GABRB1

gamma-aminobutyric acid type A receptor subunit beta1, the group of Gamma-aminobutyric acid type A receptor subunits

Basic information

Region (hg38): 4:46993722-47426447

Links

ENSG00000163288 ∙ NCBI:2560 ∙ OMIM:137190 ∙ HGNC:4081 ∙ Uniprot:P18505 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy, 45 (Limited), mode of inheritance: AD
• developmental and epileptic encephalopathy, 45 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 45	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	23934111; 26950270; 27273810

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GABRB1 gene.

• not provided (250 variants)
• Developmental and epileptic encephalopathy, 45 (12 variants)
• Inborn genetic diseases (7 variants)
• not specified (1 variants)
• Seizure (1 variants)
• GABRB1-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GABRB1 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				72	12	84
missense		3	97	2	2	104
nonsense			3			3
start loss						0
frameshift			1			1
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region			8	12		20
non coding				37	9	46
Total	0	3	103	111	23

Variants in GABRB1

This is a list of pathogenic ClinVar variants found in the GABRB1 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-47031658-A-G		not specified	Uncertain significance (Apr 04, 2023)
4-47031662-T-C			Uncertain significance (Nov 07, 2023)
4-47031664-C-G			Uncertain significance (Feb 28, 2022)
4-47031668-A-G			Uncertain significance (Dec 06, 2023)
4-47031671-G-A			Uncertain significance (Oct 30, 2022)
4-47031677-G-C			Uncertain significance (Aug 27, 2022)
4-47031678-T-A		not specified	Uncertain significance (Jan 02, 2024)
4-47031684-G-C			Likely benign (Dec 07, 2023)
4-47031684-G-T		GABRB1-related disorder	Likely benign (Jun 22, 2021)
4-47031685-C-T			Uncertain significance (Nov 19, 2023)
4-47031687-T-A			Likely benign (Aug 11, 2023)
4-47031688-C-G			Uncertain significance (Nov 14, 2022)
4-47031688-C-T			Uncertain significance (Jan 11, 2022)
4-47031697-C-A			Uncertain significance (Aug 09, 2022)
4-47031697-C-T			Uncertain significance (Mar 21, 2023)
4-47031698-C-A			Uncertain significance (Dec 16, 2023)
4-47031703-A-G		GABRB1-related disorder • not specified	Uncertain significance (Jan 24, 2024)
4-47031709-A-G			Uncertain significance (Dec 13, 2023)
4-47031711-C-T			Likely benign (Jan 02, 2024)
4-47031712-A-G			Uncertain significance (Jan 19, 2024)
4-47031714-G-C			Uncertain significance (Nov 27, 2023)
4-47031722-G-T			Uncertain significance (Dec 10, 2023)
4-47031724-G-T			Uncertain significance (May 01, 2023)
4-47031725-C-G		Developmental and epileptic encephalopathy, 45	Uncertain significance (-)
4-47031734-G-A		GABRB1-related disorder	Conflicting classifications of pathogenicity (Dec 18, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GABRB1	protein_coding	protein_coding	ENST00000295454	9	432722

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.981	0.0188	125741	0	6	125747	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.65	156	281	0.555	0.0000156	3108
Missense in Polyphen		36	118.1	0.30482		1397
Synonymous	-0.998	121	108	1.12	0.00000636	918
Loss of Function	4.11	3	25.3	0.118	0.00000155	257

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000869	0.0000869
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000545	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.00000880	0.00000879
Middle Eastern	0.0000545	0.0000544
South Asian	0.0000327	0.0000327
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:26950270}.
• Disease: DISEASE: Epileptic encephalopathy, early infantile, 45 (EIEE45) [MIM:617153]: 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. {ECO:0000269|PubMed:23934111, ECO:0000269|PubMed:26950270, ECO:0000269|PubMed:27273810}. 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);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: 0.112

Intolerance Scores

• loftool: 0.0690
• rvis_EVS: -0.36
• rvis_percentile_EVS: 28.93

Haploinsufficiency Scores

• pHI: 0.318
• hipred: Y
• hipred_score: 0.774
• ghis: 0.578

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.302

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gabrb1
• Phenotype: homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; reproductive system 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: ion transport;signal transduction;gamma-aminobutyric acid signaling pathway;chemical synaptic transmission;response to toxic substance;central nervous system neuron development;response to progesterone;ion transmembrane transport;regulation of membrane potential;ovulation cycle;nervous system process;regulation of postsynaptic membrane potential;cellular response to histamine;chloride transmembrane transport
• Cellular component: nuclear envelope;cytoplasm;plasma membrane;integral component of plasma membrane;cell junction;dendrite;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;ligand-gated ion channel activity;GABA-gated chloride ion channel activity;GABA receptor binding;transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential