CPSF4

Chr 7

cleavage and polyadenylation specific factor 4

Also known as: CPSF30, NAR, NEB-1, NEB1

NCBI Gene: 10898ENSG00000160917UniProt: O95639

Inhibition of the nuclear export of poly(A)-containing mRNAs caused by the influenza A virus NS1 protein requires its effector domain. The NS1 effector domain functionally interacts with the cellular 30 kDa subunit of cleavage and polyadenylation specific factor 4, an essential component of the 3' end processing machinery of cellular pre-mRNAs. In influenza virus-infected cells, the NS1 protein is physically associated with cleavage and polyadenylation specific factor 4, 30kD subunit. Binding of the NS1 protein to the 30 kDa protein in vitro prevents CPSF binding to the RNA substrate and inhibits 3' end cleavage and polyadenylation of host pre-mRNAs. Thus the NS1 protein selectively inhibits the nuclear export of cellular, and not viral, mRNAs. Multiple alternatively spliced transcript variants that encode different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

37
ClinVar variants
18
Pathogenic / LP
0.27
pLI score
0
Active trials
Clinical Summary— CPSF4
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
18 Pathogenic / Likely Pathogenic· 17 VUS of 37 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.56LOEUF
pLI 0.268
Z-score 2.85
OE 0.24 (0.12–0.56)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.29Z-score
OE missense 0.30 (0.23–0.37)
51 obs / 172.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.24 (0.12–0.56)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.30 (0.23–0.37)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.07
0≤1.21.6
LoF obs/exp: 4 / 16.5Missense obs/exp: 51 / 172.4Syn Z: -0.49

ClinVar Variant Classifications

37 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic1
VUS17
Likely Benign1
Benign1
17
Pathogenic
1
Likely Pathogenic
17
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
17
0
17
Likely Pathogenic
0
0
1
0
1
VUS
0
10
7
0
17
Likely Benign
0
0
1
0
1
Benign
0
0
0
1
1
Total01026137

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CPSF4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Cleavage and polyadenylation specific factor 4 promotes colon cancer progression by transcriptionally activating hTERT.
Yang Q et al.·Biochim Biophys Acta Mol Cell Res
2019
Cleavage and Polyadenylation-Specific Factor 4 (CPSF4) Expression Is Associated with Enhanced Prostate Cancer Cell Migration and Cell Cycle Dysregulation, In Vitro.
Choudhry M et al.·Int J Mol Sci
2023
CPSF4 promotes tumor-initiating phenotype by enhancing VEGF/NRP2/TAZ signaling in lung cancer.
Song Y et al.·Med Oncol
2022
CPSF4 regulates circRNA formation and microRNA mediated gene silencing in hepatocellular carcinoma.
Wang X et al.·Oncogene
2021
Upregulation of cleavage and polyadenylation specific factor 4 in lung adenocarcinoma and its critical role for cancer cell survival and proliferation.
Chen W et al.·PLoS One
2013
SMARCD1 is an essential expression-restricted metastasis modifier.
Ross C et al.·Commun Biol
2024
RNA modification Regulators' Co-Expression Score (RMRCoeS) predicts biochemical recurrence and therapy response in prostate cancer: A multi-omics and experimental validation study.
Cai Z et al.·Int Immunopharmacol
2024
A plant-like mechanism coupling m6A reading to polyadenylation safeguards transcriptome integrity and developmental gene partitioning in Toxoplasma.
Farhat DC et al.·Elife
2021Functional
Identification of specific prognostic markers for lung squamous cell carcinoma based on tumor progression, immune infiltration, and stem index.
Wu R et al.·Front Immunol
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools