CUL7

Chr 6AR

cullin 7

Also known as: 3M1, CUL-7, KIAA0076, dJ20C7.5

NCBI Gene: 9820ENSG00000044090UniProt: Q14999

The protein encoded by this gene is a component of an E3 ubiquitin-protein ligase complex. The encoded protein interacts with TP53, CUL9, and FBXW8 proteins. Defects in this gene are a cause of 3M syndrome type 1 (3M1). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

Primary Disease Associations & Inheritance

3-M syndrome 1MIM #273750
AR
UniProt3M syndrome 1
595
ClinVar variants
69
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CUL7
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
69 Pathogenic / Likely Pathogenic· 286 VUS of 595 total submissions

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.
0.73LOEUF
pLI 0.000
Z-score 3.59
OE 0.57 (0.45–0.73)
Tolerant

Typical tolerance to LoF variation

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.
0.54Z-score
OE missense 0.95 (0.90–1.00)
959 obs / 1007.5 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.0.57 (0.45–0.73)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.90–1.00)
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.1.01
0≤1.21.6
LoF obs/exp: 47 / 82.0Missense obs/exp: 959 / 1007.5Syn Z: -0.21

ClinVar Variant Classifications

595 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic44
Likely Pathogenic25
VUS286
Likely Benign187
Benign29
Conflicting24
44
Pathogenic
25
Likely Pathogenic
286
VUS
187
Likely Benign
29
Benign
24
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
20
1
23
0
44
Likely Pathogenic
17
2
6
0
25
VUS
2
252
23
9
286
Likely Benign
0
4
68
115
187
Benign
0
3
22
4
29
Conflicting
—24
Total39262142128595

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

View in ClinVar →

Protein Context — Lollipop Plot

CUL7 · protein map & ClinVar variants

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

Gene2Phenotype Curations

CUL7-related 3-M 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
CULLIN 7; CUL7
MIM #609577 · *

3-M syndrome 1

MIM #273750

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — CUL7
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Tet methylcytosine dioxygenase 2 (TET2) deficiency elicits EGFR-TKI (tyrosine kinase inhibitors) resistance in non-small cell lung cancer.
Zhang J et al.·Signal Transduct Target Ther
2024
USP5 stabilizes YTHDF1 to control cancer immune surveillance through mTORC1-mediated phosphorylation.
Shao N et al.·Nat Commun
2025
The 3M syndrome.
Huber C et al.·Best Pract Res Clin Endocrinol Metab
2011
Clinical and molecular spectrum along with genotype-phenotype correlation of 25 patients diagnosed with 3 M syndrome: a study from Turkey.
Akalın A et al.·Eur J Pediatr
2024Cohort
Identification and verification of the prognostic value of CUL7 in colon adenocarcinoma.
Wang C et al.·Front Immunol
2022
[Genetic analysis of a case of Miller-McKusick-Malvaux syndrome type 1 caused by CUL7 gene variant and a literature review].
Zhang L et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2025Review
Structural and functional insights into a novel homozygous missense pathogenic variant in CUL7 identified in consanguineous Pakistani family.
Zaka A et al.·J Biomol Struct Dyn
2024Functional
Cullin-7 (CUL7) is overexpressed in glioma cells and promotes tumorigenesis via NF-κB activation.
Xu J et al.·J Exp Clin Cancer Res
2020
[Clinical characteristics of four children with 3M syndrome and a literature review].
Xu N et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2023Review
The genetics of 3-M syndrome: unravelling a potential new regulatory growth pathway.
Hanson D et al.·Horm Res Paediatr
2011Review
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