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
Phenotypes
GenCC
Source:
- epilepsy, childhood absence, susceptibility to, 5 (Definitive), mode of inheritance: AD
- Lennox-Gastaut syndrome (Supportive), mode of inheritance: AD
- childhood absence epilepsy (Supportive), mode of inheritance: AD
- developmental and epileptic encephalopathy, 43 (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
- genetic developmental and epileptic encephalopathy (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| 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
- Epilepsy,_childhood_absence,_susceptibility_to,_5 (496 variants)
- Epilepsy,_childhood_absence,_susceptibility_to,_1 (489 variants)
- not_provided (175 variants)
- Developmental_and_epileptic_encephalopathy,_43 (65 variants)
- Inborn_genetic_diseases (49 variants)
- not_specified (29 variants)
- GABRB3-related_disorder (17 variants)
- Intellectual_disability (5 variants)
- Seizure (5 variants)
- Epileptic_encephalopathy (4 variants)
- Epilepsy (2 variants)
- Neurodevelopmental_delay (2 variants)
- Schizophrenia (1 variants)
- Global_developmental_delay (1 variants)
- See_cases (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 | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 123 | 125 | ||||
| missense | 18 | 59 | 226 | 25 | 332 | |
| nonsense | 16 | |||||
| start loss | 0 | |||||
| frameshift | 14 | |||||
| splice donor/acceptor (+/-2bp) | 7 | |||||
| Total | 34 | 65 | 241 | 148 | 6 |
Highest pathogenic variant AF is 0.000005198532
Loading clinvar variants...
GnomAD
Source:
| 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 |
|---|---|---|---|---|---|---|
| 0.951 | 0.0486 | 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:
- 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
Haploinsufficiency Scores
- pHI
- 0.874
- hipred
- Y
- hipred_score
- 0.808
- ghis
- 0.585
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 |
Mouse Genome Informatics
- Gene name
- Gabrb3
- Phenotype
- craniofacial phenotype; growth/size/body region phenotype; reproductive system phenotype; digestive/alimentary 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; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); normal phenotype; 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);
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