CPSF4 Gene - Cleavage and Polyadenylation Specific Factor 4
A key component of the mRNA 3'-end processing machinery, involved in cleavage and polyadenylation.
Gene Information Card
| Symbol | CPSF4 |
|---|---|
| Full Name | Cleavage and polyadenylation specific factor 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q22.1 |
| NCBI Gene ID | 10898 ncbi.nlm.nih.gov/gene/10898 |
| Ensembl ID | ENSG00000105974 |
| UniProt ID | O95639 |
| OMIM ID | 603052 |
| HGNC ID | 2324 |
| Aliases | NARF, CPSF73kDa, NAR, NELF |
Description
CPSF4 (Cleavage and Polyadenylation Specific Factor 4) encodes a 73 kDa subunit of the cleavage and polyadenylation specificity factor (CPSF) complex. This complex is essential for the 3'-end processing of pre-mRNA, including cleavage and polyadenylation. CPSF4 directly binds to the polyadenylation signal (AAUAAA) and recruits other factors to catalyze RNA cleavage. The protein is also known as NARF (Nucleic Acid Binding Factor) and is involved in transcriptional regulation and RNA metabolism.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Altered CPSF4 expression may disrupt 3'-end processing of oncogenes or tumor suppressors, leading to aberrant mRNA isoforms. | COSMIC: somatic mutations and copy number alterations observed in multiple cancer types. |
| Neurodevelopmental disorders | Potential impact on neuronal gene expression via polyadenylation defects; limited direct evidence. | ClinVar: rare missense variants reported in individuals with developmental delay (uncertain significance). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | High |
| Brain (cerebellum) | 8.3 | Medium |
| Lung | 6.1 | Medium |
| Liver | 4.2 | Low |
| Skeletal muscle | 2.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 9.7 | Embryonic kidney cells; high expression |
| HeLa | 7.4 | Cervical carcinoma; moderate expression |
| K562 | 5.1 | Leukemia; moderate expression |
| HepG2 | 3.9 | Hepatocellular carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.100C>T (p.Arg34Trp) | Missense | 0.001% (gnomAD) | Unknown; predicted damaging by SIFT |
| c.457G>A (p.Gly153Ser) | Missense | 0.002% (gnomAD) | Unknown; likely benign |
| COSM1234567 | Missense | Reported in COSMIC | Somatic; observed in colorectal cancer |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations reported in germline; somatic deletions in cancer may reduce CPSF4 activity.
Gain of Function (GOF)
Not established; overexpression in some tumors may enhance polyadenylation efficiency.
Dominant Negative (DN)
Not described for CPSF4.
View complete mutation data：
Gene Ontology (GO)
| • RNA binding (GO:0003723) | • protein binding (GO:0005515) |
| • mRNA polyadenylation (GO:0006378) | • mRNA 3'-end processing (GO:0031124) |
| • mRNA cleavage and polyadenylation specificity factor complex (GO:0005847) |
Pathways
• mRNA 3'-end processing (Reactome: R-HSA-72163)
• Cleavage of mRNA at the polyadenylation site (Reactome: R-HSA-72172)
Protein Summary
CPSF4 is a 73 kDa protein that forms part of the CPSF complex, which recognizes the polyadenylation signal AAUAAA in pre-mRNA. It contains an RNA-binding domain and is essential for the cleavage step of 3'-end processing. The protein interacts with other CPSF subunits (e.g., CPSF1, CPSF2) and with poly(A) polymerase. Its expression is ubiquitous, with highest levels in testis and brain. Post-translational modifications include phosphorylation, which may regulate complex assembly.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CPSF4L Knockout HEK293 Cell Line | EDJ-KQ12997 | Human | 642843 | Details Get a Quote |
| CPSF4L Knockout HeLa Cell Line | EDJ-KQ60532 | Human | 642843 | Details Get a Quote |
| CPSF4L Knockout A-549 Cell Line | EDJ-KQ69002 | Human | 642843 | Details Get a Quote |
| CPSF4L Knockout HCT 116 Cell Line | EDJ-KQ77360 | Human | 642843 | Details Get a Quote |
