CDC40

Chr 6AR

cell division cycle 40

Also known as: EHB3, PCH15, PRP17, PRPF17

NCBI Gene: 51362ENSG00000168438UniProt: O60508

Pre-mRNA splicing occurs in two sequential transesterification steps. The protein encoded by this gene is found to be essential for the catalytic step II in pre-mRNA splicing process. It is found in the spliceosome, and contains seven WD repeats, which function in protein-protein interactions. This protein has a sequence similarity to yeast Prp17 protein, which functions in two different cellular processes: pre-mRNA splicing and cell cycle progression. It suggests that this protein may play a role in cell cycle progression. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

?Pontocerebellar hypoplasia, type 15MIM #619302
AR
0
Active trials
19
Pathogenic / LP
77
ClinVar variants
2
Pubs (1 yr)
2.7
Missense Z
0.31
LOEUF· LoF intolerant
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 Pathogenic / Likely Pathogenic· 56 VUS of 77 total submissions

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

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.31

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

77 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 →

CDC40 · protein map & ClinVar variants

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

Gene2Phenotype Curations

CDC40-related neurodegenerative pontocerebellar hypoplasia with microcephaly

limited
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

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 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