GCDH

Chr 19AR

glutaryl-CoA dehydrogenase

Also known as: ACAD5, GCD

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]

OMIMResearchGenerating clinical summary…
LOFmechanismARLOEUF 0.641 OMIM phenotype
Clinical SummaryGCDH
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Gene-Disease Validity (ClinGen)
glutaryl-CoA dehydrogenase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.64LOEUF
pLI 0.005
Z-score 2.85
OE 0.35 (0.210.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.31Z-score
OE missense 0.95 (0.851.05)
247 obs / 260.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.35 (0.210.64)
00.351.4
Missense OE?0.95 (0.851.05)
00.61.4
Synonymous OE?1.02
01.21.6
LoF obs/exp: 8 / 22.6Missense obs/exp: 247 / 260.9Syn Z: -0.14
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveGCDH-related glutaricacidemiaLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.76top 25%
GOF
0.7125th %ile
LOF
0.2969th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GCDH · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.