GABRA5

gamma-aminobutyric acid type A receptor subunit alpha5, the group of Gamma-aminobutyric acid type A receptor subunits

Basic information

Region (hg38): 15:26866911-26949208

Links

ENSG00000186297 ∙ NCBI:2558 ∙ OMIM:137142 ∙ HGNC:4079 ∙ Uniprot:P31644 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy, 79 (Moderate), mode of inheritance: AD
• undetermined early-onset epileptic encephalopathy (Supportive), mode of inheritance: AD
• developmental and epileptic encephalopathy, 79 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 79	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	29961870; 31056671

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GABRA5 gene.

• not_provided (66 variants)
• Inborn_genetic_diseases (23 variants)
• Developmental_and_epileptic_encephalopathy,_79 (22 variants)
• not_specified (5 variants)
• GABRA5-related_disorder (2 variants)
• Focal_epilepsy (1 variants)
• Schizophrenia (1 variants)
• Autism_spectrum_disorder (1 variants)
• Seizure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GABRA5 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000810.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	20	4	25
missense	4	2	56	6	1	69
nonsense			3			3
start loss			1			1
frameshift			1			1
splice donor/acceptor (+/-2bp)			1			1
Total	4	2	63	26	5

Highest pathogenic variant AF is 7.11656e-7

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GABRA5	protein_coding	protein_coding	ENST00000335625	9	82845

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.905	0.0946	124653	0	6	124659	0.0000241

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.23	127	279	0.456	0.0000170	3027
Missense in Polyphen		54	151.91	0.35548		1655
Synonymous	-0.248	120	117	1.03	0.00000868	882
Loss of Function	3.62	3	20.8	0.144	0.00000105	235

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000579	0.0000579
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000560	0.0000556
Finnish	0.00	0.00
European (Non-Finnish)	0.0000269	0.0000265
Middle Eastern	0.0000560	0.0000556
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);Prader-Willi and Angelman Syndrome;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: 0.194

Intolerance Scores

• loftool: 0.131
• rvis_EVS: -0.36
• rvis_percentile_EVS: 29.16

Haploinsufficiency Scores

• pHI: 0.409
• hipred: Y
• hipred_score: 0.768
• ghis: 0.528

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.478

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gabra5
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hearing/vestibular/ear phenotype; 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); skeleton phenotype

Gene ontology

• Biological process: behavioral fear response;signal transduction;gamma-aminobutyric acid signaling pathway;chemical synaptic transmission;brain development;sensory perception of sound;associative learning;ion transmembrane transport;regulation of membrane potential;negative regulation of neuron apoptotic process;nervous system process;synaptic transmission, GABAergic;regulation of postsynaptic membrane potential;inner ear receptor cell development;innervation;cochlea development;chloride transmembrane transport
• Cellular component: nucleoplasm;cytosol;plasma membrane;integral component of plasma membrane;cell junction;dendrite membrane;neuronal cell body membrane;chloride channel complex;neuron projection;synapse;postsynapse;GABA-ergic synapse;integral component of presynaptic membrane;integral component of postsynaptic specialization membrane;GABA-A receptor complex
• Molecular function: GABA-A receptor activity;transporter 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;signaling receptor activity;GABA receptor binding;transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential