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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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UNC13C
unc-13 homolog C
Chromosome 15 · 15q21.3
NCBI Gene: 440279Ensembl: ENSG00000137766.18HGNC: HGNC:23149UniProt: A0A3B3ISZ1
19PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
plasma membraneneuromuscular junctionpresynaptic membraneterminal boutonalcohol drinkingbenign neoplasm of eyeAllergyovarian neoplasm
✦AI Summary

UNC13C is a presynaptic protein essential for synaptic vesicle priming and exocytosis 1. It functions as a target of the diacylglycerol second messenger pathway and mediates calcium and phospholipid binding at the presynaptic active zone 1. The protein plays a regulatory role in synaptic transmission, particularly at parallel fiber-Purkinje cell and glutamatergic synapses 1. UNC13C has emerged as clinically significant in multiple disease contexts. It exhibits a neuroprotective role in Alzheimer's disease, though exome sequencing has identified potentially damaging variants in familial dementia cases 21. In cancer biology, UNC13C is aberrantly expressed and functions as an independent prognostic biomarker in hepatocellular carcinoma, correlating with tumor stage and overall survival 3. UNC13C expression is also dysregulated in oral squamous cell carcinoma, where it is regulated through the miR-96-5p/UNC13C axis and influences cell migration, invasion, and glycolysis 4. A genome-wide association study identified variants near UNC13C associated with breast cancer risk in African populations 5. Recent studies demonstrate that biallelic UNC13C variants cause severe neurodevelopmental impairment, with specific mutations affecting ethanol sensitivity through C1 domain alterations 6. These findings establish UNC13C as a multifunctional protein with implications for neurological and oncological disorders, potentially serving as a therapeutic target.

Sources cited
1
UNC13C family proteins are evolutionarily conserved and crucial for synaptic vesicle priming and exocytosis; UNC13C has neuroprotective role in Alzheimer's disease and is implicated in oral squamous cell carcinoma and hepatocellular carcinoma
PMID: 38188011
2
High expression of UNC13C is significantly correlated with T stage, AJCC stage, and overall survival rates in hepatocellular carcinoma; UNC13C is an independent prognostic indicator for HCC patients
PMID: 37575271
3
Exome sequencing revealed potentially damaging variants in UNC13C in families with inherited dementia (Alzheimer's disease and frontotemporal dementia)
PMID: 29476165
4
In oral squamous cell carcinoma, circ-KIAA0907 regulates UNC13C expression through the miR-96-5p/UNC13C axis; UNC13C overexpression inhibits migration, invasion, and glycolysis while promoting apoptosis and radiosensitivity
PMID: 33715625
5
Genome-wide association study identified a risk locus for breast cancer located between UNC13C and RAB27A on chromosome 15 in South African Black women
PMID: 40229280
6
Biallelic UNC13C single-nucleotide variants cause severe neurodevelopmental impairments; the Thr1729Met substitution within the C1 domain results in increased ethanol sensitivity and altered protein conformation
PMID: 41399760
Disease Associationsⓘ20
alcohol drinkingOpen Targets
0.43Moderate
benign neoplasm of eyeOpen Targets
0.39Weak
AllergyOpen Targets
0.34Weak
ovarian neoplasmOpen Targets
0.33Weak
COVID-19Open Targets
0.31Weak
severe acute respiratory syndromeOpen Targets
0.31Weak
diabetes mellitusOpen Targets
0.29Weak
bone remodeling diseaseOpen Targets
0.28Weak
Benign Thyroid Gland NeoplasmOpen Targets
0.25Weak
response to xenobiotic stimulusOpen Targets
0.25Weak
depressive disorderOpen Targets
0.25Weak
chronic fatigue syndromeOpen Targets
0.24Weak
chronic pancreatitisOpen Targets
0.24Weak
deficiency anemiaOpen Targets
0.24Weak
restless legs syndromeOpen Targets
0.24Weak
preeclampsiaOpen Targets
0.23Weak
connective tissue diseaseOpen Targets
0.23Weak
knee injuryOpen Targets
0.23Weak
lung diseaseOpen Targets
0.23Weak
occlusion precerebral arteryOpen Targets
0.23Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RIMS2Protein interaction97%UNC13AProtein interaction76%UNC13BProtein interaction72%SV2AShared pathway40%SNAP25Shared pathway29%CADPS2Shared pathway29%
Tissue Expression6 tissues
Brain
100%
Ovary
4%
Heart
1%
Lung
0%
Liver
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
UNC13CRIMS2UNC13AUNC13BSV2ASNAP25CADPS2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8NB66
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.86LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.74 [0.65–0.86]
RankingsWhere UNC13C stands among ~20K protein-coding genes
  • #14,591of 20,598
    Most Researched19
  • #7,489of 17,882
    Most Constrained (LOEUF)0.86
Genes detectedUNC13C
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Role of the UNC13 family in human diseases: A literature review.
PMID: 38188011
AIMS Neurosci · 2023
1.00
2
Prognostic and Clinical Implications of UNC13C expression in Hepatocellular Carcinoma Patients.
PMID: 37575271
Int J Med Sci · 2023
0.90
3
Genome-wide association study identifies common variants associated with breast cancer in South African Black women.
PMID: 40229280
Nat Commun · 2025
0.80
4
Molecular Subtypes of Head and Neck Cancer in Patients of African Ancestry.
PMID: 36508165
Clin Cancer Res · 2023
0.70
5
Genetics of dementia in a Finnish cohort.
PMID: 29476165
Eur J Hum Genet · 2018
0.60