Human Gene Module / Chromosome 2 / SNTG2

SNTG2syntrophin gamma 2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 7
Rare Variants / Common Variants
6 / 0
Aliases
SNTG2, G2SYN,  MGC133174,  SYN5
Associated Syndromes
-
Chromosome Band
2p25.3
Associated Disorders
-
Relevance to Autism

A deletion containing part of the SNTG2 gene was identified in a patient with autistic features that was inherited from a mother with a mild personality disorder and was absent in a normal brother (Rosenfeld et al., 2010). In a subsequent study, a translocation disrupting the SNTG2 gene was identified in a female proband diagnosed with autism (Talkowski et al., 2012).

Molecular Function

his gene encodes a protein belonging to the syntrophin family. Syntrophins are cytoplasmic peripheral membrane proteins that bind to components of mechanosenstive sodium channels and the extreme carboxy-terminal domain of dystrophin and dystrophin-related proteins. The PDZ domain of this protein product interacts with a protein component of a mechanosensitive sodium channel that affects channel gating. Absence or reduction of this protein product has been associated with Duchenne muscular dystrophy.

SFARI Genomic Platforms
Reports related to SNTG2 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited Neuroligins 3 and 4X interact with syntrophin-gamma2, and the interactions are affected by autism-related mutations Yamakawa H , et al. (2007) No -
2 Primary Copy number variations associated with autism spectrum disorders contribute to a spectrum of neurodevelopmental disorders Rosenfeld JA , et al. (2010) Yes -
3 Recent Recommendation Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries Talkowski ME , et al. (2012) Yes -
4 Support Identification of rare copy number variants in high burden schizophrenia families Van Den Bossche MJ , et al. (2013) No -
5 Support Exome sequencing in multiplex autism families suggests a major role for heterozygous truncating mutations Toma C , et al. (2013) Yes -
6 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
7 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - translocation Unknown - - 22521361 Talkowski ME , et al. (2012)
- - copy_number_loss Familial Maternal Simplex 20808228 Rosenfeld JA , et al. (2010)
- - copy_number_gain Familial Paternal Multiplex 23505263 Van Den Bossche MJ , et al. (2013)
c.1273C>T p.Gln425Ter stop_gained Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.1115T>C p.Leu372Ser missense_variant Familial Maternal Multiplex 23999528 Toma C , et al. (2013)
c.435_442del p.Asp146TyrfsTer5 frameshift_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A deletion containing part of the SNTG2 gene was identified in a patient with autistic features that was inherited from a mother with a mild personality disorder and was absent in a normal brother (PMID 20808228). In a subsequent study, a translocation disrupting the SNTG2 gene was identified in a female proband diagnosed with autism (PMID 22521361).

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

A deletion containing part of the SNTG2 gene was identified in a patient with autistic features that was inherited from a mother with a mild personality disorder and was absent in a normal brother (PMID 20808228). In a subsequent study, a translocation disrupting the SNTG2 gene was identified in a female proband diagnosed with autism (PMID 22521361).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A deletion containing part of the SNTG2 gene was identified in a patient with autistic features that was inherited from a mother with a mild personality disorder and was absent in a normal brother (PMID 20808228). In a subsequent study, a translocation disrupting the SNTG2 gene was identified in a female proband diagnosed with autism (PMID 22521361).

Reports Added
[New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

A deletion containing part of the SNTG2 gene was identified in a patient with autistic features that was inherited from a mother with a mild personality disorder and was absent in a normal brother (PMID 20808228). In a subsequent study, a translocation disrupting the SNTG2 gene was identified in a female proband diagnosed with autism (PMID 22521361).

7/1/2014
No data
icon
4

Increased from No data to 4

Description

A deletion containing part of the SNTG2 gene was identified in a patient with autistic features that was inherited from a mother with a mild personality disorder and was absent in a normal brother (PMID 20808228). In a subsequent study, a translocation disrupting the SNTG2 gene was identified in a female proband diagnosed with autism (PMID 22521361).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

A deletion containing part of the SNTG2 gene was identified in a patient with autistic features that was inherited from a mother with a mild personality disorder and was absent in a normal brother (PMID 20808228). In a subsequent study, a translocation disrupting the SNTG2 gene was identified in a female proband diagnosed with autism (PMID 22521361).

Krishnan Probability Score

Score 0.49532960903435

Ranking 3044/25841 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 9.1760883234385E-7

Ranking 15055/18225 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 0.93806249011806

Ranking 13735/18665 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 8

Ranking 236/461 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 0.11926285572312

Ranking 5740/20870 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
EPSTI1 Epithelial-stromal interaction protein 1 Human Protein Binding 94240 Q96J88-2
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