CUL9

Chr 6

cullin 9

Also known as: H7AP1, PARC

NCBI Gene: 23113ENSG00000112659UniProt: Q8IWT3

Predicted to enable ubiquitin protein ligase activity. Involved in microtubule cytoskeleton organization; protein ubiquitination; and regulation of mitotic nuclear division. Located in cytosol. Part of cullin-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Jul 2025]

0
Active trials
8
Pathogenic / LP
325
ClinVar variants
4
Pubs (1 yr)
3.1
Missense Z· constrained
0.28
LOEUF· LoF intolerant
Clinical Summary— CUL9
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 280 VUS of 325 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.28LOEUF
pLI 0.992
Z-score 8.27
OE 0.20 (0.14–0.28)
Highly constrained

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

Missense Constraint
3.10Z-score
OE missense 0.77 (0.74–0.81)
1154 obs / 1490.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.20 (0.14–0.28)
0≤0.351.4
Missense OE0.77 (0.74–0.81)
0≤0.61.4
Synonymous OE0.98
0≤1.21.6
LoF obs/exp: 25 / 124.6Missense obs/exp: 1154 / 1490.4Syn Z: 0.42
LOF
DN
0.2898th %ile
GOF
0.3491th %ile
LOF
0.68top 25%

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

LOFprediction above median · LOEUF 0.28

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

325 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
VUS280
Likely Benign25
Benign12
8
Pathogenic
280
VUS
25
Likely Benign
12
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
0
0
0
VUS
1
278
0
1
280
Likely Benign
0
20
1
4
25
Benign
0
5
1
6
12
Total13031011325

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

View in ClinVar →

CUL9 · protein map & ClinVar variants

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

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
TMEM120B strengthens breast cancer cell stemness and accelerates chemotherapy resistance via beta1-integrin/FAK-TAZ-mTOR signaling axis by binding to MYH9
Hu R et al.·Breast Cancer Res
2024
Prion protein-dependent regulation of p53-MDM2 crosstalk during endoplasmic reticulum stress and doxorubicin treatments might be essential for cell fate in human breast cancer cell line, MCF-7.
Tuğrul B et al.·Exp Cell Res
2023
Cullin-9/p53 mediates HNRNPC degradation to inhibit erastin-induced ferroptosis and is blocked by MDM2 inhibition in colorectal cancer.
Yang L et al.·Oncogene
2022
Screening and regulatory mechanisms of biomarkers related to neddylation in laryngeal squamous cell carcinoma.
Wang X et al.·Front Mol Biosci
2025Functional
Circulating exosomal mRNA signatures for the early diagnosis of clear cell renal cell carcinoma
He X et al.·BMC Med
2022
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 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