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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

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Genetic and expression analyses reveal elevated expression of syntaxin 1A ( STX1A) in high functioning autism.
ASD
Positive Association
STX1A and Asperger syndrome: a replication study.
ASD
Positive Association
Replication study of Japanese cohorts supports the role of STX1A in autism susceptibility.
ASD
Support
A part of patients with autism spectrum disorder has haploidy of HPC-1/syntaxin1A gene that possibly causes behavioral disturbance as in experiment...
ASD
Support
Diagnostic Yield and Novel Candidate Genes by Exome Sequencing in 152 Consanguineous Families With Neurodevelopmental Disorders.
ID, hypotonia
Support
Rare autism-associated variants implicate syntaxin 1 (STX1 R26Q) phosphorylation and the dopamine transporter (hDAT R51W) in dopamine neurotransmis...
ASD
Recent Recommendation
DD, ID
ASD or autistic features, epilepsy/seizures

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN600R001 
 missense_variant 
 c.77G>A 
 p.Arg26Gln 
 Familial 
 Paternal 
 Simplex 
 GEN600R002a 
 splice_site_variant 
 c.284-1G>A 
  
 Familial 
 Both parents 
 Multiplex 
 GEN600R003 
 copy_number_loss 
  
  
  
  
  
 GEN600R004 
 copy_number_loss 
  
  
  
  
  
 GEN600R005 
 missense_variant 
 c.435C>G 
 p.Cys145Trp 
 De novo 
  
 Simplex 
 GEN600R006 
 missense_variant 
 c.435C>G 
 p.Cys145Trp 
 De novo 
  
 Simplex 
 GEN600R007 
 missense_variant 
 c.554C>G 
 p.Ser185Cys 
 De novo 
  
 Simplex 
 GEN600R008 
 inframe_deletion 
 c.668_670del 
 p.Val223del 
 Unknown 
  
 Unknown 
 GEN600R009 
 missense_variant 
 c.677A>G 
 p.Gln226Arg 
 De novo 
  
 Simplex 
 GEN600R010 
 inframe_deletion 
 c.722_724del 
 p.Val241del 
 De novo 
  
 Simplex 

Common

Variant ID
Polymorphism
SNP ID
Allele Change
Residue Change
Population Origin
Population Stage
Author, Year
 GEN600C001 
 synonymous_variant 
 rs2228607 
 c.204T>C 
 p.(=) 
 249 AGRE trios with male ASD probands; probands of 102 trios with IQ>70 (considered as high functioning autism; HFA) 
 Discovery 
 GEN600C002 
 intron_variant 
 rs4717806 
 c.678+698A>T;c.793+583A>T 
 T/A 
 249 AGRE trios with male ASD probands; probands of 102 trios with IQ>70 (considered as high functioning autism; HFA) 
 Discovery 
 GEN600C003 
 gene_variant 
 rs69510130 
  
  
 Japanese ASD trios 
 Discovery 
 GEN600C004 
 intron_variant 
 rs4717806 
 c.678+698A>T;c.793+583A>T 
 T/A 
 479 individuals with Asperger syndrome, 650 controls (all of Caucasian ancestry) 
 Replication 
 GEN600C005 
 intron_variant 
 rs941298 
 c.31-1811C>T 
 G/A 
 479 individuals with Asperger syndrome, 650 controls (all of Caucasian ancestry) 
 Discovery 
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
7
Deletion
 2
 
7
Deletion
 1
 
7
Duplication
 10
 
7
Deletion
 3
 
7
Deletion-Duplication
 86
  construct

Model Summary

Syntaxin 1A heterozygous knockout model shows deficits in latent inhibition. Using a pharmaceutical agent TTK21 that is a KAT3 activator, Stx1a expression is increased in the heterozygous and the latent inhibition phenotype is rescued.

References

Type
Title
Author, Year
Primary
Activator of KAT3 histone acetyltransferase family ameliorates a neurodevelopmental disorder phenotype in the syntaxin 1A ablated mouse model

M_STX1A_1_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: The Stx1a knockout allele (MGI:3629049) replaces the sequence encompassing exon 9 and part of exon 10, encoding the H3 and transmembrane domains, with a neomycin resistance gene.
Allele Type: Knockout
Strain of Origin: C57BL/6NCrlj x CBA/JNCrlj
Genetic Background: C57BL/6J
ES Cell Line: TT2
Mutant ES Cell Line:
Model Source: Kimio Akagawa lab

M_STX1A_2_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: The Stx1a knockout allele (MGI:3629049) replaces the sequence encompassing exon 9 and part of exon 10, encoding the H3 and transmembrane domains, with a neomycin resistance gene.
Allele Type: Knockout
Strain of Origin: C57BL/6NCrlj x CBA/JNCrlj
Genetic Background: C57BL/6J
ES Cell Line: TT2
Mutant ES Cell Line:
Model Source: Kimio Akagawa lab

M_STX1A_1_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Bioactive compound levels: serotonin1
Decreased
Description: Heterozygous knockout mice show decreased levels of 5-HIAA, and 5-HIAA/5-HT ratio in hypothalamus.
Exp Paradigm: electrochemical detection (ECD) coupled with HPLC
 High-performance liquid chromatography (HPLC)
 9-16 weeks
Cued or contextual fear conditioning: latent inhibition1
Decreased
Description: Heterozygous knockout mice show a deficit in latent inhibition.
 Fear conditioning test
 9-16 weeks
Targeted expression1
Decreased
Description: Heterozygous knockout mice show a reduction in STX1A protein.
 Western blot
 9-16 weeks
Cued or contextual fear conditioning1
 No change
 Fear conditioning test
 9-16 weeks
 Not Reported:

M_STX1A_2_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Cued or contextual fear conditioning: latent inhibition1
Decreased
Description: Knockout mice show a deficit in latent inhibition.
 Fear conditioning test
 9-16 weeks
Cued or contextual fear conditioning1
 No change
 Fear conditioning test
 9-16 weeks
 Not Reported:





Download STX1A's Cytoscape file

Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
C14ORF104 Protein kintoun 55172 Q9NVR5-2 IP; LC-MS/MS
Huttlin EL , et al. 2015
CDR2 cerebellar degeneration-related protein 2, 62kDa 1039 Q01850 IP; LC-MS/MS
Huttlin EL , et al. 2015
DGUOK deoxyguanosine kinase 1716 E5KSL5 IP; LC-MS/MS
Huttlin EL , et al. 2015
HAX1 HCLS1 associated protein X-1 10456 O00165 IP; LC-MS/MS
Huttlin EL , et al. 2015
NAPB N-ethylmaleimide-sensitive factor attachment protein, beta 63908 Q9H115 Y2H
Corominas R , et al. 2014
NUFIP1 Nuclear FMRP Interacting Protein 1 26747 Q9UHK0 IP; LC-MS/MS
Huttlin EL , et al. 2015
OIP5 Protein Mis18-beta 11339 O43482 IP; LC-MS/MS
Huttlin EL , et al. 2015
PSMA3 proteasome (prosome, macropain) subunit, alpha type, 3 5684 P25788 Y2H
Corominas R , et al. 2014
SLC6A3 solute carrier family 6 (neurotransmitter transporter, dopamine), member 3 6531 Q01959 GST; IP/WB
Binda F , et al. 2008
SNAP23 synaptosomal-associated protein, 23kDa 8773 A8K287 Y2H
Corominas R , et al. 2014
SNAP29 synaptosomal-associated protein, 29kDa 9342 O95721 Y2H
Corominas R , et al. 2014
STX1A syntaxin 1A (brain) 6804 Q16623 Y2H
Corominas R , et al. 2014
STXBP6 Syntaxin-binding protein 6 29091 Q8NFX7-2 IP; LC-MS/MS
Huttlin EL , et al. 2015
SUMO1P1 SUMO1 pseudogene 1 NR_002189 Y2H
Corominas R , et al. 2014
SYT3 synaptotagmin III 20981 G3X9Y1 GST
Kee Y and Scheller RH 1996
TXLNA taxilin alpha 200081 P40222 Y2H
Corominas R , et al. 2014
TXLNB taxilin beta 167838 Q8N3L3 Y2H
Corominas R , et al. 2014
VAMP5 vesicle-associated membrane protein 5 10791 O95183 Y2H
Corominas R , et al. 2014
SNAP25 synaptosomal-associated protein 25 20614 P60879 IP/WB
Shimojo M , et al. 2015
APP amyloid beta (A4) precursor protein 351 P05067 in vitro binding assay
Yang Y , et al. 2015
ATP2B2 ATPase, Ca++ transporting, plasma membrane 2 24215 P11506 IP/WB; GST
Garside ML , et al. 2009
Cplx1 complexin 1 64832 P63041 FRET
Choi UB , et al. 2016
SLC6A4 Sodium-dependent serotonin transporter 6532 P31652 IP/WB
Quick MW 2002
SNAP25 synaptosomal-associated protein 25 25012 P60881 in vitro binding assay; ITC; Fluorescence anisotropy
Zhang Y , et al. 2015
Stxbp1 syntaxin binding protein 1 25558 P61765 Fluorescence anisotropy; Biolayer interferometry
Zhang Y , et al. 2015
Vamp2 vesicle-associated membrane protein 2 24803 P63045 ITC; Fluorescence anisotropy
Zhang Y , et al. 2015
Vamp2 vesicle-associated membrane protein 2 24803 P63045 FRET
Lou X , et al. 2015
Vamp2 vesicle-associated membrane protein 2 24803 P63045 FRET
Choi UB , et al. 2016

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