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Severe Paediatric Disorders

Gene: STXBP1

Green List (high evidence)

STXBP1 (syntaxin binding protein 1)
EnsemblGeneIds (GRCh38): ENSG00000136854
EnsemblGeneIds (GRCh37): ENSG00000136854
OMIM: 602926, Gene2Phenotype
STXBP1 is in 8 panels

2 reviews

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

PMID: 31855252 reports a homozygous STXBP1 variant (NM_001032221.6(STXBP1):c.1336C>T (p.Leu446Phe)) in two sisters with developmental and epileptic encephalopathy 4 (OMIM:612164). Their mother and unaffected sister were heterozygous for NM_001032221.6(STXBP1):c.1336C>T (p.Leu446Phe)(the father was deceased). Functional studies showed that this variant had a lesser effect on protein stability in comparison with the heterozygous variants previously reported. However, patch clamp recordings demonstrated that p.Leu446Phe causes a 2-fold increase in evoked synaptic transmission, leading to the conclusion that this variant was having a gain-of-function effect. Although the majority of STXBP1 variants are heterozygous, with a loss-of -function effect, the results published in PMID: 31855252, suggest that there maybe further complexity to mechanisms involved in the development of developmental and epileptic encephalopathy 4. PMID: 35190816 used a computational approach, together with biomedical ontologies, to characterize phenotypic features in STXBP1-related disorders, such that groups of HPO terms could be associated with certain STXBP1 variants.
Created: 28 Feb 2023, 4:33 p.m. | Last Modified: 28 Feb 2023, 4:33 p.m.
Panel Version: 1.141
Comment on mode of inheritance: Due to the report of biallelic STXBP1 variants in a family with encephalopathy, developmental delay, intellectual disability and epilepsy (PMID: 31855252), the mode of inheritance for this gene has been changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal.
Created: 28 Feb 2023, 4:26 p.m. | Last Modified: 28 Feb 2023, 4:26 p.m.
Panel Version: 1.141

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Louise Daugherty (Genomics England Curator)

I don't know

Initial gene list (NGC_genelist-20190823_GREEN_dis_moi_forCuration_20200211.xlsx) collated by Dr Courtney French (University of Cambridge University Hospital NHS Foundation), Dr Karyn Megy (Clinical Feedback Lead, NIHR BioResource - Rare Diseases Study, University of Cambridge University Hospital NHS Foundation), Dr Alba Sanchis-Juan (NIHR BioResource - Rare Diseases Study, University of Cambridge University Hospital NHS Foundation) and Lucy Raymond (Professor of Medical Genetics and Neurodevelopment, University of Cambridge University Hospital NHS Foundation). Submitted to the PanelApp resource January 2020 on behalf of the Next Generation Children Projec