STXBP1

syntaxin binding protein 1

Basic information

Region (hg38): 9:127579370-127696027

Links

ENSG00000136854 ∙ NCBI:6812 ∙ OMIM:602926 ∙ HGNC:11444 ∙ Uniprot:P61764 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy, 4 (Definitive), mode of inheritance: AD
• genetic developmental and epileptic encephalopathy (Supportive), mode of inheritance: AD
• infantile spasms (Supportive), mode of inheritance: AD
• atypical Rett syndrome (Supportive), mode of inheritance: AD
• Dravet syndrome (Supportive), mode of inheritance: AD
• autosomal dominant non-syndromic intellectual disability (Supportive), mode of inheritance: AD
• undetermined early-onset epileptic encephalopathy (Supportive), mode of inheritance: AD
• intellectual disability (Limited), mode of inheritance: AD
• autism spectrum disorder (Limited), mode of inheritance: AD
• developmental and epileptic encephalopathy, 4 (Definitive), mode of inheritance: AR
• developmental and epileptic encephalopathy, 4 (Strong), mode of inheritance: AD
• genetic developmental and epileptic encephalopathy (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 4	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	18469812; 18065176; 19557857; 20876469; 21062273; 21376300; 21762454; 21770924; 22596016; 23020937; 24623842
As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the STXBP1 gene.

• Developmental_and_epileptic_encephalopathy (729 variants)
• not_provided (370 variants)
• Developmental_and_epileptic_encephalopathy,_4 (229 variants)
• not_specified (105 variants)
• Inborn_genetic_diseases (102 variants)
• Infantile_epilepsy_syndrome (42 variants)
• STXBP1-related_disorder (28 variants)
• Intellectual_disability (15 variants)
• Epileptic_encephalopathy (9 variants)
• Seizure (6 variants)
• See_cases (4 variants)
• Global_developmental_delay (3 variants)
• Spastic_ataxia (3 variants)
• West_syndrome (2 variants)
• Cerebellar_vermis_hypoplasia (2 variants)
• Cerebellar_ataxia (2 variants)
• Autism (2 variants)
• Congenital_cerebellar_hypoplasia (2 variants)
• STXBP1-related_neurodevelopmental_disorder (2 variants)
• Early_onset_epileptic_encephalopathy (2 variants)
• Photosensitive_tonic-clonic_seizure (1 variants)
• Autism_spectrum_disorder (1 variants)
• Microcephaly (1 variants)
• Infantile_spasms (1 variants)
• Delayed_speech_and_language_development (1 variants)
• Severe_intellectual_deficiency (1 variants)
• Prostate_cancer (1 variants)
• Neurodegeneration (1 variants)
• Axial_hypotonia (1 variants)
• Atypical_behavior (1 variants)
• Multiple_congenital_anomalies/dysmorphic_syndrome (1 variants)
• Horizontal_nystagmus (1 variants)
• Neurodevelopmental_disorder (1 variants)
• Moderate_global_developmental_delay (1 variants)
• Hand_tremor (1 variants)
• Strabismus (1 variants)
• Generalized_hypotonia (1 variants)
• Tremor (1 variants)
• Variant_of_unknown_significance (1 variants)
• Spasticity (1 variants)
• STXBP1-associated_neurodevelopmental_disorder (1 variants)
• Neurodevelopmental_delay (1 variants)
• Severe_global_developmental_delay (1 variants)
• Intellectual_disability,_severe (1 variants)
• Non-syndromic_intellectual_disability (1 variants)
• Developmental_disorder (1 variants)
• Macrocephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the STXBP1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001032221.6. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1	2	6	166	8	183
missense	47	90	235	56	14	442
nonsense	55	3				58
start loss		1	1			2
frameshift	92	15	3			110
splice donor/acceptor (+/-2bp)	53	21				74
Total	248	132	245	222	22

Highest pathogenic variant AF is 0.000027881317

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
STXBP1	protein_coding	protein_coding	ENST00000373302	19	82917

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000419	125693	0	2	125695	0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.26	127	352	0.361	0.0000235	3991
Missense in Polyphen		35	113.74	0.30773		1348
Synonymous	0.963	122	136	0.895	0.00000948	1139
Loss of Function	5.46	0	34.7	0.00	0.00000185	410

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May participate in the regulation of synaptic vesicle docking and fusion, possibly through interaction with GTP-binding proteins. 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. May play a role in determining the specificity of intracellular fusion reactions.
• Pathway: Synaptic vesicle cycle - Homo sapiens (human);Synaptic Vesicle Pathway;EGF-EGFR Signaling Pathway;Insulin Signaling;Effects of Botulinum toxin;Neuronal System;Glutamate Neurotransmitter Release Cycle;Dopamine Neurotransmitter Release Cycle;Acetylcholine Neurotransmitter Release Cycle;GABA synthesis, release, reuptake and degradation;Neurotransmitter release cycle;Neurexins and neuroligins;Transmission across Chemical Synapses;Protein-protein interactions at synapses;Serotonin Neurotransmitter Release Cycle;Norepinephrine Neurotransmitter Release Cycle (Consensus)

Recessive Scores

• pRec: 0.221

Intolerance Scores

• loftool: 0.0349
• rvis_EVS: -0.69
• rvis_percentile_EVS: 14.97

Haploinsufficiency Scores

• pHI: 0.695
• hipred: Y
• hipred_score: 0.775
• ghis: 0.660

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.754

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Stxbp1
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: stxbp1b
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: increased pigmentation

Gene ontology

• Biological process: platelet degranulation;developmental process involved in reproduction;vesicle docking involved in exocytosis;neuromuscular synaptic transmission;axon target recognition;regulation of synaptic vesicle priming;protein transport;synaptic vesicle priming;synaptic vesicle maturation;negative regulation of protein complex assembly;regulation of synaptic vesicle fusion to presynaptic active zone membrane;negative regulation of synaptic transmission, GABAergic;response to estradiol;regulation of SNARE complex assembly;positive regulation of mast cell degranulation;negative regulation of neuron apoptotic process;positive regulation of calcium ion-dependent exocytosis;protein stabilization;long-term synaptic depression;platelet aggregation;cellular response to interferon-gamma;protein localization to plasma membrane;presynaptic dense core vesicle exocytosis;positive regulation of vesicle docking;positive regulation of glutamate secretion, neurotransmission
• Cellular component: nucleoplasm;cytoplasm;mitochondrion;cytosol;cytoskeleton;plasma membrane;axon;platelet alpha granule;protein-containing complex;myelin sheath;phagocytic vesicle;perinuclear region of cytoplasm;presynaptic active zone membrane;extracellular exosome;postsynapse;glutamatergic synapse
• Molecular function: SNARE binding;RNA binding;protein binding;syntaxin-1 binding;protein kinase binding;protein domain specific binding;syntaxin binding;identical protein binding;phospholipase binding;protein N-terminus binding