STX4

protein-coding

syntaxin 4, the group of Syntaxins

Gene summary

Enables sphingomyelin phosphodiesterase activator activity. Involved in several processes, including cornified envelope assembly; positive regulation of immune effector process; and positive regulation of protein localization. Located in several cellular components, including basolateral plasma membrane; cytoplasmic vesicle; and obsolete extracellular space. Part of SNARE complex. Is active in glutamatergic synapse and postsynapse. Implicated in autosomal recessive nonsyndromic deafness. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

STX4A

MANE transcript

NM_004604.5

Inheritance

ClinVar variants

U:33B:2

Top phenotype

Deafness, autosomal recessive 123

gnomAD constraint

pLI —, LoF o/e 0.73

Max pathogenic AF

—

Genomic locus

chr16:31,032,889-31,042,975

External References & Databases

Ensembl (ENSG00000103496)

Transcript & Mutation Effects

hg38 • Region Span ~10.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hearing loss, autosomal recessive 123MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0958277

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Deafness, autosomal recessive 123 AR

Manifestation: Audiologic/Otolaryngologic

Intervention: Audiologic/Otolaryngologic

Rationale: As some presentations may involve prelingual hearing loss, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development

Refs: 36355422

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to STX4 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 26

not providedTotal: 3

Sensorineural hearing loss disorderTotal: 1

Hearing loss, autosomal recessive 123Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004604.5. 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			2 clinvar			2
missense			27 clinvar	2 clinvar		29
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	33	2	0	35

Highest pathogenic variant AF is 0.0000020523457

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004604.5	RefSeq	NP_004595.2	10	MANE Select
ENST00000313843.8	Ensembl	ENSP00000317714.3	10	MANE Select
NM_001272095.1	RefSeq	NP_001259024.1	7	Standard
NM_001272096.1	RefSeq	NP_001259025.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Vasopressin-regulated water reabsorption - Homo sapiens (human)
SNARE interactions in vesicular transport - Homo sapiens (human)
Nicotine Pathway (Dopaminergic Neuron), Pharmacodynamics
Insulin Signaling
Clathrin derived vesicle budding

Biological Process

intracellular protein transport
exocytosis
vesicle fusion
positive regulation of cell population proliferation
regulation of exocytosis

Molecular Function

SNARE binding
SNAP receptor activity
protein binding
sphingomyelin phosphodiesterase activator activity

Cellular Component

storage vacuole
extracellular space
endosome
vacuole
trans-Golgi network

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000313843
Coding exons: 10
Length: 10087
Individuals with no LoFs: 125703
Homozygous LoFs: 0
Heterozygous LoFs: 45
Defined: 125748
p: 0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.11	135	176	0.765	0.0000107	1947
Missense (PolyPhen)		38	57.412	0.66189		632
Synonymous	0.159	72	73.7	0.976	0.00000473	556
Loss of Function	1.06	13	17.9	0.728	8.25e-7	211

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00012	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00017	0.00016	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00030	0.00030	rare
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plasma membrane t-SNARE that mediates docking of transport vesicles. Necessary for the translocation of SLC2A4 from intracellular vesicles to the plasma membrane. Together with STXB3 and VAMP2, may also play a role in docking/fusion of intracellular GLUT4-containing vesicles with the cell surface in adipocytes (By similarity). May also play a role in docking of synaptic vesicles at presynaptic active zones. {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.705
RVIS EVS: -0.58
RVIS percentile EVS: 18.44

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.936

Gene Damage Prediction

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