GAD1

Protein identityUniProt · HPA

UniProt accession

Q99259

Gene

GAD1

Ensembl

ENSG00000128683

Chromosome

2

Canonical length

594 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Vesicles,Plasma membrane,Cytosol

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes one of several forms of glutamic acid decarboxylase, identified as a major autoantigen in insulin-dependent diabetes. The enzyme encoded is responsible for catalyzing the production of gamma-aminobutyric acid from L-glutamic acid. A pathogenic role for this enzyme has been identified in the human pancreas since it has been identified as an autoantigen and an autoreactive T cell target in insulin-dependent diabetes. This gene may also play a role in the stiff man syndrome. Deficiency in this enzyme has been shown to lead to pyridoxine dependency with seizures. Alternative splicing of this gene results in two products, the predominant 67-kD form and a less-frequent 25-kD form. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

594 residues, UniProt reviewed canonical sequence.

>Q99259|GAD1
     1  MASSTPSSSA TSSNAGADPN TTNLRPTTYD TWCGVAHGCT RKLGLKICGF LQRTNSLEEK
    61  SRLVSAFKER QSSKNLLSCE NSDRDARFRR TETDFSNLFA RDLLPAKNGE EQTVQFLLEV
   121  VDILLNYVRK TFDRSTKVLD FHHPHQLLEG MEGFNLELSD HPESLEQILV DCRDTLKYGV
   181  RTGHPRFFNQ LSTGLDIIGL AGEWLTSTAN TNMFTYEIAP VFVLMEQITL KKMREIVGWS
   241  SKDGDGIFSP GGAISNMYSI MAARYKYFPE VKTKGMAAVP KLVLFTSEQS HYSIKKAGAA
   301  LGFGTDNVIL IKCNERGKII PADFEAKILE AKQKGYVPFY VNATAGTTVY GAFDPIQEIA
   361  DICEKYNLWL HVDAAWGGGL LMSRKHRHKL NGIERANSVT WNPHKMMGVL LQCSAILVKE
   421  KGILQGCNQM CAGYLFQPDK QYDVSYDTGD KAIQCGRHVD IFKFWLMWKA KGTVGFENQI
   481  NKCLELAEYL YAKIKNREEF EMVFNGEPEH TNVCFWYIPQ SLRGVPDSPQ RREKLHKVAP
   541  KIKALMMESG TTMVGYQPQG DKANFFRMVI SNPAATQSDI DFLIEEIERL GQDL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GAD1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.28

Highest tissue expression

69 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GAD1.

Disease | AllUniProt

Conditions GAD1 is implicated in, by any mechanism.

• Developmental and epileptic encephalopathy 89 (DEE89) MIM:619124

Disease | GeneticClinVar

18 pathogenic / likely-pathogenic of 309 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Developmental and epileptic encephalopathy 89
• Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities

Disease | ImmuneIEDB

Conditions an epitope on GAD1 was assayed in.

• rubella T cell
• type 1 diabetes mellitus B and T cell
• Stiff-Person syndrome B cell
• prediabetes syndrome B cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against GAD1 are reported. Each links to that disease's full target list.

• Diabetes Mellitus, Type 1 15

ReferencesPubMed · IEDB

Publications for GAD1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.47

gnomAD pLI

0.05

gnomAD missense Z

2.32

DepMap mean gene effect

-0.01

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• chemical synaptic transmission
• gamma-aminobutyrate shunt
• gamma-aminobutyric acid biosynthetic process
• L-glutamate catabolic process
• locomotory exploration behavior
• social behavior

Molecular functions

• glutamate decarboxylase activity
• identical protein binding
• pyridoxal phosphate binding

Cellular components

• axon terminus
• cell cortex
• clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane
• cytoplasm
• GABA-ergic synapse
• inhibitory synapse
• perinuclear region of cytoplasm
• plasma membrane
• presynaptic active zone
• vesicle membrane

Protein domainsUniProt · Pfam · InterPro

• Pyridoxal phosphate-dependent decarboxylase, major domain
• Pyridoxal phosphate-dependent transferase, major domain
• Pyridoxal phosphate-dependent transferase
• Pyridoxal-phosphate binding site
• Pyridoxal-dependent decarboxylase conserved domain

KeywordsUniProt

• Decarboxylase
• Epilepsy
• Intellectual disability
• Lyase
• Neurotransmitter biosynthesis
• Phosphoprotein
• Pyridoxal phosphate

InteractionsUniProt · HPA

Protein binding partners of GAD1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MAL2