WT1

Summary

WT1 (WT1 transcription factor, HGNC:12796) is a protein-coding gene on chromosome 11p13, encoding Wilms tumor protein (P19544). Transcription factor that plays an important role in cellular development and cell survival. In precision oncology, WT1 Exon 7 Mutation is associated with resistance to Daunorubicin + Cytarabine in Acute Myeloid Leukemia (CIViC Level B). It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a transcription factor that contains four zinc-finger motifs at the C-terminus and a proline/glutamine-rich DNA-binding domain at the N-terminus. It has an essential role in the normal development of the urogenital system, and it is mutated in a small subset of patients with Wilms tumor. This gene exhibits complex tissue-specific and polymorphic imprinting pattern, with biallelic, and monoallelic expression from the maternal and paternal alleles in different tissues. Multiple transcript variants have been described. In several variants, there is evidence for the use of a non-AUG (CUG) translation initiation codon upstream of, and in-frame with the first AUG. Authors of PMID:7926762 also provide evidence that WT1 mRNA undergoes RNA editing in human and rat, and that this process is tissue-restricted and developmentally regulated.

Source: NCBI Gene 7490 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Wilms tumor 1 (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 28
• Clinical variants (ClinVar): 1,381 total — 75 pathogenic, 48 likely-pathogenic
• Phenotypes (HPO): 199
• Druggable target: yes
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 3 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 163 downstream targets (CollecTRI)
• MANE Select transcript: NM_024426

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12796
Approved symbol	WT1
Name	WT1 transcription factor
Location	11p13
Locus type	gene with protein product
Status	Approved
Aliases	WAGR, WIT-2, AWT1, NPHS4, WT-1
Ensembl gene	ENSG00000184937
Ensembl biotype	protein_coding
OMIM	607102
Entrez	7490

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 12 protein_coding, 7 retained_intron, 5 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000332351, ENST00000379077, ENST00000379079, ENST00000448076, ENST00000452863, ENST00000526685, ENST00000527775, ENST00000527882, ENST00000530998, ENST00000639563, ENST00000639907, ENST00000640146, ENST00000650745, ENST00000650861, ENST00000650986, ENST00000651459, ENST00000651533, ENST00000651668, ENST00000651794, ENST00000651819, ENST00000652579, ENST00000652724, ENST00000850606, ENST00000850608, ENST00000850609, ENST00000850610

RefSeq mRNA: 18 — MANE Select: NM_024426 NM_000378, NM_001198551, NM_001198552, NM_001367854, NM_001407044, NM_001407045, NM_001407046, NM_001407047, NM_001407048, NM_001407049, NM_001407050, NM_001407051, NM_001429031, NM_001429032, NM_001429033, NM_001429034, NM_024424, NM_024426

CCDS: CCDS44561, CCDS44562, CCDS55750, CCDS55751, CCDS7878

Canonical transcript exons

ENST00000452863 — 10 exons

Exon	Start	End
ENSE00002336249	32417577	32417654
ENSE00002388440	32427956	32428058
ENSE00003458892	32416490	32416540
ENSE00003550044	32399948	32400044
ENSE00003583682	32428497	32428619
ENSE00003589791	32387775	32389179
ENSE00003615755	32392666	32392755
ENSE00003631512	32396257	32396407
ENSE00003846384	32434700	32435539
ENSE00004282315	32391972	32392064

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 99.82.

FANTOM5 (CAGE): breadth broad, TPM avg 2.4800 / max 176.4858, expressed in 341 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119179	1.1018	247
119180	0.5336	191
119184	0.3288	115
119177	0.1310	77
119176	0.0842	51
119181	0.0775	42
119182	0.0519	23
119175	0.0483	23
119169	0.0359	10
119174	0.0305	4

Top tissues by expression

280 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	99.82	gold quality
renal glomerulus	UBERON:0000074	98.79	gold quality
metanephric glomerulus	UBERON:0004736	98.66	gold quality
parietal pleura	UBERON:0002400	98.20	gold quality
right uterine tube	UBERON:0001302	97.57	gold quality
left uterine tube	UBERON:0001303	96.64	gold quality
body of uterus	UBERON:0009853	96.57	gold quality
decidua	UBERON:0002450	96.43	gold quality
myometrium	UBERON:0001296	96.06	gold quality
ovary	UBERON:0000992	95.01	gold quality
left ovary	UBERON:0002119	94.78	gold quality
right ovary	UBERON:0002118	94.68	gold quality
endometrium	UBERON:0001295	93.81	gold quality
cauda epididymis	UBERON:0004360	93.65	gold quality
uterus	UBERON:0000995	92.88	gold quality
pericardium	UBERON:0002407	92.01	gold quality
pleura	UBERON:0000977	91.92	gold quality
adult organism	UBERON:0007023	91.77	gold quality
right testis	UBERON:0004534	91.18	gold quality
kidney epithelium	UBERON:0004819	90.71	gold quality
left testis	UBERON:0004533	90.41	gold quality
testis	UBERON:0000473	90.26	gold quality
metanephros	UBERON:0000081	89.03	gold quality
peritoneum	UBERON:0002358	88.59	gold quality
omental fat pad	UBERON:0010414	88.57	gold quality
female reproductive system	UBERON:0000474	88.45	gold quality
caput epididymis	UBERON:0004358	87.92	gold quality
spleen	UBERON:0002106	87.70	gold quality
corpus epididymis	UBERON:0004359	86.94	gold quality
male germ cell	CL:0000015	86.84	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-114530	yes	2511.89
E-MTAB-10287	yes	101.82
E-CURD-119	yes	29.81
E-HCAD-10	yes	22.79
E-ANND-3	yes	6.84

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

163 targets.

Target	Regulation
ABCB1	Unknown
ABCC3
ADAMTS16
ADAT2
ADGRE5	Activation
AKT1
ALDH1A2
AMER1
AMH	Activation
AMHR2
AR	Repression
AREG	Activation
ATP7A
BAIAP3
BAK1
BASP1
BCL2	Unknown
BCL2L1	Activation
CALCA
CAMP	Repression
CAT	Repression
CCN2	Unknown
CCN3	Unknown
CCNE1	Repression
CD14	Activation
CD34
CDC73	Repression
CDH1	Repression
CDH17
CDH2

Upstream regulators (CollecTRI, top): CCNA1, CREBZF, CTCF, EGR1, EP300, ESR1, ETS1, ETV4, ETV5, GATA1, GATA2, HDAC4, HDAC5, HIF1A, HNF4A, HOXA10, IFI16, KAT7, MYB, MYC, NFKB1, NFKB, NKX2-5, NOTO, PAX2, PAX8, POU4F2, PPARD, RELA, SP1, SP3, SPI1, SRY, TFCP2, TLX1, TP53, WT1

miRNA regulators (miRDB)

79 targeting WT1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-4261	99.59	70.30	3415

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• review: role in testis descent (PMID:11738793)
• requirement for Wt1 in normal retina formation with a critical role in Pou4f2-dependent ganglion cell differentiation. (PMID:11889045)
• reduced expression of WT1 causes crescentic glomerulonephritis and mesengial sclerosis and thus a regulator of podocyte function (PMID:11912180)
• Cyclin E is a target of WT1 transcriptional repression (PMID:11919196)
• A review of the phenotypic variation due to the Denys-Drash syndrome-associated germline WT1 mutation R362X (PMID:11933209)
• uterine papillary serous carcinomas were nonreactive for WT1 (PMID:11939727)
• Induction of the interleukin-2/15 receptor beta-chain by the EWS-WT1 translocation product. (PMID:11960373)
• The coexpression of the apoptosis-related genes bcl-2 and wt1 in predicting survival in adult acute myeloid leukemia. (PMID:11986946)
• quantitation of WT1 RNA in Japanese patients with paroxysmal nocturnal hemoglobinuria (PMID:12070003)
• A peptide representing positions 124-148 of the Kruppel-like zinc finger protein was predicted to bind to the HLA-DRB1*0401 molecule. Its sequence is PQQMGSDVRDLNALL. (PMID:12111123)
• WT1 protein contributes to breast cancer progression by promoting breast cancer cell proliferation (PMID:12127961)
• The retinoblastoma-derived human cell line, Y-79, contained robust amounts of Wt1 mRNA and protein. Wt1 expression was down-regulated upon laminin-induced differentiation of Y-79 into neuron-like cells. (PMID:12133898)
• WT1 missense mutations in exon 7, which affect zinc finger 1, alter not only renal function but also male gonadal development in a patient with Denys-Drash syndrome and a 46,XY karyotype. (PMID:12161615)
• abnormal WT1 expression may contribute to the disturbed differentiation of haaematopoietic cells in MDS patients (PMID:12199781)
• CD8 T-cell responses to Wilms tumor gene product WT1 and proteinase 3 were observed in patients with acute myeloid leukemia, and not in controls. (PMID:12200377)
• WT1 and DAX-1 inhibit aromatase P450 expression in human endometrial and endometriotic stromal cells (PMID:12213901)
• Results suggest that bone marrow zinc finger 2 (BMZF2) interferes with the transactivation potential of Wilms tumor suppressor gene (WT1). (PMID:12239212)
• Two distinct HLA-A0201-presented epitopes of the Wilms tumor antigen 1 can function as targets for leukemia-reactive CTL (PMID:12411326)
• Interacts with p53 in insulin-like growth factor-I receptor gene regulation (PMID:12444079)
• Correlation between a specific Wilms tumour suppressor gene (WT1) mutation and the histological findings in Wilms tumour (WT) (PMID:12471221)
• Alternative splicing, RNA editing, and the use of alternative translation initiation sites generate a multitude of isoforms, which seem to have overlapping but also distinct functions during embryonic development and the maintenance of organ function. (PMID:12665546)
• role in regulating taurine transporter gene (PMID:12681485)
• Epigenetic silencing of WT1 by promoter hypermethylation with loss of heterozygosity is consistent with the revised two-hit model in Wilms’ tumorigenesis. (PMID:12761165)
• Overexpression of the Wilms’ tumor gene WT1 is associated with head and neck squamous cell carcinoma (PMID:12824878)
• Overexpressed in human bone and soft-tissue sarcomas. (PMID:12824921)
• WT1 is reexpressed in the cirrhotic liver in relation to disease progression and may play a role in the development of hepatic insufficiency in cirrhosis. (PMID:12829997)
• evidence demonstrating that the WT1 gene is involved in the development and differentiation of T-lineage cells (PMID:12841384)
• findings indicate an important role of the wild-type WT1 gene in the tumorigenesis of primary thyroid cancer (PMID:12841869)
• Expression of WT1 protein was detected in 41 (89%) of 46 cases of colonic and rectal adenocarcinoma. (PMID:12901797)
• Wilms’ tumor suppressor is a mediator of neuronal degeneration associated with the pathogenesis of Alzheimer’s disease. (PMID:12914969)
• WT1 gene is novel downstream target for IGF-I action. Reduced levels of WT1 may facilitate IGF-I-stimulated cell cycle progression. Inhibition of WT1 gene expression by IGF-I be significant in cancer initiation and/or progression. (PMID:12960088)
• WT1 was restricted to nucleus of glomerular podocytes. (PMID:12961083)
• These results suggest that WT1 forms a complex with SRY to regulate transcription and that this WT1-SRY interaction is important in testis development. (PMID:12970737)
• WT1 inhibits the transformed phenotype of breast cancer cells and down-regulates the beta-catenin/TCF signaling pathway through destabilization of beta-catenin. (PMID:14666652)
• There is a molecular basis for the strong bias of paternal allele mutations and variable penetrance observed in syndromes with inherited WT1 mutations. (PMID:14681303)
• BASP1 can confer WT1 cosuppressor activity in transfection assays, and elimination of endogenous BASP1 expression augments transcriptional activation by WT1. (PMID:14701728)
• WT1 has a role in suppressing prostate tumor cell growth (PMID:14767530)
• Co-expression of this gene with MDR1 did not significantly influence the complete response rate to induction therapy. (PMID:14962262)
• The transcription factor PEA3 activates the WT1 promoter. (PMID:14988020)
• Cytotoxic T lymphocytes display strong cytotoxic activity against leukemia cells expressing WT1 endogenously but not against WT1(-) human tumor cells. (PMID:14988155)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	wt1a	ENSDARG00000031420
mus_musculus	Wt1	ENSMUSG00000016458
rattus_norvegicus	Wt1	ENSRNOG00000013074

Paralogs (4): EGR1 (ENSG00000120738), EGR2 (ENSG00000122877), EGR4 (ENSG00000135625), EGR3 (ENSG00000179388)

Protein

Protein identifiers

Wilms tumor protein — P19544 (reviewed: P19544)

Alternative names: WT33

All UniProt accessions (9): A0A0A0MT54, A0A1W2PQQ0, A0A1W2PR07, A0A494C0I9, P19544, H0Y3F0, H0Y7K5, H0YED9, J3KNN9

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that plays an important role in cellular development and cell survival. Recognizes and binds to the DNA sequence 5’-GCG(T/G)GGGCG-3’. 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. Isoforms containing the KTS motif may bind mRNA and play a role in mRNA metabolism or splicing. Isoform 1 has lower affinity for DNA, and can bind RNA.

Subunit / interactions. Homodimer. Interacts with WTIP. Interacts with actively translating polysomes. Detected in nuclear ribonucleoprotein (mRNP) particles. Interacts with HNRNPU via the zinc-finger region. Interacts with U2AF2. Interacts with CITED2. Interacts with ZNF224 via the zinc-finger region. Interacts with WTAP and SRY. Interacts with AMER1. Interacts with RBM4.

Subcellular location. Nucleus. Nucleolus. Cytoplasm Nucleus speckle Nucleus. Nucleoplasm.

Tissue specificity. Expressed in the kidney and a subset of hematopoietic cells.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry. A chromosomal aberration involving WT1 may be a cause of desmoplastic small round cell tumor (DSRCT). Translocation t(11;22)(p13;q12) with EWSR1. 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. The disease may be caused by variants affecting the gene represented in this entry.

Domain organisation. Binds to DNA motifs with the sequence 5’-GCG(T/G)GGGCG-3’ via its C2H2-type zinc fingers. Starting from the N-terminus, the second zinc finger binds to the 3’-GCG motif, the middle zinc finger interacts with the central TGG motif, and the C-terminal zinc finger binds to the 5’-GCG motif. Binds double-stranded target DNA, irrespective of the cytosine methylation status. Has reduced affinity for target DNA where the cytosines have been oxidized to 5-hydroxymethylcytosine, 5-formylcytosine or 5-carboxylcytosine. The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.

Miscellaneous. Presence of the KTS motif hinders interactions between DNA and zinc-finger 4. Detected in nucleus speckle, may bind mRNA. Produced by alternative initiation of isoform 1. Extended N-terminus. Produced by alternative initiation of isoform 1. Extended N-terminus.

Similarity. Belongs to the EGR C2H2-type zinc-finger protein family.

Isoforms (8)

UniProt ID	Names	Canonical?
P19544-1	1	yes
P19544-2	2
P19544-3	3
P19544-4	4
P19544-6	6
P19544-7	7
P19544-8	8
P19544-9	9

RefSeq proteins (17): NP_000369, NP_001185480, NP_001185481, NP_001393973, NP_001393974, NP_001393975, NP_001393976, NP_001393977, NP_001393978, NP_001393979, NP_001393980, NP_001415960, NP_001415961, NP_001415962, NP_001415963, NP_077742, NP_077744* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000976	Wilms_tumour_N	Domain
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096, PF02165

UniProt features (86 total): sequence variant 40, strand 8, mutagenesis site 7, splice variant 5, helix 5, zinc finger region 4, cross-link 3, region of interest 3, sequence conflict 3, site 2, turn 2, short sequence motif 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

28 structures.

PDB	Method	Resolution (Å)
5KL3	X-RAY DIFFRACTION	1.45
4R2Q	X-RAY DIFFRACTION	1.54
6B0O	X-RAY DIFFRACTION	1.55
5KL7	X-RAY DIFFRACTION	1.58
5KL6	X-RAY DIFFRACTION	1.64
5KL2	X-RAY DIFFRACTION	1.69
5KL4	X-RAY DIFFRACTION	1.78
4R2P	X-RAY DIFFRACTION	1.79
6B0R	X-RAY DIFFRACTION	1.82
6BLW	X-RAY DIFFRACTION	1.83
4R2E	X-RAY DIFFRACTION	1.84
3MYJ	X-RAY DIFFRACTION	1.89
3HPJ	X-RAY DIFFRACTION	2
6B0P	X-RAY DIFFRACTION	2.08
4R2R	X-RAY DIFFRACTION	2.09
5KL5	X-RAY DIFFRACTION	2.29
7SR5	X-RAY DIFFRACTION	2.35
8ISN	X-RAY DIFFRACTION	2.48
4R2S	X-RAY DIFFRACTION	2.49
7BBG	X-RAY DIFFRACTION	2.64
6B0Q	X-RAY DIFFRACTION	2.79
6RSY	X-RAY DIFFRACTION	2.95
4WUU	X-RAY DIFFRACTION	3.05
2PRT	X-RAY DIFFRACTION	3.15
1XF7	SOLUTION NMR
2JP9	SOLUTION NMR
2JPA	SOLUTION NMR
6WLH	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P19544-F1	52.09	0.11

Antibody-complex structures (SAbDab): 3 — 4WUU, 7BBG, 7SR5

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 424 (important for interaction with target dna); 430 (important for interaction with target dna)

Post-translational modifications (3): 73, 177, 444

Mutagenesis-validated functional residues (7):

Position	Phenotype
73	abolishes sumoylation; when associated with r-177.
177	abolishes sumoylation; when associated with r-77.
343	reduced rna binding.
366	strongly reduced binding of dna and rna.
372	strongly reduced binding of dna and rna.
394	strongly reduced binding of dna and rna.
434	reduced rna binding.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-9690406	Transcriptional regulation of testis differentiation
R-HSA-9764725	Negative Regulation of CDH1 Gene Transcription
R-HSA-9831926	Nephron development

MSigDB gene sets: 748 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_METANEPHRIC_NEPHRON_MORPHOGENESIS, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_EPITHELIUM_DEVELOPMENT, MORF_FLT1, GOBP_MUSCLE_TISSUE_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_AXIS_SPECIFICATION, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_METANEPHROS_DEVELOPMENT, PID_TELOMERASE_PATHWAY, LU_IL4_SIGNALING

GO Biological Process (53): negative regulation of transcription by RNA polymerase II (GO:0000122), vasculogenesis (GO:0001570), ureteric bud development (GO:0001657), branching involved in ureteric bud morphogenesis (GO:0001658), kidney development (GO:0001822), regulation of animal organ formation (GO:0003156), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), germ cell development (GO:0007281), thorax and anterior abdomen determination (GO:0007356), heart development (GO:0007507), sex determination (GO:0007530), negative regulation of cell population proliferation (GO:0008285), RNA splicing (GO:0008380), gonad development (GO:0008406), male gonad development (GO:0008584), tissue development (GO:0009888), positive regulation of gene expression (GO:0010628), negative regulation of translation (GO:0017148), negative regulation of cell growth (GO:0030308), adrenal gland development (GO:0030325), male genitalia development (GO:0030539), epithelial cell differentiation (GO:0030855), glomerulus development (GO:0032835), glomerular basement membrane development (GO:0032836), adrenal cortex formation (GO:0035802), camera-type eye development (GO:0043010), positive regulation of apoptotic process (GO:0043065), negative regulation of apoptotic process (GO:0043066), negative regulation of gene expression via chromosomal CpG island methylation (GO:0044027), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), mesenchymal to epithelial transition (GO:0060231), positive regulation of heart growth (GO:0060421), diaphragm development (GO:0060539), cardiac muscle cell fate commitment (GO:0060923), visceral serous pericardium development (GO:0061032), cellular response to cAMP (GO:0071320), cellular response to gonadotropin stimulus (GO:0071371)

GO Molecular Function (15): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), RNA binding (GO:0003723), zinc ion binding (GO:0008270), double-stranded methylated DNA binding (GO:0010385), sequence-specific DNA binding (GO:0043565), hemi-methylated DNA-binding (GO:0044729), C2H2 zinc finger domain binding (GO:0070742), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872), sequence-specific double-stranded DNA binding (GO:1990837)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear speck (GO:0016607)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Developmental Biology	1
Regulation of CDH1 Gene Transcription	1
Kidney development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
animal organ development	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
double-stranded DNA binding	3
cellular anatomical structure	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
regulation of gene expression	2
regulation of DNA-templated transcription	2
developmental process involved in reproduction	2
negative regulation of cellular process	2
nucleic acid binding	2
nuclear lumen	2
negative regulation of DNA-templated transcription	1
cell differentiation	1
blood vessel morphogenesis	1
mesonephric tubule development	1
branching morphogenesis of an epithelial tube	1
ureteric bud morphogenesis	1
renal system development	1
animal organ formation	1
regulation of animal organ morphogenesis	1
DNA-templated transcription	1
regulation of RNA biosynthetic process	1
gamete generation	1
cellular process involved in reproduction in multicellular organism	1
cell development	1
zygotic determination of anterior/posterior axis, embryo	1
anterior/posterior pattern specification	1
circulatory system development	1
cell population proliferation	1
regulation of cell population proliferation	1
RNA processing	1
development of primary sexual characteristics	1
reproductive structure development	1
gonad development	1
development of primary male sexual characteristics	1
anatomical structure development	1
gene expression	1
positive regulation of macromolecule biosynthetic process	1
translation	1

Protein interactions and networks

STRING

3730 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WT1	WTAP	Q15007	995
WT1	TP53	P04637	957
WT1	NPHS1	O60500	934
WT1	NPHS2	Q9NP85	918
WT1	NR0B1	P51843	904
WT1	SOX9	P48436	903
WT1	EWSR1	Q01844	888
WT1	SRY	Q05066	876
WT1	PAWR	Q96IZ0	873
WT1	GATA4	P43694	863
WT1	PAX2	Q02962	853
WT1	AMER1	Q5JTC6	849
WT1	NR5A1	Q13285	845
WT1	SYNPO	Q8N3V7	843
WT1	AMH	P03971	828

IntAct

113 interactions, top by confidence:

A	B	Type	Score
WT1	KRT40	psi-mi:“MI:0915”(physical association)	0.670
KRT40	WT1	psi-mi:“MI:0915”(physical association)	0.670
WT1	DVL3	psi-mi:“MI:0915”(physical association)	0.670
DVL3	WT1	psi-mi:“MI:0915”(physical association)	0.670
WT1	TET2	psi-mi:“MI:0915”(physical association)	0.600
TET2	WT1	psi-mi:“MI:0915”(physical association)	0.600
TET2	WT1	psi-mi:“MI:0407”(direct interaction)	0.600
WT1	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	WT1	psi-mi:“MI:0915”(physical association)	0.560
WT1		psi-mi:“MI:0915”(physical association)	0.490
	WT1	psi-mi:“MI:0915”(physical association)	0.490
YAP1	WT1	psi-mi:“MI:0407”(direct interaction)	0.440
TP53	WT1	psi-mi:“MI:0915”(physical association)	0.400
CCL1	WT1	psi-mi:“MI:0915”(physical association)	0.370
CCL11	WT1	psi-mi:“MI:0915”(physical association)	0.370
	WT1	psi-mi:“MI:0915”(physical association)	0.370
CCL22	WT1	psi-mi:“MI:0915”(physical association)	0.370
CCL24	WT1	psi-mi:“MI:0915”(physical association)	0.370
CCL26	WT1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (95): KRT40 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), CASZ1 (Two-hybrid), CCL5 (Two-hybrid), DIRAS3 (Two-hybrid), KLK7 (Two-hybrid), NAT2 (Two-hybrid), THRSP (Two-hybrid), WT1 (Affinity Capture-MS), WT1 (Affinity Capture-Western), CCDC136 (Two-hybrid), CCDC33 (Two-hybrid), CEP70 (Two-hybrid), DVL2 (Two-hybrid)

ESM2 similar proteins: A0JC51, A5ABV9, O08656, O09100, O18896, O57311, O60481, O73689, O95409, P09022, P10070, P19544, P22561, P23769, P23770, P23771, P23772, P23824, P25932, P46684, P49639, P49952, P54655, P55878, P70062, P70063, Q08DV0, Q0VGT2, Q15915, Q62520, Q62521, Q6DJQ6, Q6VVD7, Q6XP49, Q7TQ40, Q800Q5, Q8JJC0, Q91689, Q924A0, Q924Y4

Diamond homologs: B5DE03, B7ZSG3, O08876, O14901, O62651, O89091, P19544, P22561, P49952, P49953, P50902, P57682, P79958, Q13118, Q13887, Q19A41, Q5JT82, Q60980, Q8K1S5, A5ABV9, O08584, O35738, O35819, O43474, O62259, O70494, O75840, O89090, O95600, P08047, P0CG40, P46099, P58334, Q01714, Q02086, Q02446, Q02447, Q0VA40, Q13351, Q14V87

SIGNOR signaling

22 interactions.

A	Effect	B	Mechanism
WT1	up-regulates	SRY	binding
WT1	down-regulates	RBM4	binding
AMER1	up-regulates	WT1	binding
PAWR	“down-regulates activity”	WT1	binding
WT1	“up-regulates quantity by expression”	AREG	“transcriptional regulation”
WT1	“down-regulates quantity by repression”	REN	“transcriptional regulation”
WT1	“up-regulates quantity by expression”	SOD1	“transcriptional regulation”
TET2	“up-regulates activity”	WT1	binding
WT1	down-regulates	Proliferation
WT1	“up-regulates quantity by expression”	DNMT3A	“transcriptional regulation”
CCNA1	“down-regulates quantity by repression”	WT1	“transcriptional regulation”
GSK3B	“down-regulates quantity by destabilization”	WT1	phosphorylation
PRKACA	down-regulates	WT1	phosphorylation
PAX2	“up-regulates quantity by expression”	WT1	“transcriptional regulation”
PAX2/TLE4	“down-regulates quantity by repression”	WT1	“transcriptional regulation”
WT1	“down-regulates quantity by repression”	PAX2	“transcriptional regulation”
WT1	“up-regulates quantity by expression”	NPHS1	“transcriptional regulation”
WT1	“up-regulates quantity by expression”	PODXL	“transcriptional regulation”
WT1	“up-regulates activity”	Urogenital_tract
WT1	“up-regulates quantity by expression”	SLC29A4	“transcriptional regulation”
USP9X	“up-regulates quantity by stabilization”	WT1	deubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 79 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Chemokine receptors bind chemokines	6	19.7×	3e-04
Keratinization	8	7.8×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
eosinophil chemotaxis	7	74.3×	3e-09
chemokine-mediated signaling pathway	7	32.9×	7e-07
antimicrobial humoral immune response mediated by antimicrobial peptide	8	18.8×	2e-06
positive regulation of endothelial cell proliferation	5	16.7×	1e-03
chemotaxis	7	13.8×	1e-04
positive regulation of cell migration	10	8.9×	3e-05
inflammatory response	14	7.7×	8e-07
cell-cell signaling	7	7.1×	6e-03

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

WT1 is a tumor suppressor gene associated with the development of Wilms’ Tumor, from which it was named. Mutations in exon 7 and 9 of WT1 have been recurrently identified in acute myeloid leukemia and associated with poorer prognosis and chemotherapy resistance.

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 3 cancer types — AML, MEL, PAAD.

Clinical variants and AI predictions

ClinVar

1381 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	75
Likely pathogenic	48
Uncertain significance	636
Likely benign	444
Benign	34

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069921	NC_000011.10:g.32396408del	Pathogenic
1073615	NC_000011.9:g.(?32456236)(32460464_?)del	Pathogenic
1073616	NC_000011.9:g.(?32421484)(32421600_?)del	Pathogenic
1076730	NM_024426.6(WT1):c.798C>G (p.Tyr266Ter)	Pathogenic
1077036	NM_024426.6(WT1):c.1534C>T (p.Gln512Ter)	Pathogenic
1327577	NM_024426.6(WT1):c.834dup (p.Thr279fs)	Pathogenic
1378543	NM_024426.6(WT1):c.1121_1122insGGGG (p.Arg375fs)	Pathogenic
1457778	NM_024426.6(WT1):c.1240C>T (p.Gln414Ter)	Pathogenic
1503278	NM_024426.6(WT1):c.882_887+3del	Pathogenic
1675456	NM_024426.6(WT1):c.900C>G (p.Tyr300Ter)	Pathogenic
2028955	NM_024426.6(WT1):c.1077C>G (p.Tyr359Ter)	Pathogenic
2033498	NM_024426.6(WT1):c.1299T>A (p.Cys433Ter)	Pathogenic
2100281	NM_024426.6(WT1):c.913C>T (p.Gln305Ter)	Pathogenic
2137049	NM_024426.6(WT1):c.1372T>C (p.Cys458Arg)	Pathogenic
2426824	NC_000011.9:g.(?32410604)(32460464_?)del	Pathogenic
2500727	NM_024426.6(WT1):c.1447+1G>A	Pathogenic
2577898	NM_024426.6(WT1):c.716_722del (p.His239fs)	Pathogenic
2633663	NM_024426.6(WT1):c.796_797dup (p.Ser267fs)	Pathogenic
2664781	NM_024426.6(WT1):c.769C>T (p.Gln257Ter)	Pathogenic
2925474	NM_024426.6(WT1):c.1373G>A (p.Cys458Tyr)	Pathogenic
2925477	NM_024426.6(WT1):c.368C>A (p.Ser123Ter)	Pathogenic
2944909	NM_024426.6(WT1):c.225del (p.Ser76fs)	Pathogenic
2949440	NM_024426.6(WT1):c.1029del (p.Tyr344fs)	Pathogenic
2952265	NM_024426.6(WT1):c.834del (p.Thr279fs)	Pathogenic
2953324	NM_024426.6(WT1):c.1374del (p.Gln457_Cys458insTer)	Pathogenic
3062359	NM_024426.6(WT1):c.1032C>G (p.Tyr344Ter)	Pathogenic
3244687	NC_000011.9:g.(?32449492)(32450175_?)del	Pathogenic
3244688	NC_000011.9:g.(?32421474)(32439220_?)del	Pathogenic
3244689	NC_000011.9:g.(?32410601)(32421600_?)del	Pathogenic
3377813	NC_000011.9:g.(?32409321)(32457085_?)del	Pathogenic

SpliceAI

1413 predictions. Top by Δscore:

Variant	Effect	Δscore
11:32399943:CTCA:C	donor_loss	1.0000
11:32399944:TCA:T	donor_loss	1.0000
11:32399945:CACCT:C	donor_loss	1.0000
11:32399946:A:C	donor_loss	1.0000
11:32399947:C:A	donor_loss	1.0000
11:32400043:GG:G	acceptor_gain	1.0000
11:32400044:GCTG:G	acceptor_loss	1.0000
11:32400045:C:CC	acceptor_gain	1.0000
11:32400046:T:C	acceptor_loss	1.0000
11:32417575:ACC:A	donor_gain	1.0000
11:32417576:CCC:C	donor_gain	1.0000
11:32417653:CA:C	acceptor_gain	1.0000
11:32417655:C:CC	acceptor_gain	1.0000
11:32428058:CCTG:C	acceptor_loss	1.0000
11:32428492:CTTA:C	donor_loss	1.0000
11:32428493:TTA:T	donor_loss	1.0000
11:32428494:TACC:T	donor_loss	1.0000
11:32428495:A:AC	donor_gain	1.0000
11:32428495:A:AG	donor_loss	1.0000
11:32428495:AC:A	donor_gain	1.0000
11:32428496:C:CC	donor_gain	1.0000
11:32428496:C:CT	donor_loss	1.0000
11:32428496:CC:C	donor_gain	1.0000
11:32428496:CCCAG:C	donor_gain	1.0000
11:32428619:CCTG:C	acceptor_loss	1.0000
11:32428620:C:CA	acceptor_loss	1.0000
11:32428629:C:CT	acceptor_gain	1.0000
11:32428630:G:T	acceptor_gain	1.0000
11:32389180:C:A	acceptor_loss	0.9900
11:32389181:T:C	acceptor_loss	0.9900

AlphaMissense

3412 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000002937 (11:32415094 C>T), RS1000032776 (11:32415838 A>C,T), RS1000059262 (11:32430080 G>A), RS1000111245 (11:32406306 G>A), RS1000222820 (11:32398744 T>A,C), RS1000229618 (11:32431149 G>T), RS1000299056 (11:32424642 C>T), RS1000454924 (11:32407518 T>C), RS1000558455 (11:32399851 C>G,T), RS1000559226 (11:32436778 T>C), RS1000565302 (11:32432363 G>A), RS1000616968 (11:32393945 C>T), RS1000675882 (11:32405509 A>T), RS1000856087 (11:32421646 T>C), RS1001014790 (11:32432534 T>C)

Disease associations

OMIM: gene MIM:607102 | disease phenotypes: MIM:136680, MIM:194070, MIM:194072, MIM:194080, MIM:156240, MIM:256370, MIM:608978, MIM:106210, MIM:611755, MIM:256300, MIM:601626, MIM:167000

GenCC curated gene-disease

Disease	Classification	Inheritance
Wilms tumor 1	Definitive	Autosomal dominant
Denys-Drash syndrome	Definitive	Autosomal dominant
Frasier syndrome	Supportive	Autosomal dominant
familial idiopathic steroid-resistant nephrotic syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Wilms tumor 1	Definitive	AD
Denys-Drash syndrome	Definitive	AD

Mondo (28): Frasier syndrome (MONDO:0007635), Wilms tumor 1 (MONDO:0008679), WAGR syndrome (MONDO:0008681), Denys-Drash syndrome (MONDO:0008682), malignant mesothelioma (MONDO:0006292), nephrotic syndrome, type 4 (MONDO:0009733), Meacham syndrome (MONDO:0012164), aniridia 1 (MONDO:0024507), hereditary neoplastic syndrome (MONDO:0015356), disorder of sexual differentiation (MONDO:0002145), Leber congenital amaurosis 10 (MONDO:0012723), cholestasis (MONDO:0001751), gonadal dysgenesis (MONDO:0001967), proteinuria (MONDO:0003634), familial idiopathic steroid-resistant nephrotic syndrome (MONDO:0019006)

Orphanet (19): Denys-Drash syndrome (Orphanet:220), Frasier syndrome (Orphanet:347), Nephroblastoma (Orphanet:654), WAGR syndrome (Orphanet:893), Isolated aniridia (Orphanet:250923), Meacham syndrome (Orphanet:3097), Pleural mesothelioma (Orphanet:50251), Hereditary steroid-resistant nephrotic syndrome (Orphanet:656), Inherited cancer-predisposing syndrome (Orphanet:140162), Difference of sex development (Orphanet:90771), Leber congenital amaurosis (Orphanet:65), Atypical hemolytic uremic syndrome (Orphanet:2134), Congenital nephrotic syndrome, Finnish type (Orphanet:839), Precursor B-cell acute lymphoblastic leukemia (Orphanet:99860), Male infertility with azoospermia or oligozoospermia due to single gene mutation (Orphanet:399805)

HPO phenotypes

199 total (30 of 199 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000027	Azoospermia
HP:0000028	Cryptorchidism
HP:0000030	Testicular gonadoblastoma
HP:0000033	Ambiguous genitalia, male
HP:0000037	Male pseudohermaphroditism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000045	Abnormal scrotum morphology
HP:0000047	Hypospadias
HP:0000054	Micropenis
HP:0000058	Abnormal labia morphology
HP:0000061	Ambiguous genitalia, female
HP:0000062	Ambiguous genitalia
HP:0000083	Renal insufficiency
HP:0000085	Horseshoe kidney
HP:0000086	Ectopic kidney
HP:0000093	Proteinuria
HP:0000097	Focal segmental glomerulosclerosis
HP:0000100	Nephrotic syndrome
HP:0000105	Enlarged kidney
HP:0000112	Nephropathy
HP:0000130	Abnormality of the uterus
HP:0000133	Gonadal dysgenesis
HP:0000142	Abnormal vagina morphology
HP:0000147	Polycystic ovaries
HP:0000148	Vaginal atresia
HP:0000149	Ovarian gonadoblastoma
HP:0000150	Gonadoblastoma
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly

GWAS associations

28 associations (top):

Study	Trait	p-value
GCST001398_1	Tuberculosis	3.000000e-11
GCST002197_1	Tuberculosis	1.000000e-12
GCST002198_12	Tuberculosis	3.000000e-06
GCST003198_4	Inguinal hernia	4.000000e-14
GCST005176_1	Rubella-specific interleukin-6 secretion	5.000000e-08
GCST006138_1	Resting-state electroencephalogram vigilance	5.000000e-06
GCST006462_35	Uterine fibroids	5.000000e-16
GCST006464_15	Endometrial cancer	1.000000e-08
GCST006465_23	Endometrial cancer (endometrioid histology)	2.000000e-06
GCST006626_10	Pulse pressure	1.000000e-12
GCST007928_16	Medication use (diuretics)	5.000000e-10
GCST008362_3	Birth weight	3.000000e-09
GCST008363_81	Offspring birth weight	1.000000e-09
GCST008423_9	Uterine fibroids	1.000000e-24
GCST009158_31	Uterine fibroids	1.000000e-25
GCST010174_9	Pelvic organ prolapse	8.000000e-07
GCST010241_229	Apolipoprotein A1 levels	2.000000e-09
GCST010320_68	PR interval	6.000000e-07
GCST010321_66	PR interval	5.000000e-08
GCST010796_172	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-13
GCST010796_173	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_174	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-12
GCST010866_79	Coronary artery disease	2.000000e-09
GCST012228_535	Waist-hip index	5.000000e-08
GCST012230_29	Waist-to-hip ratio adjusted for BMI	3.000000e-08
GCST90002396_462	Mean reticulocyte volume	2.000000e-10
GCST90002397_521	Mean spheric corpuscular volume	6.000000e-12
GCST90086158_15	Brugada syndrome	2.000000e-09

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004810	interleukin-6 measurement
EFO:0004357	electroencephalogram measurement
EFO:0005763	pulse pressure measurement
EFO:0009928	Diuretic use measurement
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004462	PR interval
EFO:0004327	electrocardiography
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (19)

Descriptor	Name	Tree numbers
D065766	Atypical Hemolytic Uremic Syndrome	C12.050.351.968.419.936.463.500; C12.200.777.419.936.463.500; C12.950.419.936.463.500; C15.378.050.141.610.500; C15.378.140.855.925.500.500; C15.378.243.937.925.500.500
D002779	Cholestasis	C06.130.120.135
D030321	Denys-Drash Syndrome	C04.557.435.595.220; C04.588.945.947.535.585.220; C04.700.900.220; C12.050.351.875.253.096.562; C12.050.351.937.820.535.585.220; C12.050.351.968.419.473.585.220; C12.200.706.316.096.562; C12.200.758.820.750.585.220; C12.200.777.419.473.585.220; C12.800.316.096.562; C12.900.820.535.585.220; C12.950.419.473.585.220; C12.950.983.535.585.220; C16.131.939.316.096.562; C16.320.700.900.220; C19.391.119.096.562
D012734	Disorders of Sex Development	C12.050.351.875.253; C12.200.706.316; C12.800.316; C16.131.939.316; C19.391.119
D052159	Frasier Syndrome	C12.050.351.875.253.096.624; C12.050.351.968.419.780.750.500.500; C12.200.706.316.096.624; C12.200.777.419.780.750.500.500; C12.800.316.096.624; C12.950.419.780.750.500.500; C16.131.939.316.096.624; C16.320.306; C19.391.119.096.624; C23.550.291.500.906.500.500
D005923	Glomerulosclerosis, Focal Segmental	C12.050.351.968.419.570.363.640; C12.200.777.419.570.363.660; C12.950.419.570.363.640
D006059	Gonadal Dysgenesis	C12.050.351.875.253.309; C12.200.706.316.309; C12.800.316.309; C16.131.939.316.309; C19.391.119.309
D007674	Kidney Diseases	C12.050.351.968.419; C12.200.777.419; C12.950.419
D015470	Leukemia, Myeloid, Acute	C04.557.337.539.275; C15.378.508.539.275
D008654	Mesothelioma	C04.557.470.035.510; C04.557.470.660.510
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D009404	Nephrotic Syndrome	C12.050.351.968.419.630.643; C12.200.777.419.630.643; C12.950.419.630.643
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
D011507	Proteinuria	C12.050.351.968.934.734; C12.200.777.934.734; C12.950.934.734; C23.888.942.750
D017624	WAGR Syndrome	C04.557.435.595.950; C04.588.945.947.535.585.950; C04.700.900.950; C10.597.606.360.969; C11.250.060.950; C11.270.060.950; C11.941.375.060.950; C12.050.351.875.253.096.875; C12.050.351.937.820.535.585.950; C12.050.351.968.419.473.585.950; C12.200.706.316.096.875; C12.200.758.820.750.585.950; C12.200.777.419.473.585.950; C12.800.316.096.875; C12.900.820.535.585.950; C12.950.419.473.585.950; C12.950.983.535.585.950; C16.131.260.940; C16.131.384.079.950; C16.131.939.316.096.875; C16.320.180.940; C16.320.290.078.950; C16.320.700.900.950; C19.391.119.096.875
D009396	Wilms Tumor	C04.557.435.595; C04.588.945.947.535.585; C04.700.900; C12.050.351.937.820.535.585; C12.050.351.968.419.473.585; C12.200.758.820.750.585; C12.200.777.419.473.585; C12.900.820.535.585; C12.950.419.473.585; C12.950.983.535.585; C16.320.700.900
C565720	Leber Congenital Amaurosis 10 (supp.)
C538162	Meacham Winn Culler syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4662942 (SINGLE PROTEIN)

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items; also 10 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
WT1 Exon 7 Mutation	Daunorubicin + Cytarabine	Acute Myeloid Leukemia	Resistance	CIViC B	EID139

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs16754	WT1		0.00	0

CTD chemical–gene interactions

54 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tretinoin	decreases expression, increases reaction, increases expression	8
sodium arsenite	increases expression, increases reaction, decreases expression, decreases reaction, affects cotreatment (+1 more)	5
Bortezomib	decreases expression	4
bisphenol A	affects cotreatment, decreases methylation, increases expression, increases methylation	3
(+)-JQ1 compound	decreases expression	3
Arsenic Trioxide	decreases expression, increases expression	3
Valproic Acid	affects reaction, increases expression, decreases methylation	3
manganese chloride	affects cotreatment, increases abundance, increases expression, decreases expression	2
Fulvestrant	decreases response to substance, affects cotreatment, decreases methylation	2
Cannabidiol	decreases expression	2
Curcumin	decreases expression	2
Manganese	decreases expression, affects cotreatment, increases abundance, increases expression	2
Oxygen	decreases expression, increases expression	2
Tamoxifen	decreases response to substance	2
Sirolimus	decreases expression	2
naringenin	affects cotreatment, increases expression	1
trichostatin A	increases expression	1
arsenite	increases methylation	1
cobaltous chloride	increases expression, affects cotreatment	1
benzo(e)pyrene	decreases methylation	1
bisdemethoxycurcumin	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
demethoxycurcumin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
abrine	decreases expression	1
4-(4-(3-(pyridin-2-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-N-(tetrahydro-2H-pyran-4-yl)benzamide	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
bisphenol S	decreases methylation	1
NSC 689534	affects binding, decreases expression	1

Cellosaurus cell lines

97 cell lines: 72 cancer cell line, 13 finite cell line, 4 conditionally immortalized cell line, 3 induced pluripotent stem cell, 3 embryonic stem cell, 2 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0007	U-937	Cancer cell line	Male
CVCL_1326	Karpas-45	Cancer cell line	Male
CVCL_1424	MOLT-16	Cancer cell line	Female
CVCL_1667	RPMI-8402	Cancer cell line	Female
CVCL_1775	TUR	Cancer cell line	Male
CVCL_1807	AP-1060	Cancer cell line	Male
CVCL_1820	HPB-ALL	Cancer cell line	Male
CVCL_2082	JOSK-I	Cancer cell line	Male
CVCL_2083	JOSK-M	Cancer cell line	Male
CVCL_2810	U-937 cl1-14	Cancer cell line	Male

