TSNARE1

Chr 8

t-SNARE domain containing 1

NCBI Gene: 203062ENSG00000171045UniProt: Q96NA8

The protein functions as a SNARE complex component that facilitates synaptic vesicle fusion and intracellular protein transport at synapses. Mutations cause neurodevelopmental disorders with intellectual disability, autism spectrum disorder, and seizures. The gene shows autosomal recessive inheritance and has low constraint against loss-of-function variants.

Summary from RefSeq
Research Assistant →
0
Active trials
3
Pubs (1 yr)
59
P/LP submissions
0%
P/LP missense
0.83
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— TSNARE1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
59 unique Pathogenic / Likely Pathogenic· 125 VUS of 225 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.83LOEUF
pLI 0.000
Z-score 2.22
OE 0.53 (0.35–0.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.05Z-score
OE missense 1.01 (0.92–1.10)
326 obs / 323.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.53 (0.35–0.83)
0≤0.351.4
Missense OE1.01 (0.92–1.10)
0≤0.61.4
Synonymous OE0.97
0≤1.21.6
LoF obs/exp: 14 / 26.3Missense obs/exp: 326 / 323.3Syn Z: 0.25
DN
0.74top 25%
GOF
0.6541th %ile
LOF
0.3356th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

225 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic55
Likely Pathogenic4
VUS125
Likely Benign10
Benign3
55
Pathogenic
4
Likely Pathogenic
125
VUS
10
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
55
0
55
Likely Pathogenic
0
0
4
0
4
VUS
1
119
5
0
125
Likely Benign
1
7
0
2
10
Benign
0
1
1
1
3
Total2127653197

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

View in ClinVar →

Protein Context — Lollipop Plot

TSNARE1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients