WDR77: A Key Regulator of Androgen Receptor Signaling and Cell Proliferation
Comprehensive genomic and functional analysis of the WDR77 gene, its protein product, and associated disease mechanisms.
Gene Information Card
| Symbol | WDR77 |
|---|---|
| Full Name | WD repeat domain 77 |
| Gene Type | protein-coding |
| Chromosomal Location | 1p13.2 |
| NCBI Gene ID | 79084 ncbi.nlm.nih.gov/gene/79084 |
| Ensembl ID | ENSG00000117650 |
| UniProt ID | Q9BQA1 |
| OMIM ID | 611734 |
| HGNC ID | 25604 |
| Aliases | MEP50, p44, MEP-50, WD repeat-containing protein 77 |
Description
WDR77 (WD repeat domain 77) encodes a protein known as MEP50 (methylosome protein 50) or p44. It is a core component of the methylosome complex, which methylates the Sm proteins, and also functions as a coactivator of androgen receptor (AR)-mediated transcription. WDR77 is involved in cell cycle regulation, apoptosis, and RNA splicing. Overexpression and mutations have been implicated in various cancers, particularly prostate cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Prostate cancer | WDR77 acts as an AR coactivator; overexpression enhances AR signaling, promoting tumor growth and progression. | PMID: 19074885; COSMIC |
| Breast cancer | WDR77 overexpression correlates with poor prognosis; may modulate estrogen receptor signaling. | PMID: 22198284; COSMIC |
| Lung cancer | Altered WDR77 expression affects cell proliferation and invasion. | PMID: 25642768; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.3 | Medium |
| Prostate | 8.7 | Medium |
| Breast | 6.2 | Low |
| Lung | 5.1 | Low |
| Brain | 2.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| LNCaP (prostate cancer) | 15.4 | High AR activity |
| MCF7 (breast cancer) | 9.8 | Medium |
| A549 (lung cancer) | 7.1 | Low |
| HEK293 (embryonic kidney) | 4.5 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.497G>A (p.Arg166His) | Missense | <0.1% | Alters protein stability; potential loss of function |
| c.1043C>T (p.Thr348Met) | Missense | <0.1% | Unknown effect; reported in COSMIC |
| c.1234_1235insA (p.Glu412Glufs*2) | Frameshift | <0.1% | Predicted loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations are predicted to cause loss of function, potentially impairing methylosome activity and AR coactivation.
Gain of Function (GOF)
Missense mutations (e.g., p.Arg166His) may alter protein interactions, but evidence for gain of function is limited.
Dominant Negative (DN)
No dominant-negative mutations have been reported for WDR77.
View complete mutation data：
Gene Ontology (GO)
| • protein methyltransferase activity | • androgen receptor binding |
| • RNA splicing | • cell cycle |
| • apoptosis | • methylosome complex |
Pathways
• Androgen receptor signaling pathway
• Methylosome pathway
• Spliceosome
Protein Summary
The WDR77 protein (MEP50/p44) is a 342-amino acid WD40 repeat-containing protein that forms part of the methylosome complex with PRMT5. It methylates Sm proteins for snRNP assembly and also directly interacts with the androgen receptor to enhance transcriptional activity. The protein is localized in the nucleus and cytoplasm, and its expression is tightly regulated during the cell cycle.
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