SYT13 Gene – Synaptotagmin 13: Function, Expression, Mutations & Disease

SYT13 (synaptotagmin 13) is a member of the synaptotagmin family, characterized by an N-terminal transmembrane region and two C-terminal C2 domains (C2A and C2B) that mediate calcium-dependent phospholipid binding. Unlike classical synaptotagmins, SYT13 lacks a calcium-binding motif in its C2A domain, suggesting a distinct regulatory role in vesicle trafficking, exocytosis, and endocytosis. The gene is located on chromosome 11p12 and is expressed in brain, endocrine tissues, and various cancers. SYT13 has been implicated in neuronal function, insulin secretion, and tumor progression, with altered expression linked to poor prognosis in several malignancies.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Synaptic vesicle cycle (Reactome: R-HSA-421837)

• Calcium-dependent exocytosis (Reactome: R-HSA-114608)

• Insulin secretion (KEGG: hsa04911)

• Neurotransmitter release cycle (Reactome: R-HSA-112310)

Synaptotagmin 13 (SYT13) is a 671-amino acid protein with a molecular weight of approximately 75 kDa. It contains an N-terminal transmembrane domain that anchors it to vesicle membranes, and two C-terminal C2 domains (C2A and C2B). Unlike classical synaptotagmins, the C2A domain of SYT13 lacks the critical aspartate residues required for calcium binding, indicating a calcium-independent regulatory function. The C2B domain retains calcium-binding capacity and mediates interactions with phospholipids and SNARE proteins. SYT13 is predominantly localized to secretory vesicles and the plasma membrane, where it modulates vesicle docking, fusion, and recycling. In neurons, it regulates synaptic vesicle exocytosis; in pancreatic beta cells, it facilitates insulin granule release. Overexpression in multiple cancers suggests an oncogenic role through enhanced vesicle trafficking of growth factors and matrix metalloproteinases, promoting invasion and metastasis.