LRRC8C

Leucine-rich repeat-containing protein 8C is a protein encoded by the human LRRC8C gene.^[5]

LRRC8C
Identifiers
Aliases	LRRC8C, AD158, FAD158, leucine-rich repeat containing 8 family member C, leucine rich repeat containing 8 family member C, leucine rich repeat containing 8 VRAC subunit C
External IDs	OMIM: 612889; MGI: 2140839; HomoloGene: 12997; GeneCards: LRRC8C; OMA:LRRC8C - orthologs
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p22.2 Start 89,633,072 bp[1] End 89,769,903 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5|5 E5 Start 105,667,254 bp[2] End 105,760,884 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in sperm secondary oocyte cartilage tissue myocardium of left ventricle buccal mucosa cell white blood cell monocyte lower lobe of lung superficial temporal artery right ventricle Top expressed in left lung lobe carotid body ciliary body vestibular membrane of cochlear duct right lung lobe body of femur endothelial cell of lymphatic vessel Epithelium of choroid plexus mesenteric lymph nodes iris More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding volume-sensitive anion channel activity Cellular component cytoplasm integral component of membrane integral component of plasma membrane endoplasmic reticulum membrane membrane endoplasmic reticulum ion channel complex plasma membrane Biological process anion transmembrane transport ion transport fat cell differentiation regulation of anion transport signal transduction transmembrane transport transport cell volume homeostasis inorganic anion transport taurine transport aspartate transmembrane transport protein hexamerization cellular response to osmotic stress Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 84230 100604 Ensembl ENSG00000171488 ENSMUSG00000054720 UniProt Q8TDW0 Q8R502 RefSeq (mRNA) NM_032270 NM_133897 RefSeq (protein) NP_115646 NP_598658 Location (UCSC) Chr 1: 89.63 – 89.77 Mb Chr 5: 105.67 – 105.76 Mb PubMed search [3] [4]
Wikidata
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Function

LRRC8C is one of five LRRC8 proteins—along with LRRC8A, LRRC8B, LRRC8D, and LRRC8E—that can form subunits of the heteromeric volume-regulated anion channel (VRAC).^[6] These channels play a vital role in cell volume regulation by transporting chloride ions and organic osmolytes—including taurine and glutamate—across the plasma membrane.^[7]

Although LRRC8C can contribute to VRAC composition, it appears to be less essential for VRAC activity than core subunits LRRC8A and LRRC8D.^[8][9][10] However, studies have shown that LRRC8A and LRRC8D alone are not sufficient to support the full functional diversity of VRACs.^[11] The presence of additional LRRC8 subunits, including LRRC8C, modulates substrate selectivity and functional properties of VRACs.^[12][10]

Clinical significance

Recent findings suggest that LRRC8C may have more critical roles than previously recognized. A 2024 study identified monoallelic de novo variants in LRRC8C in two children with a severe congenital multisystem disorder (TIMES syndrome; see OMIM: https://omim.org/entry/621056).^[13] These variants led to constitutive VRAC activation, resulting in channel hyperactivity and dysregulated ion transport, highlighting a pathogenic mechanism involving LRRC8C dysfunction.

Beyond its role in VRACs, the LRRC8 protein family has also been linked to agammaglobulinemia-5, a primary immunodeficiency disorder.^[14]