SIAH1

Chr 16

siah E3 ubiquitin protein ligase 1

Also known as: BURHAS, SIAH1A

NCBI Gene: 6477 ENSG00000196470 UniProt: Q8IUQ4

The protein is an E3 ubiquitin ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins involved in apoptosis, transcription regulation, cell cycle control, and other cellular processes. Mutations cause Buratti-Harel syndrome, which follows autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (LOEUF = 0.499), suggesting intolerance to protein-disrupting mutations.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein that is a member of the seven in absentia homolog (SIAH) family. The protein is an E3 ligase and is involved in ubiquitination and proteasome-mediated degradation of specific proteins. The activity of this ubiquitin ligase has been implicated in the development of certain forms of Parkinson's disease, the regulation of the cellular response to hypoxia and induction of apoptosis. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtBuratti-Harel syndrome

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)

—

P/LP submissions

—

P/LP missense

0.50

LOEUF

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429