SYT1

Chr 12AD

synaptotagmin 1

Also known as: BAGOS, P65, SVP65, SYT

NCBI Gene: 6857ENSG00000067715UniProt: P21579

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.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Baker-Gordon syndromeMIM #618218
AD
1
Active trials
60
Pubs (1 yr)
51
P/LP submissions
52%
P/LP missense
0.45
LOEUF
DN
Mechanism· predicted
Clinical Summary— SYT1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.60) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
33 unique Pathogenic / Likely Pathogenic· 73 VUS of 133 total submissions
💊
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 OE0.20 (0.10–0.45)
0≤0.351.4
Missense OE0.47 (0.41–0.56)
0≤0.61.4
Synonymous OE0.97
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
DN
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.PMID:25705886

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

ClinVar Variant Classifications

133 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic19
VUS73
Likely Benign14
Benign4
Conflicting1
14
Pathogenic
19
Likely Pathogenic
73
VUS
14
Likely Benign
4
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
13
0
14
Likely Pathogenic
0
16
3
0
19
VUS
4
54
15
0
73
Likely Benign
0
2
1
11
14
Benign
0
0
1
3
4
Conflicting
—1
Total4733314125

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

View in ClinVar →

Protein Context — Lollipop Plot

SYT1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients