CUL3

Chr 2

cullin 3

Also known as: CUL-3, NEDAUS, PHA2E

NCBI Gene: 8452ENSG00000036257UniProt: Q13618

This gene encodes a member of the cullin protein family. The encoded protein plays a critical role in the polyubiquitination and subsequent degradation of specific protein substrates as the core component and scaffold protein of an E3 ubiquitin ligase complex. Complexes including the encoded protein may also play a role in late endosome maturation. Mutations in this gene are a cause of type 2E pseudohypoaldosteronism. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPseudohypoaldosteronism 2E
UniProtNeurodevelopmental disorder with or without autism or seizures

Clinical highlights

Gene-disease validity (ClinGen)
pseudohypoaldosteronism type 2E · ADDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
118
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.23
LOEUF· LoF intol.
LOF
Mechanism· G2P
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GeneReview available — CUL3
Authoritative clinical overview · Recommended first read
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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?
0.23LOEUF
pLI 1.000
Z-score 5.28
OE 0.10 (0.05–0.23)
Highly constrained

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

Missense Constraint?
4.75Z-score
OE missense 0.35 (0.30–0.40)
145 obs / 418.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.10 (0.05–0.23)
0≤0.351.4
Missense OE?0.35 (0.30–0.40)
0≤0.61.4
Synonymous OE?1.12
0≤1.21.6
LoF obs/exp: 4 / 40.1Missense obs/exp: 145 / 418.7Syn Z: -1.10

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

CUL3 · protein map & ClinVar variants

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

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