LRRC8C

Leucine-rich repeat-containing protein 8C is a protein that in humans is encoded by the LRRC8C gene.^[5] Researchers have found out that this protein, along with the other LRRC8 proteins LRRC8A, LRRC8B, LRRC8D, and LRRC8E, is sometimes a subunit of the heteromer protein Volume-Regulated Anion Channel.^[6] Volume-Regulated Anion Channels (VRACs) are crucial to the regulation of cell size by transporting chloride ions and various organic osmolytes, such as taurine or glutamate, across the plasma membrane,^[7] and that is not the only function these channels have been linked to.

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
View/Edit Human View/Edit Mouse

While LRRC8C is one of many proteins that can be part of VRAC, research has found that it is not as crucial to the activity of the channel in comparison to LRRC8A and LRRC8D.^[8][9][10] However, while we know that LRRC8A and LRRC8D are necessary for VRAC function, other studies have found that they are not sufficient for the full range of usual VRAC activity.^[11] This is where the other LRRC8 proteins come in, such as LRRC8C, as the different composition of these subunits affects the range of specificity for VRACs.^[12][10]

In fact, a research study published in December 2024 seems to contradict the "non-crucial" role of LRRC8C and rather suggest multiple roles in different cell types. The study showed that two children bearing different, monoallelic variants in LRRC8C ^[13] had severe multi-organ congenital disease (TIMES syndrome; see OMIM https://omim.org/entry/621056). The genetic variants lead to constitutional activation of VRACs that become de-regulated and hyperactive.

In addition to its role in VRACs, the LRRC8 protein family is also associated with agammaglobulinemia-5.^[14]