LRRC8A Gene

Name	leucine rich repeat containing 8 family, member A
Description	This gene encodes a protein belonging to the leucine-rich repeat family of proteins, which are involved in diverse biological processes, including cell adhesion, cellular trafficking, and hormone-receptor interactions. This family member is a putative four-pass transmembrane protein that plays a role in B cell development. Defects in this gene cause autosomal dominant non-Bruton type agammaglobulinemia, an immunodeficiency disease resulting from defects in B cell maturation. Multiple alternatively spliced transcript variants, which encode the same protein, have been identified for this gene. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LRRC8A, also known as SWELL1, is an essential transmembrane protein that forms the core subunit of volume‐regulated anion channels (VRACs), which mediate chloride and organic osmolyte flux in response to cell swelling. In complex with other LRRC8 family members, LRRC8A assembles into hexameric channels that are critical for regulatory volume decrease, thereby maintaining cellular homeostasis under osmotic stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " LRRC8A‐dependent VRACs contribute not only to volume regulation but also to diverse cellular processes. For instance, these channels facilitate the release and uptake of signaling molecules such as cyclic dinucleotides that potentiate interferon responses during viral infections"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", and they mediate non–vesicular glutamate release from astrocytes, thereby modulating synaptic efficacy and influencing neurological outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, mutations or aberrant regulation of LRRC8A have been implicated in developmental immunodeficiencies—where disruption leads to defects in B cell development"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "—as well as in cancer, where altered LRRC8A expression is associated with changes in tumor cell proliferation, migration, and chemoresistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Structural studies have revealed that LRRC8A comprises a transmembrane pore domain coupled to a cytoplasmic leucine‐rich repeat (LRR) domain that modulates channel gating allosterically; recent cryo-electron microscopy analyses and nanobody-based perturbation experiments have further elucidated key determinants of its activity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its canonical role in cell volume regulation, LRRC8A influences a broad range of physiological functions, including endothelial signaling and alignment in response to shear stress"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", neuronal excitability"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": ", and overall anion conductance in various cell types."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " Collectively, these observations underscore the multifaceted role of LRRC8A as a critical regulator of cellular homeostasis and intercellular communication across many biological contexts.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Felizia K Voss, Florian Ullrich, Jonas Münch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1252826"}], "href": "https://doi.org/10.1126/science.1252826"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24790029"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24790029"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Zhaozhu Qiu, Adrienne E Dubin, Jayanti Mathur, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SWELL1, a plasma membrane protein, is an essential component of volume-regulated anion channel."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2014.03.024"}], "href": "https://doi.org/10.1016/j.cell.2014.03.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24725410"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24725410"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Chun Zhou, Xia Chen, Rosa Planells-Cases, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transfer of cGAMP into Bystander Cells via LRRC8 Volume-Regulated Anion Channels Augments STING-Mediated Interferon Responses and Anti-viral Immunity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunity (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.immuni.2020.03.016"}], "href": "https://doi.org/10.1016/j.immuni.2020.03.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32277911"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32277911"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Junhua Yang, Maria Del Carmen Vitery, Jianan Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glutamate-Releasing SWELL1 Channel in Astrocytes Modulates Synaptic Transmission and Promotes Brain Damage in Stroke."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2019.03.029"}], "href": "https://doi.org/10.1016/j.neuron.2019.03.029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30982627"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30982627"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Akihisa Sawada, Yoshihiro Takihara, Ji Yoo Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A congenital mutation of the novel gene LRRC8 causes agammaglobulinemia in humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI18937"}], "href": "https://doi.org/10.1172/JCI18937"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14660746"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14660746"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Belinda Halling Sørensen, Dorthe Nielsen, Unnur Arna Thorsteinsdottir, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of LRRC8A protects human ovarian and alveolar carcinoma cells against Cisplatin-induced expression of p53, MDM2, p21Waf1/Cip1, and Caspase-9/-3 activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00256.2015"}], "href": "https://doi.org/10.1152/ajpcell.00256.2015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26984736"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26984736"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Haifeng Zhang, Zhiqin Deng, Dongxia Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High expression of leucine‑rich repeat‑containing 8A is indicative of a worse outcome of colon cancer patients by enhancing cancer cell growth and metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2018.6556"}], "href": "https://doi.org/10.3892/or.2018.6556"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30015914"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30015914"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Dawid Deneka, Marta Sawicka, Andy K M Lam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure of a volume-regulated anion channel of the LRRC8 family."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41586-018-0134-y"}], "href": "https://doi.org/10.1038/s41586-018-0134-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29769723"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29769723"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jennifer M Kefauver, Kei Saotome, Adrienne E Dubin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure of the human volume regulated anion channel."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.38461"}], "href": "https://doi.org/10.7554/eLife.38461"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30095067"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30095067"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Craig D Platt, Janet Chou, Patrick Houlihan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Leucine-rich repeat containing 8A (LRRC8A)-dependent volume-regulated anion channel activity is dispensable for T-cell development and function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Allergy Clin Immunol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jaci.2016.12.974"}], "href": "https://doi.org/10.1016/j.jaci.2016.12.974"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28192143"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28192143"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Dawid Deneka, Sonja Rutz, Cedric A J Hutter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Allosteric modulation of LRRC8 channels by targeting their cytoplasmic domains."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-021-25742-w"}], "href": "https://doi.org/10.1038/s41467-021-25742-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34521847"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34521847"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Ahmad F Alghanem, Javier Abello, Joshua M Maurer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The SWELL1-LRRC8 complex regulates endothelial AKT-eNOS signaling and vascular function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.61313"}], "href": "https://doi.org/10.7554/eLife.61313"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33629656"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33629656"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Runping Wang, Yongjun Lu, Susheel Gunasekar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The volume-regulated anion channel (LRRC8) in nodose neurons is sensitive to acidic pH."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "JCI Insight (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/jci.insight.90632"}], "href": "https://doi.org/10.1172/jci.insight.90632"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28289711"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28289711"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Toshiaki Okada, Md Rafiqul Islam, Nargiza A Tsiferova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Specific and essential but not sufficient roles of LRRC8A in the activity of volume-sensitive outwardly rectifying anion channel (VSOR)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Channels (Austin) (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/19336950.2016.1247133"}], "href": "https://doi.org/10.1080/19336950.2016.1247133"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27764579"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27764579"}]}]}]}
Synonyms	LRRC8, AGM5, SWELL1
Proteins	LRC8A_HUMAN
NCBI Gene ID	56262
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

LRRC8A has 5,731 functional associations with biological entities spanning 8 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 117 datasets.

Click the + buttons to view associations for LRRC8A from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

LRRC8A 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 LRRC8A 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 LRRC8A gene relative to other tissues from the Allen Brain Atlas Adult Mouse 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 LRRC8A 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 LRRC8A 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 LRRC8A 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 LRRC8A gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of LRRC8A 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 LRRC8A 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 LRRC8A 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 LRRC8A gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with LRRC8A protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with LRRC8A 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 LRRC8A gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of LRRC8A 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 LRRC8A gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with LRRC8A gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing LRRC8A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing LRRC8A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing LRRC8A protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with LRRC8A 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 LRRC8A protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with LRRC8A gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with LRRC8A gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with LRRC8A 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 LRRC8A 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 LRRC8A 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 LRRC8A 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 LRRC8A 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 LRRC8A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with LRRC8A 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 LRRC8A 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 LRRC8A gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of LRRC8A 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 LRRC8A from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with LRRC8A gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with LRRC8A gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing LRRC8A from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of LRRC8A gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of LRRC8A gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Kinase Perturbations	kinase perturbations changing expression of LRRC8A gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.