GAD2

protein-coding

glutamate decarboxylase 2

Gene summary

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 autoantibody and an autoreactive T cell target in insulin-dependent diabetes. This gene may also play a role in the stiff man syndrome. Alternative splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Oct 2008]

MANE transcript

NM_001134366.2

Inheritance

—

ClinVar variants

U:79B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr10:26,216,665-26,304,558

External References & Databases

Ensembl (ENSG00000136750)

Transcript & Mutation Effects

hg38 • Region Span ~87.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GAD2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 78

not providedTotal: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001134366.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar	3 clinvar	4
missense			79 clinvar	2 clinvar	2 clinvar	83
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	79	3	5	87

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001134366.2	RefSeq	NP_001127838.1	16	MANE Select
ENST00000376261.8	Ensembl	ENSP00000365437.3	16	MANE Select
NM_000818.3	RefSeq	NP_000809.1	16	Standard
ENST00000259271.7	Ensembl	ENSP00000259271.3	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Alanine, aspartate and glutamate metabolism - Homo sapiens (human)
Type I diabetes mellitus - Homo sapiens (human)
GABAergic synapse - Homo sapiens (human)
Butanoate metabolism - Homo sapiens (human)
beta-Alanine metabolism - Homo sapiens (human)

Biological Process

glutamate decarboxylation to succinate
chemical synaptic transmission
neurotransmitter biosynthetic process
response to drug

Molecular Function

glutamate decarboxylase activity
protein binding
glutamate binding
pyridoxal phosphate binding
protein heterodimerization activity

Cellular Component

Golgi membrane
cytosol
plasma membrane
cell junction
axon

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000376261
Coding exons: 16
Length: 88252
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125748
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.53	258	337	0.766	0.0000175	3863
Missense (PolyPhen)		100	174.89	0.5718		2023
Synonymous	0.0258	123	123	0.997	0.00000688	1062
Loss of Function	4.42	7	35.4	0.198	0.00000167	409

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the production of GABA.;

Recessive Scores

pRec: 0.862

Intolerance Scores

LoFtool: 0.533
RVIS EVS: -0.11
RVIS percentile EVS: 45.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.995

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium