HERC1
Chr 15ARHECT and RLD domain containing E3 ubiquitin protein ligase family member 1
This protein functions as a guanine nucleotide exchange factor for ARF1 and Rab proteins and may act as an E3 ubiquitin ligase, playing roles in membrane trafficking and clathrin binding. Biallelic mutations cause autosomal recessive macrocephaly, dysmorphic facies, and psychomotor retardation. The gene is highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.24), indicating that heterozygous loss-of-function variants are likely not tolerated in the general population.
Some data sources returned errors (1)
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Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
HERC1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools