WT1 |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- WT1 (HGNC:12796) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- WT1 transcription factor
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- GUD
- Alias symbols
- WAGR, WIT-2, AWT1, NPHS4, WT-1
- %HI
- 1.09(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 1(Read more about gnomAD pLI score)
- LOEUF
- 0.25(Read more about gnomAD LOEUF score)
- Cytoband
- 11p13
- Genomic Coordinates
-
GRCh37/hg19: chr11:32409321-32457085 NCBI Ensembl UCSC GRCh38/hg38: chr11:32387775-32435539 NCBI Ensembl UCSC - MANE Select Transcript
- NM_024426.6 ENST00000452863.10 (Read more about MANE Select)
- 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 a... (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Dosage ID:
ISCA-3923
Curation Status:
Complete
Issue Type:
Dosage Curation -
Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency
(3)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
Related Links:
Last Evaluated:
01/25/2022
Haploinsufficiency (HI) Score Details
HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency
(Disclaimer)
HI Disease:
- WT1 related disorder Monarch
HI Evidence:
-
PUBMED:
25613702
Finken et al (PMID 25613702) reports a case of a phenotypically female 46,XY patient presenting with severe partial gonadal dysgenesis, gonadoblastoma, and early bilateral Wilms tumors detected at 9 months of age. Heterozygous whole gene deletion observed on array [Agilent 180k Oligo-Array: arr 11p13(32,190,449– 32,542,286), confirmed by MLPA at the exon level]. No relevant family history and the deletion was not observed in parents.
-
PUBMED:
17551084
Uschkereit et al (PMID 17551084) describes a case of a 10 month old female patient with a germline heterozygous WT1 p.Ser50X c.149C>A. Patient presented at 10 months with large bilateral Wilms tumors. After excision of these tumors, additional bilateral tumors arose one year later and were demonstrated to be independent events. No mention of parental testing.
-
PUBMED:
15503171
Little et al (PMID 15503171) reports the case of a phenotypically female child (46,XY) presenting with bilateral Wilms tumor at 8 months. Detected a c.40delT p.(Phe40fs) germline variant in WT1 that was confirmed absent in the parents.
HI Evidence Comments:
WT1 encodes a zinc finger transcription factor expressed during development of the urogenital system and hematopoesis. It consists of ten exons and includes two different alternative splice sites. pLI = 1, o/e = .08 (.03-.25 (LOEUF = 0.247)). Germline copy number loss of WT1 is often observed as part of contiguous gene deletions of the 11p13 region, with a critical region of PAX6 and WT1, that gives rise to WAGR syndrome (Wilms Tumor, Aniridia, Genitourinary Anomalies, and mental Retardation syndrome). Germline single gene deletions of WT1 are less frequently observed. Nonsense and frameshifting mutations are reported in patients with Wilms tumor, with or without additional urogenital and renal findings, a spectrum described as WT1 disorder.
Triplosensitivity (TS) Score Details
TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
Genomic View
Select assembly:
(NC_000011.9)
(NC_000011.10)