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Proteins/UNIPROT:Q8IWT6
Essential component of the volume-regulated anion channel (VRAC, also named VSOAC channel), an anion channel required to maintain a constant cell volume in response to extracellular or intracellular osmotic changes. The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine. Mediates efflux of amino acids, such as aspartate and glutamate, in response to osmotic stress. LRRC8A and LRRC8D are required for the uptake of the drug cisplatin. In complex with LRRC8C or LRRC8E, acts as a transporter of immunoreactive cyclic dinucleotide GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytosol: mediates both import and export of 2'-3'-cGAMP, thereby promoting transfer of 2'-3'-cGAMP to bystander cells. In contrast, complexes containing LRRC8D inhibit transport of 2'-3'-cGAMP. Required for in vivo channel activity, together with at least one other family member (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel characteristics depend on the precise subunit composition. Can form functional channels by itself (in vitro). Involved in B-cell development: required for the pro-B cell to pre-B cell transition. Also required for T-cell development (By similarity). Required for myoblast differentiation: VRAC activity promotes membrane hyperpolarization and regulates insulin-stimulated glucose metabolism and oxygen consumption (By similarity). Also acts as a regulator of glucose-sensing in pancreatic beta cells: VRAC currents, generated in response to hypotonicity- or glucose-induced beta cell swelling, depolarize cells, thereby causing electrical excitation, leading to increase glucose sensitivity and insulin secretion. Also plays a role in lysosome homeostasis by forming functional lysosomal VRAC channels in response to low cytoplasmic ionic strength condition: lysosomal VRAC channels are necessary for the formation of large lysosome-derived vacuoles, which store and then expel excess water to maintain cytosolic water homeostasis. Acts as a key factor in NLRP3 inflammasome activation by modulating itaconate efflux and mitochondria function..
Function from UniProtKB (Q8IWT6), read 2026-09-23. CC BY 4.0.
Curated compounds routed: 3 · transported by
3 compounds
3 compounds.
0 reported routes3 assembled routes
1 row
82 statements
82 statements · 6 reference databases · Subject: LRRC8A · Sources: Bgee, gene ontology, Hetionet, Reactome, Rhea, WikiPathways
7 reactions
6 names
Resolves to: LRRC8A
Transported by LRRC8A
Reaction pageDirection not assertedBalanced
Rhea RHEA:32867CC BY 4.0Reference data
Transported by GJA1 or GJC1 or LRRC8E or LRRC8A or LRRC8C
Reaction pageReversibleBalanced
Rhea RHEA:66320CC BY 4.0Reference data
Transported by GPHRA or CLIC1 or CLDN4 or SLC26A4 or GPHRB or CLCN1 or SLC1A4 or CLCN2 or CLCNKA or CLCNKB or CLDN8 or CLDN17 and 14 more alternatives
Reaction pageReversibleBalanced
Rhea RHEA:66324CC BY 4.0Reference data
Transported by SLC16A6 or LRRC8E or LRRC8B or LRRC8D or LRRC8A or LRRC8C
Reaction pageReversibleBalanced
Rhea RHEA:66328CC BY 4.0Reference data
Transported by SLC38A8 or SLC25A14 or UCP2 or LRRC8A or PANX1 or SLC17A5
Reaction pageLeft to rightBalanced
Rhea RHEA:66332CC BY 4.0Reference data
L-glutamate(1-)L-glutamate(1-)
Transported by KCNK1 or BEST1 or KCNK2 or SLC25A14 or VDAC1 or LRRC8A or SLC38A6 or SLC17A8 or BEST2 or PANX1 or TTYH2 or TTYH3 and 5 more alternatives
Reaction pageReversibleBalanced
Rhea RHEA:66336CC BY 4.0Reference data