CDC5L

Chr 6

cell division cycle 5 like

Also known as: CDC5, CDC5-LIKE, CEF1, PCDC5RP, dJ319D22.1

NCBI Gene: 988ENSG00000096401UniProt: Q99459

The protein encoded by this gene shares a significant similarity with Schizosaccharomyces pombe cdc5 gene product, which is a cell cycle regulator important for G2/M transition. This protein has been demonstrated to act as a positive regulator of cell cycle G2/M progression. It was also found to be an essential component of a non-snRNA spliceosome, which contains at least five additional protein factors and is required for the second catalytic step of pre-mRNA splicing. [provided by RefSeq, Jul 2008]

119
ClinVar variants
9
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— CDC5L
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 66 VUS of 119 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.13LOEUF
pLI 1.000
Z-score 6.21
OE 0.04 (0.02–0.13)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

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.
2.78Z-score
OE missense 0.62 (0.56–0.69)
268 obs / 430.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.04 (0.02–0.13)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.62 (0.56–0.69)
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.1.08
0≤1.21.6
LoF obs/exp: 2 / 48.8Missense obs/exp: 268 / 430.4Syn Z: -0.73

ClinVar Variant Classifications

119 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic1
VUS66
Likely Benign14
Benign30
8
Pathogenic
1
Likely Pathogenic
66
VUS
14
Likely Benign
30
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
1
0
1
VUS
0
64
1
1
66
Likely Benign
0
2
3
9
14
Benign
0
2
22
6
30
Total0683516119

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

View in ClinVar →

Protein Context — Lollipop Plot

CDC5L · 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
Prp19/CDC5L promotes gastric cancer via activation of the MAPK pathway-mediated homologous recombination.
Qiu S et al.·Int J Biol Sci
2025
CDC5L binds to ELAVL1 to inhibit pyroptosis in hepatocellular carcinoma through the Caspase 3/GSDME signaling pathway.
Liang S et al.·Int J Mol Med
2025
Expression and Clinical Role of Cdc5L as a Novel Cell Cycle Protein in Hepatocellular Carcinoma.
Qiu H et al.·Dig Dis Sci
2016
Expression, DNA methylation pattern and transcription factor EPB41L3 in gastric cancer: a study of 262 cases.
Cai M et al.·Cell Commun Signal
2024Cohort
Expression of CDC5L is associated with tumor progression in gliomas.
Chen W et al.·Tumour Biol
2016
FOXA1 prolongs S phase and promotes cancer progression in non-small cell lung cancer through upregulation of CDC5L and activation of the ERK1/2 and JAK2 pathways.
Chen G et al.·Kaohsiung J Med Sci
2023
A Systems Biology Approach for Prioritizing ASD Genes in Large or Noisy Datasets.
Remori V et al.·Int J Mol Sci
2025
Prognostic value of aberrantly expressed methylation genes in human hepatocellular carcinoma.
Zhen L et al.·Biosci Rep
2020
Mapping the landscape of childhood obesity: genomic insights and socioeconomic status in Indian school-going children.
Nair JM et al.·Obesity (Silver Spring)
2025
ZNF76 predicts prognosis and response to platinum chemotherapy in human ovarian cancer.
Hua T et al.·Biosci Rep
2021
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