CUL7

Chr 6AR

cullin 7

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

NCBI Gene: 9820 ENSG00000044090 UniProt: Q14999 OMIM: 609577

CUL7 encodes a core component of E3 ubiquitin ligase complexes that mediate proteasomal degradation of target proteins and regulate microtubule dynamics and genome integrity. Mutations cause 3-M syndrome type 1, an autosomal recessive condition characterized by severe pre- and postnatal growth restriction. This gene is extremely intolerant to loss-of-function variants (pLI ~0), indicating that complete loss of CUL7 function is likely incompatible with normal development.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.731 OMIM phenotype

Clinical Summary— CUL7

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

131 unique Pathogenic / Likely Pathogenic· 464 VUS of 1053 total submissions

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GeneReview available — CUL7

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.73LOEUF

pLI 0.000

Z-score 3.59

OE 0.57 (0.45–0.73)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.54Z-score

OE missense 0.95 (0.90–1.00)

959 obs / 1007.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.57 (0.45–0.73)

0≤0.351.4

Missense OE?0.95 (0.90–1.00)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 47 / 82.0Missense obs/exp: 959 / 1007.5Syn Z: -0.21

ClinVar Variant Classifications

1053 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic75

Likely Pathogenic56

VUS464

Likely Benign324

Benign44

Conflicting64

Pathogenic

Likely Pathogenic

464

VUS

324

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	73	0	2	0	75
Likely Pathogenic	47	7	2	0	56
VUS	4	416	24	20	464
Likely Benign	0	22	106	196	324
Benign	0	5	27	12	44
Conflicting	—				64
Total	124	450	161	228	1,027

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

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9 pathogenic / likely-pathogenic (of 12) ClinVar copy-number / structural variants overlap CUL7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →