WDR33: WD Repeat Domain 33
A key component of the mRNA polyadenylation machinery
Gene Information Card
| Symbol | WDR33 |
|---|---|
| Full Name | WD repeat domain 33 |
| Gene Type | protein-coding |
| Chromosomal Location | 2q14.3 |
| NCBI Gene ID | 55339 ncbi.nlm.nih.gov/gene/55339 |
| Ensembl ID | ENSG00000115970 |
| UniProt ID | Q9C0J8 |
| OMIM ID | 618082 |
| HGNC ID | 25662 |
| Aliases | WDC146, NET14, FLJ11273 |
Description
WDR33 (WD repeat domain 33) encodes a protein containing multiple WD40 repeats, which are involved in protein-protein interactions. It is a core component of the cleavage and polyadenylation specificity factor (CPSF) complex, essential for 3' end processing of pre-mRNA. WDR33 directly binds the polyadenylation signal (AAUAAA) and recruits other factors to facilitate mRNA cleavage and polyadenylation. The gene is ubiquitously expressed and plays a critical role in gene expression regulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (general) | Altered WDR33 expression may disrupt mRNA 3' end processing, affecting oncogene or tumor suppressor transcript stability and translation. | COSMIC database reports somatic mutations in various cancers; limited functional validation. |
| Neurodevelopmental disorders | Potential impact on neuronal gene expression via polyadenylation defects. | OMIM #618082: heterozygous WDR33 variants identified in patients with intellectual disability and developmental delay. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 18.2 | High |
| Lymph node | 12.5 | Medium |
| Brain (cortex) | 10.8 | Medium |
| Liver | 7.3 | Low |
| Heart | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.4 | Embryonic kidney; high expression |
| HeLa | 12.1 | Cervical carcinoma; moderate expression |
| K562 | 9.8 | Leukemia; moderate expression |
| HepG2 | 6.5 | Hepatocellular carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1123C>T (p.Arg375Trp) | Missense | <0.01% | Unknown; reported in ClinVar as variant of uncertain significance |
| c.1567G>A (p.Glu523Lys) | Missense | <0.01% | Unknown; reported in ClinVar as variant of uncertain significance |
| c.2014_2015insA (p.Thr672Asnfs*2) | Frameshift | <0.01% | Predicted loss-of-function; reported in COSMIC in colorectal cancer |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations predicted to truncate the protein, likely impairing CPSF complex assembly and polyadenylation.
Gain of Function (GOF)
No evidence for gain-of-function mutations in WDR33.
Dominant Negative (DN)
Missense mutations in WD40 domains may disrupt protein interactions, potentially exerting dominant-negative effects on polyadenylation.
View complete mutation data：
Gene Ontology (GO)
| • mRNA 3'-end processing | • cleavage and polyadenylation specificity factor complex |
| • RNA binding | • protein binding |
| • nucleus | • cytoplasm |
Pathways
• mRNA 3'-end processing (Reactome: R-HSA-72172)
• Cleavage of Growing Transcript in the Termination Region (Reactome: R-HSA-75203)
Protein Summary
WDR33 is a 964-amino acid protein with multiple WD40 repeats that form a beta-propeller structure. It is a stable component of the CPSF complex, directly recognizing the AAUAAA polyadenylation signal in pre-mRNA. WDR33 interacts with CPSF1, CPSF2, CPSF3, and FIP1L1 to coordinate cleavage and polyadenylation. The protein is predominantly nuclear but may shuttle to the cytoplasm. Post-translational modifications include phosphorylation, which may regulate complex assembly.
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