OGDH

Chr 7AR

oxoglutarate dehydrogenase

Also known as: AKGDH, E1k, E1o, HsOGDH, KGD1, OGDC, OGDH-E1, OGDH2

NCBI Gene: 4967 ENSG00000105953 UniProt: Q02218 OMIM: 613022

This gene encodes one subunit of the 2-oxoglutarate dehydrogenase complex. This complex catalyzes the overall conversion of 2-oxoglutarate (alpha-ketoglutarate) to succinyl-CoA and CO(2) during the Krebs cycle. The protein is located in the mitochondrial matrix and uses thiamine pyrophosphate as a cofactor. A congenital deficiency in 2-oxoglutarate dehydrogenase activity is believed to lead to hypotonia, metabolic acidosis, and hyperlactatemia. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Sep 2009]

OMIM Research

OMIM ResearchGenerating clinical summary…

ARLOEUF 0.271 OMIM phenotype

Clinical Summary— OGDH

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Gene-Disease Validity (ClinGen)

mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

5 unique Pathogenic / Likely Pathogenic· 107 VUS of 278 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.27LOEUF

pLI 0.997

Z-score 5.70

OE 0.15 (0.09–0.27)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

4.76Z-score

OE missense 0.47 (0.43–0.52)

304 obs / 643.9 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.15 (0.09–0.27)

0≤0.351.4

Missense OE?0.47 (0.43–0.52)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 8 / 52.6Missense obs/exp: 304 / 643.9Syn Z: 0.04

ClinVar Variant Classifications

278 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic1

VUS107

Likely Benign107

Benign19

Conflicting3

Pathogenic

Likely Pathogenic

107

VUS

107

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	4	0	0	4
Likely Pathogenic	0	0	1	0	1
VUS	2	98	7	0	107
Likely Benign	0	5	31	71	107
Benign	0	1	5	13	19
Conflicting	—				3
Total	2	108	44	84	241

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

View in ClinVar →

24 pathogenic / likely-pathogenic (of 31) ClinVar copy-number / structural variants overlap OGDH — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →