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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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WBP2
WW domain binding protein 2
Chromosome 17 Β· 17q25.1
NCBI Gene: 23558Ensembl: ENSG00000132471.12HGNC: HGNC:12738UniProt: A6NG10
86PubMed Papers
21Diseases
0Drugs
1Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
RNA polymerase II cis-regulatory region sequence-specific DNA bindingtranscription coactivator activityprotein bindingnuclear estrogen receptor bindinghearing loss, autosomal recessivedeafnesspsoriasisHypercholesterolemia
✦AI Summary

WBP2 (WW domain binding protein 2) is a multifunctional transcriptional coactivator and adaptor protein with roles spanning hormone signaling, cell survival, and disease pathogenesis. Primary Function: WBP2 acts as a transcriptional coactivator of estrogen receptor (ESR1) and progesterone receptor (PGR), binding to hormone-responsive promoters upon estrogen activation and synergizing with YAP1 to enhance PGR activity 1. Beyond nuclear hormone signaling, WBP2 functions as a molecular chaperone in cytoprotective pathways. Mechanism: WBP2 interacts with multiple WW domain-containing proteins (YAP, TAZ, WWOX) through its PPxY motifs 2, positioning it as a central hub connecting diverse signaling pathways including EGFR, PI3K, Hippo, and Wnt 3. At the protein level, WBP2 restrains lysosomal degradation of GPX4 (glutathione peroxidase 4) by competing with HSC70 for GPX4 binding, thereby inhibiting ferroptosis 4. Disease Relevance: WBP2 is an emerging oncogene implicated in breast, ovarian, and prostate cancers, where dysregulation promotes malignant progression and drug resistance 56. Additionally, WBP2 promotes neointimal hyperplasia post-vascular injury by facilitating YBX1 nuclear translocation 7. Clinical Significance: WBP2 serves as a biomarker for early detection and prognosis in breast cancer and represents a promising therapeutic target, with nuclear WBP2 being particularly meaningful for diagnosis and progression prediction 6.

Sources cited
1
Primary Function: WBP2 acts as a transcriptional coactivator of estrogen receptor (ESR1) and progesterone receptor (PGR), binding to hormone-responsive promoters upon estrogen activation and synergizing with YAP1 to enhance PGR activity .
PMID: 16772533
2
Mechanism: WBP2 interacts with multiple WW domain-containing proteins (YAP, TAZ, WWOX) through its PPxY motifs , positioning it as a central hub connecting diverse signaling pathways including EGFR, PI3K, Hippo, and Wnt .
PMID: 28724435
3
Mechanism: WBP2 interacts with multiple WW domain-containing proteins (YAP, TAZ, WWOX) through its PPxY motifs , positioning it as a central hub connecting diverse signaling pathways including EGFR, PI3K, Hippo, and Wnt .
PMID: 32393834
4
At the protein level, WBP2 restrains lysosomal degradation of GPX4 (glutathione peroxidase 4) by competing with HSC70 for GPX4 binding, thereby inhibiting ferroptosis .
PMID: 37516014
5
Additionally, WBP2 promotes neointimal hyperplasia post-vascular injury by facilitating YBX1 nuclear translocation .
PMID: 41546484
6
Disease Relevance: WBP2 is an emerging oncogene implicated in breast, ovarian, and prostate cancers, where dysregulation promotes malignant progression and drug resistance , .
PMID: 36654949
Disease Associationsβ“˜21
hearing loss, autosomal recessiveOpen Targets
0.47Moderate
deafnessOpen Targets
0.35Weak
psoriasisOpen Targets
0.24Weak
HypercholesterolemiaOpen Targets
0.23Weak
hyperlipidemiaOpen Targets
0.18Weak
morbid obesityOpen Targets
0.18Weak
metabolic diseaseOpen Targets
0.18Weak
response to statinOpen Targets
0.13Weak
breast cancerOpen Targets
0.11Weak
coronary artery diseaseOpen Targets
0.10Weak
cancerOpen Targets
0.10Suggestive
autosomal dominant nonsyndromic hearing lossOpen Targets
0.08Suggestive
gliomaOpen Targets
0.08Suggestive
triple-negative breast cancerOpen Targets
0.08Suggestive
acute kidney injuryOpen Targets
0.07Suggestive
lung cancerOpen Targets
0.07Suggestive
mucous membrane pemphigoidOpen Targets
0.06Suggestive
Non-syndromic genetic deafnessOpen Targets
0.06Suggestive
X-linked nonsyndromic hearing lossOpen Targets
0.06Suggestive
autosomal recessive nonsyndromic hearing loss 9Open Targets
0.05Suggestive
Deafness, autosomal recessive, 107UniProt
Pathogenic Variants1
NM_012478.4(WBP2):c.161C>G (p.Pro54Arg)Likely pathogenic
Hearing loss, autosomal recessive 107
β˜…β˜†β˜†β˜†2021β†’ Residue 54
View on ClinVar β†—
Related Genes
UQCR10Protein interaction100%UQCRFS1Protein interaction100%UQCRC2Protein interaction100%CYC1Protein interaction100%UQCRBProtein interaction100%UQCRQProtein interaction100%
Tissue Expression6 tissues
Brain
100%
Liver
67%
Lung
60%
Heart
54%
Ovary
51%
Bone Marrow
31%
Gene Interaction Network
Click a node to explore
WBP2UQCR10UQCRFS1UQCRC2CYC1UQCRBUQCRQ
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q969T9
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.08LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.76 [0.55–1.08]
RankingsWhere WBP2 stands among ~20K protein-coding genes
  • #5,585of 20,598
    Most Researched86
  • #4,941of 5,498
    Most Pathogenic Variants1
  • #10,928of 17,882
    Most Constrained (LOEUF)1.08
Genes detectedWBP2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
WBP2 restrains the lysosomal degradation of GPX4 to inhibit ferroptosis in cisplatin-induced acute kidney injury.
PMID: 37516014
Redox Biol Β· 2023
1.00
2
WBP2 and its network of transcription coregulators in an expanding repertoire of human cancers.
PMID: 40958198
Int J Cancer Β· 2026
0.90
3
Reciprocal Regulation of Hippo and WBP2 Signalling-Implications in Cancer Therapy.
PMID: 34831354
Cells Β· 2021
0.80
4
The emerging roles of WBP2 oncogene in human cancers.
PMID: 32393834
Oncogene Β· 2020
0.70
5
WW domain binding protein 2 (WBP2) as an oncogene in breast cancer: mechanisms and therapeutic prospects-a narrative review.
PMID: 36654949
Gland Surg Β· 2022
0.60