Human Gene Module / Chromosome 7 / GNB2

GNB2G protein subunit beta 2

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
3 / 7
Rare Variants / Common Variants
16 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
7q22.1
Associated Disorders
-
Relevance to Autism

Heterozygous mutations in the GNB2 gene are responsible for neurodevelopmental disorder with hypotonia and dysmorphic facies (NEDHYDF; OMIM 619503) (Fukuda et al., 2020; Lansdon et al., 2021; Tan et al., 2021). Tan et al., 2021 identified 12 unrelated individuals with five de novo missense variants in the GNB2 gene; all individuals presented with developmental delay/intellectual disability with variable dysmorphism and extraneurologic features, and autistic behaviors were observed in six of these individuals, two of whom were diagnosed with autism spectrum disorder. A de novo missense variant in this gene was observed in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014).

Molecular Function

Heterotrimeric guanine nucleotide-binding proteins (G proteins), which integrate signals between receptors and effector proteins, are composed of an alpha, a beta, and a gamma subunit. These subunits are encoded by families of related genes. This gene encodes a beta subunit. Beta subunits are important regulators of alpha subunits, as well as of certain signal transduction receptors and effectors.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to GNB2 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Support - Fukuda T et al. (2020) No -
3 Support - Lansdon LA et al. (2021) No -
4 Primary - Tan NB et al. (2021) No ASD or autistic behavior, stereotypy
5 Support - Zhou X et al. (2022) Yes -
6 Support - Cirnigliaro M et al. (2023) Yes -
7 Support - Axel Schmidt et al. (2024) No -
Rare Variants   (16)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.217G>A p.Ala73Thr missense_variant De novo - - 34183358 Tan NB et al. (2021)
c.229G>A p.Gly77Arg missense_variant De novo - - 34183358 Tan NB et al. (2021)
c.265A>G p.Lys89Glu missense_variant De novo - - 34183358 Tan NB et al. (2021)
c.266A>C p.Lys89Thr missense_variant De novo - - 34183358 Tan NB et al. (2021)
c.217G>A p.Ala73Thr missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.803A>T p.Asn268Ile missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.229G>A p.Gly77Arg missense_variant De novo - - 31698099 Fukuda T et al. (2020)
c.229G>T p.Gly77Trp missense_variant De novo - - 33971351 Lansdon LA et al. (2021)
c.217G>A p.Ala73Thr missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.217G>A p.Ala73Thr missense_variant De novo - - 39039281 Axel Schmidt et al. (2024)
c.217G>A p.Ala73Thr missense_variant De novo - Simplex 34183358 Tan NB et al. (2021)
c.229G>A p.Gly77Arg missense_variant De novo - Simplex 34183358 Tan NB et al. (2021)
c.265A>G p.Lys89Glu missense_variant De novo - Simplex 34183358 Tan NB et al. (2021)
c.266A>C p.Lys89Thr missense_variant De novo - Simplex 34183358 Tan NB et al. (2021)
c.440C>T p.Ser147Leu missense_variant De novo - Simplex 34183358 Tan NB et al. (2021)
c.-89_-55del - splice_site_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

Score Delta: Score remained at S

criteria met
See SFARI Gene'scoring criteria
S

Syndromic

See all Category S Genes

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."

Krishnan Probability Score

Score 0.61246222882569

Ranking 169/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.98923943467318

Ranking 1828/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.71078855815418

Ranking 1228/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Zhang D Score

Score 0.028977159325268

Ranking 7814/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
Submit New Gene

Report an Error