WT1
Wilms tumor protein
Also known as: AWT1, GUD, NPHS4, WAGR, WIT-2, WT-1, WT1_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P19544
- Gene
- WT1
- Ensembl
- ENSG00000184937
- Chromosome
- 11
- Canonical length
- 449 aa
- Protein class
- Cancer-related genes, Disease related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors
- Subcellular location
- Nucleoplasm,Cytosol
- Quaternary structure
- Homodimer
OverviewNCBI Gene
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. [provided by RefSeq, Mar 2015]
Canonical amino-acid sequenceUniProt
449 residues, UniProt reviewed canonical sequence.
>P19544|WT1
1 MGSDVRDLNA LLPAVPSLGG GGGCALPVSG AAQWAPVLDF APPGASAYGS LGGPAPPPAP
61 PPPPPPPPHS FIKQEPSWGG AEPHEEQCLS AFTVHFSGQF TGTAGACRYG PFGPPPPSQA
121 SSGQARMFPN APYLPSCLES QPAIRNQGYS TVTFDGTPSY GHTPSHHAAQ FPNHSFKHED
181 PMGQQGSLGE QQYSVPPPVY GCHTPTDSCT GSQALLLRTP YSSDNLYQMT SQLECMTWNQ
241 MNLGATLKGV AAGSSSSVKW TEGQSNHSTG YESDNHTTPI LCGAQYRIHT HGVFRGIQDV
301 RRVPGVAPTL VRSASETSEK RPFMCAYPGC NKRYFKLSHL QMHSRKHTGE KPYQCDFKDC
361 ERRFSRSDQL KRHQRRHTGV KPFQCKTCQR KFSRSDHLKT HTRTHTGKTS EKPFSCRWPS
421 CQKKFARSDE LVRHHNMHQR NMTKLQLALLocalizationUniProt · AlphaFold · HPA
Whether an antibody against WT1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.65
- Highest tissue expression
- 49 nTPM
Expression across tissuesHPA
Tissue
- fallopian tube: 49 nTPM
- endometrium: 42 nTPM
- smooth muscle: 31 nTPM
- ovary: 28 nTPM
- testis: 18 nTPM
- adipose tissue: 15 nTPM
Single-cell type
- podocytes: 814 nCPM
- sertoli cells: 350 nCPM
- mesothelial cells: 320 nCPM
- granulosa cells: 316 nCPM
- endometrial stromal cells: 174 nCPM
- epicardial cells: 164 nCPM
Immune cell
- basophil: 0 nTPM
- classical monocyte: 0 nTPM
- eosinophil: 0 nTPM
- gdT-cell: 0 nTPM
- intermediate monocyte: 0 nTPM
- MAIT T-cell: 0 nTPM
Brain region
- medulla oblongata: 0.4 nTPM
- basal ganglia: 0.2 nTPM
- cerebral cortex: 0.2 nTPM
- hippocampal formation: 0.2 nTPM
- midbrain: 0.2 nTPM
- hypothalamus: 0.1 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about WT1.
Disease | AllUniProt
Conditions WT1 is implicated in, by any mechanism.
- Frasier syndrome (FS) MIM:136680
- Wilms tumor 1 (WT1) MIM:194070
- Denys-Drash syndrome (DDS) MIM:194080
- Nephrotic syndrome 4 (NPHS4) MIM:256370
- Meacham syndrome (MEACHS) MIM:608978
- Mesothelioma, malignant (MESOM) MIM:156240
Disease | GeneticClinVar
158 pathogenic / likely-pathogenic of 2,009 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Wilms tumor 1
- Drash syndrome
- Frasier syndrome
- 11p partial monosomy syndrome
- Nephrotic syndrome, type 4
Disease | ImmuneIEDB
Conditions an epitope on WT1 was assayed in.
- acute myeloid leukemia B and T cell
- cancer B and T cell
- acute lymphoblastic leukemia T cell
- pancreatic ductal adenocarcinoma T cell
- melanoma T cell
- sarcoma B cell
- pancreatic adenocarcinoma T cell
- glioblastoma B and T cell
- pancreatic ductal carcinoma T cell
- brain glioma T cell
- ovarian cancer T cell
- chronic myeloid leukemia T cell
- lung cancer T cell
- anaplastic oligodendroglioma T cell
- myeloid leukemia T cell
- HTLV-1-associated myelopathy/tropical spastic paraparesis T cell
- prostate cancer T cell
- ovary epithelial cancer T cell
- cholangiocarcinoma T cell
- malignant pleural mesothelioma T cell
ReferencesPubMed · IEDB
Publications for WT1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
4 publications
- Autoantibodies as diagnostic biomarkers for lung cancer: A systematic review.
2019 · Cell Death Discov · RCR 1.8 · 47 citations - Association of WT1 IgG antibody against WT1 peptide with prolonged survival in glioblastoma multiforme patients vaccinated with WT1 peptide.
2016 · Int J Cancer · RCR 1.6 · 54 citations - Prognostic significance of WT1 mRNA and anti-WT1 antibody levels in peripheral blood in patients with myelodysplastic syndromes.
2010 · Leuk Res · RCR 0.6 · 23 citations - Serum WT1-271 IgM antibody as a novel diagnostic marker for Gastric Cancer.
2022 · Mol Clin Oncol · RCR 0.1 · 1 citations
Reference: B cellIEDB
8 publications
- Association of WT1 IgG antibody against WT1 peptide with prolonged survival in glioblastoma multiforme patients vaccinated with WT1 peptide.
2016 · Int J Cancer · RCR 1.6 · 54 citations - Identification of the Targets of T-cell Receptor Therapeutic Agents and Cells by Use of a High-Throughput Genetic Platform.
2020 · Cancer Immunol Res · RCR 1.2 · 35 citations - Therapeutic efficacy of an Fc-enhanced TCR-like antibody to the intracellular WT1 oncoprotein.
2014 · Clin Cancer Res · RCR 1 · 45 citations - WT1 Trio Peptide-Based Cancer Vaccine for Rare Cancers Expressing Shared Target WT1.
2023 · Cancers (Basel) · RCR 0.8 · 9 citations - Immunoreactivity to WT1 peptide vaccine is associated with prognosis in elderly patients with acute myeloid leukemia: follow-up study of randomized phase II trial of OCV-501, an HLA class II-binding WT1 polypeptide.
2023 · Cancer Immunol Immunother · RCR 0.8 · 7 citations
Show 3 more
- A new peptide vaccine OCV-501: in vitro pharmacology and phase 1 study in patients with acute myeloid leukemia.
2017 · Cancer Immunol Immunother · RCR 0.6 · 19 citations - WT1 epitope-specific IgG and IgM antibodies for immune-monitoring in patients with advanced sarcoma treated with a WT1 peptide cancer vaccine.
2022 · Oncol Lett · RCR 0.5 · 7 citations - Generation and evaluation of cancer binding capacity of HLA-A2-WT1 complex-targeting antibody.
2024 · Immunol Lett
Reference: T cellIEDB
69 publications
- Discovery of tumor-reactive T cell receptors by massively parallel library synthesis and screening.
2025 · Nat Biotechnol · RCR 10 · 39 citations - Induction of WT1 (Wilms' tumor gene)-specific cytotoxic T lymphocytes by WT1 peptide vaccine and the resultant cancer regression.
2004 · Proc Natl Acad Sci U S A · RCR 8.4 · 457 citations - Sensitive identification of neoantigens and cognate TCRs in human solid tumors.
2022 · Nat Biotechnol · RCR 4.9 · 84 citations - Safety and persistence of WT1-specific T-cell receptor gene-transduced lymphocytes in patients with AML and MDS.
2017 · Blood · RCR 4.5 · 150 citations - Phase 2 trial of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia.
2018 · Blood Adv · RCR 4.3 · 131 citations
Show 20 more of 69 total
- Enhancing T Cell Receptor Stability in Rejuvenated iPSC-Derived T Cells Improves Their Use in Cancer Immunotherapy.
2018 · Cell Stem Cell · RCR 3.7 · 129 citations - Specificity of bispecific T cell receptors and antibodies targeting peptide-HLA.
2020 · J Clin Invest · RCR 2.7 · 71 citations - Treatment with chemotherapy and dendritic cells pulsed with multiple Wilms' tumor 1 (WT1)-specific MHC class I/II-restricted epitopes for pancreatic cancer.
2014 · Clin Cancer Res · RCR 2.7 · 106 citations - CRISPR-based gene disruption and integration of high-avidity, WT1-specific T cell receptors improve antitumor T cell function.
2022 · Sci Transl Med · RCR 2.4 · 42 citations - Targeting an alternate Wilms' tumor antigen 1 peptide bypasses immunoproteasome dependency.
2022 · Sci Transl Med · RCR 2.2 · 35 citations - Combination Gemcitabine and WT1 Peptide Vaccination Improves Progression-Free Survival in Advanced Pancreatic Ductal Adenocarcinoma: A Phase II Randomized Study.
2018 · Cancer Immunol Res · RCR 1.9 · 57 citations - A New Plasmacytoid Dendritic Cell-Based Vaccine in Combination with Anti-PD-1 Expands the Tumor-Specific CD8+ T Cells of Lung Cancer Patients.
2023 · Int J Mol Sci · RCR 1.8 · 20 citations - α-type-1 polarized dendritic cell-based vaccination in recurrent high-grade glioma: a phase I clinical trial.
2012 · BMC Cancer · RCR 1.8 · 71 citations - A phase I clinical study of a cocktail vaccine of Wilms' tumor 1 (WT1) HLA class I and II peptides for recurrent malignant glioma.
2019 · Cancer Immunol Immunother · RCR 1.7 · 46 citations - WT1 vaccination in AML and MDS: A pilot trial with synthetic analog peptides.
2015 · Am J Hematol · RCR 1.7 · 58 citations - Analysis of Wilms' tumor protein 1 specific TCR repertoire in AML patients uncovers higher diversity in patients in remission than in relapsed.
2025 · Ann Hematol · RCR 1.7 · 5 citations - WT1-specific TCRs directed against newly identified peptides install antitumor reactivity against acute myeloid leukemia and ovarian carcinoma.
2022 · J Immunother Cancer · RCR 1.5 · 22 citations - WT1-specific T-cell responses in high-risk multiple myeloma patients undergoing allogeneic T cell-depleted hematopoietic stem cell transplantation and donor lymphocyte infusions.
2013 · Blood · RCR 1.5 · 57 citations - A Randomized Phase II Trial of Adjuvant Galinpepimut-S, WT-1 Analogue Peptide Vaccine, After Multimodality Therapy for Patients with Malignant Pleural Mesothelioma.
2017 · Clin Cancer Res · RCR 1.4 · 50 citations - Wilms' Tumour 1 (WT1) peptide vaccination in patients with acute myeloid leukaemia induces short-lived WT1-specific immune responses.
2014 · Br J Haematol · RCR 1.2 · 47 citations - Human CLEC9A antibodies deliver Wilms' tumor 1 (WT1) antigen to CD141+ dendritic cells to activate naïve and memory WT1-specific CD8+ T cells.
2020 · Clin Transl Immunology · RCR 1.1 · 32 citations - Enhanced stimulation of antigen-specific immune responses against nucleophosmin 1 mutated acute myeloid leukaemia by an anti-programmed death 1 antibody.
2022 · Br J Haematol · RCR 1.1 · 15 citations - Identification of a tumor-specific allo-HLA-restricted γδTCR.
2019 · Blood Adv · RCR 1.1 · 33 citations - Human Langerhans cells use an IL-15R-α/IL-15/pSTAT5-dependent mechanism to break T-cell tolerance against the self-differentiation tumor antigen WT1.
2012 · Blood · RCR 1 · 47 citations - Efficient and Non-genotoxic RNA-Based Engineering of Human T Cells Using Tumor-Specific T Cell Receptors With Minimal TCR Mispairing.
2018 · Front Immunol · RCR 1 · 32 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.25
- gnomAD pLI
- 1
- gnomAD missense Z
- 1.78
- DepMap mean gene effect
- 0.08
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- adrenal cortex formation
- adrenal gland development
- branching involved in ureteric bud morphogenesis
- camera-type eye development
- cardiac muscle cell fate commitment
- cellular response to cAMP
- cellular response to gonadotropin stimulus
- diaphragm development
- epithelial cell differentiation
- germ cell development
- glomerular basement membrane development
- glomerulus development
- gonad development
- heart development
- kidney development
- male genitalia development
- male gonad development
- mesenchymal to epithelial transition
- metanephric epithelium development
- metanephric mesenchyme development
- metanephric S-shaped body morphogenesis
- negative regulation of apoptotic process
- negative regulation of cell growth
- negative regulation of cell population proliferation
- negative regulation of DNA-templated transcription
- negative regulation of female gonad development
- negative regulation of gene expression via chromosomal CpG island methylation
- negative regulation of transcription by RNA polymerase II
- negative regulation of translation
- podocyte differentiation
- positive regulation of apoptotic process
- positive regulation of DNA-templated transcription
- positive regulation of gene expression
- positive regulation of heart growth
- positive regulation of male gonad development
- positive regulation of metanephric ureteric bud development
- positive regulation of miRNA transcription
- positive regulation of transcription by RNA polymerase II
- posterior mesonephric tubule development
- regulation of animal organ formation
- regulation of DNA-templated transcription
- regulation of transcription by RNA polymerase II
- RNA splicing
- sex determination
- thorax and anterior abdomen determination
- tissue development
- ureteric bud development
- vasculogenesis
- visceral serous pericardium development
- negative regulation of metanephric glomerular mesangial cell proliferation
Molecular functions
- C2H2 zinc finger domain binding
- DNA-binding transcription activator activity, RNA polymerase II-specific
- DNA-binding transcription factor activity
- DNA-binding transcription factor activity, RNA polymerase II-specific
- double-stranded methylated DNA binding
- hemi-methylated DNA-binding
- RNA binding
- RNA polymerase II cis-regulatory region sequence-specific DNA binding
- sequence-specific DNA binding
- transcription cis-regulatory region binding
- zinc ion binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Zinc finger C2H2-type
- Zinc finger C2H2 superfamily
- Zinc finger, C2H2 type
- Wilm's tumour protein, N-terminal
- Wilm's tumour protein
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of WT1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads WT1 as an antibody target. Whether an autoantibody or antibody against WT1 could matter depends on whether native WT1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
WT1 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label WT1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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