STX18

Chr 4

syntaxin 18

Also known as: Ufe1

The STX18 protein is a syntaxin SNARE that mediates vesicular transport between the endoplasmic reticulum and Golgi complex and is important for organizing ER subdomains. Mutations cause autosomal recessive neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed myelination. The gene shows minimal constraint against loss-of-function variants, consistent with the recessive inheritance pattern.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
102
P/LP submissions
0%
P/LP missense
0.96
LOEUF
Multiple*
Mechanism· predicted
Clinical SummarySTX18
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
102 unique Pathogenic / Likely Pathogenic· 57 VUS of 180 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.96LOEUF
pLI 0.000
Z-score 1.72
OE 0.61 (0.400.96)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.70Z-score
OE missense 0.86 (0.750.98)
158 obs / 184.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.61 (0.400.96)
00.351.4
Missense OE0.86 (0.750.98)
00.61.4
Synonymous OE1.12
01.21.6
LoF obs/exp: 14 / 22.9Missense obs/exp: 158 / 184.7Syn Z: -0.77
DN
0.73top 25%
GOF
0.6541th %ile
LOF
0.2776th %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

180 submitted variants in ClinVar

Classification Summary

Pathogenic98
Likely Pathogenic4
VUS57
Likely Benign3
98
Pathogenic
4
Likely Pathogenic
57
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
98
0
98
Likely Pathogenic
0
0
4
0
4
VUS
0
55
2
0
57
Likely Benign
0
1
2
0
3
Benign
0
0
0
0
0
Total0561060162

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

View in ClinVar →

Protein Context — Lollipop Plot

STX18 · 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

No active trials found for this gene.

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Clinical Literature
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