Human Gene Module / Chromosome 22 / GNB1L

GNB1Lguanine nucleotide binding protein (G protein), beta polypeptide 1-like

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
7 / 1
Aliases
GNB1L, FKSG1,  DGCRK3,  GY2,  WDR14,  WDVCF
Associated Syndromes
-
Chromosome Band
22q11.21
Associated Disorders
-
Relevance to Autism

Rare mutations in the GNB1L gene, including a translocation, duplications and missense variants, have been identified in patients with ASD (Chen et al., 2011).

Molecular Function

This gene encodes a G-protein beta-subunit-like polypeptide which is a member of the WD repeat protein family. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This protein contains 6 WD repeats and is highly expressed in the heart. Transcripts from this gene share exons with some transcripts from the C22orf29 gene.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to GNB1L (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Evidence for involvement of GNB1L in autism Chen YZ , et al. (2011) Yes -
2 Positive Association A genome-wide investigation into parent-of-origin effects in autism spectrum disorder identifies previously associated genes including SHANK3 Connolly S , et al. (2016) Yes -
3 Support - Zhou X et al. (2022) Yes -
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - translocation Familial Paternal - 22095694 Chen YZ , et al. (2011)
- - copy_number_gain De novo - Multiplex 22095694 Chen YZ , et al. (2011)
- - copy_number_gain Familial Paternal Multiplex 22095694 Chen YZ , et al. (2011)
c.852G>A p.Thr284%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.262C>T p.Arg88Trp missense_variant Familial Paternal Multiplex 22095694 Chen YZ , et al. (2011)
c.848G>A p.Arg283Gln missense_variant Familial Maternal Multiplex 22095694 Chen YZ , et al. (2011)
c.868G>T p.Val290Leu missense_variant Familial Maternal Multiplex 22095694 Chen YZ , et al. (2011)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.-21+1553T>C - intron_variant - - - 27876814 Connolly S , et al. (2016)
SFARI Gene score
2

Strong Candidate

Rare mutations in the GNB1L gene, including a translocation, duplications and missense variants, have been identified in patients with ASD (Chen et al., 2011).

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We 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.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

Rare mutations in the GNB1L gene, including a translocation, duplications and missense variants, have been identified in patients with ASD (Chen et al., 2011).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Rare mutations in the GNB1L gene, including a translocation, duplications and missense variants, have been identified in patients with ASD (Chen et al., 2011).

Reports Added
[New Scoring Scheme]
10/1/2016
4
icon
4

Decreased from 4 to 4

Description

Rare mutations in the GNB1L gene, including a translocation, duplications and missense variants, have been identified in patients with ASD (Chen et al., 2011).

Reports Added
[A genome-wide investigation into parent-of-origin effects in autism spectrum disorder identifies previously associated genes including SHANK3.2016]
7/1/2014
No data
icon
4

Increased from No data to 4

Description

Rare mutations in the GNB1L gene, including a translocation, duplications and missense variants, have been identified in patients with ASD (Chen et al., 2011).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

Rare mutations in the GNB1L gene, including a translocation, duplications and missense variants, have been identified in patients with ASD (Chen et al., 2011).

Krishnan Probability Score

Score 0.40184942593076

Ranking 23351/25841 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 0.0012634523374608

Ranking 11613/18225 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 0.94337201420374

Ranking 15662/18665 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
Larsen Cumulative Evidence Score

Score 5

Ranking 281/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Original Source
Zhang D Score

Score -0.50779324077535

Ranking 19320/20870 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
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
ASPRV1 Retroviral-like aspartic protease 1 Human Protein Binding 151516 Q53RT3
GAS2L1 VASH1 Human Protein Binding 10634 A0A5E8
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