CPLX2 Gene

Name	complexin 2
Description	Proteins encoded by the complexin/synaphin gene family are cytosolic proteins that function in synaptic vesicle exocytosis. These proteins bind syntaxin, part of the SNAP receptor. The protein product of this gene binds to the SNAP receptor complex and disrupts it, allowing transmitter release. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Complexin 2 (CPLX2) is a pivotal regulator of vesicle fusion that modulates the efficacy and timing of neurotransmitter release by binding to assembled SNARE complexes. Functionally, CPLX2 facilitates vesicle priming and synchronizes Ca<sup>2+</sup>-triggered exocytosis, thereby ensuring rapid and efficient synaptic transmission."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In multiple studies, reduced CPLX2 expression has been linked to synaptic deficits in neuropsychiatric and neurodegenerative conditions. For example, decreased complexin II mRNA levels have been observed in schizophrenia‐affected brain regions"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", and genetic polymorphisms in the CPLX2 gene have been associated with impaired cognitive performance and altered neural activity in patients with schizophrenia."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": " Similarly, in Huntington’s disease models, CPLX2 depletion has been linked directly to reduced Ca<sup>2+</sup>-evoked neurotransmitter release and progressive neuropathology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Beyond its neuronal role, CPLX2 has been implicated in other secretory processes; for instance, its expression is modulated by microRNAs in the amygdala to govern stress-related excitatory transmission"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", and its dysregulation—via transcriptional repression by REST—can impair clinically relevant exocytosis in pancreatic β cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Moreover, in kidney cortical collecting duct cells, aberrant complexin II levels disrupt the regulated insertion of membrane channels."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Finally, in the context of ischemic stroke, gene silencing of complexin II was shown to reduce glutamate release and ameliorate neuronal injury, thereby linking oxidative stress to excitotoxicity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these findings underscore CPLX2’s role as a critical modulator of both fast neurotransmission and secretory processes. Its precise regulation is essential for maintaining synaptic homeostasis and proper cognitive function, while genetic and environmental factors that alter CPLX2 expression or function may contribute to the pathogenesis of neuropsychiatric disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Madhurima Dhara, Antonio Yarzagaray, Yvonne Schwarz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Complexin synchronizes primed vesicle exocytosis and regulates fusion pore dynamics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201311085"}], "href": "https://doi.org/10.1083/jcb.201311085"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24687280"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24687280"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Daniel Parisotto, Jörg Malsam, Andrea Scheutzow, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SNAREpin assembly by Munc18-1 requires previous vesicle docking by synaptotagmin 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.386805"}], "href": "https://doi.org/10.1074/jbc.M112.386805"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22810233"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22810233"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "S L Eastwood, P J Harrison "}, {"type": "b", "children": [{"type": "t", "text": "Decreased expression of vesicular glutamate transporter 1 and complexin II mRNAs in schizophrenia: further evidence for a synaptic pathology affecting glutamate neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Schizophr Res (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.schres.2004.05.010"}], "href": "https://doi.org/10.1016/j.schres.2004.05.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15653259"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15653259"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Martin Begemann, Sabrina Grube, Sergi Papiol, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Modification of cognitive performance in schizophrenia by complexin 2 gene polymorphisms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Gen Psychiatry (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1001/archgenpsychiatry.2010.107"}], "href": "https://doi.org/10.1001/archgenpsychiatry.2010.107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20819981"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20819981"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Hee Jae Lee, Ji Young Song, Jong Woo Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association study of polymorphisms in synaptic vesicle-associated genes, SYN2 and CPLX2, with schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Behav Brain Funct (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1744-9081-1-15"}], "href": "https://doi.org/10.1186/1744-9081-1-15"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16131404"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16131404"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "K Radyushkin, A El-Kordi, S Boretius, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Complexin2 null mutation requires a 'second hit' for induction of phenotypic changes relevant to schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Brain Behav (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1601-183X.2010.00590.x"}], "href": "https://doi.org/10.1111/j.1601-183X.2010.00590.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20412316"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20412316"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "J Michael Edwardson, Chih-Tien Wang, Belvin Gong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of mutant huntingtin blocks exocytosis in PC12 cells by depletion of complexin II."}]}, {"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.M304615200"}], "href": "https://doi.org/10.1074/jbc.M304615200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12807877"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12807877"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Whitney Freeman, A Jennifer Morton "}, {"type": "b", "children": [{"type": "t", "text": "Regional and progressive changes in brain expression of complexin II in a mouse transgenic for the Huntington's disease mutation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain Res Bull (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.brainresbull.2003.12.004"}], "href": "https://doi.org/10.1016/j.brainresbull.2003.12.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15121238"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15121238"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Cecilia Mannironi, Antonio Biundo, Samyutha Rajendran, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-135a Regulates Synaptic Transmission and Anxiety-Like Behavior in Amygdala."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Neurobiol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12035-017-0564-9"}], "href": "https://doi.org/10.1007/s12035-017-0564-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28488209"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28488209"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "D Martin, F Allagnat, G Chaffard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional significance of repressor element 1 silencing transcription factor (REST) target genes in pancreatic beta cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetologia (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00125-008-0984-1"}], "href": "https://doi.org/10.1007/s00125-008-0984-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18385973"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18385973"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "M B Butterworth, R A Frizzell, J P Johnson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PKA-dependent ENaC trafficking requires the SNARE-binding protein complexin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Renal Physiol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajprenal.00390.2003"}], "href": "https://doi.org/10.1152/ajprenal.00390.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15972388"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15972388"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Ziying Wang, Xinbing Wei, Kang Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NOX2 deficiency ameliorates cerebral injury through reduction of complexin II-mediated glutamate excitotoxicity in experimental stroke."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Free Radic Biol Med (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.freeradbiomed.2013.08.166"}], "href": "https://doi.org/10.1016/j.freeradbiomed.2013.08.166"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23982049"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23982049"}]}]}]}
Synonyms	921-L, HFB1, CPX2, CPX-2
Proteins	CPLX2_HUMAN
NCBI Gene ID	10814
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CPLX2 has 5,732 functional associations with biological entities spanning 8 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) extracted from 110 datasets.

Click the + buttons to view associations for CPLX2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CPLX2 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 CPLX2 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of CPLX2 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CPLX2 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 CPLX2 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 CPLX2 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 CPLX2 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 CPLX2 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 CPLX2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of CPLX2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CPLX2 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 CPLX2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CPLX2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CPLX2 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 CPLX2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CPLX2 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 CPLX2 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 CPLX2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CPLX2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CPLX2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CPLX2 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 CPLX2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing CPLX2 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CPLX2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CPLX2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CPLX2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CPLX2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with CPLX2 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CPLX2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CPLX2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CPLX2 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 CPLX2 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 CPLX2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CPLX2 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 CPLX2 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 CPLX2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CPLX2 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 CPLX2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with CPLX2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with CPLX2 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of CPLX2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.