CDC6

Chr 17AR

cell division cycle 6

Also known as: CDC18L, HsCDC18, HsCDC6, MGORS5

NCBI Gene: 990UniProt: Q99741

The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Cdc6, a protein essential for the initiation of DNA replication. This protein functions as a regulator at the early steps of DNA replication. It localizes in cell nucleus during cell cyle G1, but translocates to the cytoplasm at the start of S phase. The subcellular translocation of this protein during cell cyle is regulated through its phosphorylation by Cdks. Transcription of this protein was reported to be regulated in response to mitogenic signals through transcriptional control mechanism involving E2F proteins. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Meier-Gorlin syndrome 5MIM #613805
AR
0
Active trials
262
ClinVar variants
9
Pathogenic / LP
0.6
Missense Z
1.00
LOEUF
13
Pubs (2 yr)
Clinical Summary— CDC6
🧬
Gene-Disease Validity (ClinGen)
Meier-Gorlin syndrome 5 · ARLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 159 VUS of 262 total submissions
Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.00LOEUF
pLI 0.000
Z-score 1.54
OE 0.68 (0.47–1.00)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.61Z-score
OE missense 0.90 (0.81–1.00)
255 obs / 283.7 exp
Tolerant

Mild missense constraint

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.0.68 (0.47–1.00)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.81–1.00)
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.0.93
0≤1.21.6
LoF obs/exp: 18 / 26.6Missense obs/exp: 255 / 283.7Syn Z: 0.54

ClinVar Variant Classifications

262 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic1
VUS159
Likely Benign72
Benign12
Conflicting10
8
Pathogenic
1
Likely Pathogenic
159
VUS
72
Likely Benign
12
Benign
10
Conflicting

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
7
126
23
3
159
Likely Benign
0
2
31
39
72
Benign
0
3
7
2
12
Conflicting
—10
Total71317044262

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

View in ClinVar →

Protein Context — Lollipop Plot

CDC6 · protein map & ClinVar variants

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

Gene2Phenotype Curations

CDC6-related Meier-Gorlin syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkeletal
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Meier-Gorlin syndrome 5

MIM #613805

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A Distinguished Roadmap of Fibroblast Senescence in Predicting Immunotherapy Response and Prognosis Across Human Cancers.
Chen D et al.·Adv Sci (Weinh)
2025
Meier-Gorlin syndrome.
de Munnik SA et al.·Orphanet J Rare Dis
2015Review
CDC6 is a prognostic biomarker and correlated with immune infiltrates in glioma.
Wang F et al.·Mol Cancer
2022
Establishment and validation of exhausted CD8+ T cell feature as a prognostic model of HCC.
Shi J et al.·Front Immunol
2023Functional
Dual Inhibition of SYK and EGFR Overcomes Chemoresistance by Inhibiting CDC6 and Blocking DNA Replication.
Mandal J et al.·Cancer Res
2024
Identifying the prognostic significance of mitophagy-associated genes in multiple myeloma: a novel risk model construction.
Min R et al.·Clin Exp Med
2024Functional
Interaction between CDC6 and Tmod3 accelerates resistance to paclitaxel through focal adhesion assembly.
Liu Y et al.·Signal Transduct Target Ther
2025
SETDB1 is critically required for uveal melanoma growth and represents a promising therapeutic target.
Krossa I et al.·Cell Death Dis
2025
Clofarabine Enhances the Transduction Efficiency of Recombinant AAV2 in the Retina.
Diao Y et al.·Invest Ophthalmol Vis Sci
2025
High throughput sequencing revealed enhanced cell cycle signaling in SLE patients.
Yang M et al.·Sci Rep
2023Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Comprehensive multi-omics analysis showed that CDC6 is a potential prognostic and immunotherapy biomarker for multiple cancer types including HCC
Li C et al.·Transl Oncol
2025
CDC6 as a Key Inhibitory Regulator of CDK1 Activation Dynamics and the Timing of Mitotic Entry and Progression
El Dika M et al.·Biology (Basel)
2023
The structure of ORC-Cdc6 on an origin DNA reveals the mechanism of ORC activation by the replication initiator Cdc6
Feng X et al.·Nat Commun
2021Functional
Role of TOP2A and CDC6 in liver cancer
Jia W et al.·Medicine (Baltimore)
2023
A GATA2-CDC6 axis modulates androgen receptor blockade-induced senescence in prostate cancer
Mourkioti I et al.·J Exp Clin Cancer Res
2023
RRM2 and CDC6 are novel effectors of XBP1-mediated endocrine resistance and predictive markers of tamoxifen sensitivity
Barua D et al.·BMC Cancer
2023
Screening and verification of hub genes in esophageal squamous cell carcinoma by integrated analysis
Wu H et al.·Sci Rep
2024
Top 7 full-text resultsSearch PubTator3 ↗

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

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