GABRB3

gamma-aminobutyric acid type A receptor subunit beta3, the group of Gamma-aminobutyric acid type A receptor subunits

Basic information

Region (hg38): 15:26543552-26939539

Links

ENSG00000166206 ∙ NCBI:2562 ∙ OMIM:137192 ∙ HGNC:4083 ∙ Uniprot:P28472 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 17.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
ENST00000299267.9	ENSP00000299267.4	9	-	-
ENST00000311550.10	ENSP00000308725.5	9	yes	-
ENST00000400188.7	ENSP00000383049.3	7	-	-
ENST00000541819.6	ENSP00000442408.2	10	-	-

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy, 43 (Definitive), mode of inheritance: AD
• genetic developmental and epileptic encephalopathy (Definitive), mode of inheritance: AD
• developmental and epileptic encephalopathy, 43 (Strong), mode of inheritance: AD
• epilepsy, childhood absence, susceptibility to, 5 (Limited), mode of inheritance: Unknown
• Lennox-Gastaut syndrome (Supportive), mode of inheritance: AD
• childhood absence epilepsy (Supportive), mode of inheritance: AD
• epilepsy, childhood absence, susceptibility to, 5 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epilepsy, childhood absence, susceptibility to, 5; Developmental and epileptic encephalopathy 43	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	12189488; 11920158; 11810291; 16835263; 17957331; 18514161; 22303015; 23934111; 27476654
As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GABRB3 gene.

• Epilepsy,_childhood_absence,_susceptibility_to,_5 (532 variants)
• Epilepsy,_childhood_absence,_susceptibility_to,_1 (525 variants)
• not_provided (181 variants)
• Developmental_and_epileptic_encephalopathy,_43 (67 variants)
• Inborn_genetic_diseases (51 variants)
• not_specified (30 variants)
• GABRB3-related_disorder (17 variants)
• Intellectual_disability (5 variants)
• Seizure (5 variants)
• Epileptic_encephalopathy (4 variants)
• Epilepsy (2 variants)
• Neurodevelopmental_delay (2 variants)
• See_cases (2 variants)
• Schizophrenia (1 variants)
• Global_developmental_delay (1 variants)
• Insomnia (1 variants)
• Myoepithelial_tumor (1 variants)
• SUDDEN_INFANT_DEATH_SYNDROME (1 variants)
• Developmental_and_epileptic_encephalopathy,_1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GABRB3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000814.6. 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	131	2	134
missense	20	60	246	26	4	356
nonsense	8	2	7			17
start loss						0
frameshift	7		8			15
splice donor/acceptor (+/-2bp)	2	6	3			11
Total	37	68	265	157	6

Highest pathogenic variant AF is 0.000010559688

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GABRB3	protein_coding	protein_coding	ENST00000311550	9	395994

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125741	0	5	125746	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.39	107	261	0.410	0.0000149	3083
Missense in Polyphen		27	134.25	0.20112		1590
Synonymous	-0.724	113	104	1.09	0.00000635	929
Loss of Function	3.83	3	22.7	0.132	0.00000134	252

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand- gated chloride channel. {ECO:0000269|PubMed:18281286, ECO:0000269|PubMed:18514161, ECO:0000269|PubMed:22243422, ECO:0000269|PubMed:22303015, ECO:0000269|PubMed:24909990, ECO:0000269|PubMed:26950270}.
• Disease: DISEASE: Epilepsy, childhood absence 5 (ECA5) [MIM:612269]: A subtype of idiopathic generalized epilepsy characterized by an onset at age 6-7 years, frequent absence seizures (several per day) and bilateral, synchronous, symmetric 3-Hz spike waves on EEG. Tonic-clonic seizures often develop in adolescence. Absence seizures may either remit or persist into adulthood. {ECO:0000269|PubMed:18514161, ECO:0000269|PubMed:22303015}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Epileptic encephalopathy, early infantile, 43 (EIEE43) [MIM:617113]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE43 inheritance is autosomal dominant. {ECO:0000269|PubMed:23934111, ECO:0000269|PubMed:25356899, ECO:0000269|PubMed:26950270, ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:27476654, ECO:0000269|PubMed:27864847}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Retrograde endocannabinoid signaling - Homo sapiens (human);GABAergic synapse - Homo sapiens (human);Serotonergic synapse - Homo sapiens (human);Nicotine addiction - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Morphine addiction - Homo sapiens (human);Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Prader-Willi and Angelman Syndrome;GABA receptor Signaling;GABA A receptor activation;Neuronal System;GABA receptor activation;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses (Consensus)

Recessive Scores

• pRec: 0.291

Intolerance Scores

• loftool: 0.124
• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.36

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.740

Gene Damage Prediction

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

Gene ontology

• Biological process: signal transduction;gamma-aminobutyric acid signaling pathway;chemical synaptic transmission;sensory perception of sound;ion transmembrane transport;regulation of membrane potential;negative regulation of neuron apoptotic process;nervous system process;roof of mouth development;inhibitory postsynaptic potential;inner ear receptor cell development;innervation;cellular response to histamine;cochlea development;chloride transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane;cell junction;cytoplasmic vesicle membrane;chloride channel complex;neuron projection;synapse;postsynaptic membrane;GABA-ergic synapse;GABA-A receptor complex
• Molecular function: GABA-A receptor activity;extracellular ligand-gated ion channel activity;GABA-gated chloride ion channel activity;identical protein binding;transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential