STXBP5

protein-coding

syntaxin binding protein 5, the group of WD repeat domain containing

Gene summary

Syntaxin 1 is a component of the 7S and 20S SNARE complexes which are involved in docking and fusion of synaptic vesicles with the presynaptic plasma membrane. This gene encodes a syntaxin 1 binding protein. In rat, a similar protein dissociates syntaxin 1 from the Munc18/n-Sec1/rbSec1 complex to form a 10S complex, an intermediate which can be converted to the 7S SNARE complex. Thus this protein is thought to be involved in neurotransmitter release by stimulating SNARE complex formation. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001127715.4

Inheritance

—

ClinVar variants

U:132B:24

Top phenotype

STXBP5-related disorder

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr6:147,204,180-147,391,010

External References & Databases

Ensembl (ENSG00000164506)

Transcript & Mutation Effects

hg38 • Region Span ~186.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to STXBP5 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 107

STXBP5-related disorderTotal: 29

not providedTotal: 18

Autism spectrum disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001127715.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	12 clinvar	3 clinvar	16
missense			122 clinvar	6 clinvar	2 clinvar	130
nonsense			1 clinvar			1
start loss						0
frameshift				1 clinvar		1
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	132	19	5	156

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001127715.4	RefSeq	NP_001121187.1	28	MANE Select
ENST00000321680.11	Ensembl	ENSP00000321826.6	28	MANE Select
NM_001394409.1	RefSeq	NP_001381338.1	27	Standard
NM_139244.6	RefSeq	NP_640337.3	26	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

exocytosis
protein transport
regulation of exocytosis
positive regulation of GTPase activity
positive regulation of exocytosis

Molecular Function

GTPase activator activity
syntaxin-1 binding
Rab GTPase binding
syntaxin binding

Cellular Component

cytoplasm
cytosol
plasma membrane
acetylcholine-gated channel complex
synaptic vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000321680
Coding exons: 28
Length: 181306
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125746
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.00	401	609	0.658	0.0000313	7451
Missense (PolyPhen)		58	128.97	0.44971		1561
Synonymous	0.178	221	224	0.985	0.0000122	2234
Loss of Function	6.41	10	66.3	0.151	0.00000348	821

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000036	0.000035	rare
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a regulatory role in calcium-dependent exocytosis and neurotransmitter release. Inhibits membrane fusion between transport vesicles and the plasma membrane. May modulate the assembly of trans-SNARE complexes between transport vesicles and the plasma membrane. Inhibits translocation of GLUT4 from intracellular vesicles to the plasma membrane. Competes with STXBP1 for STX1 binding (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.143

Intolerance Scores

LoFtool: 0.305
RVIS EVS: -0.4
RVIS percentile EVS: 26.98

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.733

Gene Damage Prediction

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