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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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WTAP
WT1 associated protein
Chromosome 6 · 6q25.3
NCBI Gene: 9589Ensembl: ENSG00000146457.16HGNC: HGNC:16846UniProt: A0A087X1R4
177PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingidentical protein bindingregulation of alternative mRNA splicing, via spliceosomemRNA processingneurodegenerative diseasealcohol drinkingesophageal ulcerprostate carcinoma
✦AI Summary

WTAP (Wilms tumor 1-associated protein) is a regulatory component of the m6A RNA methylation machinery that plays crucial roles in RNA processing and disease pathogenesis. As part of the m6A methyltransferase complex, WTAP associates with METTL3 and METTL14 to catalyze N6-methyladenosine modifications on RNAs 12. WTAP is essential for proper localization of the methyltransferase complex to nuclear speckles and is required for catalytic activity in vivo 2. The protein facilitates recruitment of the m6A methyltransferase complex to mRNA targets and regulates alternative splicing of genes involved in transcription and RNA processing 2. In disease contexts, WTAP shows significant clinical relevance. It is highly expressed in hepatocellular carcinoma where it promotes tumor progression through m6A-mediated epigenetic silencing of tumor suppressor ETS1 via the HuR pathway 3. Additionally, WTAP contributes to hyperinflammatory responses by undergoing p65-dependent transcriptional upregulation and facilitating phase separation to enhance m6A modification of inflammatory transcripts 4. WTAP also participates in immunosuppression through the circCCAR1/miR-127-5p/WTAP feedback loop that promotes CD8+ T-cell dysfunction and anti-PD1 therapy resistance in hepatocellular carcinoma 5. These findings establish WTAP as both a critical RNA processing regulator and potential therapeutic target.

Sources cited
1
WTAP interacts with METTL3 and METTL14 to form the m6A methyltransferase complex
PMID: 24316715
2
WTAP is required for localization of METTL3/METTL14 to nuclear speckles and for methyltransferase catalytic activity
PMID: 24407421
3
WTAP is highly expressed in hepatocellular carcinoma and promotes tumor progression via m6A-HuR-dependent silencing of ETS1
PMID: 31438961
4
WTAP promotes hyperinflammation through p65-dependent upregulation and facilitates phase separation of the writer complex
PMID: 39007267
5
WTAP participates in the circCCAR1/miR-127-5p/WTAP feedback loop that causes CD8+ T-cell dysfunction and anti-PD1 resistance
PMID: 36932387
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.39Weak
alcohol drinkingOpen Targets
0.30Weak
esophageal ulcerOpen Targets
0.27Weak
prostate carcinomaOpen Targets
0.18Weak
cutaneous melanomaOpen Targets
0.13Weak
renal cell carcinomaOpen Targets
0.10Weak
hepatocellular carcinomaOpen Targets
0.10Suggestive
systemic lupus erythematosusOpen Targets
0.09Suggestive
diffuse large B-cell lymphomaOpen Targets
0.08Suggestive
non-alcoholic steatohepatitisOpen Targets
0.08Suggestive
glioblastoma multiformeOpen Targets
0.07Suggestive
adolescent idiopathic scoliosisOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.07Suggestive
esophageal squamous cell carcinomaOpen Targets
0.07Suggestive
microphthalmia with limb anomaliesOpen Targets
0.06Suggestive
nasopharyngeal carcinomaOpen Targets
0.06Suggestive
gliomaOpen Targets
0.05Suggestive
gastric cancerOpen Targets
0.05Suggestive
osteosarcomaOpen Targets
0.05Suggestive
colorectal carcinomaOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SMAD3Protein interaction100%METTL13Protein interaction100%WT1Protein interaction100%SMAD2Protein interaction98%RSPH3Protein interaction95%METTL3Protein interaction95%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
46%
Brain
43%
Ovary
40%
Liver
28%
Heart
24%
Gene Interaction Network
Click a node to explore
WTAPSMAD3METTL13WT1SMAD2RSPH3METTL3
PROTEIN STRUCTURE
Preparing viewer…
PDB7YFJ · 2.40 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.34Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.19 [0.11–0.34]
RankingsWhere WTAP stands among ~20K protein-coding genes
  • #2,475of 20,598
    Most Researched177 · top quartile
  • #1,490of 17,882
    Most Constrained (LOEUF)0.34 · top 10%
Genes detectedWTAP
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
The role of m6A modification in the biological functions and diseases.
PMID: 33611339
Signal Transduct Target Ther · 2021
1.00
2
WTAP facilitates progression of hepatocellular carcinoma via m6A-HuR-dependent epigenetic silencing of ETS1.
PMID: 31438961
Mol Cancer · 2019
0.90
3
A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation.
PMID: 24316715
Nat Chem Biol · 2014
0.80
4
WTAP-mediated m
PMID: 35304463
Nat Commun · 2022
0.76
5
The potential role of RNA N6-methyladenosine in Cancer progression.
PMID: 32398132
Mol Cancer · 2020
0.70