HECTD4

Chr 12AR

HECT domain E3 ubiquitin protein ligase 4

Also known as: C12ord51, C12orf51, HEEL, NEDSSCC, POTAGE

NCBI Gene: 283450 ENSG00000173064 UniProt: Q9Y4D8 OMIM: 620209

The protein functions as an E3 ubiquitin-protein ligase that transfers ubiquitin to targeted substrates and is involved in glucose homeostasis. Biallelic mutations cause autosomal recessive neurodevelopmental disorder with seizures, spasticity, and complete or partial agenesis of the corpus callosum. The gene is highly constrained against loss-of-function variants, indicating it is essential for normal cellular function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Predicted to enable ubiquitin protein ligase activity. Involved in glucose homeostasis and glucose metabolic process. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with seizures, spasticity, and complete or partial agenesis of the corpus callosumMIM #620250

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.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.13

LOEUF· LoF intol.

LOF

Mechanism· predicted