OGDH

oxoglutarate dehydrogenase, the group of Oxoglutarate dehydrogenase family

Basic information

Region (hg38): 7:44606572-44709066

Links

ENSG00000105953 ∙ NCBI:4967 ∙ OMIM:613022 ∙ HGNC:8124 ∙ Uniprot:Q02218 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• oxoglutaricaciduria (Limited), mode of inheritance: AR
• oxoglutaricaciduria (Limited), mode of inheritance: Unknown
• oxoglutaricaciduria (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Oxoglutarate dehydrogenase deficiency	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Neurologic	32383294

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the OGDH 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				56	13	69
missense			57	4	2	63
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			6	7		13
non coding			1	16	5	22
Total	0	0	59	76	20

Variants in OGDH

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

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

Position	Type	Phenotype	Significance	ClinVar
7-44624350-C-T		Oxoglutaricaciduria	Uncertain significance (Oct 13, 2022)
7-44624361-T-C		Oxoglutaricaciduria	Likely benign (Jun 30, 2022)
7-44624382-A-C		Oxoglutaricaciduria • OGDH-related disorder	Benign/Likely benign (Jan 22, 2024)
7-44624382-A-G		Oxoglutaricaciduria	Likely benign (May 31, 2022)
7-44624387-C-T		Oxoglutaricaciduria	Uncertain significance (May 20, 2023)
7-44624388-G-A		Oxoglutaricaciduria	Likely benign (May 20, 2023)
7-44624414-C-T		not specified	Uncertain significance (Feb 07, 2023)
7-44624423-G-T		Oxoglutaricaciduria	Uncertain significance (Feb 23, 2022)
7-44624432-C-T		Oxoglutaricaciduria	Uncertain significance (Jun 26, 2022)
7-44624454-T-A			Likely benign (May 18, 2018)
7-44624456-G-A		not specified	Uncertain significance (Aug 14, 2023)
7-44624473-G-T		not specified	Uncertain significance (Feb 06, 2024)
7-44624504-G-A		not specified	Uncertain significance (Feb 05, 2024)
7-44624507-C-T		Oxoglutaricaciduria • OGDH-related disorder	Benign (Jan 18, 2024)
7-44624511-C-A		not specified	Uncertain significance (May 20, 2024)
7-44624514-T-C		OGDH-related disorder	Likely benign (Oct 12, 2022)
7-44624574-C-T		Oxoglutaricaciduria	Benign (Aug 17, 2023)
7-44645353-G-A		Oxoglutaricaciduria	Likely benign (Aug 10, 2023)
7-44645359-C-T		Oxoglutaricaciduria	Likely benign (Aug 27, 2021)
7-44645371-G-A		Oxoglutaricaciduria	Likely benign (Aug 04, 2023)
7-44645397-C-T		Oxoglutaricaciduria	Uncertain significance (Mar 02, 2022)
7-44645398-C-T		Oxoglutaricaciduria	Likely benign (Oct 17, 2022)
7-44645431-T-C		Oxoglutaricaciduria	Likely benign (Jan 18, 2024)
7-44645449-A-G		Oxoglutaricaciduria	Benign (Jan 24, 2024)
7-44645461-C-T		Oxoglutaricaciduria	Benign (Jul 03, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
OGDH	protein_coding	protein_coding	ENST00000222673	22	102495

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.997	0.00272	125734	0	14	125748	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.76	304	644	0.472	0.0000410	6748
Missense in Polyphen		110	333.03	0.33031		3419
Synonymous	0.0412	265	266	0.997	0.0000180	2001
Loss of Function	5.70	8	52.6	0.152	0.00000262	575

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000239	0.000239
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000981	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 2-oxoglutarate dehydrogenase (E1) component of the 2- oxoglutarate dehydrogenase complex, which mediates the decarboxylation of alpha-ketoglutarate (PubMed:24495017). The 2- oxoglutarate dehydrogenase complex catalyzes the overall conversion of 2-oxoglutarate to succinyl-CoA and CO(2) (PubMed:24495017). The 2-oxoglutarate dehydrogenase complex is mainly active in the mitochondrion (PubMed:29211711). A fraction of the 2-oxoglutarate dehydrogenase complex also localizes in the nucleus and is required for lysine succinylation of histones: associates with KAT2A on chromatin and provides succinyl-CoA to histone succinyltransferase KAT2A (PubMed:29211711). {ECO:0000269|PubMed:24495017, ECO:0000269|PubMed:29211711}.
• Pathway: Citrate cycle (TCA cycle) - Homo sapiens (human);Tryptophan metabolism - Homo sapiens (human);Lysine degradation - Homo sapiens (human);Valproic Acid Pathway, Pharmacodynamics;Pathway_PA165964473;Warburg Effect;The oncogenic action of Succinate;The oncogenic action of Fumarate;Pyruvate dehydrogenase deficiency (E3);Pyruvate dehydrogenase deficiency (E2);2-ketoglutarate dehydrogenase complex deficiency;Mitochondrial complex II deficiency;Fumarase deficiency;Congenital lactic acidosis;Citric Acid Cycle;Glutaminolysis and Cancer;The oncogenic action of 2-hydroxyglutarate;The oncogenic action of L-2-hydroxyglutarate in Hydroxygluaricaciduria;The oncogenic action of D-2-hydroxyglutarate in Hydroxygluaricaciduria ;TCA Cycle and Deficiency of Pyruvate Dehydrogenase complex (PDHc);fig-met-1-last-solution;Amino Acid metabolism;Tryptophan metabolism;TCA Cycle;Citrate cycle;Lysine catabolism;Citric acid cycle (TCA cycle);Pyruvate metabolism and Citric Acid (TCA) cycle;Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism;Metabolism of amino acids and derivatives;The citric acid (TCA) cycle and respiratory electron transport;Metabolism;TCA cycle;Lysine metabolism;TCA cycle;Glyoxylate metabolism and glycine degradation;superpathway of conversion of glucose to acetyl CoA and entry into the TCA cycle;2-oxoglutarate decarboxylation to succinyl-CoA (Consensus)

Recessive Scores

• pRec: 0.636

Intolerance Scores

• loftool: 0.136
• rvis_EVS: -0.48
• rvis_percentile_EVS: 22.75

Haploinsufficiency Scores

• pHI: 0.549
• hipred: Y
• hipred_score: 0.663
• ghis: 0.582

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.981

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ogdh
• Phenotype: growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue 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); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); immune system phenotype

Gene ontology

• Biological process: generation of precursor metabolites and energy;glycolytic process;tricarboxylic acid cycle;2-oxoglutarate metabolic process;succinyl-CoA metabolic process;NADH metabolic process;cerebellar cortex development;striatum development;hippocampus development;thalamus development;pyramidal neuron development;tangential migration from the subventricular zone to the olfactory bulb;olfactory bulb mitral cell layer development;histone succinylation
• Cellular component: nucleus;mitochondrion;mitochondrial matrix;mitochondrial membrane;oxoglutarate dehydrogenase complex
• Molecular function: oxoglutarate dehydrogenase (succinyl-transferring) activity;thiamine pyrophosphate binding;heat shock protein binding;oxoglutarate dehydrogenase (NAD+) activity;metal ion binding;chaperone binding