GABBR1

gamma-aminobutyric acid type B receptor subunit 1, the group of Gamma-aminobutyric acid type B receptor subunits|Sushi domain containing

Basic information

Region (hg38): 6:29555628-29633976

Links

ENSG00000204681 ∙ NCBI:2550 ∙ OMIM:603540 ∙ HGNC:4070 ∙ Uniprot:Q9UBS5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with language delay and variable cognitive abnormalities	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	Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic	36103875

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GABBR1 gene.

• Inborn genetic diseases (27 variants)
• not provided (18 variants)
• Neurodevelopmental disorder with language delay and variable cognitive abnormalities (4 variants)
• Global developmental delay;Delayed speech and language development;Intellectual disability (3 variants)
• not specified (2 variants)
• Motor delay;Atypical behavior;Global developmental delay;Delayed speech and language development;Intellectual disability (1 variants)
• Neurofibromatosis, type 1 (1 variants)
• GABBR1-associated neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GABBR1 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				8	3	11
missense		5	29	1		35
nonsense						0
start loss						0
frameshift			3			3
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			1			1
non coding				1		1
Total	0	5	33	10	3

Variants in GABBR1

This is a list of pathogenic ClinVar variants found in the GABBR1 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-29555916-G-T		not specified	Uncertain significance (Oct 16, 2023)
6-29555933-C-T			Likely benign (Jun 25, 2018)
6-29556148-G-A		not specified	Uncertain significance (Apr 05, 2023)
6-29556179-C-T		not specified	Uncertain significance (Oct 05, 2023)
6-29556340-C-T		not specified	Likely benign (Feb 28, 2024)
6-29559690-A-T		not specified	Uncertain significance (Jun 22, 2021)
6-29588133-C-A		not specified	Uncertain significance (Jan 03, 2022)
6-29588306-A-G		not specified	Uncertain significance (Apr 25, 2022)
6-29588354-G-T		not specified	Uncertain significance (Sep 26, 2023)
6-29588356-C-A		not specified	Uncertain significance (Jul 27, 2021)
6-29588390-T-C		not specified	Uncertain significance (Mar 29, 2022)
6-29588489-T-C		not specified	Uncertain significance (Dec 20, 2022)
6-29588533-G-A		not specified	Likely benign (Jan 18, 2022)
6-29588553-C-G		not specified	Uncertain significance (Dec 28, 2022)
6-29588561-T-C		not specified	Uncertain significance (Mar 11, 2022)
6-29588600-T-C		not specified	Uncertain significance (Dec 17, 2021)
6-29588621-T-C		not specified	Uncertain significance (Jun 28, 2023)
6-29588629-G-A		not specified	Uncertain significance (Jul 12, 2022)
6-29588855-G-C		not specified	Uncertain significance (Jan 26, 2022)
6-29603565-C-T		not specified	Uncertain significance (Jun 22, 2021)
6-29603586-C-T		not specified	Uncertain significance (Oct 18, 2021)
6-29603590-C-T		not specified	Uncertain significance (Jul 13, 2022)
6-29603599-C-T		not specified	Uncertain significance (May 04, 2022)
6-29603604-G-A		not specified	Uncertain significance (Jan 10, 2022)
6-29603656-G-A		not specified	Uncertain significance (Mar 02, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GABBR1	protein_coding	protein_coding	ENST00000377034	22	78348

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000879	125737	0	11	125748	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.82	236	556	0.425	0.0000324	6213
Missense in Polyphen		77	246.31	0.31262		2681
Synonymous	0.887	204	221	0.924	0.0000126	1941
Loss of Function	5.98	6	53.0	0.113	0.00000279	567

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000313	0.000308
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000272	0.0000264
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2 (PubMed:9872316, PubMed:9872744, PubMed:15617512, PubMed:18165688, PubMed:22660477, PubMed:24305054). Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins (PubMed:18165688). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase (PubMed:10906333, PubMed:10773016, PubMed:10075644, PubMed:9872744, PubMed:24305054). Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis (PubMed:10075644). Calcium is required for high affinity binding to GABA (By similarity). Plays a critical role in the fine-tuning of inhibitory synaptic transmission (PubMed:9844003). Pre-synaptic GABA receptor inhibits neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials (PubMed:9844003, PubMed:9872316, PubMed:10075644, PubMed:9872744, PubMed:22660477). Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception (Probable). Activated by (-)-baclofen, cgp27492 and blocked by phaclofen (PubMed:9844003, PubMed:9872316, PubMed:24305054). {ECO:0000250|UniProtKB:Q9Z0U4, ECO:0000269|PubMed:10075644, ECO:0000269|PubMed:10773016, ECO:0000269|PubMed:10906333, ECO:0000269|PubMed:15617512, ECO:0000269|PubMed:18165688, ECO:0000269|PubMed:22660477, ECO:0000269|PubMed:24305054, ECO:0000269|PubMed:9844003, ECO:0000269|PubMed:9872316, ECO:0000269|PubMed:9872744, ECO:0000305}.
• Pathway: GABAergic synapse - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Taste transduction - Homo sapiens (human);Morphine addiction - Homo sapiens (human);GPCRs, Class C Metabotropic glutamate, pheromone;Signaling by GPCR;Signal Transduction;Neuronal System;Class C/3 (Metabotropic glutamate/pheromone receptors);GPCR ligand binding;Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits;Activation of GABAB receptors;GABA B receptor activation;GABA receptor activation;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;G alpha (i) signalling events;Activation of G protein gated Potassium channels;GPCR downstream signalling;G protein gated Potassium channels;Inwardly rectifying K+ channels;Potassium Channels (Consensus)

Intolerance Scores

• loftool: 0.0575
• rvis_EVS: -0.43
• rvis_percentile_EVS: 25.37

Haploinsufficiency Scores

• pHI: 0.0662
• hipred: Y
• hipred_score: 0.631
• ghis: 0.564

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.809

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gabbr1
• 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); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype; 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); growth/size/body region phenotype

Zebrafish Information Network

• Gene name: gabbr1b
• Affected structure: behavioral response to nicotine
• Phenotype tag: abnormal
• Phenotype quality: decreased occurrence

Gene ontology

• Biological process: G protein-coupled receptor signaling pathway;adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway;negative regulation of adenylate cyclase activity;gamma-aminobutyric acid signaling pathway;regulation of postsynaptic membrane potential
• Cellular component: extracellular region;cytoplasm;plasma membrane;integral component of plasma membrane;cell junction;dendrite;G protein-coupled receptor heterodimeric complex;presynaptic membrane;postsynaptic membrane;Schaffer collateral - CA1 synapse;GABA-ergic synapse
• Molecular function: G protein-coupled GABA receptor activity;protein binding;G protein-coupled neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential