HACE1

Chr 6

HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1

Also known as: SPPRS

NCBI Gene: 57531 ENSG00000085382 UniProt: Q8IYU2

The protein is an E3 ubiquitin ligase that regulates Golgi membrane dynamics during cell division and mediates degradation of active RAC1, playing roles in cellular trafficking and host defense. Mutations cause autosomal recessive spastic paraplegia and psychomotor retardation with or without seizures. The gene is highly constrained against loss-of-function variants (LOEUF 0.524), suggesting complete loss of function is not well tolerated.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a HECT domain and ankyrin repeat-containing ubiquitin ligase. The encoded protein is involved in specific tagging of target proteins, leading to their subcellular localization or proteasomal degradation. The protein is a potential tumor suppressor and is involved in the pathophysiology of several tumors, including Wilm's tumor. [provided by RefSeq, Mar 2016]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSpastic paraplegia and psychomotor retardation with or without seizures

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.52

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

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