SYT17

Chr 16

synaptotagmin 17

Also known as: Syt-17, sytXVII

NCBI Gene: 51760 ENSG00000103528 UniProt: Q9BSW7 OMIM: 621518

The protein functions as a calcium sensor at glutamatergic synapses, binding SNAREs and phospholipids in a calcium-dependent manner to regulate neurotransmitter receptor internalization and dendrite extension. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability and seizures. This gene shows no constraint against loss-of-function variants in the population.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable SNARE binding activity; calcium ion sensor activity; and calcium-dependent phospholipid binding activity. Involved in positive regulation of dendrite extension and regulation of postsynaptic neurotransmitter receptor internalization. Is active in glutamatergic synapse and postsynapse. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.93

Clinical Summary— SYT17

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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

65 VUS of 82 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?

0.93LOEUF

pLI 0.000

Z-score 1.81

OE 0.56 (0.35–0.93)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.18Z-score

OE missense 0.80 (0.72–0.90)

231 obs / 287.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.56 (0.35–0.93)

0≤0.351.4

Missense OE?0.80 (0.72–0.90)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 11 / 19.7Missense obs/exp: 231 / 287.2Syn Z: 0.24

This gene — mechanism propensity

0.78top 25%

GOF

0.73top 25%

LOF

0.3259th %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

82 submitted variants in ClinVar

ClinVar

Classification Summary

VUS65

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	65	0	65
Likely Benign	0	1	1
Benign	0	0	0
Total	65	1	66

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap SYT17 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →