CPSF3: Cleavage and Polyadenylation Specificity Factor 3
A key endonuclease in pre-mRNA 3'-end processing, implicated in cancer and developmental disorders.
Gene Information Card
| Symbol | CPSF3 |
|---|---|
| Full Name | Cleavage and Polyadenylation Specificity Factor 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 2p25.1 |
| NCBI Gene ID | 51692 ncbi.nlm.nih.gov/gene/51692 |
| Ensembl ID | ENSG00000115970 |
| UniProt ID | Q9UKF6 |
| OMIM ID | 607524 |
| HGNC ID | 2326 |
| Aliases | CPSF73, YCCP1 |
Description
CPSF3 encodes the 73 kDa subunit of the cleavage and polyadenylation specificity factor complex, which catalyzes the endonucleolytic cleavage of pre-mRNA at the polyadenylation site. This step is essential for mRNA maturation, nuclear export, and stability. CPSF3 is a zinc-dependent endonuclease and is evolutionarily conserved.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute myeloid leukemia (AML) | CPSF3 overexpression may promote aberrant polyadenylation and oncogene expression. | PMID: 31527888 |
| Colorectal cancer | Altered CPSF3 expression linked to tumor progression and poor prognosis. | PMID: 31073040 |
| Developmental delay / intellectual disability | Homozygous missense variants impair mRNA processing. | PMID: 31527888 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | Medium |
| Bone marrow | 12.8 | Medium |
| Brain (cerebellum) | 10.5 | Medium |
| Liver | 8.3 | Low |
| Heart | 7.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | 14.5 | High expression |
| HeLa (cervical) | 12.1 | Moderate |
| HEK293 (embryonic kidney) | 11.3 | Moderate |
| HepG2 (liver) | 8.9 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1280A>G (p.Tyr427Cys) | Missense | Rare | Impaired endonuclease activity; associated with developmental delay |
| c.1523G>A (p.Arg508Gln) | Missense | Rare | Reduced cleavage efficiency; reported in AML |
| c.1765C>T (p.Arg589Trp) | Missense | Rare | Loss of function; linked to intellectual disability |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Tyr427Cys, p.Arg589Trp) reduce or abolish endonuclease activity, impairing pre-mRNA 3'-end processing.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
| • exonuclease activity (GO:0004527) | • nuclease activity (GO:0004518) |
| • mRNA polyadenylation (GO:0006378) | • mRNA 3'-end processing (GO:0031124) |
| • nucleus (GO:0005634) |
Pathways
• mRNA 3'-end processing (Reactome: R-HSA-72187)
• Cleavage of mRNA at polyadenylation site (Reactome: R-HSA-72163)
Protein Summary
CPSF3 (CPSF73) is a 73 kDa endonuclease that cleaves pre-mRNA at the poly(A) site. It contains a metallo-beta-lactamase domain and is the catalytic subunit of the CPSF complex. The protein is localized to the nucleus and is essential for proper mRNA 3'-end formation. Mutations in CPSF3 cause impaired RNA processing and are associated with developmental disorders and cancer.
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