GCDH

Chr 19AR

glutaryl-CoA dehydrogenase

NCBI Gene: 2639ENSG00000105607UniProt: Q92947

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. Isoform Short is inactive

Primary Disease Associations & Inheritance

Glutaricaciduria, type IMIM #231670
AR
UniProtGlutaric aciduria 1
1061
ClinVar variants
198
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— GCDH
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
198 Pathogenic / Likely Pathogenic· 161 VUS of 1061 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.64LOEUF
pLI 0.005
Z-score 2.85
OE 0.35 (0.21–0.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.31Z-score
OE missense 0.95 (0.85–1.05)
247 obs / 260.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.35 (0.21–0.64)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.85–1.05)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 8 / 22.6Missense obs/exp: 247 / 260.9Syn Z: -0.14

ClinVar Variant Classifications

1061 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic92
Likely Pathogenic106
VUS161
Likely Benign186
Benign7
Conflicting29
92
Pathogenic
106
Likely Pathogenic
161
VUS
186
Likely Benign
7
Benign
29
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
30
38
24
0
92
Likely Pathogenic
28
51
26
1
106
VUS
0
124
31
6
161
Likely Benign
0
5
98
83
186
Benign
0
0
4
3
7
Conflicting
—29
Total5821818393581

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

Gene2Phenotype Curations

GCDH-related glutaricacidemia

definitive
ARLoss Of FunctionAltered Gene Product Structure
Dev. Disorders
G2P ↗
splice region variantframeshift variantstop gainedmissense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Glutaricaciduria, type I

MIM #231670

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Recommendations for diagnosing and managing individuals with glutaric aciduria type 1: Third revision.
Boy N et al.·J Inherit Metab Dis
2023
Exploring genotype-phenotype correlations in glutaric aciduria type 1.
Schuurmans IME et al.·J Inherit Metab Dis
2023
Glutaryl-CoA dehydrogenase suppresses tumor progression and shapes an anti-tumor microenvironment in hepatocellular carcinoma.
Lao Y et al.·J Hepatol
2024
Compilation of Genotype and Phenotype Data in GCDH-LOVD for Variant Classification and Further Application.
Tibelius A et al.·Genes (Basel)
2023
Two novel compound heterozygous variants of the GCDH gene in two Chinese families with glutaric acidaemia type I identified by high-throughput sequencing and a literature review.
Guo Z et al.·Mol Genet Genomics
2023Review
Glutaric aciduria type 1: Insights into diagnosis and neurogenetic outcomes.
Yoldas Celik M et al.·Eur J Pediatr
2024
Glutaryl-CoA Dehydrogenase Misfolding in Glutaric Acidemia Type 1.
Barroso M et al.·Int J Mol Sci
2023
Identification of novel pathogenic variants in the GCDH gene and assessment of neurodevelopmental outcomes in 24 children with glutaric aciduria type 1.
Paria P et al.·Eur J Paediatr Neurol
2022
Genetic Polymorphisms Associated with Fetal Hemoglobin (HbF) Levels and F-Cell Numbers: A Systematic Review of Genome-Wide Association Studies.
Stephanou C et al.·Int J Mol Sci
2024Review
Striatal neuronal death mediated by astrocytes from the Gcdh-/- mouse model of glutaric acidemia type I.
Olivera-Bravo S et al.·Hum Mol Genet
2015Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Crotonylation-related gene GCDH promotes osteoarthritis pathogenesis through flavin adenine dinucleotide signaling: mechanism exploration and experimental validation.
Di J et al.·Front Nutr
2025🔓 Open AccessFunctional
GCDH Promotes Breast Cancer Glutaminolysis Reprogramming by Inducing GLS1 Expression Through Histone Crotonylation at Its Promoter Region.
Zhang J et al.·Cancer Manag Res
2025🔓 Open Access
Glutaryl-CoA dehydrogenase (GCDH) enhances renal malignancy risk via modulating glutarylcarnitine levels.
Liu X et al.·Discov Oncol
2025🔓 Open Access
GCDH Acetylation Orchestrates DNA Damage Response and Autophagy via Mitochondrial ROS to Suppress Hepatocellular Carcinoma Progression.
Tian W et al.·Research (Wash D C)
2025🔓 Open Access
Interplay of YEATS2 and GCDH regulates histone crotonylation and drives EMT in head and neck cancer.
Pant D et al.·Elife
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Glutaric Acidemia Type IGlutaric Aciduria Type I

A Study to Evaluate the Tolerability, Safety and Efficacy of VGM-R02b

RECRUITING
NCT06217861Phase PHASE1Shanghai Vitalgen BioPharma Co., Ltd.Started 2024-04-29
VGM-R02b

External Resources

Links to major genomics databases and tools