ETHE1

Chr 19AR

ETHE1 persulfide dioxygenase

Also known as: HSCO, YF13H12

NCBI Gene: 23474 ENSG00000105755 UniProt: O95571 OMIM: 608451

The ETHE1 protein is a sulfur dioxygenase that catalyzes the oxidation of persulfide substrates in the mitochondrial sulfide oxidation pathway, preventing toxic accumulation of hydrogen sulfide that can inhibit cytochrome c oxidase. Mutations cause ethylmalonic encephalopathy, an infantile-onset metabolic disorder affecting the brain, gastrointestinal tract, and peripheral vessels with autosomal recessive inheritance. This gene shows relatively low constraint against loss-of-function variants (pLI near zero, LOEUF 1.46).

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the metallo beta-lactamase family of iron-containing proteins involved in the mitochondrial sulfide oxidation pathway. The encoded protein catalyzes the oxidation of a persulfide substrate to sulfite. Certain mutations in this gene cause ethylmalonic encephalopathy, an infantile metabolic disorder affecting the brain, gastrointestinal tract and peripheral vessels. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Ethylmalonic encephalopathyMIM #602473

Clinical highlights

Gene-disease validity (ClinGen)

Leigh syndrome · ARDefinitivesufficient evidence for diagnostic panels

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

1.46

LOEUF

LOF

Mechanism· G2P

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GeneReview available — ETHE1