GCDH

glutaryl-CoA dehydrogenase, the group of Acyl-CoA dehydrogenase family

Basic information

Region (hg38): 19:12891159-12914207

Links

ENSG00000105607 ∙ NCBI:2639 ∙ OMIM:608801 ∙ HGNC:4189 ∙ Uniprot:Q92947 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glutaryl-CoA dehydrogenase deficiency (Definitive), mode of inheritance: AR
• glutaryl-CoA dehydrogenase deficiency (Definitive), mode of inheritance: AR
• glutaryl-CoA dehydrogenase deficiency (Moderate), mode of inheritance: AR
• glutaryl-CoA dehydrogenase deficiency (Strong), mode of inheritance: AR
• glutaryl-CoA dehydrogenase deficiency (Supportive), mode of inheritance: AR
• glutaryl-CoA dehydrogenase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glutaric aciduria, type I	AR	Biochemical	Early detection to allow treatment to decrease morbidity/mortality related to acute metabolic compensation, as well as dietary measures to reduce lysine oxidation and influx (eg, with low lysine diet and arginine supplementation) and increase glutaryl-CoA detoxification (eg, with carnitine supplementation) can be beneficial	Biochemical; Cardiovascular; Neurologic	1137568; 624191; 3658174; 2027453; 1951469; 8139602; 8541831; 7564239; 8552212; 8900227; 11060535; 10699052; 12473778; 12888985; 15505396; 15954035; 15985591; 16641220; 17188916; 17203377; 17478444; 17622945; 17957492; 18775269; 19260933; 20084589; 20301313; 20732827; 21031586; 21912879; 22520952; 23225040; 23395213; 23884036

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GCDH gene.

• Glutaric aciduria, type 1 (673 variants)
• not provided (124 variants)
• not specified (46 variants)
• Inborn genetic diseases (41 variants)
• GCDH-related condition (8 variants)
• Elevated circulating glutaric acid concentration (4 variants)
• Abnormality of metabolism/homeostasis (2 variants)
• Intellectual disability (2 variants)
• Hypomyelinating leukodystrophy 2 (1 variants)
• BLOOD GROUP--LUTHERAN INHIBITOR;Congenital dyserythropoietic anemia type 4;Fetal hemoglobin quantitative trait locus 6 (1 variants)
• Primary ciliary dyskinesia 29 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GCDH gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	184	2	189
missense	59	82	98	2		241
nonsense	14	22				36
start loss	1	2				3
frameshift	15	25				40
inframe indel	1	1	4			6
splice donor/acceptor (+/-2bp)	8	17	1			26
splice region	1	1	3	31		36
non coding			17	59	20	96
Total	98	149	123	245	22

Highest pathogenic variant AF is 0.000263

Variants in GCDH

This is a list of pathogenic ClinVar variants found in the GCDH region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-12891168-T-C		Glutaric aciduria, type 1	Uncertain significance (Jan 13, 2018)
19-12891169-G-GT		Elevated circulating glutaric acid concentration	Uncertain significance (Jun 14, 2016)
19-12891187-C-T		Glutaric aciduria, type 1	Uncertain significance (Jan 13, 2018)
19-12891188-G-A		Glutaric aciduria, type 1	Uncertain significance (Jan 13, 2018)
19-12891190-G-A		Glutaric aciduria, type 1	Uncertain significance (Jan 22, 2019)
19-12891202-G-A		not specified • Glutaric aciduria, type 1	Conflicting classifications of pathogenicity (Jan 13, 2018)
19-12891205-A-G		not specified	Likely benign (Aug 11, 2016)
19-12891211-G-A		Glutaric aciduria, type 1	Uncertain significance (Jan 12, 2018)
19-12891219-A-G		Glutaric aciduria, type 1	Benign (Jun 10, 2021)
19-12891219-AGC-GG		not specified	Likely benign (Mar 10, 2017)
19-12891221-C-T			Likely benign (Mar 14, 2018)
19-12891260-C-A		Glutaric aciduria, type 1	Uncertain significance (Dec 21, 2022)
19-12891301-G-C		Glutaric aciduria, type 1	Uncertain significance (May 10, 2021)
19-12891305-A-C		Glutaric aciduria, type 1	Likely pathogenic (Dec 20, 2022)
19-12891305-A-G			Pathogenic (Mar 02, 2023)
19-12891307-G-A		Glutaric aciduria, type 1	Likely pathogenic (Mar 28, 2017)
19-12891310-C-T		Glutaric aciduria, type 1	Likely benign (Sep 10, 2023)
19-12891310-CCT-C		Glutaric aciduria, type 1	Likely pathogenic (Mar 11, 2023)
19-12891311-C-T		Glutaric aciduria, type 1	Likely benign (Oct 05, 2022)
19-12891311-C-CT		Glutaric aciduria, type 1	Pathogenic (Apr 12, 2020)
19-12891319-C-A		not specified • Glutaric aciduria, type 1	Likely benign (Apr 28, 2023)
19-12891319-C-T		Glutaric aciduria, type 1	Likely benign (Dec 11, 2023)
19-12891333-T-C		Glutaric aciduria, type 1	Uncertain significance (Aug 14, 2020)
19-12891342-G-A		Glutaric aciduria, type 1 • GCDH-related disorder	Conflicting classifications of pathogenicity (Jan 04, 2024)
19-12891345-GA-T		Glutaric aciduria, type 1	Likely pathogenic (Jun 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GCDH	protein_coding	protein_coding	ENST00000222214	11	23182

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00486	0.994	125689	0	59	125748	0.000235

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.306	247	261	0.947	0.0000175	2821
Missense in Polyphen		96	117.27	0.8186		1293
Synonymous	-0.144	118	116	1.02	0.00000873	915
Loss of Function	2.85	8	22.6	0.354	0.00000118	249

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000556	0.000556
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00125	0.00125
Finnish	0.00	0.00
European (Non-Finnish)	0.0000971	0.0000967
Middle Eastern	0.00125	0.00125
South Asian	0.000131	0.000131
Other	0.000333	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 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. {ECO:0000269|PubMed:17176108, ECO:0000269|PubMed:6423663, ECO:0000269|PubMed:8541831}.
• Pathway: Tryptophan metabolism - Homo sapiens (human);Lysine degradation - Homo sapiens (human);Fatty acid degradation - Homo sapiens (human);Long chain acyl-CoA dehydrogenase deficiency (LCAD);Lysine Degradation;Hyperlysinemia I, Familial;2-aminoadipic 2-oxoadipic aciduria;Trifunctional protein deficiency;Carnitine palmitoyl transferase deficiency (II);Very-long-chain acyl coa dehydrogenase deficiency (VLCAD);Medium chain acyl-coa dehydrogenase deficiency (MCAD);Pyridoxine dependency with seizures;Saccharopinuria/Hyperlysinemia II;Short Chain Acyl CoA Dehydrogenase Deficiency (SCAD Deficiency);Fatty acid Metabolism;Glutaric Aciduria Type I;Glutaric Aciduria Type I;Ethylmalonic Encephalopathy;Hyperlysinemia II or Saccharopinuria;Carnitine palmitoyl transferase deficiency (I);Fatty Acid Beta Oxidation;Tryptophan metabolism;Lysine catabolism;Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism;Metabolism of amino acids and derivatives;Saturated fatty acids beta-oxidation;Metabolism;Lysine degradation;Lysine metabolism;glutaryl-CoA degradation;Tryptophan degradation (Consensus)

Recessive Scores

• pRec: 0.684

Intolerance Scores

• loftool: 0.0905
• rvis_EVS: -0.51
• rvis_percentile_EVS: 21.65

Haploinsufficiency Scores

• pHI: 0.0809
• hipred: Y
• hipred_score: 0.528
• ghis: 0.501

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.998

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gcdh
• Phenotype: homeostasis/metabolism phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system phenotype

Gene ontology

• Biological process: lysine catabolic process;tryptophan metabolic process;fatty acid beta-oxidation using acyl-CoA dehydrogenase;fatty-acyl-CoA biosynthetic process
• Cellular component: mitochondrion;mitochondrial matrix
• Molecular function: fatty-acyl-CoA binding;glutaryl-CoA dehydrogenase activity;flavin adenine dinucleotide binding