STXBP4

protein-coding

syntaxin binding protein 4, the group of PDZ domain containing

Gene summary

Involved in several processes, including positive regulation of cell cycle G1/S phase transition; positive regulation of keratinocyte proliferation; and protein stabilization. Located in extracellular exosome. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_178509.6

Inheritance

—

ClinVar variants

U:74B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.78

Max pathogenic AF

—

Genomic locus

chr17:54,968,727-55,173,632

External References & Databases

Ensembl (ENSG00000166263)

Transcript & Mutation Effects

hg38 • Region Span ~204.9 kb

Loading mutation effect viewer...

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 STXBP4 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 76

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_178509.6. 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			1
missense			73 clinvar	6 clinvar		79
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	74	6	0	80

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_178509.6	RefSeq	NP_848604.3	16	MANE Select
ENST00000376352.6	Ensembl	ENSP00000365530.2	16	MANE Select
NM_001398481.1	RefSeq	NP_001385410.1	16	Standard
NM_001398482.1	RefSeq	NP_001385411.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Insulin Signaling
Insulin-mediated glucose transport
Validated transcriptional targets of deltaNp63 isoforms

Biological Process

protein targeting
cellular response to DNA damage stimulus
insulin receptor signaling pathway
regulation of glucose transmembrane transport
positive regulation of keratinocyte proliferation

Molecular Function

protein binding
syntaxin binding

Cellular Component

phagocytic vesicle
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000376352
Coding exons: 16
Length: 195559
Individuals with no LoFs: 125657
Homozygous LoFs: 0
Heterozygous LoFs: 90
Defined: 125747
p: 0.000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.736	241	275	0.875	0.0000137	3575
Missense (PolyPhen)		47	63.718	0.73763		851
Synonymous	1.69	74	95.0	0.779	0.00000446	1046
Loss of Function	1.15	25	32.0	0.781	0.00000152	426

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00041	0.00040	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00066	0.00065	rare
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.00033	0.00033	rare
South Asian	0.00053	0.00052	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in the translocation of transport vesicles from the cytoplasm to the plasma membrane. Inhibits the translocation of SLC2A4 from intracellular vesicles to the plasma membrane by STX4A binding and preventing the interaction between STX4A and VAMP2. Stimulation with insulin disrupts the interaction with STX4A, leading to increased levels of SLC2A4 at the plasma membrane. May also play a role in the regulation of insulin release by pancreatic beta cells after stimulation by glucose (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.0911

Intolerance Scores

LoFtool: 0.880
RVIS EVS: 0.17
RVIS percentile EVS: 65.96

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0386

Gene Damage Prediction

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