HECTD3

Chr 1

HECT domain E3 ubiquitin protein ligase 3

The protein functions as an E3 ubiquitin ligase that transfers ubiquitin to target substrates including TRIOBP and STX8, leading to their proteasomal degradation and facilitating cell cycle progression. Mutations cause neurodevelopmental disorders with intellectual disability, autism spectrum disorder, and seizures, inherited in an autosomal recessive pattern. The gene shows high constraint against loss-of-function variants (LOEUF 0.403), indicating intolerance to protein-disrupting mutations.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.40
Clinical SummaryHECTD3
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.40LOEUF
pLI 0.089
Z-score 4.83
OE 0.25 (0.160.40)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.15Z-score
OE missense 0.73 (0.670.80)
367 obs / 502.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.25 (0.160.40)
00.351.4
Missense OE0.73 (0.670.80)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 12 / 48.2Missense obs/exp: 367 / 502.6Syn Z: 0.59

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

HECTD3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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