Clinical trials (associated diseases)

155 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00003034	PHASE3	UNKNOWN	ONCONASE Plus Doxorubicin Versus Doxorubicin Alone For Patients With Malignant Pleural or Peritoneal Mesothelioma Who Have Had No More Than One Prior Chemotherapy Regimen
NCT00004920	PHASE3	COMPLETED	Cisplatin With or Without Raltitrexed in Treating Patients With Malignant Mesothelioma of the Pleura
NCT00005636	PHASE3	COMPLETED	Cisplatin With or Without Pemetrexed Disodium in Treating Patients With Malignant Mesothelioma of the Pleura That Cannot be Removed by Surgery
NCT00006231	PHASE3	COMPLETED	Radiation Therapy in Preventing Metastatic Cancer in Patients Who Have Diagnostic Procedures to Identify Malignant Mesothelioma
NCT00075699	PHASE3	COMPLETED	Active Symptom Control With or Without Chemotherapy in Treating Patients With Malignant Pleural Mesothelioma
NCT00821860	PHASE3	COMPLETED	Video-Assisted Surgery or Talc Pleurodesis in Treating Patients With Malignant Mesothelioma
NCT02349412	PHASE3	COMPLETED	Early Palliative Care With Standard Care or Standard Care Alone in Improving Quality of Life of Patients With Incurable Lung or Non-colorectal Gastrointestinal Cancer and Their Family Caregivers
NCT00038207	PHASE2	COMPLETED	Liposomal Vincristine for Pediatric and Adolescent Patients With Relapsed Malignancies
NCT00335556	PHASE2	COMPLETED	Combination Chemotherapy, Radiation Therapy, and/or Surgery in Treating Patients With High-Risk Kidney Tumors
NCT00002475	PHASE2	COMPLETED	Cyclophosphamide Plus Vaccine Therapy in Treating Patients With Advanced Cancer
NCT00002608	PHASE2	COMPLETED	Combination Chemotherapy and Tamoxifen in Treating Patients With Solid Tumors
NCT00003508	PHASE2	TERMINATED	Antineoplaston Therapy in Treating Patients With Advanced Mesothelioma
NCT00003723	PHASE2	COMPLETED	S9810: Gemcitabine Plus Cisplatin in Treating Patients With Malignant Mesothelioma of the Pleura That Cannot Be Removed by Surgery
NCT00004033	PHASE2	COMPLETED	Liposomal-Cisplatin Analogue (L-NDDP) in Treating Patients With Malignant Pleural Mesothelioma
NCT00004183	PHASE2	COMPLETED	Capecitabine in Treating Patients With Malignant Mesothelioma
NCT00004254	PHASE2	COMPLETED	Raltitrexed in Treating Patients With Malignant Mesothelioma That Cannot Be Surgically Removed
NCT00006014	PHASE2	COMPLETED	SU5416 in Treating Patients With Malignant Mesothelioma
NCT00017186	PHASE2	COMPLETED	Gemcitabine and Epirubicin in Treating Patients With Malignant Mesothelioma
NCT00024076	PHASE2	COMPLETED	Radiofrequency Ablation in Treating Patients With Refractory or Advanced Lung Cancer
NCT00024271	PHASE2	UNKNOWN	Surgery, Chemotherapy, and Radiation Therapy in Treating Patients With Peritoneal Cancer
NCT00025207	PHASE2	COMPLETED	Gefitinib in Treating Patients With Malignant Mesothelioma
NCT00027508	PHASE2	TERMINATED	Ecteinascidin 743 in Treating Patients With Malignant Mesothelioma
NCT00027703	PHASE2	COMPLETED	Combination Chemotherapy With or Without Bevacizumab in Treating Patients With Malignant Mesothelioma
NCT00030459	PHASE2	UNKNOWN	Palliative Therapy With or Without Chemotherapy in Treating Patients With Malignant Mesothelioma
NCT00030745	PHASE2	COMPLETED	Combination Chemotherapy Before Surgery in Treating Patients With Mesothelioma of the Lung
NCT00039182	PHASE2	COMPLETED	Erlotinib in Treating Patients With Malignant Mesothelioma of the Lung
NCT00053885	PHASE2	COMPLETED	PTK787/ZK 222584 in Treating Patients With Unresectable Malignant Mesothelioma
NCT00054002	PHASE2	COMPLETED	Surgery and Photodynamic Therapy in Treating Patients With Malignant Mesothelioma
NCT00062283	PHASE2	COMPLETED	Alanosine in Treating Patients With Cancer
NCT00107432	PHASE2	COMPLETED	Sorafenib Tosylate in Treating Patients With Malignant Mesothelioma.
NCT00227630	PHASE2	COMPLETED	Pemetrexed Disodium and Cisplatin Followed By Surgery and Radiation Therapy in Treating Patients With Malignant Pleural Mesothelioma
NCT00243074	PHASE2	COMPLETED	S0509 - AZD2171 in Treating Patients With Malignant Pleural Mesothelioma That Cannot Be Removed By Surgery
NCT00309946	PHASE2	COMPLETED	Cediranib Maleate in Treating Patients With Malignant Mesothelioma That Cannot Be Removed By Surgery
NCT00334594	PHASE2	COMPLETED	Pemetrexed Disodium and Cisplatin Followed by Surgery With or Without Radiation Therapy in Treating Patients With Malignant Pleural Mesothelioma
NCT00354393	PHASE2	COMPLETED	Combination Chemotherapy With or Without Surgery & Chemoradiotherapy in Patients With Malignant Pleural Mesothelioma
NCT00365053	PHASE2	COMPLETED	PXD101 as Second-Line Therapy in Treating Patients With Malignant Mesothelioma of the Chest That Cannot Be Removed By Surgery
NCT00392444	PHASE2	COMPLETED	Sunitinib in Treating Patients With Advanced Malignant Pleural Mesothelioma
NCT00458913	PHASE2	COMPLETED	Bortezomib and Cisplatin as First-Line Therapy in Treating Patients With Malignant Mesothelioma
NCT00459862	PHASE2	COMPLETED	Pazopanib in Treating Patients With Malignant Pleural Mesothelioma
NCT00509041	PHASE2	COMPLETED	Dasatinib in Treating Patients With Previously Treated Malignant Mesothelioma