GCDH

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

Basic information

Region (hg38): 19:12891128-12915126

Links

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

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 34.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
NM_000159.4	NP_000150.1	11	yes	-
ENST00000222214.10	ENSP00000222214.4	11	yes	-
NM_013976.5	NP_039663.1	11	-	-
ENST00000591470.5	ENSP00000466845.1	11	-	-

Phenotypes

GenCC

Source: genCC

• 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 (Definitive), 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 (890 variants)
• not_provided (157 variants)
• not_specified (85 variants)
• Inborn_genetic_diseases (81 variants)
• GCDH-related_disorder (23 variants)
• Intellectual_disability (3 variants)
• Abnormality_of_metabolism/homeostasis (2 variants)
• Glutaric_acidaemia_I_newborn_screening_follow_up (2 variants)
• Hypomyelinating_leukodystrophy_2 (1 variants)
• FETAL_HEMOGLOBIN_QUANTITATIVE_TRAIT_LOCUS_6 (1 variants)
• See_cases (1 variants)
• Tyrosinemia_type_III (1 variants)
• BLOOD_GROUP--LUTHERAN_INHIBITOR (1 variants)
• Congenital_dyserythropoietic_anemia_type_4 (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. These statistics are base on transcript: NM_000159.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		2	12	242	3	259
missense	54	168	172	9		403
nonsense	21	22				43
start loss		3				3
frameshift	37	25	1			63
splice donor/acceptor (+/-2bp)	9	22	3			34
Total	121	242	188	251	3

Highest pathogenic variant AF is 0.00039448417

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
		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

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

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