DOC2A: Double C2 Domain Alpha – A Calcium Sensor for Neurotransmitter Release
Comprehensive genomic and proteomic analysis of DOC2A, a key regulator of synaptic vesicle exocytosis and calcium-dependent membrane fusion.
Gene Information Card
| Symbol | DOC2A |
|---|---|
| Full Name | Double C2 Domain Alpha |
| Gene Type | Protein coding |
| Chromosomal Location | 16p11.2 |
| NCBI Gene ID | 8448 ncbi.nlm.nih.gov/gene/8448 |
| Ensembl ID | ENSG00000103197 |
| UniProt ID | Q14183 |
| OMIM ID | 604567 |
| HGNC ID | 2989 |
| Aliases | DOC2, DOC2A, KIAA1356 |
Description
DOC2A (Double C2 Domain Alpha) encodes a calcium-binding protein that contains two C2 domains (C2A and C2B) and is involved in calcium-dependent exocytosis of synaptic vesicles. It acts as a calcium sensor that regulates neurotransmitter release by interacting with SNARE proteins and phospholipids. The protein is primarily expressed in the brain and endocrine tissues.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Schizophrenia | Altered DOC2A expression may disrupt synaptic vesicle recycling and neurotransmission, contributing to pathophysiology. | PMID: 21743477 |
| Bipolar disorder | Genetic variants in DOC2A have been associated with risk, possibly through impaired calcium-dependent exocytosis. | PMID: 22443457 |
| Epilepsy | DOC2A mutations may lower seizure threshold by affecting synaptic vesicle release probability. | ClinVar: VCV000429496 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | High |
| Brain (cerebellum) | 10.2 | High |
| Pituitary gland | 8.1 | Medium |
| Adrenal gland | 6.3 | Medium |
| Testis | 4.7 | Low |
| Pancreas | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.8 | Neuronal model; high DOC2A expression |
| SK-N-SH (neuroblastoma) | 12.3 | Neuronal model |
| HEK293 (embryonic kidney) | 2.1 | Low endogenous expression |
| HeLa (cervical carcinoma) | 1.5 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.112G>A (p.Gly38Arg) | Missense | 0.001% | Reduced calcium binding affinity; potential loss of function |
| c.454C>T (p.Arg152Cys) | Missense | 0.002% | Altered C2 domain structure; decreased exocytosis efficiency |
| c.789_790insA (p.Glu264Argfs*12) | Frameshift | <0.001% | Premature truncation; loss of C2B domain |
Mutation functional classification
Loss of Function (LOF)
Missense and frameshift mutations that impair calcium binding or truncate the C2B domain reduce DOC2A's ability to promote vesicle fusion.
Gain of Function (GOF)
No documented gain-of-function mutations in DOC2A.
Dominant Negative (DN)
Not reported; DOC2A is thought to act as a monomer, and dominant-negative effects have not been described.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Synaptic vesicle cycle (Reactome: R-HSA-421837)
• Calcium-dependent exocytosis of synaptic vesicles (Reactome: R-HSA-9603798)
• Neurotransmitter release cycle (KEGG: hsa04728)
Protein Summary
DOC2A is a 400-amino-acid protein with two tandem C2 domains (C2A and C2B) that bind calcium and phospholipids. It localizes to synaptic vesicles and the plasma membrane, where it facilitates calcium-triggered exocytosis by interacting with syntaxin-1 and SNAP-25. The protein is essential for fast synchronous neurotransmitter release and is highly expressed in the brain.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DOC2A Knockout HEK293 Cell Line | EDJ-KQ6247 | Human | 8448 | Details Get a Quote |
| DOC2A Knockout A-549 Cell Line | EDJ-KQ30106 | Human | 8448 | Details Get a Quote |
| DOC2A Knockout HCT 116 Cell Line | EDJ-KQ30107 | Human | 8448 | Details Get a Quote |
| DOC2A Knockout HeLa Cell Line | EDJ-KQ54911 | Human | 8448 | Details Get a Quote |
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