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.

SFARI Genomic Platforms
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

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).

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.
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
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).
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.
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.
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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