Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol LRRC8A contributors: mct - updated : 20-01-2022
HGNC name leucine rich repeat containing 8 VRAC subunit A
HGNC id 19027
Corresponding disease
AGM5 agammaglobulinemia 5
Location 9q34.11      Physical location : 131.644.390 - 131.680.315
Genatlas name volume-regulated anion channel subunit LRRC8A
Synonym name
  • leucine rich repeat containing 8 member A
  • leucine rich repeat containing 8
  • swelling protein 1
    • Synonym symbol(s) KIAA1437, FLJ10337, LRRC8, FLJ41617, SWELL1
    DNA
    TYPE functioning gene
    STRUCTURE 35.91 kb     4 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 4492 94.07 810 - 2021 34083438
    4 - 4334 - 810 - 2021 34083438
    3 - 4227 - 810 - 2021 34083438
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveliver    
    Endocrinepancreas     Homo sapiens
    Nervousbrain   highly
    Reproductivefemale systemovary   
    Urinarykidney    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...) Homo sapiens
    Lymphoid/ImmuneB cell
    Lymphoid/ImmuneT cell
    Nervousastrocyte Homo sapiens
    cell lineage B-lineage cells
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal, neonatal
    Text brain and liver
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • four transmembrane domains
  • one isolated and eightsequentially located leucine-rich repeats
    • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to murine LRRC8
    Homologene
    FAMILY
  • LRRC8 family
    • CATEGORY receptor membrane
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    text
  • is expressed in the plasma membrane of primary cortical astrocytes and in situ in astrocytes at the perivascular interface with endothelial cells
    • basic FUNCTION
  • required for B cells development
  • implicated in proliferation and activation of lymphocytes and monocytes
  • essential role for LRRC8A in T cell development, survival, and function
  • LRRC8A/D-containing permeability pathway appears to dominate the release of uncharged osmolytes, while an alternative channel (or channels) is composed of LRRC8A/C/D/E and responsible for the loss of charged molecules
  • LRRC8A has been shown to be instrumental in cell swelling
  • LRRC8A/VRAC anion channels enhance beta-cell glucose sensing and insulin secretion
  • is an essential subunit of VRAC and a key factor for astroglial volume homeostasis
  • is the only essential subunit of the Volume Regulated Anion Channel (VRAC), which regulates cellular volume homeostasis and is activated by hypotonic solutions
  • likely an important role of LRRC8A as VRAC component in human keratinocytes
  • LRRC8A modulates tumor progression by influencing cell cycle, apoptosis, and migration
  • LRRC8A/LRRC8E-containing VRACs transport cGAMP and cyclic dinucleotides across the plasma membrane
  • LRRC8A and LRRC8D have been implicated in the proliferation, migration, death, and multidrug resistance of cancer cells through their involvement in various signal pathways
  • regulates skeletal muscle cell size, intracellular signaling, adiposity and glucose metabolism (PMID;
  • LRRC8A, is an essential component of volume-regulated anion channels (VRAC), as a vital regulator of hypotonicity-induced
  • LRRC8A is an essential component of VRAC and is required for cell volume homeostasis during osmotic challenge in basilar smooth muscle cells (BASMCs)
    • CELLULAR PROCESS cell life, differentiation
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    a component
  • LRRC8A/LRRC8C and LRRC8A/LRRC8D heteromers were strongly inhibited by oxidation
  • LRRC8A forms complexes with LRRC8C and/or LRRC8E, depending on their expression levels, to transport cGAMP and other 2'3'-cyclic dinucleotides
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • LRRC8D interacts with LRRC8A, LRRC8B, and LRRC8C
  • combinatory expression of LRRC8A with LRRC8D and LRRC8C is essential for Volume-sensitive outwardly rectifying anion channels (VSOR) activity, whereas none of LRRC8 family members is involved in acid-sensitive outwardly rectifying anion channels (ASOR) activity
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) AGM5
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   translocation    
    disrupted in 1 case of agammaglobulinemia, non-Bruton type,AD with a t(9;20)(q33.2;q12); truncated LRRC8 gene, resulting in a deletion of three of the nine LRR, inhibiting B cells development
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • function as an effector or biomarker of esophageal squamous cell carcinoma (ESCC)
    • Therapy target
    SystemTypeDisorderPubmed
    miscelleaneoushypertension 
    potential therapeutic target for vascular remodeling in hypertension
    ANIMAL & CELL MODELS
  • Lrrc8a(-/-) mice displayed a modest block in B cell development but intact intrinsic B cell function