CUL5

Chr 11

cullin 5

Also known as: CUL-5, VACM-1, VACM1

NCBI Gene: 8065 ENSG00000166266 UniProt: Q93034

Enables ubiquitin ligase complex scaffold activity and ubiquitin protein ligase binding activity. Involved in several processes, including negative regulation of cell-substrate junction organization; proteasome-mediated ubiquitin-dependent protein catabolic process; and protein K11-linked ubiquitination. Located in site of DNA damage. Part of Cul5-RING ubiquitin ligase complex. Is active in nucleus. [provided by Alliance of Genome Resources, Jun 2026]

Research

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.16

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.16LOEUF

pLI 1.000

Z-score 6.07

OE 0.06 (0.03–0.16)

Highly constrained

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

Missense Constraint?

4.59Z-score

OE missense 0.35 (0.30–0.40)

136 obs / 391.9 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.06 (0.03–0.16)

0≤0.351.4

Missense OE?0.35 (0.30–0.40)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 3 / 48.8Missense obs/exp: 136 / 391.9Syn Z: -0.91

Background carrier burden — how many people carry a rare variant somewhere in CUL5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 310

558 rare PASS variants

Rare truncating (LoF)

1 in 10,000

50 rare PASS variants

Rare synonymous (reference)

1 in 140

359 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CUL5. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 330	1 in 15,000
South Asian	~43k	1 in 330	1 in 6,000
Remaining (unassigned)	~30k	1 in 320	1 in 4,800
European (Finnish)	~27k	1 in 410	1 in 5,200
Admixed American	~22k	1 in 340	≈ 1 in 7,600
African / African American	~21k	1 in 330	≈ 1 in 7,600
East Asian	~20k	1 in 250	≈ 1 in 19,000
Ashkenazi Jewish	~13k	1 in 870	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 580	≈ 1 in 2,800

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 10 of 19 coding exons well covered in gnomAD exomes; exons 3, 7, 10, 11, 13 and 4 more marginal. Genomes: all 19.? see exons ↓