UNC13B Gene

HGNC Family	C2 domain containing
Name	unc-13 homolog B (C. elegans)
Description	This gene is expressed in the kidney cortical epithelial cells and is upregulated by hyperglycemia. The encoded protein shares a high level of similarity to the rat homolog, and contains 3 C2 domains and a diacylglycerol-binding C1 domain. Hyperglycemia increases the levels of diacylglycerol, which has been shown to induce apoptosis in cells transfected with this gene and thus contribute to the renal cell complications of hyperglycemia. Studies in other species also indicate a role for this protein in the priming step of synaptic vesicle exocytosis. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nUNC13B encodes the mammalian uncoordinated 13‐2 protein (Munc13‐2), a member of the Munc13 family that is indispensable for priming secretory vesicles through regulation of SNARE complex assembly. Studies of its paralog Munc13‐1 in pancreatic β cells have shown that Munc13 proteins enhance and regulate vesicle fusion events—in this case promoting insulin secretion—and that their activity is modulated by second messengers such as diacylglycerol and calcium through calmodulin interactions. These findings, along with detailed analyses of Ca²⁺‐dependent protein interactions, highlight a conserved role of Munc13 proteins in initiating the SNARE assembly process necessary for vesicle exocytosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStructural investigations further reveal that the Munc13 functional core can adopt distinct conformations—transitioning from an “open” state that bridges membranes to a “closed” state forming a lateral hexamer—which collectively template the assembly of a defined number of SNARE complexes. Such high‐resolution models enhance our understanding of how Munc13 proteins, including those encoded by UNC13B, orchestrate the precise docking and priming of vesicles for rapid release."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond the neuronal terminal, the function of UNC13B extends to non‐neuronal secretory processes. In renal cells, for example, a homolog of Munc13‐2 (hmunc13) is upregulated by hyperglycemia and translocates to the Golgi where it binds GTP‐bound Rab34. This interaction is implicated in the regulation of intracellular trafficking and lysosome positioning, thereby contributing to increased protein secretion under diabetic conditions. Consistent with this role, candidate gene studies and functional assays have linked alterations in Munc13‐2 activity to enhanced secretion of proteins such as fibronectin in mesangial cells and to the susceptibility of developing diabetic nephropathy."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nWithin the central nervous system, UNC13B is predominantly expressed in the cerebral cortex, where it plays a pivotal role in synaptic vesicle priming and neurotransmitter release. Variants in UNC13B have been identified in patients with partial epilepsy; experimental models in Drosophila further demonstrate that loss-of-function of UNC13B leads to increased neuronal excitability. In addition, rare missense variants and splice-site mutations in UNC13B have been detected in cohorts of patients with schizophrenia and bipolar disorder, respectively—findings that emphasize its critical function in modulating synaptic transmission and the fine-tuning of neural circuits."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "12"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent work has also illuminated a role for UNC13B in cardiac physiology. In the heart, diacylglycerol (DAG) stimulates the exocytosis of TRPC6‐containing vesicles via binding to the C1 domain of Munc13‐2. This DAG-dependent priming event, which is counteracted by the cardioprotective hormone soluble klotho, underscores an additional dimension in which UNC13B contributes to vesicle fusion dynamics with broad implications for stress-induced cardiac remodeling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Laura Sheu, Eva A Pasyk, Junzhi Ji, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of insulin exocytosis by Munc13-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M303203200"}], "href": "https://doi.org/10.1074/jbc.M303203200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12871971"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12871971"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kalina Dimova, Stefan Kalkhof, Ines Pottratz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural insights into the calmodulin-Munc13 interaction obtained by cross-linking and mass spectrometry."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi900300r"}], "href": "https://doi.org/10.1021/bi900300r"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19492809"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19492809"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sabine Herbst, Noa Lipstein, Olaf Jahn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural insights into calmodulin/Munc13 interaction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1515/hsz-2014-0134"}], "href": "https://doi.org/10.1515/hsz-2014-0134"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24854537"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24854537"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kirill Grushin, R Venkat Kalyana Sundaram, Charles V Sindelar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Munc13 structural transitions and oligomers that may choreograph successive stages in vesicle priming for neurotransmitter release."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.2121259119"}], "href": "https://doi.org/10.1073/pnas.2121259119"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35135883"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35135883"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "David-Alexandre Trégouet, Per-Henrik Groop, Steven McGinn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "G/T substitution in intron 1 of the UNC13B gene is associated with increased risk of nephropathy in patients with type 1 diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db08-0073"}], "href": "https://doi.org/10.2337/db08-0073"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18633107"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18633107"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Pam Speight, Mel Silverman "}, {"type": "b", "children": [{"type": "t", "text": "Diacylglycerol-activated Hmunc13 serves as an effector of the GTPase Rab34."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Traffic (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1600-0854.2005.00321.x"}], "href": "https://doi.org/10.1111/j.1600-0854.2005.00321.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16138900"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16138900"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Neil M Goldenberg, Mel Silverman "}, {"type": "b", "children": [{"type": "t", "text": "Rab34 and its effector munc13-2 constitute a new pathway modulating protein secretion in the cellular response to hyperglycemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00286.2009"}], "href": "https://doi.org/10.1152/ajpcell.00286.2009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19641095"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19641095"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Sara Lopes, Rita Costa, João Maciel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lung Hernia Related with a Rope Bullfight: Case Report."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Rev Port Cir Cardiotorac Vasc (2019)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31734975"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31734975"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jie Wang, Jing-Da Qiao, Xiao-Rong Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "UNC13B variants associated with partial epilepsy with favourable outcome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/brain/awab164"}], "href": "https://doi.org/10.1093/brain/awab164"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33876820"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33876820"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Jun Egawa, Satoshi Hoya, Yuichiro Watanabe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rare UNC13B variations and risk of schizophrenia: Whole-exome sequencing in a multiplex family and follow-up resequencing and a case-control study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet B Neuropsychiatr Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.b.32444"}], "href": "https://doi.org/10.1002/ajmg.b.32444"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26990377"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26990377"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Yun Li, Shen Wang, Tianzhi Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tomosyn guides SNARE complex formation in coordination with Munc18 and Munc13."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1873-3468.13018"}], "href": "https://doi.org/10.1002/1873-3468.13018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29485200"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29485200"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Takumi Nakamura, Kotori Jimbo, Kazuo Nakajima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "De novo UNC13B mutation identified in a bipolar disorder patient increases a rare exon-skipping variant."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropsychopharmacol Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/npr2.12027"}], "href": "https://doi.org/10.1002/npr2.12027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30117296"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30117296"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Jian Xie, Sung-Wan An, Xin Jin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Munc13 mediates klotho-inhibitable diacylglycerol-stimulated exocytotic insertion of pre-docked TRPC6 vesicles."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0229799"}], "href": "https://doi.org/10.1371/journal.pone.0229799"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32134975"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32134975"}]}]}]}
Synonyms	UNC13, MUNC13, UNC13H2
Proteins	UN13B_HUMAN
NCBI Gene ID	10497
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

UNC13B has 7,996 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 117 datasets.

Click the + buttons to view associations for UNC13B from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

UNC13B Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of UNC13B gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of UNC13B gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of UNC13B gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of UNC13B gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of UNC13B gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of UNC13B gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of UNC13B gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of UNC13B gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of UNC13B gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of UNC13B gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with UNC13B protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with UNC13B gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of UNC13B gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of UNC13B gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of UNC13B gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of UNC13B gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing UNC13B protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing UNC13B protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing UNC13B protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing UNC13B protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with UNC13B protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with UNC13B protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of UNC13B gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with UNC13B gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with UNC13B gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with UNC13B gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of UNC13B protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by UNC13B gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with UNC13B gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with UNC13B gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with UNC13B gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with UNC13B gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with UNC13B gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at UNC13B gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of UNC13B gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of UNC13B gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing UNC13B from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with UNC13B gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of UNC13B gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with UNC13B gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.