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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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UNC13B
unc-13 homolog B
Chromosome 9 · 9p13.3
NCBI Gene: 10497Ensembl: ENSG00000198722.15HGNC: HGNC:12566UniProt: A0A1B0GUS7
57PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
Golgi apparatusmembraneprotein bindingGTP-dependent protein bindingdiabetes mellitusepilepsybrain diseasesialadenitis
✦AI Summary

UNC13B (unc-13 homolog B) encodes Munc13-2, a presynaptic protein essential for synaptic vesicle priming and exocytosis 1. The protein functions as a target of the diacylglycerol signaling pathway and facilitates synaptic vesicle maturation selectively in excitatory glutamatergic synapses 2. UNC13B collaborates with UNC13A in regulating dense core vesicle fusion and controlling the location and efficiency of their synaptic release. Mechanistically, UNC13B acts upstream of vesicle fusion by priming synaptic vesicles and participates in activity-dependent refilling of the readily releasable pool 2. The protein is highly expressed in the cerebral cortex and plays a critical role in maintaining neuronal excitability 1. Disease relevance is emerging across multiple neurological conditions. UNC13B variants are associated with partial epilepsy with favorable prognosis, where affected patients demonstrate focal seizures responsive to antiepileptic therapy despite initial frequent seizures 1. UNC13B is implicated in autism spectrum disorders and schizophrenia 2, and polymorphisms show association with diabetic kidney disease susceptibility in Asian populations 3. Additionally, UNC13A-related pathology (linked functionally to UNC13B through shared mechanisms) involves TDP-43-dependent cryptic splicing in ALS, FTD, and Alzheimer's disease 456.

Sources cited
1
UNC13B encodes Munc13-2, a presynaptic protein essential for synaptic vesicle priming and fusion; highly expressed in cerebral cortex; variants associated with partial epilepsy with favorable outcome
PMID: 33876820
2
UNC13B plays roles in synaptic vesicle priming and exocytosis; implicated in autism spectrum disorders, epilepsy, and schizophrenia
PMID: 38188011
3
TDP-43 represses cryptic exon inclusion in UNC13A; UNC13A variants strongly associated with FTD and ALS risk in GWAS
PMID: 35197626
4
TDP-43 depletion induces cryptic exon inclusion in UNC13A resulting in protein depletion; UNC13A intronic SNPs associated with ALS and FTD risk overlap TDP-43 binding sites
PMID: 35197628
5
Cryptic splicing of UNC13A occurs in Alzheimer's disease patients with TDP-43 pathology; correlates with cognitive decline
PMID: 38175301
6
UNC13B gene polymorphisms associated with diabetic kidney disease susceptibility in Chinese Han population
PMID: 31713534
Disease Associationsⓘ20
diabetes mellitusOpen Targets
0.28Weak
epilepsyOpen Targets
0.23Weak
brain diseaseOpen Targets
0.23Weak
sialadenitisOpen Targets
0.22Weak
ovarian dysfunctionOpen Targets
0.21Weak
inherited retinal dystrophyOpen Targets
0.19Weak
polycythemiaOpen Targets
0.14Weak
46,XX testicular disorder of sex developmentOpen Targets
0.06Suggestive
azoospermiaOpen Targets
0.06Suggestive
46,XY complete gonadal dysgenesisOpen Targets
0.06Suggestive
Wilms tumorOpen Targets
0.05Suggestive
46,XY disorder of sex development due to 5-alpha-reductase 2 deficiencyOpen Targets
0.05Suggestive
46,XX ovotesticular disorder of sex developmentOpen Targets
0.05Suggestive
hypogonadotropic hypogonadism 11 with or without anosmiaOpen Targets
0.05Suggestive
diabetic nephropathyOpen Targets
0.05Suggestive
familial male-limited precocious pubertyOpen Targets
0.05Suggestive
Testicular regression syndromeOpen Targets
0.05Suggestive
cryptorchidismOpen Targets
0.05Suggestive
spermatogenic failure 71Open Targets
0.05Suggestive
spermatogenic failure, X-linked, 2Open Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CALML4Protein interaction100%CALML5Protein interaction100%CALML6Protein interaction100%ERC1Protein interaction99%CALML3Protein interaction97%DOC2AProtein interaction97%
Tissue Expression6 tissues
Lung
100%
Heart
59%
Liver
48%
Brain
29%
Ovary
26%
Bone Marrow
9%
Gene Interaction Network
Click a node to explore
UNC13BCALML4CALML5CALML6ERC1CALML3DOC2A
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt O14795
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.73LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.64 [0.55–0.73]
RankingsWhere UNC13B stands among ~20K protein-coding genes
  • #8,029of 20,598
    Most Researched57
  • #5,725of 17,882
    Most Constrained (LOEUF)0.73
Genes detectedUNC13B
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
TDP-43 represses cryptic exon inclusion in the FTD-ALS gene UNC13A.
PMID: 35197626
Nature · 2022
1.00
2
TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A.
PMID: 35197628
Nature · 2022
0.90
3
Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses.
PMID: 22306606
Nat Neurosci · 2012
0.80
4
UNC13B and focal epilepsy.
PMID: 35380630
Brain · 2022
0.70
5
UNC13B variants associated with partial epilepsy with favourable outcome.
PMID: 33876820
Brain · 2021
0.60