GABRA4

gamma-aminobutyric acid type A receptor subunit alpha4, the group of Gamma-aminobutyric acid type A receptor subunits

Basic information

Region (hg38): 4:46918899-46993581

Links

ENSG00000109158 ∙ NCBI:2557 ∙ OMIM:137141 ∙ HGNC:4078 ∙ Uniprot:P48169 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GABRA4 gene.

• Inborn genetic diseases (12 variants)
• not provided (7 variants)
• GABRA4-related Epileptic and Neurodevelopmental Disorder (1 variants)
• not specified (1 variants)
• GABRA4-related developmental and epileptic encephalopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GABRA4 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				3	2	5
missense			12	2	1	15
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding					1	1
Total	0	0	12	5	4

Variants in GABRA4

This is a list of pathogenic ClinVar variants found in the GABRA4 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-46928234-A-T		not specified	Uncertain significance (Dec 30, 2023)
4-46928264-T-C			Likely benign (Aug 08, 2018)
4-46928373-G-A		not specified	Uncertain significance (Nov 14, 2023)
4-46928416-T-C		not specified	Uncertain significance (Mar 08, 2024)
4-46928459-G-A			Benign (Apr 06, 2018)
4-46928463-C-T		not specified	Likely benign (Jun 06, 2023)
4-46928488-C-G		not specified	Uncertain significance (Sep 22, 2022)
4-46928613-C-T		not specified	Likely benign (May 06, 2022)
4-46928665-G-C		not specified	Uncertain significance (Sep 25, 2023)
4-46928693-A-C		not specified	Uncertain significance (Sep 14, 2022)
4-46928706-T-C		not specified	Uncertain significance (Jan 23, 2023)
4-46964994-C-G		not specified	Uncertain significance (Feb 27, 2024)
4-46965017-G-A		GABRA4-related Epileptic and Neurodevelopmental Disorder	Uncertain significance (Aug 31, 2022)
4-46965041-T-C		GABRA4-related disorder	Likely benign (Jun 02, 2023)
4-46965099-G-A			Benign (Jul 20, 2018)
4-46965129-G-C			Likely benign (Mar 29, 2018)
4-46965205-G-A			Uncertain significance (Jan 24, 2024)
4-46965205-G-T		GABRA4-related developmental and epileptic encephalopathy	Uncertain significance (Mar 31, 2022)
4-46971098-C-A		not specified	Uncertain significance (Mar 24, 2023)
4-46974235-T-A		not specified	Uncertain significance (Sep 17, 2021)
4-46974259-A-C		not specified	Uncertain significance (Oct 12, 2022)
4-46974262-C-G		not specified	Uncertain significance (Jan 27, 2022)
4-46974334-C-A		not specified	Uncertain significance (Oct 06, 2021)
4-46977528-T-G		not specified	Uncertain significance (Jul 30, 2023)
4-46977529-C-T			Likely benign (Apr 02, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GABRA4	protein_coding	protein_coding	ENST00000264318	9	75508

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.779	0.221	125732	0	14	125746	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.00	208	307	0.678	0.0000156	3608
Missense in Polyphen		62	156.91	0.39513		1901
Synonymous	-1.64	134	112	1.20	0.00000607	1108
Loss of Function	3.62	4	22.6	0.177	0.00000119	293

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000623	0.0000615
Ashkenazi Jewish	0.000113	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000133	0.0000879
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000383	0.0000327
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: 0.134

Intolerance Scores

• loftool: 0.0240
• rvis_EVS: 0.26
• rvis_percentile_EVS: 70.26

Haploinsufficiency Scores

• pHI: 0.155
• hipred: Y
• hipred_score: 0.774
• ghis: 0.472

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.881

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gabra4
• Phenotype: normal 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); 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)

Gene ontology

• Biological process: signal transduction;gamma-aminobutyric acid signaling pathway;chemical synaptic transmission;central nervous system development;ion transmembrane transport;regulation of membrane potential;nervous system process;synaptic transmission, GABAergic;regulation of postsynaptic membrane potential;chloride transmembrane transport;regulation of response to drug
• 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;benzodiazepine receptor activity;GABA-gated chloride ion channel activity;transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential