HERC3

Chr 4

HECT and RLD domain containing E3 ubiquitin protein ligase 3

NCBI Gene: 8916ENSG00000287542UniProt: Q15034OMIM: 605200

This gene encodes a member the HERC ubiquitin ligase family. The encoded protein is located in the cytosol and binds ubiquitin via a HECT domain. Mutations in this gene have been associated with colorectal and gastric carcinomas. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2012]

OMIMResearchGenerating 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.
0
Active trials
4
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.39
LOEUF
Multiple*
Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint?
0.39LOEUF
pLI 0.070
Z-score 5.23
OE 0.25 (0.16–0.39)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
3.21Z-score
OE missense 0.61 (0.56–0.67)
338 obs / 550.2 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.25 (0.16–0.39)
0≤0.351.4
Missense OE?0.61 (0.56–0.67)
0≤0.61.4
Synonymous OE?0.95
0≤1.21.6
LoF obs/exp: 14 / 56.4Missense obs/exp: 338 / 550.2Syn Z: 0.58

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

HERC3 · 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 →

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