OGDHL

Chr 10

oxoglutarate dehydrogenase L

Also known as: YOBELN

The protein functions as a component of the 2-oxoglutarate dehydrogenase complex, catalyzing the conversion of 2-oxoglutarate to succinyl-CoA in the mitochondrial tricarboxylic acid cycle. Mutations in this gene cause autosomal recessive succinic semialdehyde dehydrogenase deficiency, a metabolic disorder affecting the central nervous system. The gene shows tolerance to loss-of-function variation (LOEUF 0.686), suggesting that complete loss of function may be compatible with survival in the recessive state.

Summary from RefSeq, UniProt
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Primary Disease Associations & Inheritance

UniProtYoon-Bellen neurodevelopmental syndrome
0
Active trials
10
Pubs (1 yr)
68
P/LP submissions
5%
P/LP missense
0.69
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryOGDHL
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
66 unique Pathogenic / Likely Pathogenic· 205 VUS of 336 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.69LOEUF
pLI 0.000
Z-score 3.29
OE 0.48 (0.350.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.50Z-score
OE missense 0.94 (0.881.01)
610 obs / 645.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.48 (0.350.69)
00.351.4
Missense OE0.94 (0.881.01)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 23 / 47.5Missense obs/exp: 610 / 645.6Syn Z: -0.01
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateOGDHL-related neurodevelopmental disorder with seizures, hearing loss and gait ataxiaOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7131th %ile
GOF
0.6345th %ile
LOF
0.2776th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

336 submitted variants in ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic27
VUS205
Likely Benign24
Benign11
Conflicting3
39
Pathogenic
27
Likely Pathogenic
205
VUS
24
Likely Benign
11
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
37
1
39
Likely Pathogenic
3
2
22
0
27
VUS
0
173
32
0
205
Likely Benign
0
7
3
14
24
Benign
0
2
1
8
11
Conflicting
3
Total31859523309

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

View in ClinVar →

Protein Context — Lollipop Plot

OGDHL · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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