STX17 encodes a SNARE protein that mediates fusion of autophagosome membranes with lysosomes during autophagy and regulates transport in the early secretory pathway between the endoplasmic reticulum and Golgi. Mutations cause autosomal recessive infantile-onset epileptic encephalopathy with severe developmental delay and movement disorders. The gene shows low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.94
Clinical SummarySTX17
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
34 unique Pathogenic / Likely Pathogenic· 45 VUS of 89 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.94LOEUF
pLI 0.000
Z-score 1.73
OE 0.54 (0.330.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.59Z-score
OE missense 0.87 (0.751.00)
136 obs / 156.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.54 (0.330.94)
00.351.4
Missense OE0.87 (0.751.00)
00.61.4
Synonymous OE0.86
01.21.6
LoF obs/exp: 9 / 16.6Missense obs/exp: 136 / 156.9Syn Z: 0.81
DN
0.74top 25%
GOF
0.72top 25%
LOF
0.2386th %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

89 submitted variants in ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic3
VUS45
31
Pathogenic
3
Likely Pathogenic
45
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
31
0
31
Likely Pathogenic
0
0
3
0
3
VUS
0
42
3
0
45
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total04237079

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

View in ClinVar →

Protein Context — Lollipop Plot

STX17 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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