GLUD1

Chr 10AD

glutamate dehydrogenase 1

Also known as: GDH, GDH1, GLUD, hGDH1

NCBI Gene: 2746ENSG00000148672UniProt: P00367OMIM: 138130

This gene encodes glutamate dehydrogenase, which is a mitochondrial matrix enzyme that catalyzes the oxidative deamination of glutamate to alpha-ketoglutarate and ammonia. This enzyme has an important role in regulating amino acid-induced insulin secretion. It is allosterically activated by ADP and inhibited by GTP and ATP. Activating mutations in this gene are a common cause of congenital hyperinsulinism. Alternative splicing of this gene results in multiple transcript variants. The related glutamate dehydrogenase 2 gene on the human X-chromosome originated from this gene via retrotransposition and encodes a soluble form of glutamate dehydrogenase. Related pseudogenes have been identified on chromosomes 10, 18 and X. [provided by RefSeq, Jan 2016]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Hyperinsulinism-hyperammonemia syndromeMIM #606762
AD
UniProtHyperinsulinemic hypoglycemia, familial, 6

Clinical highlights

Gene-disease validity (ClinGen)
hyperinsulinism-hyperammonemia syndrome · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
82
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.61
LOEUF
GOF
Mechanism· G2P
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GeneReview available — GLUD1
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
0.61LOEUF
pLI 0.007
Z-score 2.98
OE 0.34 (0.20–0.61)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
3.06Z-score
OE missense 0.52 (0.45–0.59)
163 obs / 316.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.34 (0.20–0.61)
0≤0.351.4
Missense OE?0.52 (0.45–0.59)
0≤0.61.4
Synonymous OE?0.84
0≤1.21.6
LoF obs/exp: 8 / 23.6Missense obs/exp: 163 / 316.0Syn Z: 1.35

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

GLUD1 · protein map & ClinVar variants

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

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