SYT2

Chr 1ADAR

synaptotagmin 2

Also known as: CMS7, CMS7A, CMS7B, MYSPC, SytII

This gene encodes synaptotagmin-2, a synaptic vesicle membrane protein that functions as a calcium sensor in vesicular trafficking and exocytosis at nerve terminals. Mutations cause congenital myasthenic syndrome type 7 with presynaptic dysfunction, which can present with or without distal motor neuropathy, inherited in either autosomal dominant or autosomal recessive patterns. The gene is highly constrained against loss-of-function variation (pLI 0.98), reflecting its critical role in neuromuscular transmission.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/ARLOEUF 0.292 OMIM phenotypes
Clinical SummarySYT2
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Gene-Disease Validity (ClinGen)
congenital myasthenic syndrome 7 · ADModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
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GeneReview available — SYT2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.29LOEUF
pLI 0.981
Z-score 3.54
OE 0.06 (0.020.29)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.98Z-score
OE missense 0.65 (0.570.74)
159 obs / 246.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.06 (0.020.29)
00.351.4
Missense OE0.65 (0.570.74)
00.61.4
Synonymous OE0.89
01.21.6
LoF obs/exp: 1 / 16.6Missense obs/exp: 159 / 246.4Syn Z: 0.89
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSYT2-related congenital onset presynaptic myasthenic syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.5869th %ile
GOF
0.5856th %ile
LOF
0.62top 25%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

DNValidation of this new variant was accomplished by characterization of the mutation homologous to the human c. 1112T>A variant in Drosophila, confirming its dominant-negative effect on neurotransmitter release.PMID:30533528

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SYT2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