WT1

WT1 transcription factor, the group of Zinc fingers C2H2-type

Basic information

Region (hg38): 11:32387775-32435564

Previous symbols: [ "GUD" ]

Links

ENSG00000184937 ∙ NCBI:7490 ∙ OMIM:607102 ∙ HGNC:12796 ∙ Uniprot:P19544 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Denys-Drash syndrome (Definitive), mode of inheritance: AD
• Frasier syndrome (Definitive), mode of inheritance: AD
• Wilms tumor 1 (Strong), mode of inheritance: AD
• familial idiopathic steroid-resistant nephrotic syndrome (Supportive), mode of inheritance: AD
• Frasier syndrome (Supportive), mode of inheritance: AD
• Wilms tumor 1 (Definitive), mode of inheritance: AD
• Denys-Drash syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Denys-Drash syndrome; Wilms tumor, type 1; Frasier syndrome; Meacham syndrome	AD	Cardiovascular; Oncologic; Renal	Individuals are at risk for several types of neoplasm, and surveillance may allow early detection and treatment for common oncologic features (eg, Wilms tumor, gonadoblastoma); Renal transplant may be indicated (and beneficial) in individuals with end-stage renal faiure; Meacham syndrome can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Endocrine; Genitourinary; Oncologic; Renal; Pulmonary	14149008; 4292870; 4316066; 4153449; 331956; 3000666; 3130865; 3026952; 2172500; 1655284; 1338906; 1338905; 8386697; 8071974; 7645607; 7607640; 9398852; 9108089; 9529364; 9607189; 11241056; 12050205; 17853480; 18203154; 18688870; 20150449; 20301471; 21434831; 21559934; 21614510; 22585769; 22876585; 24161391

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the WT1 gene.

• Frasier syndrome;Drash syndrome;Wilms tumor 1;11p partial monosomy syndrome (13 variants)
• not provided (11 variants)
• Drash syndrome;Wilms tumor 1;11p partial monosomy syndrome;Frasier syndrome (9 variants)
• Drash syndrome (9 variants)
• Wilms tumor 1 (9 variants)
• WT1-related disorder (7 variants)
• Wilms tumor 1;11p partial monosomy syndrome;Frasier syndrome;Drash syndrome (6 variants)
• Drash syndrome;Frasier syndrome;Wilms tumor 1;11p partial monosomy syndrome (5 variants)
• Nephrotic syndrome, type 4 (5 variants)
• 8 conditions (4 variants)
• Frasier syndrome (3 variants)
• Drash syndrome;11p partial monosomy syndrome;Wilms tumor 1;Frasier syndrome (2 variants)
• Focal segmental glomerulosclerosis (1 variants)
• Inborn genetic diseases (1 variants)
• Wilms tumor 1;Frasier syndrome;Drash syndrome;11p partial monosomy syndrome (1 variants)
• Drash syndrome;Frasier syndrome;Wilms tumor 1 (1 variants)
• Drash syndrome;Frasier syndrome (1 variants)
• Meacham syndrome (1 variants)
• Familial idiopathic steroid-resistant nephrotic syndrome (1 variants)
• Wilms tumor 1;11p partial monosomy syndrome;Drash syndrome;Frasier syndrome (1 variants)
• Nephrotic syndrome, type 4;Wilms tumor 1;Frasier syndrome;Drash syndrome (1 variants)
• 11p partial monosomy syndrome;Wilms tumor 1;Frasier syndrome;Drash syndrome (1 variants)
• WT1-related Wilms tumor (1 variants)
• Nephroblastoma (1 variants)
• Frasier syndrome;Wilms tumor 1;Drash syndrome;11p partial monosomy syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WT1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	345	6	357
missense	9	25	720	2	3	759
nonsense	20	3	7			30
start loss						0
frameshift	27	5	8			40
inframe indel			16			16
splice donor/acceptor (+/-2bp)	3	6	4			13
splice region	1	2	24	42	1	70
non coding		2	50	157	36	245
Total	59	41	811	504	45

Highest pathogenic variant AF is 0.0000131

Variants in WT1

This is a list of pathogenic ClinVar variants found in the WT1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-32387819-A-T		Meacham syndrome • Wilms tumor 1 • Nephrotic syndrome, type 4	Benign/Likely benign (Jan 13, 2018)
11-32387833-A-G		Nephrotic syndrome, type 4 • Meacham syndrome • Wilms tumor 1	Uncertain significance (Jan 13, 2018)
11-32387849-T-C		Wilms tumor 1 • Meacham syndrome • Nephrotic syndrome, type 4	Benign/Likely benign (Jan 12, 2018)
11-32387891-A-C		Meacham syndrome • Wilms tumor 1 • Nephrotic syndrome, type 4	Uncertain significance (Jan 12, 2018)
11-32387926-T-A		Meacham syndrome • Nephrotic syndrome, type 4 • Wilms tumor 1	Benign/Likely benign (Jan 13, 2018)
11-32387960-G-A		Nephrotic syndrome, type 4 • Meacham syndrome • Wilms tumor 1	Benign/Likely benign (Jan 12, 2018)
11-32387992-A-C		Wilms tumor 1 • Meacham syndrome • Nephrotic syndrome, type 4	Uncertain significance (Jan 13, 2018)
11-32388000-C-A		Nephroblastoma • Meacham syndrome • Nephrotic syndrome, type 4 • 11p partial monosomy syndrome	Uncertain significance (Jun 14, 2016)
11-32388003-AACAC-A		Nephroblastoma • 11p partial monosomy syndrome • Meacham syndrome • Nephrotic syndrome, type 4	Uncertain significance (Jun 14, 2016)
11-32388003-AACACAC-A		Nephroblastoma • Nephrotic syndrome, type 4 • 11p partial monosomy syndrome • Meacham syndrome	Uncertain significance (Jun 14, 2016)
11-32388003-A-AAC		11p partial monosomy syndrome • Meacham syndrome • Nephrotic syndrome, type 4 • Nephroblastoma	Uncertain significance (Jun 14, 2016)
11-32388003-A-AACAC		Nephroblastoma • Meacham syndrome • 11p partial monosomy syndrome • Nephrotic syndrome, type 4	Uncertain significance (Jun 14, 2016)
11-32388003-A-AACACAC		Nephroblastoma • Nephrotic syndrome, type 4 • Meacham syndrome • 11p partial monosomy syndrome	Uncertain significance (Jun 14, 2016)
11-32388008-AC-A		Nephroblastoma • Meacham syndrome • Nephrotic syndrome, type 4	Benign (Jun 14, 2016)
11-32388079-A-AT		Meacham syndrome • Nephroblastoma • Nephrotic syndrome, type 4	Benign (Jun 14, 2016)
11-32388155-C-T		Wilms tumor 1 • Nephrotic syndrome, type 4 • Meacham syndrome	Benign/Likely benign (Jan 12, 2018)
11-32388161-C-G		Meacham syndrome • 11p partial monosomy syndrome • Nephrotic syndrome, type 4 • Nephroblastoma	Likely benign (Jun 14, 2016)
11-32388194-A-C		Nephrotic syndrome, type 4 • Wilms tumor 1 • Meacham syndrome	Benign/Likely benign (Jan 13, 2018)
11-32388194-A-T		Nephrotic syndrome, type 4 • Wilms tumor 1 • Meacham syndrome	Benign/Likely benign (Jan 12, 2018)
11-32388217-G-T		Nephroblastoma • 11p partial monosomy syndrome • Nephrotic syndrome, type 4 • Meacham syndrome	Uncertain significance (Jun 14, 2016)
11-32388223-T-C		Wilms tumor 1 • Meacham syndrome • Nephrotic syndrome, type 4	Benign/Likely benign (Jan 13, 2018)
11-32388238-C-G		Wilms tumor 1 • Nephrotic syndrome, type 4 • Meacham syndrome	Benign (Jan 13, 2018)
11-32388273-G-T		Nephrotic syndrome, type 4 • Meacham syndrome • Wilms tumor 1	Uncertain significance (Jan 12, 2018)
11-32388290-T-G		Meacham syndrome • Nephrotic syndrome, type 4 • 11p partial monosomy syndrome • Nephroblastoma	Uncertain significance (Jun 14, 2016)
11-32388317-C-A		11p partial monosomy syndrome • Meacham syndrome • Nephroblastoma • Nephrotic syndrome, type 4	Uncertain significance (Jun 14, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WT1	protein_coding	protein_coding	ENST00000332351	10	47856

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.996	0.00352	125743	0	5	125748	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.78	201	286	0.704	0.0000155	3341
Missense in Polyphen		72	127.08	0.56659		1496
Synonymous	-0.0334	120	120	1.00	0.00000649	1017
Loss of Function	4.31	2	25.5	0.0785	0.00000139	273

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.00000879	0.00000879
Middle Eastern	0.000163	0.000109
South Asian	0.0000980	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor that plays an important role in cellular development and cell survival (PubMed:7862533). Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3' (PubMed:7862533, PubMed:17716689, PubMed:25258363). Regulates the expression of numerous target genes, including EPO. Plays an essential role for development of the urogenital system. It has a tumor suppressor as well as an oncogenic role in tumor formation. Function may be isoform-specific: isoforms lacking the KTS motif may act as transcription factors (PubMed:15520190). Isoforms containing the KTS motif may bind mRNA and play a role in mRNA metabolism or splicing (PubMed:16934801). Isoform 1 has lower affinity for DNA, and can bind RNA (PubMed:19123921). {ECO:0000269|PubMed:15520190, ECO:0000269|PubMed:16934801, ECO:0000269|PubMed:17716689, ECO:0000269|PubMed:19123921, ECO:0000269|PubMed:19416806, ECO:0000269|PubMed:25258363, ECO:0000269|PubMed:7862533}.
• Disease: DISEASE: Frasier syndrome (FS) [MIM:136680]: Characterized by a slowly progressing nephropathy leading to renal failure in adolescence or early adulthood, male pseudohermaphroditism, and no Wilms tumor. As for histological findings of the kidneys, focal glomerular sclerosis is often observed. There is phenotypic overlap with Denys-Drash syndrome. Inheritance is autosomal dominant. {ECO:0000269|PubMed:10571943}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Wilms tumor 1 (WT1) [MIM:194070]: Embryonal malignancy of the kidney that affects approximately 1 in 10'000 infants and young children. It occurs both in sporadic and hereditary forms. {ECO:0000269|PubMed:1317572, ECO:0000269|PubMed:15150775, ECO:0000269|PubMed:9108089, ECO:0000269|PubMed:9529364}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Denys-Drash syndrome (DDS) [MIM:194080]: Typical nephropathy characterized by diffuse mesangial sclerosis, genital abnormalities, and/or Wilms tumor. There is phenotypic overlap with WAGR syndrome and Frasier syndrome. Inheritance is autosomal dominant, but most cases are sporadic. {ECO:0000269|PubMed:10738002, ECO:0000269|PubMed:10799199, ECO:0000269|PubMed:11182928, ECO:0000269|PubMed:11519891, ECO:0000269|PubMed:1302008, ECO:0000269|PubMed:1338906, ECO:0000269|PubMed:15349765, ECO:0000269|PubMed:1655284, ECO:0000269|PubMed:8111391, ECO:0000269|PubMed:8112732, ECO:0000269|PubMed:8295405, ECO:0000269|PubMed:8388765, ECO:0000269|PubMed:8411073, ECO:0000269|PubMed:8741319, ECO:0000269|PubMed:8956030, ECO:0000269|PubMed:9475094, ECO:0000269|PubMed:9529364}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Nephrotic syndrome 4 (NPHS4) [MIM:256370]: A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure. Most patients with NPHS4 show diffuse mesangial sclerosis on renal biopsy, which is a pathologic entity characterized by mesangial matrix expansion with no mesangial hypercellularity, hypertrophy of the podocytes, vacuolized podocytes, thickened basement membranes, and diminished patency of the capillary lumen. {ECO:0000269|PubMed:11182928, ECO:0000269|PubMed:15253707, ECO:0000269|PubMed:20798252, ECO:0000269|PubMed:9529364, ECO:0000269|PubMed:9607189}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Meacham syndrome (MEACHS) [MIM:608978]: Rare sporadically occurring multiple malformation syndrome characterized by male pseudohermaphroditism with abnormal internal female genitalia comprising a uterus and double or septate vagina, complex congenital heart defect and diaphragmatic abnormalities. {ECO:0000269|PubMed:17853480}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=A chromosomal aberration involving WT1 may be a cause of desmoplastic small round cell tumor (DSRCT). Translocation t(11;22)(p13;q12) with EWSR1.; DISEASE: Mesothelioma, malignant (MESOM) [MIM:156240]: An aggressive neoplasm of the serosal lining of the chest. It appears as broad sheets of cells, with some regions containing spindle- shaped, sarcoma-like cells and other regions showing adenomatous patterns. Pleural mesotheliomas have been linked to exposure to asbestos. {ECO:0000269|PubMed:8401592}. Note=The disease may be caused by mutations affecting the gene represented in this entry.
• Pathway: Transcriptional misregulation in cancer - Homo sapiens (human);Primary Focal Segmental Glomerulosclerosis FSGS;chaperones modulate interferon signaling pathway;overview of telomerase protein component gene htert transcriptional regulation;p73 transcription factor network;TGF-beta super family signaling pathway canonical;BMP2 signaling TGF-beta MV;BMP signaling Dro;Regulation of Telomerase (Consensus)

Recessive Scores

• pRec: 0.875

Intolerance Scores

• rvis_EVS: -0.45
• rvis_percentile_EVS: 24

Haploinsufficiency Scores

• pHI: 0.999
• ghis: 0.494

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.991

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Wt1
• Phenotype: immune system phenotype; renal/urinary system phenotype; embryo phenotype; respiratory system phenotype; liver/biliary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; endocrine/exocrine gland phenotype; neoplasm; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: wt1a
• Affected structure: podocyte
• Phenotype tag: abnormal
• Phenotype quality: flattened

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;vasculogenesis;ureteric bud development;branching involved in ureteric bud morphogenesis;kidney development;regulation of animal organ formation;regulation of transcription, DNA-templated;regulation of transcription by RNA polymerase II;germ cell development;thorax and anterior abdomen determination;heart development;sex determination;negative regulation of cell population proliferation;RNA splicing;gonad development;male gonad development;tissue development;positive regulation of gene expression;negative regulation of cell growth;adrenal gland development;male genitalia development;epithelial cell differentiation;glomerulus development;glomerular basement membrane development;adrenal cortex formation;camera-type eye development;negative regulation of apoptotic process;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;mesenchymal to epithelial transition;positive regulation of heart growth;diaphragm development;cardiac muscle cell fate commitment;visceral serous pericardium development;cellular response to cAMP;cellular response to gonadotropin stimulus;metanephric mesenchyme development;glomerular visceral epithelial cell differentiation;posterior mesonephric tubule development;metanephric epithelium development;metanephric S-shaped body morphogenesis;negative regulation of metanephric glomerular mesangial cell proliferation;positive regulation of pri-miRNA transcription by RNA polymerase II;positive regulation of DNA methylation;positive regulation of male gonad development;negative regulation of female gonad development;positive regulation of metanephric ureteric bud development
• Cellular component: nucleus;nucleoplasm;nucleolus;cytoplasm;cytosol;nuclear speck
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity;RNA binding;protein binding;zinc ion binding;double-stranded methylated DNA binding;sequence-specific DNA binding;transcription regulatory region DNA binding;hemi-methylated DNA-binding;C2H2 zinc finger domain binding