GCDH

Chr 19AR

glutaryl-CoA dehydrogenase

Also known as: ACAD5, GCD

NCBI Gene: 2639 ENSG00000105607 UniProt: Q92947 OMIM: 608801

The encoded protein catalyzes the oxidative decarboxylation of glutaryl-CoA to crotonyl-CoA in the mitochondrial matrix, functioning in the degradative pathway of L-lysine, L-hydroxylysine, and L-tryptophan metabolism. Mutations cause glutaric aciduria type I, an autosomal recessive metabolic disorder. The pathogenic mechanism involves dominant-negative effects of mutant protein on wild-type enzyme function.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene belongs to the acyl-CoA dehydrogenase family. It catalyzes the oxidative decarboxylation of glutaryl-CoA to crotonyl-CoA and CO(2) in the degradative pathway of L-lysine, L-hydroxylysine, and L-tryptophan metabolism. It uses electron transfer flavoprotein as its electron acceptor. The enzyme exists in the mitochondrial matrix as a homotetramer of 45-kD subunits. Mutations in this gene result in the metabolic disorder glutaric aciduria type 1, which is also known as glutaric acidemia type I. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 12. [provided by RefSeq, Mar 2013]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Glutaricaciduria, type IMIM #231670

UniProtGlutaric aciduria 1

Clinical highlights

Gene-disease validity (ClinGen)

glutaryl-CoA dehydrogenase deficiency · 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)

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P/LP submissions

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P/LP missense

0.64

LOEUF

LOF

Mechanism· G2P

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GeneReview available — GCDH