STX1B

Chr 16AD

syntaxin 1B

Also known as: GEFSP9, STX1B1, STX1B2

NCBI Gene: 112755ENSG00000099365UniProt: P61266

The protein encoded by this gene belongs to a family of proteins thought to play a role in the exocytosis of synaptic vesicles. Vesicle exocytosis releases vesicular contents and is important to various cellular functions. For instance, the secretion of transmitters from neurons plays an important role in synaptic transmission. After exocytosis, the membrane and proteins from the vesicle are retrieved from the plasma membrane through the process of endocytosis. Mutations in this gene have been identified as one cause of fever-associated epilepsy syndromes. A possible link between this gene and Parkinson's disease has also been suggested. [provided by RefSeq, Jan 2015]

Primary Disease Associations & Inheritance

Generalized epilepsy with febrile seizures plus, type 9MIM #616172
AD
468
ClinVar variants
87
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
Clinical Summary— STX1B
🧬
Gene-Disease Validity (ClinGen)
generalized epilepsy with febrile seizures plus · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
87 Pathogenic / Likely Pathogenic· 175 VUS of 468 total submissions

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.
0.27LOEUF
pLI 0.988
Z-score 3.68
OE 0.06 (0.02–0.27)
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.
2.94Z-score
OE missense 0.38 (0.31–0.47)
68 obs / 178.7 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 (0.02–0.27)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.38 (0.31–0.47)
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.0.95
0≤1.21.6
LoF obs/exp: 1 / 17.7Missense obs/exp: 68 / 178.7Syn Z: 0.30

ClinVar Variant Classifications

468 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic49
Likely Pathogenic38
VUS175
Likely Benign171
Benign25
Conflicting10
49
Pathogenic
38
Likely Pathogenic
175
VUS
171
Likely Benign
25
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
20
5
24
0
49
Likely Pathogenic
21
7
10
0
38
VUS
2
133
37
3
175
Likely Benign
0
2
102
67
171
Benign
0
0
21
4
25
Conflicting
—10
Total4314719474468

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

View in ClinVar →

Protein Context — Lollipop Plot

STX1B · protein map & ClinVar variants

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

Gene2Phenotype Curations

STX1B-related generalized epilepsy with febrile seizures plus

strong
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
SYNTAXIN 1B; STX1B
MIM #601485 · *

Generalized epilepsy with febrile seizures plus, type 9

MIM #616172

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — STX1B
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical spectrum of STX1B-related epileptic disorders.
Wolking S et al.·Neurology
2019
[A novel inherited STX1B mutation associated with generalized epilepsy with febrile seizures plus: a family analysis and literature review].
Tian Y et al.·Zhonghua Er Ke Za Zhi
2019Review
A PRRT2 variant in a Chinese family with paroxysmal kinesigenic dyskinesia and benign familial infantile seizures results in loss of interaction with STX1B.
Ma H et al.·Epilepsia
2018
Cryo-EM structures of engineered Shiga toxin-based immunogens capable of eliciting neutralizing antibodies with therapeutic potential against hemolytic uremic syndrome.
Cristófalo AE et al.·Protein Sci
2025
Delineation of epileptic and neurodevelopmental phenotypes associated with variants in STX1B.
Krenn M et al.·Seizure
2021
Haploinsufficiency of the STX1B gene is associated with myoclonic astatic epilepsy.
Vlaskamp DR et al.·Eur J Paediatr Neurol
2016Case report
Association of three candidate genetic variants in ACMSD/TMEM163, GPNMB and BCKDK /STX1B with sporadic Parkinson's disease in Han Chinese.
Wang L et al.·Neurosci Lett
2019
No association of FAM47E rs6812193, SCARB2 rs6825004 and STX1B rs4889603 polymorphisms with Parkinson's disease in a Chinese Han population.
Chen Y et al.·J Neural Transm (Vienna)
2015
Genetics and clinical correlation of Dravet syndrome and its mimics - experience of a tertiary center in Taiwan.
Liu YH et al.·Pediatr Neonatol
2021
Modular pentameric protein scaffold based on glutaraldehyde-crosslinked Stx1B for superior multivalent therapeutics.
Xu R et al.·Int J Biol Macromol
2026
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