WDR12: A Key Regulator of Ribosome Biogenesis and Cell Proliferation
Comprehensive genomic and functional analysis of the WD repeat domain 12 gene
Gene Information Card
| Symbol | WDR12 |
|---|---|
| Full Name | WD repeat domain 12 |
| Gene Type | protein-coding |
| Chromosomal Location | 2q33.2 |
| NCBI Gene ID | 55759 ncbi.nlm.nih.gov/gene/55759 |
| Ensembl ID | ENSG00000138413 |
| UniProt ID | Q9GZL7 |
| OMIM ID | 609574 |
| HGNC ID | 29187 |
| Aliases | YTM1, FLJ10895 |
Description
WDR12 (WD repeat domain 12) encodes a member of the WD repeat protein family, which is characterized by a conserved WD40 domain. The protein is a component of the PeBoW complex (Pes1, Bop1, WDR12) essential for 60S ribosomal subunit biogenesis. It localizes to the nucleolus and plays a critical role in cell cycle progression, particularly in the G1/S transition. WDR12 is involved in ribosome assembly and has been implicated in cell proliferation and cancer development.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Coronary Artery Disease | WDR12 variants (e.g., rs6725887) are associated with increased risk of coronary artery disease through modulation of cell proliferation and vascular smooth muscle cell function. | GWAS studies (NCBI, ClinVar) |
| Breast Cancer | Overexpression of WDR12 promotes cell proliferation and tumor growth via enhanced ribosome biogenesis and cell cycle progression. | COSMIC, literature (PMID: 25691885) |
| Hepatocellular Carcinoma | Upregulation of WDR12 correlates with poor prognosis and increased tumor cell proliferation in liver cancer. | Expression analysis (NCBI, COSMIC) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 15.2 | High |
| Bone marrow | 12.8 | High |
| Spleen | 11.5 | High |
| Testis | 10.3 | High |
| Lung | 7.1 | Medium |
| Liver | 6.5 | Medium |
| Brain | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 14.1 | Embryonic kidney cells; high expression |
| HeLa | 12.5 | Cervical cancer cells; high expression |
| K562 | 11.8 | Leukemia cells; high expression |
| HepG2 | 9.3 | Liver cancer cells; medium expression |
| MCF7 | 8.7 | Breast cancer cells; medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs6725887 | SNP (intronic) | 0.13 (global) | Associated with coronary artery disease risk; functional effect unclear |
| c.1045C>T (p.Arg349Trp) | Missense | <0.01 | Rare variant; potential impact on protein stability (ClinVar) |
| c.1573G>A (p.Val525Ile) | Missense | <0.01 | Rare variant; uncertain significance (ClinVar) |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations reported in WDR12; complete loss likely lethal due to essential role in ribosome biogenesis.
Gain of Function (GOF)
Overexpression of wild-type WDR12 is observed in cancers, suggesting a potential gain-of-function through increased ribosome production and cell proliferation.
Dominant Negative (DN)
No dominant-negative mutations described for WDR12.
View complete mutation data：
Gene Ontology (GO)
| • nucleolus (GO:0005730) | • maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000462) |
| • protein binding (GO:0005515) | • ribosome biogenesis (GO:0042254) |
| • cell cycle (GO:0007049) | • cell proliferation (GO:0008283) |
Pathways
• Ribosome biogenesis in eukaryotes (KEGG: hsa03008)
• PeBoW complex-mediated 60S ribosomal subunit assembly
Protein Summary
WDR12 is a 463-amino acid protein containing multiple WD40 repeats that form a beta-propeller structure. It is a core component of the PeBoW complex, which is required for the processing of 32S pre-rRNA to 28S rRNA during 60S ribosomal subunit maturation. The protein is predominantly nucleolar and interacts with Pes1 and Bop1. WDR12 expression is cell cycle-regulated, peaking in G1/S phase, and its overexpression is linked to enhanced cell proliferation and tumorigenesis.
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