GCDH

Protein identityUniProt · HPA

UniProt accession

Q92947

Gene

GCDH

Ensembl

ENSG00000105607

Chromosome

19

Canonical length

438 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Mitochondria

Quaternary structure

Homotetramer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

438 residues, UniProt reviewed canonical sequence.

>Q92947|GCDH
     1  MALRGVSVRL LSRGPGLHVL RTWVSSAAQT EKGGRTQSQL AKSSRPEFDW QDPLVLEEQL
    61  TTDEILIRDT FRTYCQERLM PRILLANRNE VFHREIISEM GELGVLGPTI KGYGCAGVSS
   121  VAYGLLAREL ERVDSGYRSA MSVQSSLVMH PIYAYGSEEQ RQKYLPQLAK GELLGCFGLT
   181  EPNSGSDPSS METRAHYNSS NKSYTLNGTK TWITNSPMAD LFVVWARCED GCIRGFLLEK
   241  GMRGLSAPRI QGKFSLRASA TGMIIMDGVE VPEENVLPGA SSLGGPFGCL NNARYGIAWG
   301  VLGASEFCLH TARQYALDRM QFGVPLARNQ LIQKKLADML TEITLGLHAC LQLGRLKDQD
   361  KAAPEMVSLL KRNNCGKALD IARQARDMLG GNGISDEYHV IRHAMNLEAV NTYEGTHDIH
   421  ALILGRAITG IQAFTASK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GCDH can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.28

Highest tissue expression

87 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GCDH.

Disease | AllUniProt

Conditions GCDH is implicated in, by any mechanism.

• Glutaric aciduria 1 (GA1) MIM:231670

Disease | GeneticClinVar

328 pathogenic / likely-pathogenic of 1,035 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Glutaric aciduria, type 1
• GCDH-related disorder
• Inborn genetic diseases
• Glutaric acidaemia I newborn screening follow up
• Colon adenocarcinoma

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.64

gnomAD pLI

0

gnomAD missense Z

0.31

DepMap mean gene effect

-0.02

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• fatty acid beta-oxidation using acyl-CoA dehydrogenase
• fatty-acyl-CoA biosynthetic process
• L-tryptophan metabolic process

Molecular functions

• fatty-acyl-CoA binding
• flavin adenine dinucleotide binding
• glutaryl-CoA dehydrogenase activity

Cellular components

• mitochondrial matrix
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Acyl-CoA dehydrogenase, conserved site
• Acyl-CoA dehydrogenase/oxidase, middle domain
• Acyl-CoA dehydrogenase/oxidase, C-terminal
• Acyl-CoA dehydrogenase/oxidase, N-terminal and middle domain superfamily
• Acyl-CoA dehydrogenase/oxidase, N-terminal
• Acyl-CoA dehydrogenase-like, C-terminal
• Acyl-CoA dehydrogenase/oxidase, N-terminal domain superfamily
• Acyl-CoA oxidase/dehydrogenase, middle domain superfamily
• Acyl-CoA dehydrogenase, C-terminal domain
• Acyl-CoA dehydrogenase, middle domain
• Acyl-CoA dehydrogenase, N-terminal domain
• Glutaryl-CoA dehydrogenase

KeywordsUniProt

• Acetylation
• FAD
• Flavoprotein
• Glutaricaciduria
• Mitochondrion
• Oxidoreductase
• Transit peptide

InteractionsUniProt · HPA

Protein binding partners of GCDH in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• NOS3