SYT1

Chr 12AD

synaptotagmin 1

Also known as: BAGOS, P65, SVP65, SYT

NCBI Gene: 6857 ENSG00000067715 UniProt: P21579 OMIM: 185605

The protein functions as a calcium sensor that triggers neurotransmitter release at synapses by binding to acidic phospholipids and interacting with key synaptic proteins including neurexins and syntaxin. Mutations cause Baker-Gordon syndrome, an autosomal dominant neurodevelopmental disorder. The gene is highly constrained against loss-of-function variants (LOEUF 0.451), reflecting its critical role in synaptic transmission.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the synaptotagmin protein family. The synaptotagmins are integral membrane proteins of synaptic vesicles that serve as calcium sensors in the process of vesicular trafficking and exocytosis. The encoded protein participates in triggering neurotransmitter release at the synapse in response to calcium binding. Mutations in this gene are associated with Baker-Gordon syndrome. [provided by RefSeq, Jan 2023]

OMIM ResearchGenerating clinical summary…

DNmechanismADLOEUF 0.451 OMIM phenotype

Clinical Summary— SYT1

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.60) — some intolerance to loss-of-function variants.

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ClinVar Variants

22 unique Pathogenic / Likely Pathogenic· 65 VUS of 115 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.45LOEUF

pLI 0.600

Z-score 3.35

OE 0.20 (0.10–0.45)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.84Z-score

OE missense 0.47 (0.41–0.56)

109 obs / 230.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.20 (0.10–0.45)

0≤0.351.4

Missense OE?0.47 (0.41–0.56)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 4 / 20.3Missense obs/exp: 109 / 230.0Syn Z: 0.23

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongSYT1-related intellectual disabilityOTHERAD

This gene — mechanism propensity

0.6357th %ile

GOF

0.6346th %ile

LOF

0.55top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median · 1 literature citation

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.

Literature Evidence

DNTogether, the clinical features, electrophysiological phenotype, and in vitro neuronal phenotype associated with this dominant negative SYT1 mutation highlight presynaptic mechanisms that mediate human motor control and cognitive development.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

References

1.PMID 25705886 ↗

ClinVar Variant Classifications

115 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic19

VUS65

Likely Benign15

Benign4

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	2	0	0	3
Likely Pathogenic	1	18	0	0	19
VUS	6	56	3	0	65
Likely Benign	0	2	1	12	15
Benign	0	0	1	3	4
Conflicting	—				1
Total	8	78	5	15	107

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 23) ClinVar copy-number / structural variants overlap SYT1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →