GAD2 (Glutamate Decarboxylase 2): Gene, Function, and Clinical Significance
A comprehensive overview of the GAD2 gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | GAD2 |
|---|---|
| Full Name | Glutamate Decarboxylase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 10p12.1 |
| NCBI Gene ID | 2572 ncbi.nlm.nih.gov/gene/2572 |
| Ensembl ID | ENSG00000136750 |
| UniProt ID | Q05329 |
| OMIM ID | 138275 |
| HGNC ID | HGNC:4084 |
| Aliases | GAD65, GAD-2, GAD65Ab, DKFZp686I04122 |
Description
The GAD2 gene encodes glutamate decarboxylase 2 (also known as GAD65), an enzyme that catalyzes the decarboxylation of glutamate to gamma-aminobutyric acid (GABA) and carbon dioxide. GAD2 is primarily expressed in the central nervous system and pancreatic beta cells. It is a key enzyme in GABA synthesis, playing a critical role in neurotransmission and insulin secretion. Autoantibodies against GAD65 are biomarkers for type 1 diabetes and stiff-person syndrome. GAD2 is also implicated in various neurological and metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Type 1 Diabetes | Autoimmune destruction of pancreatic beta cells; GAD65 is a major autoantigen, leading to autoantibody production. | ClinVar, OMIM |
| Stiff-Person Syndrome | Autoantibodies against GAD65 impair GABAergic neurotransmission, causing muscle rigidity and spasms. | OMIM, PubMed |
| Cerebellar Ataxia | Anti-GAD antibodies are associated with cerebellar dysfunction, likely due to reduced GABA synthesis. | PubMed |
| Epilepsy | Altered GAD2 expression may affect GABAergic inhibition, contributing to seizure susceptibility. | PubMed |
| Schizophrenia | Reduced GAD2 expression in cortical interneurons is linked to GABAergic deficits in schizophrenia. | PubMed |
| Pancreatic Neuroendocrine Tumors | GAD2 expression is elevated in some tumors, potentially serving as a biomarker. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High | High |
| Pancreas | Moderate | Medium |
| Testis | Low | Low |
| Adrenal Gland | Low | Low |
| Liver | Not detected | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | High | Neuronal-like expression |
| INS-1 (insulinoma) | High | Pancreatic beta cell model |
| HeLa (cervical carcinoma) | Low | Low expression |
| HEK293 (embryonic kidney) | Low | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs2236418 | SNP (intronic) | ~30% (global) | Associated with altered GAD2 expression and risk for schizophrenia in some populations. |
| rs8190646 | SNP (5' UTR) | ~15% | May affect mRNA stability and protein levels. |
| c.1123C>T (p.Arg375Cys) | Missense | Rare | Reported in a patient with epilepsy; functional impact uncertain. |
| c.163G>A (p.Gly55Arg) | Missense | Rare | Found in a case of stiff-person syndrome; may affect enzyme activity. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in GAD2 are rare and may lead to reduced GABA synthesis, contributing to neurological disorders such as epilepsy and stiff-person syndrome.
Gain of Function (GOF)
Gain-of-function mutations are not well-documented; overexpression of GAD2 in tumors may enhance GABA production, potentially promoting tumor growth.
Dominant Negative (DN)
No dominant-negative mutations have been reported for GAD2.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004351 - glutamate decarboxylase activity | • GO:0003860 - pyridoxal phosphate binding |
| • GO:0006536 - glutamate metabolic process | • GO:0009450 - gamma-aminobutyric acid biosynthetic process |
| • GO:0007268 - chemical synaptic transmission | • GO:0030073 - insulin secretion |
| • GO:0005886 - plasma membrane | • GO:0005737 - cytoplasm |
Pathways
• GABAergic synapse (KEGG: hsa04727)
• Alanine
• aspartate and glutamate metabolism (KEGG: hsa00250)
• Butanoate metabolism (KEGG: hsa00650)
• Insulin secretion (Reactome: R-HSA-422085)
Protein Summary
The GAD2 protein (GAD65) is a 585-amino acid enzyme that exists as a homodimer. It requires pyridoxal phosphate (PLP) as a cofactor. GAD65 is anchored to the membrane of synaptic vesicles and is involved in the synthesis of GABA for vesicular release. In pancreatic beta cells, GAD65 is associated with insulin-containing secretory granules. The protein has two isoforms: GAD65 (encoded by GAD2) and GAD67 (encoded by GAD1), which differ in cellular localization and regulation. GAD65 is the major autoantigen in type 1 diabetes and stiff-person syndrome.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GAD2 Knockout HEK293 Cell Line | EDJ-KQ1888 | Human | 2572 | Details Get a Quote |
| GAD2 Knockout HeLa Cell Line | EDJ-KQ53301 | Human | 2572 | Details Get a Quote |
| GAD2 Knockout A-549 Cell Line | EDJ-KQ61784 | Human | 2572 | Details Get a Quote |
| GAD2 Knockout HCT 116 Cell Line | EDJ-KQ70265 | Human | 2572 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
