CPSF3

Chr 2AR

cleavage and polyadenylation specific factor 3

Also known as: CPSF-73, CPSF73, NEDMHS, NEDMHSN

NCBI Gene: 51692ENSG00000119203UniProt: Q9UKF6

This gene encodes a member of the metallo-beta-lactamase family. The encoded protein is a 73kDa subunit of the cleavage and polyadenylation specificity factor and functions as an endonuclease that recognizes the pre-mRNA 3'-cleavage site AAUAAA prior to polyadenylation. It also cleaves after the pre-mRNA sequence ACCCA during histone 3'-end pre-mRNA processing. [provided by RefSeq, Oct 2012]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with microcephaly, hypotonia, nystagmus, and seizuresMIM #619876
AR
0
Active trials
23
Pathogenic / LP
84
ClinVar variants
6
Pubs (1 yr)
3.6
Missense Z· constrained
0.70
LOEUF
Clinical Summary— CPSF3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 53 VUS of 84 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint
0.70LOEUF
pLI 0.000
Z-score 2.98
OE 0.47 (0.32–0.70)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
3.61Z-score
OE missense 0.48 (0.42–0.54)
178 obs / 374.6 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.47 (0.32–0.70)
0≤0.351.4
Missense OE0.48 (0.42–0.54)
0≤0.61.4
Synonymous OE0.92
0≤1.21.6
LoF obs/exp: 17 / 36.4Missense obs/exp: 178 / 374.6Syn Z: 0.74

ClinVar Variant Classifications

84 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic1
VUS53
Likely Benign7
Benign1
22
Pathogenic
1
Likely Pathogenic
53
VUS
7
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
21
0
22
Likely Pathogenic
1
0
0
0
1
VUS
0
48
5
0
53
Likely Benign
0
1
0
6
7
Benign
0
0
1
0
1
Total15027684

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

View in ClinVar →

CPSF3 · protein map & ClinVar variants

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

Gene2Phenotype Curations

CPSF3-related neurodevelopmental disorder with seizures and microcephaly

moderate
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients