STXBP1Syntaxin binding protein 1
Autism Reports / Total Reports
8 / 34Rare Variants / Common Variants
134 / 0Aliases
STXBP1, RP11-56D16.3, MUNC18-1, NSEC1, P67, RBSEC1, UNC18Associated Syndromes
Atypical Rett syndrome, Ohtahara syndrome, Rett syndromeGenetic Category
Rare Single Gene Mutation, Syndromic, FunctionalChromosome Band
9q34.11Associated Disorders
EP, ASD, DD/NDD, EPS, ADHD, IDRelevance to Autism
A 67 kb monogenic deletion affecting exons 1-4 of the STXBP1 gene was identified in a female patient with ASD, severe ID, and neonatal seizures (Campbell et al., 2012).
Molecular Function
This gene encodes a syntaxin-binding protein. The encoded protein appears to play a role in release of neurotransmitters via regulation of syntaxin, a transmembrane attachment protein receptor. Mutations in this gene have been associated with infantile epileptic encephalopathy-4.
Reports related to STXBP1 (34 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Highly Cited | De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy. | Saitsu H , et al. (2008) | No | ID |
2 | Support | De novo STXBP1 mutations in mental retardation and nonsyndromic epilepsy. | Hamdan FF , et al. (2009) | No | Epilepsy |
3 | Support | Clinical spectrum of early-onset epileptic encephalopathies associated with STXBP1 mutations. | Deprez L , et al. (2010) | No | ID |
4 | Support | STXBP1 mutations in early infantile epileptic encephalopathy with suppression-burst pattern. | Saitsu H , et al. (2010) | No | - |
5 | Support | Paternal mosaicism of an STXBP1 mutation in OS. | Saitsu H , et al. (2010) | No | - |
6 | Support | STXBP1 mutations cause not only Ohtahara syndrome but also West syndrome--result of Japanese cohort study. | Otsuka M , et al. (2011) | No | - |
7 | Support | Intellectual disability without epilepsy associated with STXBP1 disruption. | Hamdan FF , et al. (2011) | No | - |
8 | Support | Patterns and rates of exonic de novo mutations in autism spectrum disorders. | Neale BM , et al. (2012) | Yes | - |
9 | Primary | Novel 9q34.11 gene deletions encompassing combinations of four Mendelian disease genes: STXBP1, SPTAN1, ENG, and TOR1A. | Campbell IM , et al. (2012) | Yes | - |
10 | Support | Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study. | Rauch A , et al. (2012) | No | Epilepsy, ASD |
11 | Support | Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1. | Carvill GL , et al. (2013) | No | ID, ASD, DD |
12 | Positive Association | De novo mutations in epileptic encephalopathies. | Epi4K Consortium , et al. (2013) | No | IS, LGS, DD, ID, ASD, ADHD |
13 | Support | Large-scale discovery of novel genetic causes of developmental disorders. | Deciphering Developmental Disorders Study (2014) | No | ASD |
14 | Support | Whole-genome sequencing of quartet families with autism spectrum disorder. | Yuen RK , et al. (2015) | Yes | - |
15 | Support | A de-novo STXBP1 gene mutation in a patient showing the Rett syndrome phenotype. | Romaniello R , et al. (2015) | No | ID, epilepsy/seizures |
16 | Support | Mutations in epilepsy and intellectual disability genes in patients with features of Rett syndrome. | Olson HE , et al. (2015) | No | Epilepsy |
17 | Recent Recommendation | Incorporating Functional Information in Tests of Excess De Novo Mutational Load. | Jiang Y , et al. (2015) | No | - |
18 | Support | Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities. | Zhang Y , et al. (2015) | No | - |
19 | Recent Recommendation | STXBP1 encephalopathy: A neurodevelopmental disorder including epilepsy. | Stamberger H , et al. (2016) | No | ASD or autistic features |
20 | Support | Mislocalization of syntaxin-1 and impaired neurite growth observed in a human iPSC model for STXBP1-related epileptic encephalopathy. | Yamashita S , et al. (2016) | No | Epilepsy |
21 | Support | Epilepsy is not a mandatory feature of STXBP1 associated ataxia-tremor-retardation syndrome. | Gburek-Augustat J , et al. (2016) | No | Ataxia |
22 | Support | De novo genic mutations among a Chinese autism spectrum disorder cohort. | Wang T , et al. (2016) | Yes | - |
23 | Support | Clinical exome sequencing: results from 2819 samples reflecting 1000 families. | Trujillano D , et al. (2016) | Yes | - |
24 | Support | Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes. | Parrini E , et al. (2016) | No | - |
25 | Support | Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains. | Geisheker MR , et al. (2017) | Yes | - |
26 | Support | Using medical exome sequencing to identify the causes of neurodevelopmental disorders: experience of two clinical units and 216 patients. | Chrot E , et al. (2017) | No | Epileptic encephalopathy, ADHD |
27 | Support | Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder. | Lim ET , et al. (2017) | Yes | - |
28 | Support | Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test. | Lionel AC , et al. (2017) | No | - |
29 | Support | Protein structure and phenotypic analysis of pathogenic and population missense variants in STXBP1. | Suri M , et al. (2017) | No | Epilepsy/seizures, ASD |
30 | Support | Germline and somatic mutations in STXBP1 with diverse neurodevelopmental phenotypes. | Uddin M , et al. (2017) | No | ASD, motor delay |
31 | Recent Recommendation | Protein instability, haploinsufficiency, and cortical hyper-excitability underlie STXBP1 encephalopathy. | Kovacevic J , et al. (2018) | No | - |
32 | Support | A novel STXBP1 mutation causes typical Rett syndrome in a Japanese girl. | Yuge K , et al. (2018) | No | Epilepsy/seizures, developmental regression, ASD, |
33 | Support | Mechanism-based rescue of Munc18-1 dysfunction in varied encephalopathies by chemical chaperones. | Guiberson NGL , et al. (2018) | No | - |
34 | Support | Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes. | Guo H , et al. (2018) | Yes | - |
Rare Variants (134)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
c.1631G>A | p.Gly544Asp | missense_variant | Unknown | - | - | 18469812 | Saitsu H , et al. (2008) | |
c.539G>A | p.Cys180Tyr | missense_variant | De novo | - | - | 18469812 | Saitsu H , et al. (2008) | |
c.1328T>G | p.Met443Arg | missense_variant | De novo | - | - | 18469812 | Saitsu H , et al. (2008) | |
c.251T>A | p.Val84Asp | missense_variant | De novo | - | - | 18469812 | Saitsu H , et al. (2008) | |
c.1162C>T | p.Arg388Ter | stop_gained | De novo | - | - | 19557857 | Hamdan FF , et al. (2009) | |
c.169+1G>A | - | splice_site_variant | De novo | - | - | 19557857 | Hamdan FF , et al. (2009) | |
c.1434G>A | p.Trp478Ter | stop_gained | De novo | - | - | 20876469 | Deprez L , et al. (2010) | |
c.893_894delAG | p.Glu278GlyfsTer15 | frameshift_variant | Unknown | - | - | 20876469 | Deprez L , et al. (2010) | |
c.1029 + 1G>T | p.[Lys343AsnfsTer13; Tyr344_Glu603del Ins11] | splice_site_variant | De novo | - | - | 20876469 | Deprez L , et al. (2010) | |
c.963 + ?_(*1967+?) del | p.Thr322_Glu603 del | copy_number_loss | De novo | - | - | 20876469 | Deprez L , et al. (2010) | |
(?_-120)_37 + ?del | - | copy_number_loss | De novo | - | - | 20876469 | Deprez L , et al. (2010) | |
c.429 + 1G>A | - | splice_site_variant | De novo | - | - | 20876469 | Deprez L , et al. (2010) | |
c.1217G>A | p.Arg406His | missense_variant | De novo | - | - | 20887364 | Saitsu H , et al. (2010) | |
c.157G>T | p.Glu53Ter | stop_gained | De novo | - | - | 20887364 | Saitsu H , et al. (2010) | |
c.388_389delCT | p.Leu130AspfsTer11 | frameshift_variant | De novo | - | - | 20887364 | Saitsu H , et al. (2010) | |
c.663 + 5G>A | - | splice_site_variant | De novo | - | - | 20887364 | Saitsu H , et al. (2010) | |
c.703C>T | p.Arg235Ter | stop_gained | De novo | - | - | 20887364 | Saitsu H , et al. (2010) | |
c.747dupT | p.Gln250SerfsTer6 | frameshift_variant | De novo | - | - | 20887364 | Saitsu H , et al. (2010) | |
c.961A>T | p.Lys321Ter | stop_gained | De novo | - | - | 20887364 | Saitsu H , et al. (2010) | |
c.902+5G>A | - | splice_site_variant | Familial | Paternal | - | 21062273 | Saitsu H , et al. (2010) | |
del(ACTC) | - | frameshift_variant | De novo | - | - | 21204804 | Otsuka M , et al. (2011) | |
c.1654T>C | p.Cys552Arg | missense_variant | De novo | - | - | 21204804 | Otsuka M , et al. (2011) | |
c.1206delT | p.Tyr402Ter | frameshift_variant | De novo | - | - | 21364700 | Hamdan FF , et al. (2011) | |
c.1651C>T | P.Arg551Cys | missense_variant | De novo | - | Simplex | 22495311 | Neale BM , et al. (2012) | |
- | - | copy_number_loss | Unknown | - | Unknown | 22722545 | Campbell IM , et al. (2012) | |
c.301G>C | p.Ala101Pro | missense_variant | De novo | - | Simplex | 23020937 | Rauch A , et al. (2012) | |
c.2471delG | p.? | splice_site_variant | De novo | - | Simplex | 23020937 | Rauch A , et al. (2012) | |
c.175G>A | p.Glu59Lys | missense_variant | De novo | - | Simplex | 23020937 | Rauch A , et al. (2012) | |
c.1154delC | p.Met387TyrfsTer17 | frameshift_variant | De novo | - | - | 23708187 | Carvill GL , et al. (2013) | |
c.1630G>T | p.Gly544Cys | missense_variant | Unknown | - | - | 23708187 | Carvill GL , et al. (2013) | |
c.125C>T | p.Ser42Phe | missense_variant | De novo | - | - | 23708187 | Carvill GL , et al. (2013) | |
c.238T>C | p.Ser80Pro | missense_variant | De novo | - | - | 23708187 | Carvill GL , et al. (2013) | |
c.568C>T | p.Arg190Trp | missense_variant | De novo | - | - | 23708187 | Carvill GL , et al. (2013) | |
c.1060T>C | p.Cys354Arg | missense_variant | De novo | - | - | 23708187 | Carvill GL , et al. (2013) | |
c.1708A>G | p.Thr570Ala | missense_variant | De novo | - | - | 23708187 | Carvill GL , et al. (2013) | |
c.1004C>T | p.Pro335Leu | missense_variant | De novo | - | - | 23934111 | Epi4K Consortium , et al. (2013) | |
c.703C>T | p.Arg235Ter | stop_gained | De novo | - | - | 23934111 | Epi4K Consortium , et al. (2013) | |
c.1217G>A | p.Arg406His | missense_variant | De novo | - | - | 23934111 | Epi4K Consortium , et al. (2013) | |
c.568C>T | p.Arg190Trp | missense_variant | De novo | - | - | 23934111 | Epi4K Consortium , et al. (2013) | |
c.1631G>A | p.Gly544Asp | missense_variant | De novo | - | - | 23934111 | Epi4K Consortium , et al. (2013) | |
c.1099C>T | p.Arg367Ter | stop_gained | De novo | - | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) | |
c.148dupA | p.Ile50AsnfsTer14 | frameshift_variant | De novo | - | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) | |
c.704G>A | p.Arg235Gln | missense_variant | De novo | - | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) | |
c.437_438delCCinsC | p.Leu147TrpfsTer18 | frameshift_variant | De novo | - | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) | |
c.778G>T | p.Glu260Ter | stop_gained | De novo | - | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) | |
c.1631G>T | p.Gly544Val | missense_variant | De novo | - | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) | |
c.1580delC | p.Pro528GlnfsTer18 | frameshift_variant | De novo | - | Multiplex | 25621899 | Yuen RK , et al. (2015) | |
c.1217G>A | p.Arg406His | missense_variant | De novo | - | Simplex | 25714420 | Romaniello R , et al. (2015) | |
c.1658delC | p.Tyr554ThrfsTer3 | frameshift_variant | Unknown | Not maternal | - | 25914188 | Olson HE , et al. (2015) | |
c.568C>T | p.Arg190Trp | missense_variant | De novo | - | Simplex | 26544041 | Zhang Y , et al. (2015) | |
c.568C>T | p.Arg190Trp | missense_variant | De novo | - | Simplex | 26544041 | Zhang Y , et al. (2015) | |
c.1022T>C | p.Leu341Pro | missense_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.704G>A | p.Arg235Gln | missense_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.1216C>T | p.Arg406Cys | missense_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.922A>T | p.Lys308Ter | stop_gained | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.1075C>T | p.Gln359Ter | stop_gained | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.1217G>A | p.Arg406His | missense_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.875G>A | p.Arg292His | missense_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.1277 T>C | Leu426Pro | missense_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.1099C>T | Arg367Ter | stop_gained | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.1651C>T | p.Arg551Cys | missense_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.1438C>T | p.Pro480Ser | missense_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.364C>T | p.Arg122Ter | stop_gained | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.1359+1 G>A | p.? | splice_site_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
- | - | copy_number_loss | Unknown | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.364C>T | p.Arg122Ter | stop_gained | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.430-1G>C | p.? | splice_site_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.38-?_(663+?_902+?) del | - | copy_number_loss | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
- | - | copy_number_loss | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.1723C>T | p.Pro575Ser | missense_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.1548-6_1559delinsAT | p.? | frameshift_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.794+5G>A | p.? | splice_site_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.795-2A>T | p.? | splice_site_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.388-389delCT | - | frameshift_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
- | - | copy_number_loss | Unknown | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.874C>T | p.Arg292Cys | missense_variant | Unknown | Not maternal | - | 26865513 | Stamberger H , et al. (2016) | |
c.874C>T | p.Arg292Cys | missense_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.1651C>T | p.Arg551Cys | missense_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.1461G>A | p.(=) | synonymous_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.17T>C | p.Leu6Pro | missense_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.518C>A | p.Ala173Glu | missense_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.1110+1G>A | p.? | splice_site_variant | Unknown | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.902+1G>A | p.? | splice_site_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.107T>A | p.Leu36Ter | stop_gained | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.1565G>A | p.Trp522Ter | stop_gained | Unknown | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.1359+5G>C | p.? | splice_site_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.1672delC | p.Gln558ArgfsTer | frameshift_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.1652G>A | p.Arg551His | missense_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.579-2A>G | p.? | splice_site_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.430-2_430+2delinsTGGGAGA | p.? | frameshift_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.874C>T | p.Arg292Cys | missense_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
- | - | copy_number_loss | Unknown | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.875G>A | p.Arg292His | missense_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.875G>T | p.Arg292Leu | missense_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.703C>G | p.Arg235Gly | missense_variant | De novo | - | - | 26865513 | Stamberger H , et al. (2016) | |
c.795-1G>A | p.? | splice_site_variant | De novo | - | Simplex | 26865513 | Stamberger H , et al. (2016) | |
c.1099C>T | p.Arg367Ter | stop_gained | De novo | - | - | 26918652 | Yamashita S , et al. (2016) | |
c.1162C>T | p.Arg388Ter | stop_gained | De novo | - | - | 27184330 | Gburek-Augustat J , et al. (2016) | |
c.695_696del | p.Ile232ThrfsTer6 | frameshift_variant | De novo | - | - | 27824329 | Wang T , et al. (2016) | |
c.517G>A | p.Ala173Thr | missense_variant | Familial | Paternal | - | 27824329 | Wang T , et al. (2016) | |
c.585C>A | p.Tyr195Ter | stop_gained | Unknown | Not maternal | - | 27824329 | Wang T , et al. (2016) | |
c.703C>T | p.Arg235Ter | stop_gained | De novo | - | Simplex | 27848944 | Trujillano D , et al. (2016) | |
c.1060T>C | p.Cys354Arg | missense_variant | De novo | - | Simplex | 27848944 | Trujillano D , et al. (2016) | |
c.1565G>A | p.Trp522Ter | stop_gained | De novo | - | - | 27864847 | Parrini E , et al. (2016) | |
c.57_59del | p.Ile19_Lys20delinsMet | frameshift_variant | De novo | - | - | 27864847 | Parrini E , et al. (2016) | |
c.1408G>T | p.Glu470Ter | stop_gained | De novo | - | - | 27864847 | Parrini E , et al. (2016) | |
c.1099C>T | p.Arg367Ter | stop_gained | De novo | - | - | 27864847 | Parrini E , et al. (2016) | |
c.1216C>T | p.Arg406Cys | missense_variant | De novo | - | - | 27864847 | Parrini E , et al. (2016) | |
- | - | copy_number_gain | De novo | - | - | 27864847 | Parrini E , et al. (2016) | |
c.1651C>T | p.Arg551Cys | missense_variant | De novo | - | - | 28628100 | Geisheker MR , et al. (2017) | |
c.1598G>C | p.Ser533Thr | missense_variant | Familial | Paternal | - | 28628100 | Geisheker MR , et al. (2017) | |
c.1598G>C | p.Ser533Thr | missense_variant | Unknown | Not maternal | - | 28628100 | Geisheker MR , et al. (2017) | |
c.1651C>T | p.Arg551Cys | missense_variant | Unknown | - | - | 28628100 | Geisheker MR , et al. (2017) | |
c.1595G>A | p.Arg532His | missense_variant | Unknown | - | - | 28628100 | Geisheker MR , et al. (2017) | |
c.1706C>T | p.Ser569Phe | missense_variant | De novo | - | - | 28708303 | Chrot E , et al. (2017) | |
c.1082C>T | p.Thr361Ile | missense_variant | De novo | - | - | 28708303 | Chrot E , et al. (2017) | |
G>A | p.Ala251Thr | missense_variant | De novo | - | - | 28714951 | Lim ET , et al. (2017) | |
c.1651C>T | p.Arg551Cys | missense_variant | De novo | - | - | 28714951 | Lim ET , et al. (2017) | |
c.755T>C | p.Met252Thr | missense_variant | De novo | - | - | 28771251 | Lionel AC , et al. (2017) | |
- | - | copy_number_loss | De novo | - | - | 28771251 | Lionel AC , et al. (2017) | |
c.713_714delACinsA | p.Ser240AlafsTer8 | frameshift_variant | De novo | - | - | 28944233 | Suri M , et al. (2017) | |
c.568C>T | p.Arg190Trp | missense_variant | De novo | - | - | 28944233 | Suri M , et al. (2017) | |
c.568C>T | p.Arg190Trp | missense_variant | De novo | - | - | 28944233 | Suri M , et al. (2017) | |
c.1651C>T | p.Arg551Cys | missense_variant | De novo | - | - | 28944233 | Suri M , et al. (2017) | |
c.533C>T | p.Thr178Ile | missense_variant | De novo | - | - | 28944233 | Suri M , et al. (2017) | |
- | - | copy_number_loss | De novo | - | - | 29264391 | Uddin M , et al. (2017) | |
c.663+1G>T | p.? | splice_site_variant | De novo | - | - | 29264391 | Uddin M , et al. (2017) | |
C>T | p.Arg292Cys | missense_variant | De novo | - | - | 29264391 | Uddin M , et al. (2017) | |
c.1099C>T | p.Arg367Ter | stop_gained | De novo | - | - | 29264391 | Uddin M , et al. (2017) | |
- | - | copy_number_loss | De novo | - | - | 29264391 | Uddin M , et al. (2017) | |
- | p.Lys526AsnfsTer23 | frameshift_variant | De novo | - | - | 29264391 | Uddin M , et al. (2017) | |
c.755T>C | p.Met252Thr | missense_variant | De novo | - | - | 29264391 | Uddin M , et al. (2017) | |
c.60delG | p.Lys21ArgfsTer16 | frameshift_variant | De novo | - | - | 29544889 | Yuge K , et al. (2018) | |
c.560C>T | p.Pro187Leu | missense_variant | De novo | - | Simplex | 30504930 | Guo H , et al. (2018) |
Common Variants
No common variants reported.
SFARI Gene score
Suggestive Evidence, Syndromic


3S
Score Delta: Increased from 3S to 4.4 + acc2 + S
criteria met
See SFARI Gene'scoring criteriaThe literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.
The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."
4/1/2018

Increased from 3S to 4.4 + acc2 + S
Description
3S
10/1/2017

Increased from 3S to 3S
Description
Heterozygous variants in the STXBP1 gene are responsible for a form of early-onset epileptic encephalopathy (EIEE4; OMIM 612164) highlighted by epilepsy and often severe intellectual disability (Saitsu et al., 2008; Deprez et al., 2010). ASD has been observed in individuals with STXBP1 variants both in the presence and absence of epilepsy and/or intellectual disability (Campbell et al., 2012; Neale et al., 2012; Deciphering Developmental Disorders Study, 2015; Yuen et al., 2015; Wang et al., 2016). A systemic review of 147 patients with STXBP1 encephalopathy, including 45 previously unreported patients, demonstrated that autism or autistic features were observed in approximately 20% of published cases, although the actual number of cases with autism/autistic features may be greater due to the focus of most studies on the intellectual disability/epilepsy phenotype (Stamberger et al., 2016). Variants in STXBP1 have also been identified in patients presenting with atypical Rett syndrome, with affected individuals frequently exhibiting autistic features and stereotyped movements (Romaniello et al., 2015; Olson et al., 2015).
7/1/2017

Increased from 3S to 3S
Description
Heterozygous variants in the STXBP1 gene are responsible for a form of early-onset epileptic encephalopathy (EIEE4; OMIM 612164) highlighted by epilepsy and often severe intellectual disability (Saitsu et al., 2008; Deprez et al., 2010). ASD has been observed in individuals with STXBP1 variants both in the presence and absence of epilepsy and/or intellectual disability (Campbell et al., 2012; Neale et al., 2012; Deciphering Developmental Disorders Study, 2015; Yuen et al., 2015; Wang et al., 2016). A systemic review of 147 patients with STXBP1 encephalopathy, including 45 previously unreported patients, demonstrated that autism or autistic features were observed in approximately 20% of published cases, although the actual number of cases with autism/autistic features may be greater due to the focus of most studies on the intellectual disability/epilepsy phenotype (Stamberger et al., 2016). Variants in STXBP1 have also been identified in patients presenting with atypical Rett syndrome, with affected individuals frequently exhibiting autistic features and stereotyped movements (Romaniello et al., 2015; Olson et al., 2015).
Reports Added
[Using medical exome sequencing to identify the causes of neurodevelopmental disorders: experience of two clinical units and 216 patients.2017] [Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test.2017] [Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder.2017] [Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains.2017]1/1/2017

Increased from 3S to 3S
Description
Heterozygous variants in the STXBP1 gene are responsible for a form of early-onset epileptic encephalopathy (EIEE4; OMIM 612164) highlighted by epilepsy and often severe intellectual disability (Saitsu et al., 2008; Deprez et al., 2010). ASD has been observed in individuals with STXBP1 variants both in the presence and absence of epilepsy and/or intellectual disability (Campbell et al., 2012; Neale et al., 2012; Deciphering Developmental Disorders Study, 2015; Yuen et al., 2015; Wang et al., 2016). A systemic review of 147 patients with STXBP1 encephalopathy, including 45 previously unreported patients, demonstrated that autism or autistic features were observed in approximately 20% of published cases, although the actual number of cases with autism/autistic features may be greater due to the focus of most studies on the intellectual disability/epilepsy phenotype (Stamberger et al., 2016). Variants in STXBP1 have also been identified in patients presenting with atypical Rett syndrome, with affected individuals frequently exhibiting autistic features and stereotyped movements (Romaniello et al., 2015; Olson et al., 2015).
10/1/2016

Increased from 3S to 3S
Description
Heterozygous variants in the STXBP1 gene are responsible for a form of early-onset epileptic encephalopathy (EIEE4; OMIM 612164) highlighted by epilepsy and often severe intellectual disability (Saitsu et al., 2008; Deprez et al., 2010). ASD has been observed in individuals with STXBP1 variants both in the presence and absence of epilepsy and/or intellectual disability (Campbell et al., 2012; Neale et al., 2012; Deciphering Developmental Disorders Study, 2015; Yuen et al., 2015; Wang et al., 2016). A systemic review of 147 patients with STXBP1 encephalopathy, including 45 previously unreported patients, demonstrated that autism or autistic features were observed in approximately 20% of published cases, although the actual number of cases with autism/autistic features may be greater due to the focus of most studies on the intellectual disability/epilepsy phenotype (Stamberger et al., 2016). Variants in STXBP1 have also been identified in patients presenting with atypical Rett syndrome, with affected individuals frequently exhibiting autistic features and stereotyped movements (Romaniello et al., 2015; Olson et al., 2015).
4/1/2016

Increased from 3S to 3S
Description
Heterozygous variants in the STXBP1 gene are responsible for a form of early-onset epileptic encephalopathy (EIEE4; OMIM 612164) highlighted by epilepsy and often severe intellectual disability (Saitsu et al., 2008; Deprez et al., 2010). ASD has been observed in individuals with STXBP1 variants both in the presence and absence of epilepsy and/or intellectual disability (Campbell et al., 2012; Neale et al., 2012; Deciphering Developmental Disorders Study, 2015; Yuen et al., 2015). A systemic review of 147 patients with STXBP1 encephalopathy, including 45 previously unreported patients, demonstrated that autism or autistic features were observed in approximately 20% of published cases, although the actual number of cases with autism/autistic features may be greater due to the focus of most studies on the intellectual disability/epilepsy phenotype (Stamberger et al., 2016). Variants in STXBP1 have also been identified in patients presenting with atypical Rett syndrome, with affected individuals frequently exhibiting autistic features and stereotyped movements (Romaniello et al., 2015; Olson et al., 2015).
Reports Added
[STXBP1 encephalopathy: A neurodevelopmental disorder including epilepsy.2016] [Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.2013] [Whole-genome sequencing of quartet families with autism spectrum disorder.2015] [De novo STXBP1 mutations in mental retardation and nonsyndromic epilepsy.2009] [Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study.2012] [Novel 9q34.11 gene deletions encompassing combinations of four Mendelian disease genes: STXBP1, SPTAN1, ENG, and TOR1A.2012] [Patterns and rates of exonic de novo mutations in autism spectrum disorders.2012] [Intellectual disability without epilepsy associated with STXBP1 disruption.2011] [De novo mutations in epileptic encephalopathies.2013] [Mislocalization of syntaxin-1 and impaired neurite growth observed in a human iPSC model for STXBP1-related epileptic encephalopathy.2016] [De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy.2008] [Epilepsy is not a mandatory feature of STXBP1 associated ataxia-tremor-retardation syndrome.2016] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Clinical spectrum of early-onset epileptic encephalopathies associated with STXBP1 mutations.2010] [STXBP1 mutations in early infantile epileptic encephalopathy with suppression-burst pattern.2010] [Mutations in epilepsy and intellectual disability genes in patients with features of Rett syndrome.2015] [Paternal mosaicism of an STXBP1 mutation in OS.2010] [STXBP1 mutations cause not only Ohtahara syndrome but also West syndrome--result of Japanese cohort study.2011] [A de-novo STXBP1 gene mutation in a patient showing the Rett syndrome phenotype.2015] [Incorporating Functional Information in Tests of Excess De Novo Mutational Load.2015] [Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities.2015]1/1/2016

Increased from to 3S
Description
Heterozygous variants in the STXBP1 gene are responsible for a form of early-onset epileptic encephalopathy (EIEE4; OMIM 612164) highlighted by epilepsy and often severe intellectual disability (Saitsu et al., 2008; Deprez et al., 2010). ASD has been observed in individuals with STXBP1 variants both in the presence and absence of epilepsy and/or intellectual disability (Campbell et al., 2012; Neale et al., 2012; Deciphering Developmental Disorders Study, 2015; Yuen et al., 2015). A systemic review of 147 patients with STXBP1 encephalopathy, including 45 previously unreported patients, demonstrated that autism or autistic features were observed in approximately 20% of published cases, although the actual number of cases with autism/autistic features may be greater due to the focus of most studies on the intellectual disability/epilepsy phenotype (Stamberger et al., 2016). Variants in STXBP1 have also been identified in patients presenting with atypical Rett syndrome, with affected individuals frequently exhibiting autistic features and stereotyped movements (Romaniello et al., 2015; Olson et al., 2015).
Reports Added
[Mislocalization of syntaxin-1 and impaired neurite growth observed in a human iPSC model for STXBP1-related epileptic encephalopathy.2016] [Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.2013] [Whole-genome sequencing of quartet families with autism spectrum disorder.2015] [De novo STXBP1 mutations in mental retardation and nonsyndromic epilepsy.2009] [STXBP1 encephalopathy: A neurodevelopmental disorder including epilepsy.2016] [Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study.2012] [Novel 9q34.11 gene deletions encompassing combinations of four Mendelian disease genes: STXBP1, SPTAN1, ENG, and TOR1A.2012] [Intellectual disability without epilepsy associated with STXBP1 disruption.2011] [De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy.2008] [Patterns and rates of exonic de novo mutations in autism spectrum disorders.2012] [Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities.2015] [Mutations in epilepsy and intellectual disability genes in patients with features of Rett syndrome.2015] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Clinical spectrum of early-onset epileptic encephalopathies associated with STXBP1 mutations.2010] [STXBP1 mutations in early infantile epileptic encephalopathy with suppression-burst pattern.2010] [Paternal mosaicism of an STXBP1 mutation in OS.2010] [STXBP1 mutations cause not only Ohtahara syndrome but also West syndrome--result of Japanese cohort study.2011] [A de-novo STXBP1 gene mutation in a patient showing the Rett syndrome phenotype.2015] [De novo mutations in epileptic encephalopathies.2013] [Incorporating Functional Information in Tests of Excess De Novo Mutational Load.2015]Krishnan Probability Score
Score 0.5751140747065
Ranking 659/25841 scored genes
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ExAC Score
Score 0.99988294322709
Ranking 702/18225 scored genes
[Show Scoring Methodology]
Sanders TADA Score
Score 0.75457231068876
Ranking 1601/18665 scored genes
[Show Scoring Methodology]
Larsen Cumulative Evidence Score
Score 5
Ranking 293/461 scored genes
[Show Scoring Methodology]
Zhang D Score
Score 0.20850596125832
Ranking 4140/20870 scored genes
[Show Scoring Methodology]
CNVs associated with STXBP1(1 CNVs)
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9q34.11 | 12 | Deletion-Duplication | 22 / 44 |