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Intellectual disability

Gene: STXBP1

Green List (high evidence)
STXBP1 (syntaxin binding protein 1)
EnsemblGeneIds (GRCh38): ENSG00000136854
EnsemblGeneIds (GRCh37): ENSG00000136854
OMIM: 602926, Gene2Phenotype
STXBP1 is in 6 panels

5 reviews

Arina Puzriakova (Genomics England Curator)

The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Created: 11 Oct 2023, 9:34 a.m. | Last Modified: 11 Oct 2023, 9:34 a.m.
Panel Version: 5.286

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Created: 11 Oct 2023, 9:34 a.m.
Last Modified: 11 Oct 2023, 9:34 a.m.
Panel version: 5.286

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

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 should be 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: 4.87
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, 4:19 p.m. | Last Modified: 28 Feb 2023, 4:19 p.m.
Panel Version: 4.83

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Created: 28 Feb 2023, 4:19 p.m.
Last Modified: 28 Feb 2023, 4:19 p.m.
Panel version: 4.83

Caroline Wright (Sanger)

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
ANGELMAN/PITT HOPKINS SYNDROME-LIKE DISORDER

Publications

  • 0

Created: 5 Nov 2017, 2:42 a.m.

Panel version: 0

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf;in_gilissen_2014_known;in_omim_20150205_epilepsies;in_UKGTN_v12 . Main mutation mechanism : Loss of function
Created: 27 Jul 2017, 8:36 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; find_uk10k; gilissen_2014_known; omim_20150205_epilepsies; sfari_20150206; UKGTN_v12; Nijmegen_ID_diagnostic; Nijmegen_ID_candidates; gonzalez_mantilla_2016; GEL_ID_green_20160217; neuro_20160418_strict; Loss of function. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust
Created: 19 Jul 2017, 1:29 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Publications

Created: 2 Aug 2017, 11:02 p.m.

Panel version: 1.354

Lu Raymond (university of cambridge )

Green List (high evidence)

Created: 23 Feb 2016, 10:47 a.m.

Panel version: 0.306

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • Victorian Clinical Genetics Services
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Developmental and epileptic encephalopathy 4, OMIM:612164
  • developmental and epileptic encephalopathy, 4, MONDO:0012812
OMIM
602926
Clinvar variants
Variants in STXBP1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

11 Oct 2023, Gel status: 3

Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag Q1_23_MOI was removed from gene: STXBP1.

11 Oct 2023, Gel status: 3

Added New Source, Set mode of inheritance

Arina Puzriakova (Genomics England Curator)

Source NHS GMS was added to STXBP1. Mode of inheritance for gene STXBP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

28 Feb 2023, Gel status: 3

Added Tag

Sarah Leigh (Genomics England Curator)

Tag Q1_23_MOI tag was added to gene: STXBP1.

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, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

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 (2); ANGELMAN/PITT HOPKINS SYNDROME-LIKE DISORDER 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 31855252; 18469812; 19557857

28 Feb 2023, Gel status: 3

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: STXBP1 were set to

29 Sep 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source Victorian Clinical Genetics Services was added to STXBP1.

12 Mar 2018, Gel status: 3

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

13 Nov 2015, Gel status: 4

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 4

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 1

Set Mode of Inheritance, Added New Source

Ellen McDonagh (Genomics England Curator)

STXBP1 was added to Intellectual disabilitypanel. Source: Expert Review Green Model of inheritance for gene STXBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

STXBP1 was added to Intellectual disabilitypanel. Sources: Radboud University Medical Center, Nijmegen