CDC40

Chr 6AR

cell division cycle 40

Also known as: EHB3, PCH15, PRP17, PRPF17

NCBI Gene: 51362ENSG00000168438UniProt: O60508OMIM: 605585

The CDC40 protein is essential for the catalytic step II of pre-mRNA splicing as a component of the activated spliceosome and plays an important role in embryonic brain development. Mutations cause pontocerebellar hypoplasia type 15, a severe neurodevelopmental disorder affecting the brainstem and cerebellum. This condition follows autosomal recessive inheritance.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.311 OMIM phenotype
Clinical Summary— CDC40
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
19 unique Pathogenic / Likely Pathogenic· 56 VUS of 87 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.31LOEUF
pLI 0.979
Z-score 4.60
OE 0.15 (0.08–0.31)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.67Z-score
OE missense 0.57 (0.50–0.65)
172 obs / 302.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.15 (0.08–0.31)
0≤0.351.4
Missense OE0.57 (0.50–0.65)
0≤0.61.4
Synonymous OE0.91
0≤1.21.6
LoF obs/exp: 5 / 33.9Missense obs/exp: 172 / 302.8Syn Z: 0.68
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedCDC40-related neurodegenerative pontocerebellar hypoplasia with microcephalyOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.3991th %ile
GOF
0.3491th %ile
LOF
0.71top 10%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

87 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic2
VUS56
Likely Benign2
17
Pathogenic
2
Likely Pathogenic
56
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
17
0
17
Likely Pathogenic
0
1
1
0
2
VUS
0
47
9
0
56
Likely Benign
0
1
0
1
2
Benign
0
0
0
0
0
Total04927177

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

View in ClinVar →

Protein Context — Lollipop Plot

CDC40 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 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