Protein:WT1 |
Protein Summary |
 Gene summary |
| Gene name: WT1 | ASpdb.0 ID: 7490 | Gene | Gene symbol | WT1 | Gene ID | 7490 |
| Gene name | WT1 transcription factor |
| Synonyms | AWT1|GUD|NPHS4|WAGR|WIT-2|WT-1|WT33 |
| Cytomap | 11p13 |
| Type of gene | protein-coding |
| Description | Wilms tumor proteinWilms tumor 1 |
| Modification date | 20240411 |
| UniProtAcc | P19544 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | WT1 | GO:0000122 | negative regulation of transcription by RNA polymerase II | 7585606 |
| Gene | WT1 | GO:0000976 | transcription cis-regulatory region binding | 1332065|7585606|7588596|9815658|16467207 |
| Gene | WT1 | GO:0000978 | RNA polymerase II cis-regulatory region sequence-specific DNA binding | 23042785 |
| Gene | WT1 | GO:0001228 | DNA-binding transcription activator activity, RNA polymerase II-specific | 23042785 |
| Gene | WT1 | GO:0005634 | nucleus | 1662794|7588596|8306891|14701728|15961562|16934801 |
| Gene | WT1 | GO:0005654 | nucleoplasm | - |
| Gene | WT1 | GO:0005829 | cytosol | - |
| Gene | WT1 | GO:0007530 | sex determination | 9815658 |
| Gene | WT1 | GO:0008270 | zinc ion binding | 15518539|25258363 |
| Gene | WT1 | GO:0008285 | negative regulation of cell population proliferation | 9553041|9765217 |
| Gene | WT1 | GO:0010385 | double-stranded methylated DNA binding | 25258363 |
| Gene | WT1 | GO:0016607 | nuclear speck | 9553041|16934801 |
| Gene | WT1 | GO:0030308 | negative regulation of cell growth | 9553041|9765217 |
| Gene | WT1 | GO:0043565 | sequence-specific DNA binding | 1662794|7720589|8119964|25258363 |
| Gene | WT1 | GO:0044729 | hemi-methylated DNA-binding | 25258363 |
| Gene | WT1 | GO:0045892 | negative regulation of DNA-templated transcription | 1332065|7585606|7720589|8119964|12802290|14701728|19050011 |
| Gene | WT1 | GO:0045893 | positive regulation of DNA-templated transcription | 8132626|9178767|9553041|9765217|12802290|14701728|16467207|21390327 |
| Gene | WT1 | GO:0045944 | positive regulation of transcription by RNA polymerase II | 23042785 |
| Gene | WT1 | GO:0071371 | cellular response to gonadotropin stimulus | 15961562 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P19544-1 | P19544-1_6blw_A.pdb | 6BLW | X-ray | 1.83 | A | 319 | 439 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P19544 | WT1 | P19544-1 | P19544-2 | 449 | 429 | 250 | 266 | Deletion | none | none | 249 | 249 |
| P19544 | WT1 | P19544-1 | P19544-2 | 449 | 429 | 408 | 410 | Deletion | none | none | 390 | 390 |
| P19544 | WT1 | P19544-1 | P19544-3 | 449 | 432 | 250 | 266 | Deletion | none | none | 249 | 249 |
| P19544 | WT1 | P19544-1 | P19544-4 | 449 | 446 | 408 | 410 | Deletion | none | none | 407 | 407 |
| P19544 | WT1 | P19544-1 | P19544-6 | 449 | 302 | 1 | 144 | Deletion | none | none | 0 | 0 |
| P19544 | WT1 | P19544-1 | P19544-6 | 449 | 302 | 145 | 147 | Substitution | RNQ | MEK | 1 | 3 |
| P19544 | WT1 | P19544-1 | P19544-6 | 449 | 302 | 408 | 410 | Deletion | none | none | 263 | 263 |
| P19544 | WT1 | P19544-1 | P19544-7 | 449 | 522 | 1 | 1 | Substitution | M | MDFLLLQDPASTCVPEPASQHTLRSGPGCLQQPEQQGVRDPGGIWAKLGAAEASAERLQGRRSRGASGSEPQQM | 1 | 74 |
| P19544 | WT1 | P19544-1 | P19544-8 | 449 | 505 | 1 | 1 | Substitution | M | MDFLLLQDPASTCVPEPASQHTLRSGPGCLQQPEQQGVRDPGGIWAKLGAAEASAERLQGRRSRGASGSEPQQM | 1 | 74 |
| P19544 | WT1 | P19544-1 | P19544-8 | 449 | 505 | 250 | 266 | Deletion | none | none | 322 | 322 |
| P19544 | WT1 | P19544-1 | P19544-9 | 449 | 288 | 1 | 144 | Deletion | none | none | 0 | 0 |
| P19544 | WT1 | P19544-1 | P19544-9 | 449 | 288 | 145 | 147 | Substitution | RNQ | MEK | 1 | 3 |
| P19544 | WT1 | P19544-1 | P19544-9 | 449 | 288 | 250 | 266 | Deletion | none | none | 105 | 105 |
| Multiple sequence alignment of our canonical and alternatively spliced WT1 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of WT1 |
| UniProt-id | ENSG | ENST | ENSP |
| P19544-6 | ENSG00000184937.16 | ENST00000379079.8 | ENSP00000368370.2 |
| P19544-7 | ENSG00000184937.16 | ENST00000452863.10 | ENSP00000415516.5 |
| P19544-8 | ENSG00000184937.16 | ENST00000639563.3 | ENSP00000492269.3 |
| P19544-9 | ENSG00000184937.16 | ENST00000530998.5 | ENSP00000435307.1 |
| UniProt-id | NM ID | NP ID |
| P19544-6 | NM_001198551.1 | NP_001185480.1 |
| P19544-7 | NM_024426.4 | NP_077744.3 |
| P19544-9 | NM_001198552.1 | NP_001185481.1 |
| Amino acid sequences of our canonical and alternatively spliced WT1 |
| accession_id | Protein sequence |
| P19544-1 | MGSDVRDLNALLPAVPSLGGGGGCALPVSGAAQWAPVLDFAPPGASAYGSLGGPAPPPAPPPPPPPPPHSFIKQEPSWGGAEPHEEQCLS AFTVHFSGQFTGTAGACRYGPFGPPPPSQASSGQARMFPNAPYLPSCLESQPAIRNQGYSTVTFDGTPSYGHTPSHHAAQFPNHSFKHED PMGQQGSLGEQQYSVPPPVYGCHTPTDSCTGSQALLLRTPYSSDNLYQMTSQLECMTWNQMNLGATLKGVAAGSSSSVKWTEGQSNHSTG YESDNHTTPILCGAQYRIHTHGVFRGIQDVRRVPGVAPTLVRSASETSEKRPFMCAYPGCNKRYFKLSHLQMHSRKHTGEKPYQCDFKDC |
| P19544-2 | MGSDVRDLNALLPAVPSLGGGGGCALPVSGAAQWAPVLDFAPPGASAYGSLGGPAPPPAPPPPPPPPPHSFIKQEPSWGGAEPHEEQCLS AFTVHFSGQFTGTAGACRYGPFGPPPPSQASSGQARMFPNAPYLPSCLESQPAIRNQGYSTVTFDGTPSYGHTPSHHAAQFPNHSFKHED PMGQQGSLGEQQYSVPPPVYGCHTPTDSCTGSQALLLRTPYSSDNLYQMTSQLECMTWNQMNLGATLKGHSTGYESDNHTTPILCGAQYR IHTHGVFRGIQDVRRVPGVAPTLVRSASETSEKRPFMCAYPGCNKRYFKLSHLQMHSRKHTGEKPYQCDFKDCERRFSRSDQLKRHQRRH |
| P19544-3 | MGSDVRDLNALLPAVPSLGGGGGCALPVSGAAQWAPVLDFAPPGASAYGSLGGPAPPPAPPPPPPPPPHSFIKQEPSWGGAEPHEEQCLS AFTVHFSGQFTGTAGACRYGPFGPPPPSQASSGQARMFPNAPYLPSCLESQPAIRNQGYSTVTFDGTPSYGHTPSHHAAQFPNHSFKHED PMGQQGSLGEQQYSVPPPVYGCHTPTDSCTGSQALLLRTPYSSDNLYQMTSQLECMTWNQMNLGATLKGHSTGYESDNHTTPILCGAQYR IHTHGVFRGIQDVRRVPGVAPTLVRSASETSEKRPFMCAYPGCNKRYFKLSHLQMHSRKHTGEKPYQCDFKDCERRFSRSDQLKRHQRRH |
| P19544-4 | MGSDVRDLNALLPAVPSLGGGGGCALPVSGAAQWAPVLDFAPPGASAYGSLGGPAPPPAPPPPPPPPPHSFIKQEPSWGGAEPHEEQCLS AFTVHFSGQFTGTAGACRYGPFGPPPPSQASSGQARMFPNAPYLPSCLESQPAIRNQGYSTVTFDGTPSYGHTPSHHAAQFPNHSFKHED PMGQQGSLGEQQYSVPPPVYGCHTPTDSCTGSQALLLRTPYSSDNLYQMTSQLECMTWNQMNLGATLKGVAAGSSSSVKWTEGQSNHSTG YESDNHTTPILCGAQYRIHTHGVFRGIQDVRRVPGVAPTLVRSASETSEKRPFMCAYPGCNKRYFKLSHLQMHSRKHTGEKPYQCDFKDC |
| P19544-6 | MEKGYSTVTFDGTPSYGHTPSHHAAQFPNHSFKHEDPMGQQGSLGEQQYSVPPPVYGCHTPTDSCTGSQALLLRTPYSSDNLYQMTSQLE CMTWNQMNLGATLKGVAAGSSSSVKWTEGQSNHSTGYESDNHTTPILCGAQYRIHTHGVFRGIQDVRRVPGVAPTLVRSASETSEKRPFM CAYPGCNKRYFKLSHLQMHSRKHTGEKPYQCDFKDCERRFSRSDQLKRHQRRHTGVKPFQCKTCQRKFSRSDHLKTHTRTHTGEKPFSCR |
| P19544-7 | MDFLLLQDPASTCVPEPASQHTLRSGPGCLQQPEQQGVRDPGGIWAKLGAAEASAERLQGRRSRGASGSEPQQMGSDVRDLNALLPAVPS LGGGGGCALPVSGAAQWAPVLDFAPPGASAYGSLGGPAPPPAPPPPPPPPPHSFIKQEPSWGGAEPHEEQCLSAFTVHFSGQFTGTAGAC RYGPFGPPPPSQASSGQARMFPNAPYLPSCLESQPAIRNQGYSTVTFDGTPSYGHTPSHHAAQFPNHSFKHEDPMGQQGSLGEQQYSVPP PVYGCHTPTDSCTGSQALLLRTPYSSDNLYQMTSQLECMTWNQMNLGATLKGVAAGSSSSVKWTEGQSNHSTGYESDNHTTPILCGAQYR IHTHGVFRGIQDVRRVPGVAPTLVRSASETSEKRPFMCAYPGCNKRYFKLSHLQMHSRKHTGEKPYQCDFKDCERRFSRSDQLKRHQRRH |
| P19544-8 | MDFLLLQDPASTCVPEPASQHTLRSGPGCLQQPEQQGVRDPGGIWAKLGAAEASAERLQGRRSRGASGSEPQQMGSDVRDLNALLPAVPS LGGGGGCALPVSGAAQWAPVLDFAPPGASAYGSLGGPAPPPAPPPPPPPPPHSFIKQEPSWGGAEPHEEQCLSAFTVHFSGQFTGTAGAC RYGPFGPPPPSQASSGQARMFPNAPYLPSCLESQPAIRNQGYSTVTFDGTPSYGHTPSHHAAQFPNHSFKHEDPMGQQGSLGEQQYSVPP PVYGCHTPTDSCTGSQALLLRTPYSSDNLYQMTSQLECMTWNQMNLGATLKGHSTGYESDNHTTPILCGAQYRIHTHGVFRGIQDVRRVP GVAPTLVRSASETSEKRPFMCAYPGCNKRYFKLSHLQMHSRKHTGEKPYQCDFKDCERRFSRSDQLKRHQRRHTGVKPFQCKTCQRKFSR |
| P19544-9 | MEKGYSTVTFDGTPSYGHTPSHHAAQFPNHSFKHEDPMGQQGSLGEQQYSVPPPVYGCHTPTDSCTGSQALLLRTPYSSDNLYQMTSQLE CMTWNQMNLGATLKGHSTGYESDNHTTPILCGAQYRIHTHGVFRGIQDVRRVPGVAPTLVRSASETSEKRPFMCAYPGCNKRYFKLSHLQ MHSRKHTGEKPYQCDFKDCERRFSRSDQLKRHQRRHTGVKPFQCKTCQRKFSRSDHLKTHTRTHTGKTSEKPFSCRWPSCQKKFARSDEL |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| WT1 (go to UniProt):P19544 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P19544 | Region | 48 | 84 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=144 |
| P19544 | Region | 48 | 84 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=144 |
| P19544 | Motif | 408 | 410 | Note=KTS motif | Type=Deletion;Start=408;End=410 |
| P19544 | Motif | 408 | 410 | Note=KTS motif | Type=Deletion;Start=408;End=410 |
| P19544 | Motif | 408 | 410 | Note=KTS motif | Type=Deletion;Start=408;End=410 |
| P19544 | Compositional bias | 53 | 72 | Note=Pro residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=144 |
| P19544 | Compositional bias | 53 | 72 | Note=Pro residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=144 |
Gene Isoform Structures and Expression Levels for WT1 |
| Gene structures of our canonical and alternative spliced genes of WT1 * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
 |
| Expression levels of gene isoforms across TCGA. |
 |
Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P19544-1 |
| 3D view using mol* of P19544-2 |
| 3D view using mol* of P19544-3 |
| 3D view using mol* of P19544-4 |
| 3D view using mol* of P19544-6 |
| 3D view using mol* of P19544-7 |
| 3D view using mol* of P19544-8 |
| 3D view using mol* of P19544-9 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P19544-1 |
 |
| pLDDT distribution across the protein length of P19544-2 |
 |
| pLDDT distribution across the protein length of P19544-3 |
 |
| pLDDT distribution across the protein length of P19544-4 |
 |
| pLDDT distribution across the protein length of P19544-6 |
 |
| pLDDT distribution across the protein length of P19544-7 |
 |
| pLDDT distribution across the protein length of P19544-8 |
 |
| pLDDT distribution across the protein length of P19544-9 |
 |
Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P19544-1 |
 |
| Ramachandran plot of P19544-2 |
 |
| Ramachandran plot of P19544-4 |
 |
| Ramachandran plot of P19544-6 |
 |
| Ramachandran plot of P19544-7 |
 |
| Ramachandran plot of P19544-8 |
 |
| Ramachandran plot of P19544-9 |
 |
Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P19544-1 | 0.986 | 161 | 1.026 | 363.58 | 0.566 | 0.642 | 0.89 | 0.458 | 0.916 | 0.5 | 0.558 | 307,308,309,310,311,312,313,314,315,318,322,323,32 4,325,326,327,328,329,330,331,333,337,340,341,344, 345,347,348,350 |
| P19544-2 | 0.933 | 83 | 0.959 | 382.445 | 0.761 | 0.647 | 0.709 | 0.261 | 0.874 | 0.299 | 0.39 | 222,223,224,225,227,229,304,313,315,316,317,318,32 2,325,326,328,329,330,336,348,349,350,351,352 |
| P19544-3 | 1.002 | 152 | 1.036 | 456.533 | 0.579 | 0.673 | 0.914 | 0.436 | 0.944 | 0.462 | 0.986 | 280,282,283,284,285,286,287,288,289,291,292,293,29 4,306,307,308,309,310,323,324,327,328,330,331,333, 335,336,337,339,350,353,354,357 |
| P19544-4 | 0.836 | 55 | 0.837 | 184.191 | 0.621 | 0.664 | 0.854 | 0.88 | 0.794 | 1.108 | 0.59 | 229,230,233,403,410,411,412,413,414,415,425,428,42 9,432,435 |
| P19544-6 | 0.831 | 57 | 0.85 | 210.945 | 0.702 | 0.619 | 0.776 | 0.628 | 0.707 | 0.888 | 0.368 | 54,55,56,57,178,179,180,181,182,183,193,196,197,20 0,203,204 |
| P19544-7 | 0.854 | 58 | 0.783 | 153.321 | 0.528 | 0.741 | 1.009 | 0.344 | 1.159 | 0.297 | 0.412 | 381,382,383,384,385,386,395,396,397,398,399,400,41 0,413,414,417,418,420,421 |
| P19544-8 | 0.969 | 93 | 0.99 | 225.008 | 0.569 | 0.674 | 0.931 | 0.45 | 0.986 | 0.456 | 0.425 | 359,360,361,362,364,365,366,367,368,378,379,380,38 1,382,383,396,397,400,401,403,404,406 |
| P19544-9 | 0.984 | 118 | 0.959 | 259.308 | 0.608 | 0.674 | 0.925 | 0.411 | 1.181 | 0.348 | 0.472 | 136,137,138,139,140,141,142,143,144,145,146,147,14 8,149,150,162,163,164,165,166,167,179,180,183,184, 186,187,189 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
 |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P19544-1_P19544-1_6blw_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P19544-1_6blw_A_P19544-2.pdb |
| 3D view using mol* of P19544-1_6blw_A_P19544-3.pdb |
| 3D view using mol* of P19544-1_6blw_A_P19544-4.pdb |
| 3D view using mol* of P19544-1_6blw_A_P19544-6.pdb |
| 3D view using mol* of P19544-1_6blw_A_P19544-7.pdb |
| 3D view using mol* of P19544-1_6blw_A_P19544-8.pdb |
| 3D view using mol* of P19544-1_6blw_A_P19544-9.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P19544-1_P19544-2.pdb |
| 3D view using mol* of P19544-1_P19544-3.pdb |
| 3D view using mol* of P19544-1_P19544-4.pdb |
| 3D view using mol* of P19544-1_P19544-6.pdb |
| 3D view using mol* of P19544-1_P19544-7.pdb |
| 3D view using mol* of P19544-1_P19544-8.pdb |
| 3D view using mol* of P19544-1_P19544-9.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P19544-1_vs_P19544-2.png |
 < |
| ./stats/secondary_structure/figure/P19544-1_vs_P19544-3.png |
 < |
| ./stats/secondary_structure/figure/P19544-1_vs_P19544-4.png |
 < |
| ./stats/secondary_structure/figure/P19544-1_vs_P19544-6.png |
 < |
| ./stats/secondary_structure/figure/P19544-1_vs_P19544-7.png |
 < |
| ./stats/secondary_structure/figure/P19544-1_vs_P19544-8.png |
 < |
| ./stats/secondary_structure/figure/P19544-1_vs_P19544-9.png |
 < |
| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P19544-1_vs_P19544-2.png |
 < |
| ./stats/relative_asa/P19544-1_vs_P19544-3.png |
 < |
| ./stats/relative_asa/P19544-1_vs_P19544-4.png |
 < |
| ./stats/relative_asa/P19544-1_vs_P19544-6.png |
 < |
| ./stats/relative_asa/P19544-1_vs_P19544-7.png |
 < |
| ./stats/relative_asa/P19544-1_vs_P19544-8.png |
 < |
| ./stats/relative_asa/P19544-1_vs_P19544-9.png |
 < |
Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to WT1 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
Related Diseases to WT1 |
| Previous studies relating to the alternative splicing of WT1 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| WT1 | 1572653 | The genomic organization and expression of the WT1 gene. | The Wilms tumor gene WT1, a proposed tumor suppressor gene, has been identified based on its location within a homozygous deletion found in tumor tissue. The gene encodes a putative transcription factor containing a Cys/His zinc finger domain. The critical homozygous deletions, however, are rarely seen, suggesting that in many cases the gene may be inactivated by more subtle alterations. To facilitate the search for smaller deletions and point mutations we have established the genomic organization of the WT1 gene and have determined the sequence of all 10 exons and flanking intron DNA. The pattern of alternative splicing in two regions has been characterized in detail. These results will form the basis for future studies of mutant alleles at this locus. | D002872 | Chromosome Deletion |
| WT1 | 7588596 | WT1 suppresses synthesis of the epidermal growth factor receptor and induces apoptosis. | The Wilms tumor suppressor gene WT1 encodes a developmentally regulated transcription factor that is mutated in a subset of embryonal tumors. To test its functional properties, we developed osteosarcoma cell lines expressing WT1 under an inducible tetracycline-regulated promoter. Induction of WT1 resulted in programmed cell death. This effect, which was differentially mediated by the alternative splicing variants of WT1, was independent of p53. WT1-mediated apoptosis was associated with reduced synthesis of the epidermal growth factor receptor (EGFR), but not of other postulated WT1-target genes, and it was abrogated by constitutive expression of EGFR. WT1 repressed transcription from the EGFR promoter, binding to two TC-rich repeat sequences. In the developing kidney, EGFR expression in renal precursor cells declined with the onset of WT1 expression. Repression of EGFR and induction of apoptosis by mechanism that may contribute to its critical role in normal kidney development and to the immortalization of tumor cells with inactivated WT1 alleles. | D012516 | Osteosarcoma |
| WT1 | 9475094 | Do intronic mutations affecting splicing of WT1 exon 9 cause Frasier syndrome? | The WT1 gene, one of the genes responsible for Wilms tumour, is thought to play a crucial role in the development of the kidneys and gonads. This gene encodes four protein isoforms resulting from two alternative splicing sites, one of which involves inclusion or exclusion of lysine, threonine, and serine (KTS) between the third and fourth zinc finger domains. WT1 is virtually always mutationally inactivated in patients with Denys-Drash syndrome. We analysed WT1 in eight patients who had been diagnosed as having this syndrome, and identified five previously unknown mutations affecting splicing donor sites of intron 9. These mutations affect alternative splicing. The isoforms retaining KTS are not produced. The clinical features of the patients with these intronic mutations were consistent with those of Frasier syndrome, characterised by a more slowly progressive nephropathy than Denys-Drash syndrome, associated streak gonads, and no Wilms tumour development. Our results indicate that WT1 isoforms, including/excluding KTS, have different functions in tumorigenesis and organogenesis of the kidneys and gonads. | D013577 | Syndrome |
| WT1 | 9475094 | Do intronic mutations affecting splicing of WT1 exon 9 cause Frasier syndrome? | The WT1 gene, one of the genes responsible for Wilms tumour, is thought to play a crucial role in the development of the kidneys and gonads. This gene encodes four protein isoforms resulting from two alternative splicing sites, one of which involves inclusion or exclusion of lysine, threonine, and serine (KTS) between the third and fourth zinc finger domains. WT1 is virtually always mutationally inactivated in patients with Denys-Drash syndrome. We analysed WT1 in eight patients who had been diagnosed as having this syndrome, and identified five previously unknown mutations affecting splicing donor sites of intron 9. These mutations affect alternative splicing. The isoforms retaining KTS are not produced. The clinical features of the patients with these intronic mutations were consistent with those of Frasier syndrome, characterised by a more slowly progressive nephropathy than Denys-Drash syndrome, associated streak gonads, and no Wilms tumour development. Our results indicate that WT1 isoforms, including/excluding KTS, have different functions in tumorigenesis and organogenesis of the kidneys and gonads. | D014564 | Urogenital Abnormalities |
| WT1 | 9475094 | Do intronic mutations affecting splicing of WT1 exon 9 cause Frasier syndrome? | The WT1 gene, one of the genes responsible for Wilms tumour, is thought to play a crucial role in the development of the kidneys and gonads. This gene encodes four protein isoforms resulting from two alternative splicing sites, one of which involves inclusion or exclusion of lysine, threonine, and serine (KTS) between the third and fourth zinc finger domains. WT1 is virtually always mutationally inactivated in patients with Denys-Drash syndrome. We analysed WT1 in eight patients who had been diagnosed as having this syndrome, and identified five previously unknown mutations affecting splicing donor sites of intron 9. These mutations affect alternative splicing. The isoforms retaining KTS are not produced. The clinical features of the patients with these intronic mutations were consistent with those of Frasier syndrome, characterised by a more slowly progressive nephropathy than Denys-Drash syndrome, associated streak gonads, and no Wilms tumour development. Our results indicate that WT1 isoforms, including/excluding KTS, have different functions in tumorigenesis and organogenesis of the kidneys and gonads. | D009396 | Wilms Tumor |
| WT1 | 9815658 | The Wilms' tumor gene WT1 can regulate genes involved in sex determination and differentiation: SRY, Müllerian-inhibiting substance, and the androgen receptor. | Genital abnormalities associated with Wilms' tumors in the WAGR and Denys-Drash syndromes and the failure of the gonads to develop in Wilms' tumor gene (wt1)-homozygous mutant mice suggest that WT1 may also function in sexual development. To elucidate the mechanism of action of WT1 in embryonal sexual development, we examined how the four isoforms of WT1 regulate the transcription of several genes involved in sexual development using cotransfection assays. SRY (the sex-determining region of the Y chromosome) promoter was strongly activated by the WT1 isoforms without the KTS tripeptide, WT1(-)KTS, but was not activated by the WT1 isoforms with the KTS tripeptide, WT1(+)KTS, in all cells tested. The second alternative splicing site, which inserts the tripeptide KTS, alters the DNA binding capability. The MüAdullerian-inhibiting substance (MIS) promoter was strongly repressed by WT1(-)KTS isoforms and more weakly repressed by the WT1(+)KTS isoforms in Sertoli cells but not in HeLa cells. The androgen receptor (AR) promoter was strongly repressed by the WT1(-)KTS isoforms in all cells tested and was more weakly or not repressed by WT1(+)KTS isoforms depending on cell lines. Electrophoretic mobility shift assays showed strong binding by recombinant WT1(-)KTS protein and weaker or no binding by the WT1(+)KTS protein to DNA probes containing WT1 binding sites from these three promoters. The results of these functional and binding assays suggest that WT1 has an important role in regulation of genes involved in embryonal sexual development and that WT1 can function as a transcriptional activator. | D007680 | Kidney Neoplasms |
| WT1 | 9815658 | The Wilms' tumor gene WT1 can regulate genes involved in sex determination and differentiation: SRY, Müllerian-inhibiting substance, and the androgen receptor. | Genital abnormalities associated with Wilms' tumors in the WAGR and Denys-Drash syndromes and the failure of the gonads to develop in Wilms' tumor gene (wt1)-homozygous mutant mice suggest that WT1 may also function in sexual development. To elucidate the mechanism of action of WT1 in embryonal sexual development, we examined how the four isoforms of WT1 regulate the transcription of several genes involved in sexual development using cotransfection assays. SRY (the sex-determining region of the Y chromosome) promoter was strongly activated by the WT1 isoforms without the KTS tripeptide, WT1(-)KTS, but was not activated by the WT1 isoforms with the KTS tripeptide, WT1(+)KTS, in all cells tested. The second alternative splicing site, which inserts the tripeptide KTS, alters the DNA binding capability. The MüAdullerian-inhibiting substance (MIS) promoter was strongly repressed by WT1(-)KTS isoforms and more weakly repressed by the WT1(+)KTS isoforms in Sertoli cells but not in HeLa cells. The androgen receptor (AR) promoter was strongly repressed by the WT1(-)KTS isoforms in all cells tested and was more weakly or not repressed by WT1(+)KTS isoforms depending on cell lines. Electrophoretic mobility shift assays showed strong binding by recombinant WT1(-)KTS protein and weaker or no binding by the WT1(+)KTS protein to DNA probes containing WT1 binding sites from these three promoters. The results of these functional and binding assays suggest that WT1 has an important role in regulation of genes involved in embryonal sexual development and that WT1 can function as a transcriptional activator. | D009396 | Wilms Tumor |
| WT1 | 10571943 | Exon 9 mutations in the WT1 gene, without influencing KTS splice isoforms, are also responsible for Frasier syndrome. | We report new mutations in exon 9 of the WT1 gene that did not alter the ratio of +/- KTS splice isoforms in two unrelated patients with Frasier syndrome (FS). The mutation of intron 9 inducing defective alternative splicing was reported to be responsible for this syndrome. The mutations found in our cases occurred in the same exon of the WT1 gene as detected in Denys-Drash syndrome (DDS) and could not be explained by the previously proposed mechanism. The results suggest that the two syndromes originate from the same WT1 gene abnormality. From a molecular biological point of view, we concluded that the two diseases were not separable, and that FS should be included as an atypical form of DDS. | D012734 | Disorders of Sex Development |
| WT1 | 10571943 | Exon 9 mutations in the WT1 gene, without influencing KTS splice isoforms, are also responsible for Frasier syndrome. | We report new mutations in exon 9 of the WT1 gene that did not alter the ratio of +/- KTS splice isoforms in two unrelated patients with Frasier syndrome (FS). The mutation of intron 9 inducing defective alternative splicing was reported to be responsible for this syndrome. The mutations found in our cases occurred in the same exon of the WT1 gene as detected in Denys-Drash syndrome (DDS) and could not be explained by the previously proposed mechanism. The results suggest that the two syndromes originate from the same WT1 gene abnormality. From a molecular biological point of view, we concluded that the two diseases were not separable, and that FS should be included as an atypical form of DDS. | D007674 | Kidney Diseases |
| WT1 | 10571943 | Exon 9 mutations in the WT1 gene, without influencing KTS splice isoforms, are also responsible for Frasier syndrome. | We report new mutations in exon 9 of the WT1 gene that did not alter the ratio of +/- KTS splice isoforms in two unrelated patients with Frasier syndrome (FS). The mutation of intron 9 inducing defective alternative splicing was reported to be responsible for this syndrome. The mutations found in our cases occurred in the same exon of the WT1 gene as detected in Denys-Drash syndrome (DDS) and could not be explained by the previously proposed mechanism. The results suggest that the two syndromes originate from the same WT1 gene abnormality. From a molecular biological point of view, we concluded that the two diseases were not separable, and that FS should be included as an atypical form of DDS. | D013577 | Syndrome |
| WT1 | 11237525 | Wilms tumor and the WT1 gene. | Wilms tumor or nephroblastoma is a pediatric kidney cancer arising from pluripotent embryonic renal precursors. Multiple genetic loci have been linked to Wilms tumorigenesis; positional cloning strategies have led to the identification of the WT1 tumor suppressor gene at chromosome 11p13. WT1 encodes a zinc finger transcription factor that is inactivated in the germline of children with genetic predisposition to Wilms tumor and in a subset of sporadic cancers. When present in the germline, specific heterozygous dominant-negative mutations are associated with severe abnormalities of renal and sexual differentiation, pointing to the essential role of WT1 for normal genitourinary development. The role of this tumor suppressor in normal organ-specific differentiation is also supported by the highly restricted temporal and spatial expression of WT1 in glomerular precursors of the developing kidney and by the failure of kidney development in wt1-null mice. Of two major alternative splicing products encoded by WT1, the (-KTS) isoform appears to mediate transcriptional activation of genes implicated in cellular differentiation, possibly also repressing proliferation-associated genes. The (+KTS) isoform, whose DNA-binding domain is disrupted by the insertion of three amino acids, may be involved in some aspect of mRNA processing. In addition to its function in genitourinary development, a role for WT1 in hematopoiesis is suggested by its aberrant expression and/or mutation in a subset of acute human leukemias. WT1 is also expressed in mesothelial cells; a specific oncogenic chromosomal translocation fusing the N-terminal domain of the Ewing sarcoma gene EWS to the three C-terminal zinc fingers of WT1 underlies desmoplastic small round cell tumor, an abdominal tumor thought to arise from the peritoneal lining. Understanding the distinct functional properties of WT1 isoforms and tumor-associated variants will provide unique insight into the link between normal organ-specific differentiation and malignancy. | D000208 | Acute Disease |
| WT1 | 11237525 | Wilms tumor and the WT1 gene. | Wilms tumor or nephroblastoma is a pediatric kidney cancer arising from pluripotent embryonic renal precursors. Multiple genetic loci have been linked to Wilms tumorigenesis; positional cloning strategies have led to the identification of the WT1 tumor suppressor gene at chromosome 11p13. WT1 encodes a zinc finger transcription factor that is inactivated in the germline of children with genetic predisposition to Wilms tumor and in a subset of sporadic cancers. When present in the germline, specific heterozygous dominant-negative mutations are associated with severe abnormalities of renal and sexual differentiation, pointing to the essential role of WT1 for normal genitourinary development. The role of this tumor suppressor in normal organ-specific differentiation is also supported by the highly restricted temporal and spatial expression of WT1 in glomerular precursors of the developing kidney and by the failure of kidney development in wt1-null mice. Of two major alternative splicing products encoded by WT1, the (-KTS) isoform appears to mediate transcriptional activation of genes implicated in cellular differentiation, possibly also repressing proliferation-associated genes. The (+KTS) isoform, whose DNA-binding domain is disrupted by the insertion of three amino acids, may be involved in some aspect of mRNA processing. In addition to its function in genitourinary development, a role for WT1 in hematopoiesis is suggested by its aberrant expression and/or mutation in a subset of acute human leukemias. WT1 is also expressed in mesothelial cells; a specific oncogenic chromosomal translocation fusing the N-terminal domain of the Ewing sarcoma gene EWS to the three C-terminal zinc fingers of WT1 underlies desmoplastic small round cell tumor, an abdominal tumor thought to arise from the peritoneal lining. Understanding the distinct functional properties of WT1 isoforms and tumor-associated variants will provide unique insight into the link between normal organ-specific differentiation and malignancy. | D004195 | Disease Models, Animal |
| WT1 | 11237525 | Wilms tumor and the WT1 gene. | Wilms tumor or nephroblastoma is a pediatric kidney cancer arising from pluripotent embryonic renal precursors. Multiple genetic loci have been linked to Wilms tumorigenesis; positional cloning strategies have led to the identification of the WT1 tumor suppressor gene at chromosome 11p13. WT1 encodes a zinc finger transcription factor that is inactivated in the germline of children with genetic predisposition to Wilms tumor and in a subset of sporadic cancers. When present in the germline, specific heterozygous dominant-negative mutations are associated with severe abnormalities of renal and sexual differentiation, pointing to the essential role of WT1 for normal genitourinary development. The role of this tumor suppressor in normal organ-specific differentiation is also supported by the highly restricted temporal and spatial expression of WT1 in glomerular precursors of the developing kidney and by the failure of kidney development in wt1-null mice. Of two major alternative splicing products encoded by WT1, the (-KTS) isoform appears to mediate transcriptional activation of genes implicated in cellular differentiation, possibly also repressing proliferation-associated genes. The (+KTS) isoform, whose DNA-binding domain is disrupted by the insertion of three amino acids, may be involved in some aspect of mRNA processing. In addition to its function in genitourinary development, a role for WT1 in hematopoiesis is suggested by its aberrant expression and/or mutation in a subset of acute human leukemias. WT1 is also expressed in mesothelial cells; a specific oncogenic chromosomal translocation fusing the N-terminal domain of the Ewing sarcoma gene EWS to the three C-terminal zinc fingers of WT1 underlies desmoplastic small round cell tumor, an abdominal tumor thought to arise from the peritoneal lining. Understanding the distinct functional properties of WT1 isoforms and tumor-associated variants will provide unique insight into the link between normal organ-specific differentiation and malignancy. | D018221 | Fibromatosis, Abdominal |
| WT1 | 11237525 | Wilms tumor and the WT1 gene. | Wilms tumor or nephroblastoma is a pediatric kidney cancer arising from pluripotent embryonic renal precursors. Multiple genetic loci have been linked to Wilms tumorigenesis; positional cloning strategies have led to the identification of the WT1 tumor suppressor gene at chromosome 11p13. WT1 encodes a zinc finger transcription factor that is inactivated in the germline of children with genetic predisposition to Wilms tumor and in a subset of sporadic cancers. When present in the germline, specific heterozygous dominant-negative mutations are associated with severe abnormalities of renal and sexual differentiation, pointing to the essential role of WT1 for normal genitourinary development. The role of this tumor suppressor in normal organ-specific differentiation is also supported by the highly restricted temporal and spatial expression of WT1 in glomerular precursors of the developing kidney and by the failure of kidney development in wt1-null mice. Of two major alternative splicing products encoded by WT1, the (-KTS) isoform appears to mediate transcriptional activation of genes implicated in cellular differentiation, possibly also repressing proliferation-associated genes. The (+KTS) isoform, whose DNA-binding domain is disrupted by the insertion of three amino acids, may be involved in some aspect of mRNA processing. In addition to its function in genitourinary development, a role for WT1 in hematopoiesis is suggested by its aberrant expression and/or mutation in a subset of acute human leukemias. WT1 is also expressed in mesothelial cells; a specific oncogenic chromosomal translocation fusing the N-terminal domain of the Ewing sarcoma gene EWS to the three C-terminal zinc fingers of WT1 underlies desmoplastic small round cell tumor, an abdominal tumor thought to arise from the peritoneal lining. Understanding the distinct functional properties of WT1 isoforms and tumor-associated variants will provide unique insight into the link between normal organ-specific differentiation and malignancy. | D007680 | Kidney Neoplasms |
| WT1 | 11237525 | Wilms tumor and the WT1 gene. | Wilms tumor or nephroblastoma is a pediatric kidney cancer arising from pluripotent embryonic renal precursors. Multiple genetic loci have been linked to Wilms tumorigenesis; positional cloning strategies have led to the identification of the WT1 tumor suppressor gene at chromosome 11p13. WT1 encodes a zinc finger transcription factor that is inactivated in the germline of children with genetic predisposition to Wilms tumor and in a subset of sporadic cancers. When present in the germline, specific heterozygous dominant-negative mutations are associated with severe abnormalities of renal and sexual differentiation, pointing to the essential role of WT1 for normal genitourinary development. The role of this tumor suppressor in normal organ-specific differentiation is also supported by the highly restricted temporal and spatial expression of WT1 in glomerular precursors of the developing kidney and by the failure of kidney development in wt1-null mice. Of two major alternative splicing products encoded by WT1, the (-KTS) isoform appears to mediate transcriptional activation of genes implicated in cellular differentiation, possibly also repressing proliferation-associated genes. The (+KTS) isoform, whose DNA-binding domain is disrupted by the insertion of three amino acids, may be involved in some aspect of mRNA processing. In addition to its function in genitourinary development, a role for WT1 in hematopoiesis is suggested by its aberrant expression and/or mutation in a subset of acute human leukemias. WT1 is also expressed in mesothelial cells; a specific oncogenic chromosomal translocation fusing the N-terminal domain of the Ewing sarcoma gene EWS to the three C-terminal zinc fingers of WT1 underlies desmoplastic small round cell tumor, an abdominal tumor thought to arise from the peritoneal lining. Understanding the distinct functional properties of WT1 isoforms and tumor-associated variants will provide unique insight into the link between normal organ-specific differentiation and malignancy. | D007938 | Leukemia |
| WT1 | 11237525 | Wilms tumor and the WT1 gene. | Wilms tumor or nephroblastoma is a pediatric kidney cancer arising from pluripotent embryonic renal precursors. Multiple genetic loci have been linked to Wilms tumorigenesis; positional cloning strategies have led to the identification of the WT1 tumor suppressor gene at chromosome 11p13. WT1 encodes a zinc finger transcription factor that is inactivated in the germline of children with genetic predisposition to Wilms tumor and in a subset of sporadic cancers. When present in the germline, specific heterozygous dominant-negative mutations are associated with severe abnormalities of renal and sexual differentiation, pointing to the essential role of WT1 for normal genitourinary development. The role of this tumor suppressor in normal organ-specific differentiation is also supported by the highly restricted temporal and spatial expression of WT1 in glomerular precursors of the developing kidney and by the failure of kidney development in wt1-null mice. Of two major alternative splicing products encoded by WT1, the (-KTS) isoform appears to mediate transcriptional activation of genes implicated in cellular differentiation, possibly also repressing proliferation-associated genes. The (+KTS) isoform, whose DNA-binding domain is disrupted by the insertion of three amino acids, may be involved in some aspect of mRNA processing. In addition to its function in genitourinary development, a role for WT1 in hematopoiesis is suggested by its aberrant expression and/or mutation in a subset of acute human leukemias. WT1 is also expressed in mesothelial cells; a specific oncogenic chromosomal translocation fusing the N-terminal domain of the Ewing sarcoma gene EWS to the three C-terminal zinc fingers of WT1 underlies desmoplastic small round cell tumor, an abdominal tumor thought to arise from the peritoneal lining. Understanding the distinct functional properties of WT1 isoforms and tumor-associated variants will provide unique insight into the link between normal organ-specific differentiation and malignancy. | D009396 | Wilms Tumor |
| WT1 | 18385267 | New insights into the function of the Wilms tumor suppressor gene WT1 in podocytes. | The Wilms tumor suppressor gene WT1 is essential for early urogenital development: homozygous mutations in WT1 result in embryonic lethality due to a failure in the development of kidneys and gonads. In the adult kidney, WT1 expression is limited to the glomerular podocytes. Several human nephrotic diseases arise from mutations of the WT1 gene, including mutations that affect its zinc-fingers and alternative splicing of +/- KTS isoforms. These include WAGR (for Wilms tumor, aniridia, genitourinary anomalies, and mental retardation), and Frasier and Denys-Drash syndromes. Recent advances including the development of transgenic mouse models and conditionally immortalized podocyte cell lines are beginning to shed light on WT1's crucial role in podocyte function. | D030321 | Denys-Drash Syndrome |
| WT1 | 18385267 | New insights into the function of the Wilms tumor suppressor gene WT1 in podocytes. | The Wilms tumor suppressor gene WT1 is essential for early urogenital development: homozygous mutations in WT1 result in embryonic lethality due to a failure in the development of kidneys and gonads. In the adult kidney, WT1 expression is limited to the glomerular podocytes. Several human nephrotic diseases arise from mutations of the WT1 gene, including mutations that affect its zinc-fingers and alternative splicing of +/- KTS isoforms. These include WAGR (for Wilms tumor, aniridia, genitourinary anomalies, and mental retardation), and Frasier and Denys-Drash syndromes. Recent advances including the development of transgenic mouse models and conditionally immortalized podocyte cell lines are beginning to shed light on WT1's crucial role in podocyte function. | D052159 | Frasier Syndrome |
Clinically important variants in WT1 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
Copyright 2024-PresentThe University of Texas Health Science Center at Houston (UTHealth Houston) Web File Viewing | Emergency Information |