WBP2

Chr 17AR

WW domain binding protein 2

Also known as: DFNB107, GRAMD6, WBP-2

NCBI Gene: 23558ENSG00000132471UniProt: Q969T9

WBP2 encodes a transcriptional coactivator that enhances the activity of estrogen and progesterone receptors and modulates expression of post-synaptic scaffolding proteins. Biallelic mutations cause autosomal recessive deafness (DFNB107), presumably through disruption of hormone receptor-mediated transcriptional regulation affecting auditory function.

Summary from RefSeq, OMIM, UniProt

Primary Disease Associations & Inheritance

Deafness, autosomal recessive 107MIM #617639
AR
0
Active trials
7
Pubs (1 yr)
15
P/LP submissions
7%
P/LP missense
0.59
LOEUF
DN
Mechanism· predicted
Clinical Summary— WBP2
🧬
Gene-Disease Validity (ClinGen)
hearing loss, autosomal recessive · ARLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.
📋
ClinVar Variants
15 unique Pathogenic / Likely Pathogenic· 81 VUS of 175 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.59LOEUF
pLI 0.349
Z-score 2.59
OE 0.23 (0.10–0.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.30Z-score
OE missense 0.93 (0.82–1.07)
151 obs / 161.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.23 (0.10–0.59)
0≤0.351.4
Missense OE0.93 (0.82–1.07)
0≤0.61.4
Synonymous OE1.03
0≤1.21.6
LoF obs/exp: 3 / 13.1Missense obs/exp: 151 / 161.6Syn Z: -0.21
DN
0.6358th %ile
GOF
0.3986th %ile
LOF
0.3843th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

175 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic2
VUS81
Likely Benign45
Benign16
Conflicting1
13
Pathogenic
2
Likely Pathogenic
81
VUS
45
Likely Benign
16
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
13
0
13
Likely Pathogenic
0
1
1
0
2
VUS
1
69
11
0
81
Likely Benign
0
2
23
20
45
Benign
0
0
13
3
16
Conflicting
—1
Total1726123158

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

WBP2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
WBP2 Attenuates Metformin Response in HER2-Positive Breast Cancer Cells by Repressing AMPK Activation and Inducing a Lower AMP:ATP Ratio State Through Enhanced ATP Production.
Lin H et al.·Cells
2026Open Access
WBP2 and its network of transcription coregulators in an expanding repertoire of human cancers.
Sabbaghian A et al.·Int J Cancer
2026
E3 ubiquitin ligase ITCH-mediated proteasomal degradation of WBP2 sensitizes breast cancer cells to chemotherapy through restraining AMOTL2/c-JUN axis.
Zhu M et al.·Biochem Pharmacol
2025
Evaluating the involvement and mutual interaction of wbp2 and yap in embryogenesis with an emphasis on liver function in zebrafish embryos.
Lykov N et al.·Tissue Cell
2024Functional
Hepatic Dyrk1b impairs systemic glucose homeostasis by modulating Wbp2 expression in a kinase activity-dependent manner.
Li L et al.·Heliyon
2024Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients