GABRA3

gamma-aminobutyric acid type A receptor subunit alpha3, the group of Gamma-aminobutyric acid type A receptor subunits|MicroRNA protein coding host genes

Basic information

Region (hg38): X:152166234-152451315

Links

ENSG00000011677 ∙ NCBI:2556 ∙ OMIM:305660 ∙ HGNC:4077 ∙ Uniprot:P34903 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features (Definitive), mode of inheritance: XL
• epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features (Strong), mode of inheritance: XL

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GABRA3 gene.

• Inborn genetic diseases (1 variants)
• Epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GABRA3 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				7		7
missense	1		12	3		16
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	5		6
non coding					1	1
Total	1	0	12	10	1

Variants in GABRA3

This is a list of pathogenic ClinVar variants found in the GABRA3 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-152168244-A-G			Uncertain significance (Feb 25, 2021)
X-152168286-T-C		Inborn genetic diseases • Epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features	Pathogenic (Sep 17, 2018)
X-152168369-G-C		GABRA3-related disorder	Benign (Dec 31, 2019)
X-152168391-A-G		Inborn genetic diseases	Uncertain significance (May 30, 2024)
X-152168424-G-C		Inborn genetic diseases	Uncertain significance (Dec 27, 2023)
X-152168449-C-T		Epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features	Benign/Likely benign (Mar 29, 2024)
X-152168569-G-A			Likely benign (Feb 01, 2024)
X-152189723-A-G		GABRA3-related disorder	Benign (Dec 31, 2019)
X-152189780-G-A		Inborn genetic diseases	Uncertain significance (May 28, 2020)
X-152189820-A-G			Benign/Likely benign (Feb 01, 2023)
X-152189836-T-C		GABRA3-related disorder	Uncertain significance (Sep 10, 2021)
X-152189865-C-T			Likely benign (Mar 27, 2018)
X-152189917-G-T		GABRA3-related disorder	Uncertain significance (May 03, 2024)
X-152197628-C-T		Epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features	Uncertain significance (Sep 04, 2023)
X-152197638-A-G			Uncertain significance (Jul 04, 2020)
X-152197639-C-G			Uncertain significance (Jan 01, 2021)
X-152197701-A-G		Inborn genetic diseases	Uncertain significance (Mar 15, 2022)
X-152197734-T-C		Epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features	Likely pathogenic (Jul 19, 2023)
X-152197789-AAG-A		not specified	Likely benign (Jun 05, 2017)
X-152208054-T-A		Epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features	Pathogenic (Nov 22, 2022)
X-152208062-G-T		GABRA3-related disorder	Likely benign (Jan 08, 2020)
X-152208105-A-G		Inborn genetic diseases	Uncertain significance (Oct 10, 2019)
X-152255817-A-G		not specified	Uncertain significance (Nov 15, 2023)
X-152255832-G-A		Epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features	Pathogenic (Nov 22, 2022)
X-152256002-G-A		GABRA3-related disorder	Likely benign (May 08, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GABRA3	protein_coding	protein_coding	ENST00000370314	9	285125

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0388	0.955	125147	1	74	125222	0.000300

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.53	97	197	0.493	0.0000153	3230
Missense in Polyphen		27	98.177	0.27501		1624
Synonymous	0.684	68	75.6	0.900	0.00000605	985
Loss of Function	2.40	5	15.0	0.333	0.00000118	253

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000764	0.0000616
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00311	0.00223
European (Non-Finnish)	0.000292	0.000203
Middle Eastern	0.00	0.00
South Asian	0.0000575	0.0000328
Other	0.000467	0.000328

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: 0.216

Intolerance Scores

• loftool: 0.253
• rvis_EVS: -0.05
• rvis_percentile_EVS: 49.76

Haploinsufficiency Scores

• pHI: 0.0407
• hipred: Y
• hipred_score: 0.768
• ghis: 0.557

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.307

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gabra3
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms 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)

Gene ontology

• Biological process: 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;dendrite membrane;chloride channel complex;neuron projection;synapse;postsynapse;GABA-ergic synapse;integral component of postsynaptic specialization membrane;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;protein binding;benzodiazepine receptor activity;GABA-gated chloride ion channel activity;transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential