GCDH

Chr 19AR

glutaryl-CoA dehydrogenase

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.641 OMIM phenotype
Clinical SummaryGCDH
🧬
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.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

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 OE0.35 (0.210.64)
00.351.4
Missense OE0.95 (0.851.05)
00.61.4
Synonymous OE1.02
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

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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →