CPSF6: Cleavage and Polyadenylation Specific Factor 6
A key RNA-binding protein in 3' end processing, nuclear speckles, and HIV-1 replication
Gene Information Card
| Symbol | CPSF6 |
|---|---|
| Full Name | Cleavage and polyadenylation specific factor 6 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q15 |
| NCBI Gene ID | 11052 ncbi.nlm.nih.gov/gene/11052 |
| Ensembl ID | ENSG00000111605 |
| UniProt ID | Q16630 |
| OMIM ID | 604979 |
| HGNC ID | 2326 |
| Aliases | CFIm68, HPBRII-4, CPSF73 |
Description
CPSF6 encodes a 68 kDa subunit of the cleavage factor Im (CFIm) complex, which is essential for pre-mRNA 3' end processing, including cleavage and polyadenylation. The protein localizes to nuclear speckles and interacts with RNA polymerase II. CPSF6 also plays a critical role in HIV-1 replication by facilitating nuclear import and integration of the viral genome. Alternative splicing generates multiple transcript variants.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| HIV-1 infection susceptibility | CPSF6 binds HIV-1 capsid, promoting nuclear entry and integration; variants may alter viral replication efficiency | PMID: 21909073, PMID: 25464849 |
| Acute myeloid leukemia (AML) | CPSF6 fusions (e.g., with MLL) have been reported in AML, disrupting normal RNA processing | PMID: 25207793 |
| Breast cancer | Dysregulated CPSF6 expression correlates with altered polyadenylation site usage in tumor cells | PMID: 29533785 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 32.5 | High |
| Lymph node | 18.2 | Medium |
| Brain cortex | 15.8 | Medium |
| Liver | 12.1 | Medium |
| Heart | 9.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 28.3 | High expression |
| HeLa | 22.1 | High expression |
| K562 | 15.6 | Medium expression |
| HepG2 | 13.4 | Medium expression |
| A549 | 11.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1246C>T (p.Arg416Trp) | Missense | <0.01% | Altered RNA binding affinity |
| c.1873G>A (p.Val625Met) | Missense | <0.01% | Unknown functional impact |
| CPSF6-MLL fusion | Gene fusion | Rare | Oncogenic in AML |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in CPSF6 impair 3' end processing and nuclear speckle integrity, leading to global changes in gene expression.
Gain of Function (GOF)
Gain-of-function fusions (e.g., CPSF6-MLL) confer aberrant transcriptional activation in leukemia.
Dominant Negative (DN)
Dominant-negative CPSF6 mutants disrupt CFIm complex assembly and polyadenylation site selection.
View complete mutation data：
Gene Ontology (GO)
| • mRNA 3'-end processing | • RNA binding |
| • nuclear speckle | • cleavage and polyadenylation specificity factor complex |
| • poly(A) RNA binding | • protein binding |
Pathways
• mRNA 3'-end processing
• HIV-1 nuclear import
• RNA polymerase II transcription termination
Protein Summary
CPSF6 is a 68 kDa RNA-binding protein that forms part of the CFIm complex, recognizing UGUA elements near polyadenylation sites. It shuttles between the nucleus and cytoplasm, regulates alternative polyadenylation, and is hijacked by HIV-1 to facilitate viral genome nuclear import. The protein contains an N-terminal RNA recognition motif (RRM) and a C-terminal proline-rich domain.
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