GABRB2

gamma-aminobutyric acid type A receptor subunit beta2, the group of Gamma-aminobutyric acid type A receptor subunits

Basic information

Region (hg38): 5:161288428-161549044

Links

ENSG00000145864 ∙ ∙ OMIM:600232 ∙ HGNC:4082 ∙ Uniprot:P47870 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• epileptic encephalopathy, infantile or early childhood, 2 (Strong), mode of inheritance: AD
• undetermined early-onset epileptic encephalopathy (Supportive), mode of inheritance: AD
• epileptic encephalopathy, infantile or early childhood, 2 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 92	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	25124326; 27789573; 29100083

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GABRB2 gene.

• Intellectual disability (329 variants)
• not provided (136 variants)
• not specified (40 variants)
• Epileptic encephalopathy, infantile or early childhood, 2 (35 variants)
• Inborn genetic diseases (6 variants)
• See cases (2 variants)
• GABRB2-related condition (1 variants)
• Malignant tumor of prostate (1 variants)
• GABRB2-related neurodevelopmental disorders (1 variants)
• GABRB2-related epileptic encephalopathy (1 variants)
• Cerebral visual impairment and intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GABRB2 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			2	95	6	103
missense	10	27	137	20	16	210
nonsense			3			3
start loss						0
frameshift			2			2
inframe indel			3	1		4
splice donor/acceptor (+/-2bp)			1	1		2
splice region			4	15	10	29
non coding				68	26	94
Total	10	27	148	185	48

Highest pathogenic variant AF is 0.00000657

Variants in GABRB2

This is a list of pathogenic ClinVar variants found in the GABRB2 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-161293870-G-A			Likely benign (Jul 06, 2018)
5-161294089-C-T		Intellectual disability	Uncertain significance (Oct 26, 2022)
5-161294090-A-G		Intellectual disability	Likely benign (Jan 27, 2024)
5-161294091-T-A		Intellectual disability	Uncertain significance (Dec 21, 2023)
5-161294102-A-G		Intellectual disability	Likely benign (May 02, 2023)
5-161294107-C-T		Intellectual disability • Inborn genetic diseases	Uncertain significance (Nov 27, 2023)
5-161294108-G-A		Intellectual disability	Likely benign (Jan 22, 2024)
5-161294110-T-C		Intellectual disability	Uncertain significance (May 30, 2023)
5-161294111-G-A		Intellectual disability	Likely benign (Oct 03, 2023)
5-161294119-A-T		Intellectual disability	Benign (Nov 15, 2022)
5-161294141-T-A		Intellectual disability	Likely benign (Jan 14, 2024)
5-161294145-C-T		Intellectual disability	Uncertain significance (Oct 31, 2019)
5-161294155-G-A			Uncertain significance (Aug 07, 2022)
5-161294186-G-A		Intellectual disability	Likely benign (Dec 19, 2023)
5-161294190-G-A		Intellectual disability	Benign (Mar 05, 2021)
5-161294201-T-C		Intellectual disability	Likely benign (Apr 09, 2023)
5-161294207-G-A		Intellectual disability	Likely benign (Apr 24, 2020)
5-161294209-C-A		Intellectual disability	Uncertain significance (Jul 30, 2022)
5-161294209-C-T		Intellectual disability	Uncertain significance (Aug 23, 2022)
5-161294210-G-A		Intellectual disability	Likely benign (Jan 23, 2024)
5-161294219-C-T		Intellectual disability	Likely benign (Jul 17, 2023)
5-161294221-G-A		Intellectual disability	Likely benign (Sep 10, 2021)
5-161294222-G-A		Intellectual disability	Likely benign (Jun 16, 2020)
5-161294223-C-T		Intellectual disability	Likely benign (Sep 01, 2022)
5-161294224-G-A		Intellectual disability	Uncertain significance (Aug 09, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GABRB2	protein_coding	protein_coding	ENST00000274547	10	260615

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.849	0.151	125692	0	3	125695	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.40	133	298	0.446	0.0000161	3376
Missense in Polyphen		18	129.91	0.13856		1537
Synonymous	-0.922	121	109	1.11	0.00000563	989
Loss of Function	3.76	4	23.8	0.168	0.00000117	280

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000995	0.0000992
East Asian	0.00	0.00
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.00000881	0.00000879
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:19763268, ECO:0000269|PubMed:27789573, ECO:0000269|PubMed:8264558}.
• Pathway: Benzodiazepine Pathway, Pharmacodynamics;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);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: 0.156

Intolerance Scores

• loftool: 0.0759
• rvis_EVS: -0.69
• rvis_percentile_EVS: 14.97

Haploinsufficiency Scores

• pHI: 0.317
• hipred: Y
• hipred_score: 0.851
• ghis: 0.674

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.871

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gabrb2
• Phenotype: skeleton 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); hearing/vestibular/ear phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

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;synaptic transmission, GABAergic;regulation of postsynaptic membrane potential;inner ear receptor cell development;innervation;cellular response to histamine;cochlea development;chloride transmembrane transport
• Cellular component: cytosol;plasma membrane;integral component of plasma membrane;cell junction;cytoplasmic vesicle membrane;chloride channel complex;neuron projection;synapse;extracellular exosome;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;GABA receptor activity;transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential