L2HGDH

Chr 14

L-2-hydroxyglutarate dehydrogenase

Also known as: C14orf160, L2HGA

NCBI Gene: 79944ENSG00000087299UniProt: Q9H9P8

This gene encodes L-2-hydroxyglutarate dehydrogenase, a FAD-dependent enzyme that oxidizes L-2-hydroxyglutarate to alpha-ketoglutarate in a variety of mammalian tissues. Mutations in this gene cause L-2-hydroxyglutaric aciduria, a rare autosomal recessive neurometabolic disorder resulting in moderate to severe cognitive disability. [provided by RefSeq, Jul 2008]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtL-2-hydroxyglutaric aciduria

Clinical highlights

Gene-disease validity (ClinGen)
mitochondrial disease · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
13
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.79
LOEUF
LOF
Mechanism· G2P
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GeneReview available — L2HGDH
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
0.79LOEUF
pLI 0.000
Z-score 2.34
OE 0.48 (0.30–0.79)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.42Z-score
OE missense 0.93 (0.83–1.03)
235 obs / 254.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.48 (0.30–0.79)
0≤0.351.4
Missense OE?0.93 (0.83–1.03)
0≤0.61.4
Synonymous OE?0.90
0≤1.21.6
LoF obs/exp: 11 / 23.1Missense obs/exp: 235 / 254.0Syn Z: 0.70

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

L2HGDH · 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

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients