Human Gene Module / Chromosome 7 / STX1A

STX1ASyntaxin 1A (brain)

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 7
Rare Variants / Common Variants
8 / 5
Aliases
STX1A, HPC-1,  P35-1,  STX1,  SYN1A
Associated Syndromes
-
Chromosome Band
7q11.23
Associated Disorders
-
Relevance to Autism

Nominal association of common variants in the STX1A gene with ASD (in particular high-functioning autism and Asperger syndrome) has been reported in several publications (Nakamura et al., 2008; Nakamura et al., 2011; Durdiakova et al., 2014).

Molecular Function

This gene encodes a member of the syntaxin superfamily. Syntaxins are nervous system-specific proteins implicated in the docking of synaptic vesicles with the presynaptic plasma membrane. This gene product is a key molecule in ion channel regulation and synaptic exocytosis.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to STX1A (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Genetic and expression analyses reveal elevated expression of syntaxin 1A ( STX1A) in high functioning autism Nakamura K , et al. (2008) Yes -
2 Positive Association Replication study of Japanese cohorts supports the role of STX1A in autism susceptibility Nakamura K , et al. (2010) Yes -
3 Positive Association STX1A and Asperger syndrome: a replication study Durdiakov J , et al. (2014) Yes -
4 Support Rare autism-associated variants implicate syntaxin 1 (STX1 R26Q) phosphorylation and the dopamine transporter (hDAT R51W) in dopamine neurotransmission and behaviors Cartier E , et al. (2015) Yes -
5 Support Diagnostic Yield and Novel Candidate Genes by Exome Sequencing in 152 Consanguineous Families With Neurodevelopmental Disorders Reuter MS , et al. (2017) No -
6 Support A part of patients with autism spectrum disorder has haploidy of HPC-1/syntaxin1A gene that possibly causes behavioral disturbance as in experimentally gene ablated mice Kofuji T , et al. (2017) Yes -
7 Recent Recommendation - Luppe J et al. (2023) No ASD or autistic features, epilepsy/seizures
Rare Variants   (8)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss - - - 28235601 Kofuji T , et al. (2017)
c.435C>G p.Cys145Trp missense_variant De novo - Simplex 36564538 Luppe J et al. (2023)
c.554C>G p.Ser185Cys missense_variant De novo - Simplex 36564538 Luppe J et al. (2023)
c.677A>G p.Gln226Arg missense_variant De novo - Simplex 36564538 Luppe J et al. (2023)
c.722_724del p.Val241del inframe_deletion De novo - Simplex 36564538 Luppe J et al. (2023)
c.668_670del p.Val223del inframe_deletion Unknown - Unknown 36564538 Luppe J et al. (2023)
c.77G>A p.Arg26Gln missense_variant Familial Paternal Simplex 25774383 Cartier E , et al. (2015)
c.284-1G>A - splice_site_variant Familial Both parents Multiplex 28097321 Reuter MS , et al. (2017)
Common Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
- - gene_variant - - - 21118708 Nakamura K , et al. (2010)
c.31-1811C>T G/A intron_variant - - - 24548729 Durdiakov J , et al. (2014)
c.204T>C p.(=) synonymous_variant - - - 18593506 Nakamura K , et al. (2008)
c.678+698A>T;c.793+583A>T T/A intron_variant - - - 18593506 Nakamura K , et al. (2008)
c.678+698A>T;c.793+583A>T T/A intron_variant - - - 24548729 Durdiakov J , et al. (2014)
SFARI Gene score
2

Strong Candidate

Nominal association of common variants in the STX1A gene with ASD (in particular high-functioning autism and Asperger syndrome) has been reported in several publications (Nakamura et al., 2008; Nakamura et al., 2011; Durdiakova et al., 2014). A paternally-inherited missense variant that was shown experimentally to decreases STX1 phosphorylation and reverse transport of dopamine without decreasing dopamine uptake was iidentified in a male ASD proband from the Simons Simplex Collection in Cartier et al., 2015; this variant was not observed in an unaffected female sibling. Exon-disrupting deletions affecting the STX1 gene were also observed in 83 Japanese ASD cases but not in 51 Japanese controls (Kofuji et al., 2017).

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

Nominal association of common variants in the STX1A gene with ASD (in particular high-functioning autism and Asperger syndrome) has been reported in several publications (Nakamura et al., 2008; Nakamura et al., 2011; Durdiakova et al., 2014). A paternally-inherited missense variant that was shown experimentally to decreases STX1 phosphorylation and reverse transport of dopamine without decreasing dopamine uptake was iidentified in a male ASD proband from the Simons Simplex Collection in Cartier et al., 2015; this variant was not observed in an unaffected female sibling. Exon-disrupting deletions affecting the STX1 gene were also observed in 83 Japanese ASD cases but not in 51 Japanese controls (Kofuji et al., 2017).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Nominal association of common variants in the STX1A gene with ASD (in particular high-functioning autism and Asperger syndrome) has been reported in several publications (Nakamura et al., 2008; Nakamura et al., 2011; Durdiakova et al., 2014). A paternally-inherited missense variant that was shown experimentally to decreases STX1 phosphorylation and reverse transport of dopamine without decreasing dopamine uptake was iidentified in a male ASD proband from the Simons Simplex Collection in Cartier et al., 2015; this variant was not observed in an unaffected female sibling. Exon-disrupting deletions affecting the STX1 gene were also observed in 83 Japanese ASD cases but not in 51 Japanese controls (Kofuji et al., 2017).

Reports Added
[New Scoring Scheme]
10/1/2017
icon
4

Increased from to 4

Description

Nominal association of common variants in the STX1A gene with ASD (in particular high-functioning autism and Asperger syndrome) has been reported in several publications (Nakamura et al., 2008; Nakamura et al., 2011; Durdiakova et al., 2014). A paternally-inherited missense variant that was shown experimentally to decreases STX1 phosphorylation and reverse transport of dopamine without decreasing dopamine uptake was iidentified in a male ASD proband from the Simons Simplex Collection in Cartier et al., 2015; this variant was not observed in an unaffected female sibling. Exon-disrupting deletions affecting the STX1 gene were also observed in 83 Japanese ASD cases but not in 51 Japanese controls (Kofuji et al., 2017).

Krishnan Probability Score

Score 0.59498796903367

Ranking 449/25841 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 0.91047575716485

Ranking 3141/18225 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 0.92442228124509

Ranking 9986/18665 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 10

Ranking 193/461 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 0.31638523507517

Ranking 2496/20870 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
CNVs associated with STX1A(1 CNVs)
Sort By:
7q11.23 82 Deletion-Duplication 112  /  450
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
STXBP6 Syntaxin-binding protein 6 Human Protein Binding 29091 Q8NFX7-2
VAMP5 vesicle-associated membrane protein 5 Human Protein Binding 10791 O95183
Submit New Gene

Report an Error