STX17

Chr 9

syntaxin 17

NCBI Gene: 55014 ENSG00000136874 UniProt: P56962

Enables SNAP receptor activity; SNARE binding activity; and protein phosphatase binding activity. Involved in several processes, including autophagosome membrane docking; endoplasmic reticulum to Golgi vesicle-mediated transport; and endoplasmic reticulum-Golgi intermediate compartment organization. Acts upstream of or within protein localization to phagophore assembly site. Located in several cellular components, including autophagosome membrane; endoplasmic reticulum-Golgi intermediate compartment; and mitochondria-associated endoplasmic reticulum membrane contact site. Part of SNARE complex. [provided by Alliance of Genome Resources, Apr 2025]

Active trials

Pathogenic / LP

ClinVar variants

Pubs (1 yr)

0.6

Missense Z

0.94

LOEUF

Clinical Summary— STX17

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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.

0.94LOEUF

pLI 0.000

Z-score 1.73

OE 0.54 (0.33–0.94)

Tolerant

Typical tolerance to LoF variation

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.

0.59Z-score

OE missense 0.87 (0.75–1.00)

136 obs / 156.9 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.0.54 (0.33–0.94)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.75–1.00)

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: 9 / 16.6Missense obs/exp: 136 / 156.9Syn Z: 0.81

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.