391991-C-T, CADD 12.70
- R440V (p.Arg440Val), gnomAD 11-32392019-CGG-C, CADD 34.00
- p.Arg463 Lys464insPhePhe, rs1372579028, gnomAD 11-32392029-T-TAA, CADD 20.30
- R440* (p.Arg440Ter), rs121907909, gnomAD 11-32392032-G-A, CADD 43.00
- T443T (p.Thr443Thr), gnomAD 11-32391988-A-G, CADD 12.40
- T443I (p.Thr443Ile), rs1851830024, gnomAD 11-32391995-G-A, REVEL 0.40, MetaLR 0.19
- T443N (p.Thr443Asn), rs766697865, gnomAD 11-32392040-G-T, REVEL 0.22, MetaLR 0.10
- T443S (p.Thr443Ser), rs751932589, gnomAD 11-32392041-T-A, REVEL 0.24, MetaLR 0.08
- T443A (p.Thr443Ala), rs751932589, gnomAD 11-32392041-T-C, REVEL 0.39, MetaLR 0.07
- K444R (p.Lys444Arg), rs1269498657, gnomAD 11-32392003-CT-C, CADD 34.00
- K444E (p.Lys444Glu), gnomAD 11-32392005-T-C, REVEL 0.38, MetaLR 0.30
- K444N (p.Lys444Asn), gnomAD 11-32392020-GGGAG, CADD 33.00
- K444I (p.Lys444Ile), gnomAD 11-32392026-ACT-A, CADD 33.00
- K464del (p.Lys464del), gnomAD 11-32392026-ACTT-, CADD 20.50
- K444M (p.Lys444Met), gnomAD 11-32392028-T-TCA, CADD 33.00
- K444* (p.Lys444Ter), rs2132914758, gnomAD 11-32392029-T-A, CADD 43.00
- K444F (p.Lys444Phe), gnomAD 11-32392029-T-TTA, CADD 33.00
- K444K (p.Lys444Lys), rs1319380075, gnomAD 11-32392688-T-C, CADD 11.80, SIFT 0.39
- L445L (p.Leu445Leu), gnomAD 11-32392691-G-T, CADD 9.40
- Q446H (p.Gln446His), gnomAD 11-32392033-C-A, REVEL 0.22, MetaLR 0.07
- Q446Q (p.Gln446Gln), rs2132914889, gnomAD 11-32392033-C-T, CADD 9.85
- Q446L (p.Gln446Leu), rs533043871, gnomAD 11-32392034-T-A, REVEL 0.34, MetaLR 0.08
- Q446R (p.Gln446Arg), gnomAD 11-32392049-T-C, REVEL 0.27, MetaLR 0.09
- L449R (p.Leu449Arg), rs1253058174, gnomAD 11-32392006-CA-C, CADD 33.00
Public WT1 analysis runs
- WT1 analysis run — WT1 (104 variants) — completed 2026-08-18