STX4

Chr 16

syntaxin 4

Also known as: DFNB123, STX4A, p35-2

NCBI Gene: 6810ENSG00000103496UniProt: Q12846

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 lamellipodium. Part of SNARE complex. Is active in glutamatergic synapse and postsynapse. Implicated in autosomal recessive nonsyndromic deafness. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

UniProtDeafness, autosomal recessive, 123
50
ClinVar variants
16
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— STX4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 31 VUS of 50 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.16LOEUF
pLI 0.000
Z-score 1.06
OE 0.73 (0.47–1.16)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.11Z-score
OE missense 0.77 (0.66–0.88)
135 obs / 176.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.73 (0.47–1.16)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.66–0.88)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 13 / 17.9Missense obs/exp: 135 / 176.4Syn Z: 0.16

ClinVar Variant Classifications

50 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic4
VUS31
Likely Benign3
12
Pathogenic
4
Likely Pathogenic
31
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
12
0
12
Likely Pathogenic
0
0
4
0
4
VUS
0
24
7
0
31
Likely Benign
0
2
1
0
3
Benign
0
0
0
0
0
Total02624050

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

STX4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Proteogenomic network analysis reveals dysregulated mechanisms and potential mediators in Parkinson's disease.
Doostparast Torshizi A et al.·Nat Commun
2024Functional
A multi-omics and mediation-based genetic screening approach identifies STX4 as a key link between epigenetic regulation, immune cells, and childhood asthma.
Zhang Y et al.·Clin Epigenetics
2025
Syntaxin 4 is essential for hearing in human and zebrafish.
Schrauwen I et al.·Hum Mol Genet
2023Functional
ITGA1, the alpha 1 subunit of integrin receptor, is a novel marker of drug-resistant senescent melanoma cells in vitro.
Słaby J et al.·Arch Toxicol
2025
Proteome-Wide and Immune Cell Phenotype Mendelian Randomization Highlights Immune Involvement in Genetic Generalized Epilepsy.
Gui J et al.·Brain Behav
2025
Identifying Risk Genes and Interpreting Pathogenesis for Parkinson's Disease by a Multiomics Analysis.
Cheng WW et al.·Genes (Basel)
2020Meta-analysis
Whole-genome analysis as a diagnostic tool for patients referred for diagnosis of Silver-Russell syndrome: a real-world study.
Alhendi ASN et al.·J Med Genet
2022Cohort
Conventional and Unconventional Mechanisms by which Exocytosis Proteins Oversee β-cell Function and Protection.
Chatterjee Bhowmick D et al.·Int J Mol Sci
2021Review
Synaptotagmin-1 overexpression under inflammatory conditions affects secretion in salivary glands from Sjögren's syndrome patients.
Cortés J et al.·J Autoimmun
2019Cohort
Exosome secretion related gene signature predicts chemoresistance in patients with colorectal cancer.
Ming L et al.·Pathol Res Pract
2024Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools