HERC1

Chr 15AR

HECT and RLD domain containing E3 ubiquitin protein ligase family member 1

Also known as: MDFPMR, p532, p619

NCBI Gene: 8925 ENSG00000103657 UniProt: Q15751 OMIM: 605109

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gen encodes a member of the HERC protein family. This protein stimulates guanine nucleotide exchange on ARF1 and Rab proteins. This protein may be involved in membrane transport processes. [provided by RefSeq, Mar 2012]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Macrocephaly, dysmorphic facies, and psychomotor retardationMIM #617011

Clinical highlights

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.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.24

LOEUF· LoF intol.

LOF

Mechanism· G2P