GeneBe

GABBR1

protein-coding

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

Gene summary

This gene encodes a receptor for gamma-aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the mammalian central nervous system. This receptor functions as a heterodimer with GABA(B) receptor 2. Defects in this gene may underlie brain disorders such as schizophrenia and epilepsy. Alternative splicing generates multiple transcript variants, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jan 2016]

MANE transcript

NM_001470.4

Inheritance

AD

ClinVar variants

P:10U:157B:15

Top phenotype

Neurodevelopmental disorder with language delay and variable cognitive abnormalities

gnomAD constraint

pLI —, LoF o/e 0.11

Max pathogenic AF

—

Genomic locus

chr6:29,555,629-29,633,976

External References & Databases

Ensembl (ENSG00000204681)NCBI Gene (2550)OMIM (603540)HGNC:4070GenCCUniProt (Q9UBS5)AlphaFoldClinVar (GABBR1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~78.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with language delay and variable cognitive abnormalitiesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0957779

Submitter: PanelApp Australia

neurodevelopmental disorder with language delay and variable cognitive abnormalitiesMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0957779

Submitter: G2P

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with language delay and variable cognitive abnormalitiesAD

Manifestation: Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic

Intervention: General

Rationale: 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

Refs: 36103875Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GABBR1 variants in ClinVar

12 Conditions Cataloged
not specifiedTotal: 83
not providedTotal: 75
Neurodevelopmental disorder with language delay and variable cognitive abnormalitiesTotal: 21
Global developmental delayTotal: 4
Intellectual disabilityTotal: 4
Delayed speech and language developmentTotal: 4
GABBR1-related conditionTotal: 3
Motor delayTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001470.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
7
clinvar
9
clinvar
3
clinvar
 19
missense
10
clinvar
131
clinvar
3
clinvar
 144
nonsense
3
clinvar
 3
start loss
0
frameshift
8
clinvar
 8
splice donor/acceptor (+/-2bp)
8
clinvar
 8
Total010157123182
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001470.4RefSeqNP_001461.122MANE Select
ENST00000377034.9EnsemblENSP00000366233.422MANE Select
NM_001319053.2RefSeqNP_001305982.118Standard
NM_021903.3RefSeqNP_068703.118Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
gabbr1bDanio rerio

Structure: behavioral response to nicotine

Quality: decreased occurrence

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • 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)

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

Molecular Function

  • G protein-coupled GABA receptor activity
  • protein binding
  • G protein-coupled neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential

Cellular Component

  • extracellular region
  • cytoplasm
  • plasma membrane
  • integral component of plasma membrane
  • cell junction

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000377034
Coding exons
22
Length
78348
Individuals with no LoFs
125737
Homozygous LoFs
0
Heterozygous LoFs
11
Defined
125748
p
0.0000437
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense4.822365560.4250.00003246213
Missense (PolyPhen)77246.310.312622681
Synonymous0.8872042210.9240.00001261941
Loss of Function5.98653.00.1130.00000279567

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000310.00031rare
Latino/Admixed American00.0absent
Ashkenazi Jewish0.0000990.000099rare
East Asian0.0000540.000054rare
Finnish0.0000460.000046rare
European (Non-Finnish)0.0000270.000026rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

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}.;

Intolerance Scores

LoFtool
0.0575
RVIS EVS
-0.43
RVIS percentile EVS
25.37

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.809

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.