Developmental Brain Disorder Gene Database

LoF Variant Gene

Gene
Search

Tier

1

STXBP1

HGNC:11444 (protein-coding gene)

syntaxin binding protein 1

Unique Cases:
115
Disorders:
ID, ASD, EP, ADHD, CP
Last Updated:
January 24, 2024

Gene Summary:

DBD Genes Classification
STXBP1 is a High Confidence candidate gene classified as Tier 1. Tier 1 genes have three or more de novo pathogenic loss-of-function variants.
Gene Function
Participates in the regulation of synaptic vesicle docking and fusion through interaction with GTP-binding proteins (By similarity). Essential for neurotransmission and binds syntaxin, a component of the synaptic vesicle fusion machinery probably in a 1:1 ratio. Can interact with syntaxins 1, 2, and 3 but not syntaxin 4. Involved in the release of neurotransmitters from neurons through interacting with SNARE complex component STX1A and mediating the assembly of the SNARE complex at synaptic memb... (Source: Uniprot)
Previous symbols
No previous symbols
Alias symbols
hUNC18, MUNC18-1, UNC18, rbSec1, nSec1
Chromosomal Location
9q34.11
Genomic Coordinates
GRCh37:chr9:130374486-130454995
GRCh38:chr9:127611912-127696029
Associated Disorders
Intellectual Disability, Autism, Epilepsy, Attention Deficit Hyperactivity Disorder, Cerebral Palsy

Predictive Scores:

HI Score (Decipher)

21.32

pLI (gnomAD)

1.00

LOEUF (gnomAD)

0.09

Classifications from External Sources:

SFARI Score (SFARI)

1

DDG2P Classification (DDG2P)

No Classification

ClinGen Classification (ClinGen)

Definitive1

GenCC Classification (GenCC)

Definitive3 Supportive6 Limited2 Strong1

Publications:

Rochtus A et. al., Genetic diagnoses in epilepsy: The impact of dynamic exome analysis in a pediatric cohort., Epilepsia, 2020
Değerliyurt A et. al., Ataxia, tremor, intellectual disability: a case of STXBP1 encephalopathy with a new mutation., Turk J Pediatr, 2019
Benson KA et. al., A comparison of genomic diagnostics in adults and children with epilepsy and comorbid intellectual disability., Eur J Hum Genet, 2020
Stödberg T et. al., Epilepsy syndromes, etiologies, and the use of next-generation sequencing in epilepsy presenting in the first 2 years of life: A population-based study., Epilepsia, 2020
Wang T et. al., Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders., Nat Commun, 2020
Gburek-Augustat J et. al., Epilepsy is not a mandatory feature of STXBP1 associated ataxia-tremor-retardation syndrome., Eur J Paediatr Neurol, 2016
Di Meglio C et. al., Epileptic patients with de novo STXBP1 mutations: Key clinical features based on 24 cases., Epilepsia, 2015
Barcia G et. al., A novel mutation in STXBP1 causing epileptic encephalopathy (late onset infantile spasms) with partial respiratory chain complex IV deficiency., Eur J Med Genet, 2013
Tan CA et. al., Characterization of patients referred for non-specific intellectual disability testing: the importance of autosomal genes for diagnosis., Clin Genet, 2016
Møller RS et. al., Parental mosaicism in epilepsies due to alleged de novo variants., Epilepsia, 2019
Boutry-Kryza N et. al., Molecular characterization of a cohort of 73 patients with infantile spasms syndrome., Eur J Med Genet, 2015
Olson HE et. al., Mutations in epilepsy and intellectual disability genes in patients with features of Rett syndrome., Am J Med Genet A, 2015
Ostrander BEP et. al., Whole-genome analysis for effective clinical diagnosis and gene discovery in early infantile epileptic encephalopathy., NPJ Genom Med, 2018
Costain G et. al., Clinical Application of Targeted Next-Generation Sequencing Panels and Whole Exome Sequencing in Childhood Epilepsy., Neuroscience, 2019
Demos M et. al., Diagnostic Yield and Treatment Impact of Targeted Exome Sequencing in Early-Onset Epilepsy., Front Neurol, 2019
Trump N et. al., Improving diagnosis and broadening the phenotypes in early-onset seizure and severe developmental delay disorders through gene panel analysis., J Med Genet, 2016
Lionel AC et. al., Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test., Genet Med, 2018
Wang J et. al., Gene mutational analysis in a cohort of Chinese children with unexplained epilepsy: Identification of a new KCND3 phenotype and novel genes causing Dravet syndrome., Seizure, 2019
Srivastava S et. al., Clinical whole exome sequencing in child neurology practice., Ann Neurol, 2014
Helbig KL et. al., Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy., Genet Med, 2016
Kodera H et. al., Targeted capture and sequencing for detection of mutations causing early onset epileptic encephalopathy., Epilepsia, 2013
Saitsu H et. al., STXBP1 mutations in early infantile epileptic encephalopathy with suppression-burst pattern., Epilepsia, 2010
Boonsawat P et. al., Elucidation of the phenotypic spectrum and genetic landscape in primary and secondary microcephaly., Genet Med, 2019
Trujillano D et. al., Clinical exome sequencing: results from 2819 samples reflecting 1000 families., Eur J Hum Genet, 2017
Deciphering Developmental Disorders Study. et. al., Large-scale discovery of novel genetic causes of developmental disorders., Nature, 2015
Weckhuysen S et. al., Reduction of seizure frequency after epilepsy surgery in a patient with STXBP1 encephalopathy and clinical description of six novel mutation carriers., Epilepsia, 2013
Lemke JR et. al., Targeted next generation sequencing as a diagnostic tool in epileptic disorders., Epilepsia, 2012
Jang SS et. al., Diagnostic Yield of Epilepsy Panel Testing in Patients With Seizure Onset Within the First Year of Life., Front Neurol, 2019
Allen AS et. al., De novo mutations in epileptic encephalopathies., Nature, 2013
Vanderver A et. al., Whole exome sequencing in patients with white matter abnormalities., Ann Neurol, 2016
Guo H et. al., Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model., Mol Autism, 2018
Hamdan FF et. al., De novo STXBP1 mutations in mental retardation and nonsyndromic epilepsy., Ann Neurol, 2009
Deprez L et. al., Clinical spectrum of early-onset epileptic encephalopathies associated with STXBP1 mutations., Neurology, 2010
Campbell IM et. al., Novel 9q34.11 gene deletions encompassing combinations of four Mendelian disease genes: STXBP1, SPTAN1, ENG, and TOR1A., Genet Med, 2012
Valence S et. al., Exome sequencing in congenital ataxia identifies two new candidate genes and highlights a pathophysiological link between some congenital ataxias and early infantile epileptic encephalopathies., Genet Med, 2019
Chen X et. al., A de novo pathogenic CSNK1E mutation identified by exome sequencing in family trios with epileptic encephalopathy., Hum Mutat, 2019
Hamdan FF et. al., Intellectual disability without epilepsy associated with STXBP1 disruption., Eur J Hum Genet, 2011
Hamdan FF et. al., Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability., Am J Hum Genet, 2011
Munnich A et. al., Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder., Mol Autism, 2019
Ko A et. al., Targeted gene panel and genotype-phenotype correlation in children with developmental and epileptic encephalopathy., Epilepsy Res, 2018
Yuskaitis CJ et. al., Infantile Spasms of Unknown Cause: Predictors of Outcome and Genotype-Phenotype Correlation., Pediatr Neurol, 2018
Yuen RK et. al., Whole-genome sequencing of quartet families with autism spectrum disorder., Nat Med, 2015
Balciuniene J et. al., Use of a Dynamic Genetic Testing Approach for Childhood-Onset Epilepsy., JAMA Netw Open, 2019
Wang Y et. al., Genetic Variants Identified from Epilepsy of Unknown Etiology in Chinese Children by Targeted Exome Sequencing., Sci Rep, 2017
Wang T et. al., De novo genic mutations among a Chinese autism spectrum disorder cohort., Nat Commun, 2016
Carvill GL et. al., Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1., Nat Genet, 2013
Yuge K et. al., A novel STXBP1 mutation causes typical Rett syndrome in a Japanese girl., Brain Dev, 2018
Saitsu H et. al., Paternal mosaicism of an STXBP1 mutation in OS., Clin Genet, 2011
Michaud JL et. al., The genetic landscape of infantile spasms., Hum Mol Genet, 2014
Jiang T et. al., Application of Trio-Whole Exome Sequencing in Genetic Diagnosis and Therapy in Chinese Children With Epilepsy., Front Mol Neurosci, 2021
Zhao X et. al., Genetic analysis and identification of novel variations in Chinese patients with pediatric epilepsy by whole-exome sequencing., Neurol Sci, 2022

NCBI: Gene

Integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.

Gene Reviews

An international point-of-care resource for busy clinicians, provides clinically relevant and medically actionable information for inherited conditions in a standardized journal-style format, covering diagnosis, management, and genetic counseling for patients and their families.

DECIPHER

DECIPHER (DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources) is an interactive web-based database which incorporates a suite of tools designed to aid the interpretation of genomic variants. DECIPHER enhances clinical diagnosis by retrieving information from a variety of bioinformatics resources relevant to the variant found in the patient.

SFARI

SFARI Gene is an evolving online database designed to permit quick entrée into the genetics of autism, and to help researchers track the ever-expanding genetic risk factors that emerge in the literature.

ClinGen

ClinGen is a National Institutes of Health (NIH)-funded resource dedicated to building an authoritative central resource that defines the clinical relevance of genes and variants for use in precision medicine and research.

GenCC

The GenCC DB provides information pertaining to the validity of gene-disease relationships, with a current focus on Mendelian diseases.

gnomAD

The Genome Aggregation Database (gnomAD) is a resource developed by an international coalition of investigators, with the goal of aggregating and harmonizing both exome and genome sequencing data from a wide variety of large-scale sequencing projects, and making summary data available for the wider scientific community.
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