UNC13A Gene: Structure, Function, and Disease Relevance
A comprehensive overview of UNC13A, a key regulator of synaptic vesicle priming, its role in ALS/FTD, and its molecular characteristics.
Gene Information Card
| Symbol | UNC13A |
|---|---|
| Full Name | unc-13 homolog A |
| Gene Type | Protein coding |
| Chromosomal Location | 19p13.11 |
| NCBI Gene ID | 23025 ncbi.nlm.nih.gov/gene/23025 |
| Ensembl ID | ENSG00000130477 |
| UniProt ID | Q9UPW8 |
| OMIM ID | 609894 |
| HGNC ID | 12568 |
| Aliases | Munc13-1, unc13a, FLJ12118 |
Description
UNC13A encodes Munc13-1, a large presynaptic protein that plays a critical role in synaptic vesicle priming, a process that makes vesicles ready for fusion with the presynaptic membrane. It is essential for neurotransmitter release and synaptic plasticity. Mutations and variants in UNC13A have been associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), and the gene is also implicated in other neurological conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Amyotrophic Lateral Sclerosis (ALS) | Risk variants (e.g., rs12608932) in intron 21 are associated with increased risk and altered splicing, potentially affecting Munc13-1 expression or function. | Genome-wide association studies (GWAS) and meta-analyses (e.g., van Es et al., 2009; Diekstra et al., 2012) |
| Frontotemporal Dementia (FTD) | The same risk variant rs12608932 is associated with FTD, particularly the behavioral variant, and may act as a modifier of disease phenotype. | Genetic association studies (e.g., Ferrari et al., 2014) |
| Schizophrenia | Rare copy number variants and common variants have been nominally associated, but evidence is less robust. | Case-control studies (e.g., Kirov et al., 2012) |
| Epilepsy | Rare mutations have been reported in patients with epilepsy, but causality is not firmly established. | Case reports and small cohort studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | High (e.g., ~30-40 nTPM) | High |
| Brain (cerebellum) | High (e.g., ~25-35 nTPM) | High |
| Spinal cord | Moderate (e.g., ~10-20 nTPM) | Moderate |
| Testis | Low (e.g., ~5-10 nTPM) | Low |
| Other tissues | Very low or not detected | Low/Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | High (e.g., ~50 nTPM) | Neuronal-like, high expression |
| U-87 MG (glioblastoma) | Moderate (e.g., ~20 nTPM) | Glial origin, moderate expression |
| HeLa (cervical carcinoma) | Low (e.g., ~5 nTPM) | Non-neuronal, low expression |
| HepG2 (hepatocellular carcinoma) | Low (e.g., ~3 nTPM) | Non-neuronal, low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs12608932 (A>C) | SNV (intronic) | Minor allele frequency ~0.3 (C allele) | Associated with increased ALS/FTD risk; may affect splicing or regulatory elements |
| c.754C>T (p.Arg252Ter) | Nonsense | Rare | Predicted to cause loss of function; reported in ALS patient |
| c.3049G>A (p.Gly1017Arg) | Missense | Rare | Unknown significance; reported in epilepsy |
| Copy number variants (deletions/duplications) | CNV | Rare | May contribute to neurodevelopmental phenotypes |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., nonsense, frameshift) are rare and may lead to haploinsufficiency, impairing synaptic vesicle priming and neurotransmitter release, potentially contributing to neurodegeneration.
Gain of Function (GOF)
No clear gain-of-function mutations have been described for UNC13A.
Dominant Negative (DN)
No evidence for dominant-negative effects; most disease-associated variants are risk alleles with incomplete penetrance.
View complete mutation data：
Gene Ontology (GO)
| • Calcium ion binding | • Diacylglycerol binding |
| • Phorbol ester binding | • Syntaxin binding |
| • SNARE binding | • Synaptic vesicle priming |
| • Neurotransmitter secretion | • Regulation of exocytosis |
| • Presynaptic active zone assembly |
Pathways
• Synaptic vesicle cycle
• Neurotransmitter release
• SNARE interactions in vesicular transport
• Regulation of exocytosis
Protein Summary
Munc13-1 is a large (approximately 200 kDa) protein that contains multiple domains, including C1 (diacylglycerol/phorbol ester binding), C2 (calcium binding), MUN (catalytic domain for SNARE complex assembly), and C-terminal domains. It localizes to presynaptic active zones and is essential for vesicle priming, a rate-limiting step in neurotransmitter release. Munc13-1 also interacts with other proteins such as RIM and ELKS to regulate synaptic plasticity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| UNC13A Knockout HEK293 Cell Line | EDJ-KQ7779 | Human | 23025 | Details Get a Quote |
| UNC13A Knockout A-549 Cell Line | EDJ-KQ33257 | Human | 23025 | Details Get a Quote |
| UNC13A Knockout HCT 116 Cell Line | EDJ-KQ33258 | Human | 23025 | Details Get a Quote |
| UNC13A Knockout HeLa Cell Line | EDJ-KQ55676 | Human | 23025 | Details Get a Quote |
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