LRRC8D

Description

The LRRC8D (leucine rich repeat containing 8 VRAC subunit D) is a protein-coding gene located on chromosome 1.

Leucine-rich repeat-containing protein 8D is a protein that in humans is encoded by the LRRC8D gene. Researchers have found out that this protein, along with the other LRRC8 proteins LRRC8A, LRRC8B, LRRC8C, and LRRC8E, is a subunit of the heteromer protein Volume-Regulated Anion Channel. 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, and that is not the only function these channels have been linked to. While LRRC8D is one of many proteins that can be part of VRAC, it is in fact one of the most important subunits for the channel’s ability to function; the other protein of importance is LRRC8A. However, while we know it is necessary for specific VRAC function, other studies have found that it is not sufficient for the full range of usual VRAC activity. This is where the other LRRC8 proteins come in, as the different composition of these subunits affects the range of specificity for VRACs. In addition to its role in VRACs, the LRRC8 protein family is also associated with agammaglobulinemia-5.

Non-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 (PubMed:24790029, PubMed:26530471, PubMed:26824658, PubMed:28193731, PubMed:32415200). The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine (PubMed:24790029, PubMed:26824658, PubMed:28193731). Plays a redundant role in the efflux of amino acids, such as aspartate, in response to osmotic stress (PubMed:28193731). LRRC8A and LRRC8D are required for the uptake of the drug cisplatin (PubMed:26530471). Channel activity requires LRRC8A plus at least one other family member (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel characteristics depend on the precise subunit composition (PubMed:24782309, PubMed:24790029, PubMed:26824658, PubMed:28193731). 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 (By similarity). VRAC channels containing LRRC8D inhibit transport of immunoreactive cyclic dinucleotide GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytosol (PubMed:33171122). Mediates the import of the antibiotic blasticidin-S into the cell (PubMed:24782309). {ECO:0000250|UniProtKB:Q8BGR2, ECO:0000269|PubMed:24782309, ECO:0000269|PubMed:24790029, ECO:0000269|PubMed:26530471, ECO:0000269|PubMed:26824658, ECO:0000269|PubMed:28193731, ECO:0000269|PubMed:32415200, ECO:0000269|PubMed:33171122}

LRRC8D is also known as HsLRRC8D, LRRC5.

Associated Diseases

WES Whole Exome Sequencing