Research panel - Severe Paediatric Disorders
Gene: STXBP1

STXBP1 (syntaxin binding protein 1)
EnsemblGeneIds (GRCh38): ENSG00000136854
EnsemblGeneIds (GRCh37): ENSG00000136854
OMIM: 602926, Gene2Phenotype
STXBP1 is in 6 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

Created: 28 Feb 2023, 4:26 p.m.
Last Modified: 28 Feb 2023, 4:26 p.m.
Panel version: 1.141

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 Project, Addenbrookes' Hospital, Cambridge. Gene Symbol submitted: STXBP1; Recommended initial gene rating: Green List (high evidence); Phenotypes: Epileptic encephalopathy, early infantile, 4, 612164 (3); Mode of inheritance: Autosomal dominant
Created: 20 Feb 2020, 5:26 p.m. | Last Modified: 20 Feb 2020, 5:26 p.m.

Panel Version: 0.12

Created: 20 Feb 2020, 5:26 p.m.
Last Modified: 20 Feb 2020, 5:26 p.m.
Panel version: 0.12

Details

Mode of Inheritance

BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Sources

Next Generation Children Project
Expert Review Green
Expert list

Phenotypes

Developmental and epileptic encephalopathy 4, OMIM:612164
developmental and epileptic encephalopathy, 4, MONDO:0012812

OMIM

602926

Clinvar variants

Variants in STXBP1

Penetrance

None

Publications

Panels with this gene

History Filter Activity

28 Feb 2023, Gel status: 3

Set mode of inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for gene: STXBP1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

28 Feb 2023, Gel status: 3

Set mode of inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for gene: STXBP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

28 Feb 2023, Gel status: 3

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: STXBP1 were changed from Epileptic encephalopathy, early infantile, 4, 612164 to Developmental and epileptic encephalopathy 4, OMIM:612164; developmental and epileptic encephalopathy, 4, MONDO:0012812

28 Feb 2023, Gel status: 3

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: STXBP1 were set to 30847515; 31855252; 18469812; 19557857

28 Feb 2023, Gel status: 3

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: STXBP1 were set to 30847515

20 Feb 2020, Gel status: 3