GABBR2gamma-aminobutyric acid type B receptor subunit 2
Autism Reports / Total Reports
6 / 15Rare Variants / Common Variants
17 / 0Aliases
GABBR2, EIEE59, GABABR2, GPR51, GPRC3B, HG20, HRIHFB2099Associated Syndromes
-Chromosome Band
9q22.33Associated Disorders
ID, ASDRelevance to Autism
De novo mutations in the GABBR2 gene are associated with a form of early-infantile epileptic encephalopathy (EIEE59; OMIM 617904) (EuroEPINOMICS-RES Consortium 2014; Hamdan et al., 2017), as well as with a Rett syndrome-like disorder called neurodevelopmental disorder with poor language and loss of hand skills (NDPLHS; OMIM 617903) (Lopes et al., 2016; Yoo et al., 2017; Vuillaume et al., 2018). One individual with GABBR2-mediated epileptic encephalopathy that was reported in EuroEPINOMICS-RES Consortium 2014 also presented with autism spectrum disorder, whereas individuals with GABBR2-mediated NDPLHS have been reported with autism spectrum disorder, autistic features, and/or stereotypic hand movements. The same recurrent de novo missense variant in GABBR2 that was observed in individuals from Lopes et al., 2016 and Yoo et al., 2017 (p.Ala567Thr) was also identified in a Japanese ASD proband in Takata et al., 2018.
Molecular Function
The multi-pass membrane protein encoded by this gene belongs to the G-protein coupled receptor 3 family and GABA-B receptor subfamily. The GABA-B receptors inhibit neuronal activity through G protein-coupled second-messenger systems, which regulate the release of neurotransmitters, and the activity of ion channels and adenylyl cyclase. This receptor subunit forms an active heterodimeric complex with GABA-B receptor subunit 1, neither of which is effective on its own.
External Links
SFARI Genomic Platforms
Reports related to GABBR2 (15 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Support | Redistribution of GABAB(1) protein and atypical GABAB responses in GABAB(2)-deficient mice | Gassmann M , et al. (2004) | No | - |
| 2 | Support | Altered anxiety and depression-related behaviour in mice lacking GABAB(2) receptor subunits | Mombereau C , et al. (2005) | No | - |
| 3 | Support | Expression of GABA(B) receptors is altered in brains of subjects with autism | Fatemi SH , et al. (2008) | Yes | - |
| 4 | Support | Deficits in GABA(B) receptor system in schizophrenia and mood disorders: a postmortem study | Fatemi SH , et al. (2011) | No | - |
| 5 | Primary | De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies | EuroEPINOMICS-RES Consortium , et al. (2014) | No | ASD |
| 6 | Support | Identification of novel genetic causes of Rett syndrome-like phenotypes | Lopes F , et al. (2016) | No | ID, developmental regression, autistic features, s |
| 7 | Support | GABBR2 mutations determine phenotype in rett syndrome and epileptic encephalopathy | Yoo Y , et al. (2017) | No | ASD |
| 8 | Support | High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies | Hamdan FF , et al. (2017) | No | - |
| 9 | Support | Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder | Takata A , et al. (2018) | Yes | - |
| 10 | Support | A novel mutation in the transmembrane 6 domain of GABBR2 leads to a Rett-like phenotype | Vuillaume ML , et al. (2018) | No | - |
| 11 | Support | De Novo Damaging DNA Coding Mutations Are Associated With Obsessive-Compulsive Disorder and Overlap With Tourette's Disorder and Autism | Cappi C , et al. (2019) | No | - |
| 12 | Support | - | Alonso-Gonzalez A et al. (2021) | Yes | - |
| 13 | Support | - | Chen S et al. (2021) | Yes | DD, ID |
| 14 | Support | - | Zhou X et al. (2022) | Yes | - |
| 15 | Support | - | Noa Bielopolski et al. (2023) | Yes | - |
Rare Variants (17)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.473C>T | p.Ala158Val | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.530C>T | p.Pro177Leu | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.745C>T | p.Arg249Trp | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.1699G>A | p.Ala567Thr | missense_variant | De novo | - | - | 34800434 | Chen S et al. (2021) | |
| c.1700C>T | p.Ala567Val | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.1723A>T | p.Thr575Ser | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.2012G>A | p.Gly671Asp | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.1338C>T | p.Ala446%3D | synonymous_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.1699G>A | p.Ala567Thr | missense_variant | De novo | - | - | 26740508 | Lopes F , et al. (2016) | |
| c.2077G>T | p.Gly693Trp | missense_variant | De novo | - | - | 29100083 | Hamdan FF , et al. (2017) | |
| c.1699G>A | p.Ala567Thr | missense_variant | De novo | - | Simplex | 28856709 | Yoo Y , et al. (2017) | |
| c.399C>T | p.Gly133= | synonymous_variant | De novo | - | Simplex | 31771860 | Cappi C , et al. (2019) | |
| c.635G>A | p.Arg212Gln | missense_variant | De novo | - | - | 38076211 | Noa Bielopolski et al. (2023) | |
| c.1699G>A | p.Ala567Thr | missense_variant | De novo | - | Simplex | 29346770 | Takata A , et al. (2018) | |
| c.1699G>A | p.Ala567Thr | missense_variant | De novo | - | Simplex | 33431980 | Alonso-Gonzalez A et al. (2021) | |
| c.2084G>T | p.Ser695Ile | missense_variant | De novo | - | Simplex | 25262651 | EuroEPINOMICS-RES Consortium , et al. (2014) | |
| c.2114T>A | p.Ile705Asn | missense_variant | De novo | - | Simplex | 25262651 | EuroEPINOMICS-RES Consortium , et al. (2014) |
Common Variants
No common variants reported.
SFARI Gene score
Strong Candidate, Syndromic
De novo mutations in the GABBR2 gene are associated with a form of early-infantile epileptic encephalopathy (EIEE59; OMIM 617904) (EuroEPINOMICS-RES Consortium 2014; Hamdan et al., 2017), as well as with a Rett syndrome-like disorder called neurodevelopmental disorder with poor language and loss of hand skills (NDPLHS; OMIM 617903) (Lopes et al., 2016; Yoo et al., 2017; Vuillaume et al., 2018). One individual with GABBR2-mediated epileptic encephalopathy that was reported in EuroEPINOMICS-RES Consortium 2014 also presented with autism spectrum disorder, whereas individuals with GABBR2-mediated NDPLHS have been reported with autism spectrum disorder, autistic features, and/or stereotypic hand movements. The same recurrent de novo missense variant in GABBR2 that was observed in individuals from Lopes et al., 2016 and Yoo et al., 2017 (p.Ala567Thr) was also identified in a Japanese ASD proband in Takata et al., 2018.
Score Delta: Score remained at 2S
criteria met
See SFARI Gene'scoring criteriaWe considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.
The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."
4/1/2022
Decreased from 3S to 2S
Description
De novo mutations in the GABBR2 gene are associated with a form of early-infantile epileptic encephalopathy (EIEE59; OMIM 617904) (EuroEPINOMICS-RES Consortium 2014; Hamdan et al., 2017), as well as with a Rett syndrome-like disorder called neurodevelopmental disorder with poor language and loss of hand skills (NDPLHS; OMIM 617903) (Lopes et al., 2016; Yoo et al., 2017; Vuillaume et al., 2018). One individual with GABBR2-mediated epileptic encephalopathy that was reported in EuroEPINOMICS-RES Consortium 2014 also presented with autism spectrum disorder, whereas individuals with GABBR2-mediated NDPLHS have been reported with autism spectrum disorder, autistic features, and/or stereotypic hand movements. The same recurrent de novo missense variant in GABBR2 that was observed in individuals from Lopes et al., 2016 and Yoo et al., 2017 (p.Ala567Thr) was also identified in a Japanese ASD proband in Takata et al., 2018.
1/1/2021
Decreased from 3S to 3S
Description
De novo mutations in the GABBR2 gene are associated with a form of early-infantile epileptic encephalopathy (EIEE59; OMIM 617904) (EuroEPINOMICS-RES Consortium 2014; Hamdan et al., 2017), as well as with a Rett syndrome-like disorder called neurodevelopmental disorder with poor language and loss of hand skills (NDPLHS; OMIM 617903) (Lopes et al., 2016; Yoo et al., 2017; Vuillaume et al., 2018). One individual with GABBR2-mediated epileptic encephalopathy that was reported in EuroEPINOMICS-RES Consortium 2014 also presented with autism spectrum disorder, whereas individuals with GABBR2-mediated NDPLHS have been reported with autism spectrum disorder, autistic features, and/or stereotypic hand movements. The same recurrent de novo missense variant in GABBR2 that was observed in individuals from Lopes et al., 2016 and Yoo et al., 2017 (p.Ala567Thr) was also identified in a Japanese ASD proband in Takata et al., 2018.
7/1/2020
Decreased from 3S to 3S
Description
De novo mutations in the GABBR2 gene are associated with a form of early-infantile epileptic encephalopathy (EIEE59; OMIM 617904) (EuroEPINOMICS-RES Consortium 2014; Hamdan et al., 2017), as well as with a Rett syndrome-like disorder called neurodevelopmental disorder with poor language and loss of hand skills (NDPLHS; OMIM 617903) (Lopes et al., 2016; Yoo et al., 2017; Vuillaume et al., 2018). One individual with GABBR2-mediated epileptic encephalopathy that was reported in EuroEPINOMICS-RES Consortium 2014 also presented with autism spectrum disorder, whereas individuals with GABBR2-mediated NDPLHS have been reported with autism spectrum disorder, autistic features, and/or stereotypic hand movements. The same recurrent de novo missense variant in GABBR2 that was observed in individuals from Lopes et al., 2016 and Yoo et al., 2017 (p.Ala567Thr) was also identified in a Japanese ASD proband in Takata et al., 2018.
1/1/2020
Decreased from 3S to 3S
Description
De novo mutations in the GABBR2 gene are associated with a form of early-infantile epileptic encephalopathy (EIEE59; OMIM 617904) (EuroEPINOMICS-RES Consortium 2014; Hamdan et al., 2017), as well as with a Rett syndrome-like disorder called neurodevelopmental disorder with poor language and loss of hand skills (NDPLHS; OMIM 617903) (Lopes et al., 2016; Yoo et al., 2017; Vuillaume et al., 2018). One individual with GABBR2-mediated epileptic encephalopathy that was reported in EuroEPINOMICS-RES Consortium 2014 also presented with autism spectrum disorder, whereas individuals with GABBR2-mediated NDPLHS have been reported with autism spectrum disorder, autistic features, and/or stereotypic hand movements. The same recurrent de novo missense variant in GABBR2 that was observed in individuals from Lopes et al., 2016 and Yoo et al., 2017 (p.Ala567Thr) was also identified in a Japanese ASD proband in Takata et al., 2018.
10/1/2019
Decreased from 4S to 3S
New Scoring Scheme
Description
De novo mutations in the GABBR2 gene are associated with a form of early-infantile epileptic encephalopathy (EIEE59; OMIM 617904) (EuroEPINOMICS-RES Consortium 2014; Hamdan et al., 2017), as well as with a Rett syndrome-like disorder called neurodevelopmental disorder with poor language and loss of hand skills (NDPLHS; OMIM 617903) (Lopes et al., 2016; Yoo et al., 2017; Vuillaume et al., 2018). One individual with GABBR2-mediated epileptic encephalopathy that was reported in EuroEPINOMICS-RES Consortium 2014 also presented with autism spectrum disorder, whereas individuals with GABBR2-mediated NDPLHS have been reported with autism spectrum disorder, autistic features, and/or stereotypic hand movements. The same recurrent de novo missense variant in GABBR2 that was observed in individuals from Lopes et al., 2016 and Yoo et al., 2017 (p.Ala567Thr) was also identified in a Japanese ASD proband in Takata et al., 2018.
Reports Added
[New Scoring Scheme]7/1/2018
Increased from to 4S
Description
De novo mutations in the GABBR2 gene are associated with a form of early-infantile epileptic encephalopathy (EIEE59; OMIM 617904) (EuroEPINOMICS-RES Consortium 2014; Hamdan et al., 2017), as well as with a Rett syndrome-like disorder called neurodevelopmental disorder with poor language and loss of hand skills (NDPLHS; OMIM 617903) (Lopes et al., 2016; Yoo et al., 2017; Vuillaume et al., 2018). One individual with GABBR2-mediated epileptic encephalopathy that was reported in EuroEPINOMICS-RES Consortium 2014 also presented with autism spectrum disorder, whereas individuals with GABBR2-mediated NDPLHS have been reported with autism spectrum disorder, autistic features, and/or stereotypic hand movements. The same recurrent de novo missense variant in GABBR2 that was observed in individuals from Lopes et al., 2016 and Yoo et al., 2017 (p.Ala567Thr) was also identified in a Japanese ASD proband in Takata et al., 2018.
Krishnan Probability Score
Score 0.64741431954756
Ranking 41/25841 scored genes
[Show Scoring Methodology]
ExAC Score
Score 0.99979026252187
Ranking 781/18225 scored genes
[Show Scoring Methodology]
Sanders TADA Score
Score 0.94545108356248
Ranking 16475/18665 scored genes
[Show Scoring Methodology]