STX1A

Chr 7

syntaxin 1A

Also known as: HPC-1, P35-1, STX1, SYN1A

NCBI Gene: 6804ENSG00000106089UniProt: Q16623

This gene encodes a member of the syntaxin superfamily. Syntaxins are nervous system-specific proteins implicated in the docking of synaptic vesicles with the presynaptic plasma membrane. Syntaxins possess a single C-terminal transmembrane domain, a SNARE [Soluble NSF (N-ethylmaleimide-sensitive fusion protein)-Attachment protein REceptor] domain (known as H3), and an N-terminal regulatory domain (Habc). Syntaxins bind synaptotagmin in a calcium-dependent fashion and interact with voltage dependent calcium and potassium channels via the C-terminal H3 domain. This gene product is a key molecule in ion channel regulation and synaptic exocytosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

212
ClinVar variants
167
Pathogenic / LP
0.98
pLI score· haploinsufficient
0
Active trials
Clinical Summary— STX1A
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
167 Pathogenic / Likely Pathogenic· 29 VUS of 212 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
LoF intolerant — likely haploinsufficient
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.
0.29LOEUF
pLI 0.979
Z-score 3.50
OE 0.06 (0.02–0.29)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
2.40Z-score
OE missense 0.51 (0.43–0.61)
98 obs / 191.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.06 (0.02–0.29)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.51 (0.43–0.61)
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.0.86
0≤1.21.6
LoF obs/exp: 1 / 16.2Missense obs/exp: 98 / 191.4Syn Z: 0.95

ClinVar Variant Classifications

212 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic156
Likely Pathogenic11
VUS29
Likely Benign15
Benign1
156
Pathogenic
11
Likely Pathogenic
29
VUS
15
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
155
0
156
Likely Pathogenic
1
3
7
0
11
VUS
1
21
7
0
29
Likely Benign
0
6
3
6
15
Benign
0
0
0
1
1
Total3301727212

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

View in ClinVar →

Protein Context — Lollipop Plot

STX1A · protein map & ClinVar variants

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

Gene2Phenotype Curations

STX1A-related neurodevelopmental disorder without epilepsy

limited
ARUndeterminedAbsent Gene Product
Dev. Disorders
G2P ↗
splice region variant

STX1A-related neurodevelopmental disorder with epilepsy

moderate
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Williams syndrome.
Kozel BA et al.·Nat Rev Dis Primers
2021Review
Diagnostic Yield and Novel Candidate Genes by Exome Sequencing in 152 Consanguineous Families With Neurodevelopmental Disorders.
Reuter MS et al.·JAMA Psychiatry
2017
SNAREs and developmental disorders.
Tang BL·J Cell Physiol
2021Review
Neuropsychological Genotype-Phenotype in Patients with Williams Syndrome with Atypical Deletions: A Systematic Review.
Serrano-Juárez CA et al.·Neuropsychol Rev
2023Review
Heterozygous and homozygous variants in STX1A cause a neurodevelopmental disorder with or without epilepsy.
Luppe J et al.·Eur J Hum Genet
2023
Molecular factors in migraine.
Kowalska M et al.·Oncotarget
2016Review
Hybrid strains of enterotoxigenic/Shiga toxin-producing Escherichia coli, United Kingdom, 2014-2023.
Rodwell EV et al.·J Med Microbiol
2025
A de novo variant in RERE causes autistic behavior by disrupting related genes and signaling pathway.
Li Q et al.·Clin Genet
2024Case report
Different roles of the C-terminal end of Stx1A and Stx2A for AB5 complex integrity and retrograde transport of Stx in HeLa cells.
Kymre L et al.·Pathog Dis
2015
SNARE complex in developmental psychiatry: neurotransmitter exocytosis and beyond.
Cupertino RB et al.·J Neural Transm (Vienna)
2016Review
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