GABRA2

gamma-aminobutyric acid type A receptor subunit alpha2, the group of Gamma-aminobutyric acid type A receptor subunits

Basic information

Region (hg38): 4:46243547-46475230

Links

ENSG00000151834 ∙ NCBI:2555 ∙ OMIM:137140 ∙ HGNC:4076 ∙ Uniprot:P47869 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy, 78 (Moderate), mode of inheritance: AD
• undetermined early-onset epileptic encephalopathy (Supportive), mode of inheritance: AD
• developmental and epileptic encephalopathy, 78 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 78	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	29422393; 29961870; 31032849

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GABRA2 gene.

• not provided (161 variants)
• Inborn genetic diseases (18 variants)
• Developmental and epileptic encephalopathy, 78 (10 variants)
• GABRA2-related condition (2 variants)
• Early infantile epileptic encephalopathy with suppression bursts (1 variants)
• not specified (1 variants)
• Alcohol dependence (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GABRA2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	33	2	36
missense		5	69	12	1	87
nonsense			2			2
start loss						0
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				5	2	7
non coding			14	23	7	44
Total	0	5	88	68	10

Variants in GABRA2

This is a list of pathogenic ClinVar variants found in the GABRA2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-46250306-A-T		GABRA2-related disorder	Benign (Nov 25, 2019)
4-46250318-A-G			Likely benign (Aug 24, 2023)
4-46250320-C-T			Likely benign (Jul 06, 2022)
4-46250330-G-T			Uncertain significance (Dec 23, 2023)
4-46250331-G-A			Uncertain significance (Jan 26, 2022)
4-46250333-T-A			Uncertain significance (Aug 20, 2022)
4-46250336-C-T			Uncertain significance (Dec 27, 2023)
4-46250341-T-C			Likely benign (Feb 15, 2023)
4-46250367-T-C			Uncertain significance (Jul 07, 2022)
4-46250371-G-A			Likely benign (Aug 09, 2022)
4-46250395-T-C			Uncertain significance (Sep 29, 2023)
4-46250405-A-G			Uncertain significance (Jun 01, 2022)
4-46250422-A-G			Likely benign (Aug 10, 2023)
4-46250423-A-G		Inborn genetic diseases	Uncertain significance (Apr 20, 2023)
4-46250443-T-A			Likely benign (Jan 24, 2023)
4-46250444-G-T		Inborn genetic diseases	Likely benign (Apr 13, 2023)
4-46250444-GC-TT		not specified	Conflicting classifications of pathogenicity (Dec 21, 2023)
4-46250450-G-A		GABRA2-related disorder	Conflicting classifications of pathogenicity (Nov 27, 2023)
4-46250454-G-T			Uncertain significance (Mar 01, 2022)
4-46250456-T-A			Uncertain significance (Aug 20, 2022)
4-46250458-G-C			Uncertain significance (Dec 21, 2023)
4-46250462-T-A			Uncertain significance (Sep 18, 2023)
4-46250469-T-G		Inborn genetic diseases	Uncertain significance (May 24, 2023)
4-46250470-C-A			Uncertain significance (Oct 14, 2022)
4-46250470-C-T			Likely benign (Mar 13, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GABRA2	protein_coding	protein_coding	ENST00000510861	9	226804

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.996	0.00402	125657	0	4	125661	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.13	97	231	0.420	0.0000110	2970
Missense in Polyphen		17	107.67	0.15788		1427
Synonymous	0.493	77	82.7	0.931	0.00000414	858
Loss of Function	4.01	1	20.7	0.0483	9.94e-7	259

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000359	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
• Pathway: Retrograde endocannabinoid signaling - Homo sapiens (human);GABAergic synapse - Homo sapiens (human);Nicotine addiction - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Taste transduction - Homo sapiens (human);Morphine addiction - Homo sapiens (human);GABA receptor Signaling;cardiac protection against ros;gamma-aminobutyric acid receptor life cycle pathway;GABA A receptor activation;Neuronal System;GABA receptor activation;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses (Consensus)

Recessive Scores

• pRec: 0.135

Intolerance Scores

• loftool: 0.167
• rvis_EVS: -0.27
• rvis_percentile_EVS: 33.97

Haploinsufficiency Scores

• pHI: 0.317
• hipred: Y
• hipred_score: 0.837
• ghis: 0.632

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.164

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gabra2
• Phenotype: homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: gabra2a
• Affected structure: third ventricle
• Phenotype tag: abnormal
• Phenotype quality: apoptotic

Gene ontology

• Biological process: regulation of neurotransmitter levels;neurotransmitter transport;signal transduction;gamma-aminobutyric acid signaling pathway;chemical synaptic transmission;ion transmembrane transport;regulation of membrane potential;nervous system process;synaptic transmission, GABAergic;regulation of postsynaptic membrane potential;chloride transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane;cell junction;integral component of synaptic vesicle membrane;dendrite membrane;chloride channel complex;neuron projection;synapse;postsynaptic membrane;postsynapse;GABA-A receptor complex
• Molecular function: GABA-A receptor activity;extracellular ligand-gated ion channel activity;inhibitory extracellular ligand-gated ion channel activity;chloride channel activity;benzodiazepine receptor activity;GABA-gated chloride ion channel activity;transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential