STX19

Chr 3

syntaxin 19

NCBI Gene: 415117 ENSG00000178750 UniProt: Q8N4C7

The STX19 protein is a SNARE complex component that facilitates synaptic vesicle fusion at presynaptic active zones and participates in endosomal trafficking of growth factor receptors. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in early infancy, characterized by severe intellectual disability, refractory seizures, and progressive microcephaly. The gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed in affected patients.

ResearchSummary from RefSeq, UniProt

Predicted to enable SNAP receptor activity and SNARE binding activity. Predicted to be involved in intracellular protein transport; synaptic vesicle fusion to presynaptic active zone membrane; and vesicle docking. Predicted to be located in cytoplasm and membrane. Predicted to be part of SNARE complex. Predicted to be active in endomembrane system and presynaptic active zone membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.68

Clinical Summary— STX19

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Population Constraint (gnomAD)

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

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ClinVar Variants

37 VUS of 41 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.68LOEUF

pLI 0.000

Z-score -0.05

OE 1.02 (0.63–1.68)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.46Z-score

OE missense 1.11 (0.97–1.26)

159 obs / 143.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.02 (0.63–1.68)

0≤0.351.4

Missense OE?1.11 (0.97–1.26)

0≤0.61.4

Synonymous OE?1.20

0≤1.21.6

LoF obs/exp: 10 / 9.8Missense obs/exp: 159 / 143.4Syn Z: -1.08

This gene — mechanism propensity

0.76top 25%

GOF

0.6735th %ile

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

41 submitted variants in ClinVar

ClinVar

Classification Summary

VUS37

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	34	3	37
Likely Benign	2	0	2
Benign	0	0	0
Total	36	3	39

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

View in ClinVar →

12 pathogenic / likely-pathogenic (of 27) ClinVar copy-number / structural variants overlap STX19 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →