UBE3C

Chr 7AR

ubiquitin protein ligase E3C

Also known as: HECTH2, NDSMBA, NEDSMBA, RAUL

NCBI Gene: 9690 ENSG00000009335 UniProt: Q15386 OMIM: 614454

This E3 ubiquitin-protein ligase catalyzes Lys-29 and Lys-48-linked polyubiquitin chains and associates with the proteasome to regulate protein degradation, autophagy, and type I interferon signaling. Mutations cause autosomal dominant intellectual disability with autism spectrum disorder and behavioral abnormalities. The gene is highly constrained against loss-of-function variants in the population, indicating that such mutations are likely to be pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

Enables ubiquitin protein ligase activity. Involved in protein K29-linked ubiquitination; protein K48-linked ubiquitination; and ubiquitin-dependent protein catabolic process. Predicted to be part of proteasome complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with absent speech and movement and behavioral abnormalitiesMIM #620270

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

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.18

LOEUF· LoF intol.

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Mechanism