GLUD1: Glutamate Dehydrogenase 1
Key enzyme in glutamate metabolism and ammonia detoxification
Gene Information Card
| Symbol | GLUD1 |
|---|---|
| Full Name | Glutamate Dehydrogenase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q23.2 |
| NCBI Gene ID | 2746 ncbi.nlm.nih.gov/gene/2746 |
| Ensembl ID | ENSG00000148672 |
| UniProt ID | P00367 |
| OMIM ID | 138130 |
| HGNC ID | 4335 |
| Aliases | GDH, GDH1, GLUD |
Description
GLUD1 encodes glutamate dehydrogenase 1 (GDH), a mitochondrial matrix enzyme that catalyzes the reversible oxidative deamination of glutamate to alpha-ketoglutarate and ammonia, using NAD+ or NADP+ as cofactors. This enzyme plays a critical role in amino acid metabolism, ammonia detoxification, and insulin secretion regulation. Mutations in GLUD1 cause hyperinsulinism-hyperammonemia syndrome, characterized by hypoglycemia and elevated ammonia levels.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hyperinsulinism-hyperammonemia syndrome | Gain-of-function mutations in GLUD1 reduce sensitivity to allosteric inhibition by GTP, leading to increased GDH activity, excessive insulin secretion, and elevated ammonia production. | ClinVar, OMIM #138130 |
| Congenital hyperinsulinism | GLUD1 mutations cause a dominant form of hyperinsulinism with leucine sensitivity, due to dysregulated glutamate metabolism in pancreatic beta-cells. | ClinVar, OMIM #606762 |
| Epileptic encephalopathy | Rare de novo missense variants in GLUD1 have been associated with early-onset seizures and developmental delay, likely due to altered neurotransmitter cycling. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.3 | High |
| Pancreas | 8.7 | Medium |
| Brain | 6.5 | Medium |
| Kidney | 9.1 | Medium |
| Heart | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.5 | Hepatocyte model |
| SH-SY5Y | 7.8 | Neuroblastoma line |
| HEK293 | 5.3 | Embryonic kidney |
| MIN6 | 11.2 | Pancreatic beta-cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1493C>T (p.Ser498Leu) | Missense | ~40% of HIHA cases | Gain-of-function; reduces GTP inhibition |
| c.965G>A (p.Arg322His) | Missense | ~15% of HIHA cases | Gain-of-function; alters allosteric regulation |
| c.1519G>A (p.Gly507Arg) | Missense | Rare | Gain-of-function; associated with severe hypoglycemia |
| c.820C>T (p.Arg274Cys) | Missense | Rare | Gain-of-function; leucine-sensitive hyperinsulinism |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations reported in human disease; homozygous knockout is lethal in mice.
Gain of Function (GOF)
Most GLUD1 mutations are gain-of-function, reducing sensitivity to allosteric inhibition by GTP and ADP, leading to increased enzyme activity.
Dominant Negative (DN)
Not described for GLUD1; all pathogenic mutations are dominant gain-of-function.
View complete mutation data：
Gene Ontology (GO)
| • glutamate dehydrogenase (NAD+) activity (GO:0004352) | • glutamate dehydrogenase (NADP+) activity (GO:0004353) |
| • mitochondrion (GO:0005739) | • glutamate metabolic process (GO:0006536) |
| • oxidation-reduction process (GO:0055114) |
Pathways
• KEGG: hsa00250 - Alanine
• aspartate and glutamate metabolism
• KEGG: hsa00330 - Arginine and proline metabolism
• Reactome: R-HSA-210500 - Glutamate and glutamine metabolism
Protein Summary
Glutamate dehydrogenase 1 (GDH) is a 558-amino acid mitochondrial enzyme encoded by GLUD1. It forms homohexamers and catalyzes the reversible conversion of glutamate to alpha-ketoglutarate and ammonia. GDH is allosterically regulated by GTP (inhibitor) and ADP (activator). The enzyme is highly expressed in liver, pancreas, kidney, and brain, where it integrates carbon and nitrogen metabolism. Gain-of-function mutations cause hyperinsulinism-hyperammonemia syndrome.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GLUD1 Knockout HEK293 Cell Line | EDJ-KQ50303 | Human | 2746 | Details Get a Quote |
| GLUD1 Knockout HeLa Cell Line | EDJ-KQ53359 | Human | 2746 | Details Get a Quote |
| GLUD1 Knockout A-549 Cell Line | EDJ-KQ61837 | Human | 2746 | Details Get a Quote |
| GLUD1 Knockout HCT 116 Cell Line | EDJ-KQ70322 | Human | 2746 | Details Get a Quote |
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