CPSF2
protein-codingcleavage and polyadenylation specific factor 2, the group of Cleavage and polyadenylation specific factor subunits|MBL fold containing DNA/RNA interacting subfamily
Gene summary
Predicted to enable RNA binding activity. Involved in mRNA 3'-end processing by stem-loop binding activity and cleavage. Located in membrane. Part of mRNA cleavage and polyadenylation specificity factor complex. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~50.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CPSF2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017437.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 2 | 5 | |||
| missense | 60 | 60 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 64 | 2 | 0 | 66 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_059133.1 | 14 | MANE Select | |
| Ensembl | ENSP00000298875.4 | 14 | MANE Select | |
| RefSeq | NP_001309199.1 | 13 | Standard | |
| RefSeq | NP_001309200.1 | 11 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- mRNA surveillance pathway - Homo sapiens (human)
- mRNA Processing
- Gene expression (Transcription)
- polyadenylation of mrna
- RNA Polymerase II Transcription
Biological Process
- mRNA splicing, via spliceosome
- termination of RNA polymerase II transcription
- mRNA polyadenylation
- mRNA cleavage
- mRNA 3'-end processing by stem-loop binding and cleavage
Molecular Function
- RNA binding
- protein binding
Cellular Component
- nucleoplasm
- mRNA cleavage and polyadenylation specificity factor complex
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000298875
- Coding exons
- 14
- Length
- 42475
- Individuals with no LoFs
- 125685
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 63
- Defined
- 125748
- p
- 0.000251
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.34 | 222 | 413 | 0.538 | 0.0000204 | 5169 |
| Missense (PolyPhen) | 57 | 160.22 | 0.35576 | 1999 | ||
| Synonymous | 0.632 | 132 | 142 | 0.932 | 0.00000685 | 1450 |
| Loss of Function | 2.78 | 18 | 36.0 | 0.499 | 0.00000175 | 486 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.000090 | 0.000087 | rare |
| Ashkenazi Jewish | 0.0011 | 0.0011 | notable |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00027 | 0.00027 | rare |
| South Asian | 0.00026 | 0.00026 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the cleavage and polyadenylation specificity factor (CPSF) complex that play a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. Involved in the histone 3' end pre-mRNA processing. {ECO:0000269|PubMed:14749727, ECO:0000269|PubMed:18688255}.;
Recessive Scores
- pRec
- 0.148
Intolerance Scores
- LoFtool
- 0.735
- RVIS EVS
- -0.67
- RVIS percentile EVS
- 15.76
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.972
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |