LRRC8C
Leucine Rich Repeat Containing 8 VRAC Subunit C
Gene Information Card
| Symbol | LRRC8C |
|---|---|
| Full Name | Leucine Rich Repeat Containing 8 VRAC Subunit C |
| Gene Type | Protein coding |
| Chromosomal Location | 1p22.2 |
| NCBI Gene ID | 84230 ncbi.nlm.nih.gov/gene/84230 |
| Ensembl ID | ENSG00000143178 |
| UniProt ID | Q8N4N8 |
| OMIM ID | 612889 |
| HGNC ID | 28618 |
| Aliases | AD158, FLJ38507, KIAA1178, SWELL3 |
Description
LRRC8C encodes a member of the leucine-rich repeat-containing 8 (LRRC8) family, which forms heteromeric volume-regulated anion channels (VRACs). The protein is essential for regulatory volume decrease in response to cell swelling and mediates transport of chloride ions and organic osmolytes. LRRC8C is widely expressed and involved in cellular homeostasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Agammaglobulinemia 5 (autosomal dominant) | Loss-of-function mutations in LRRC8C impair VRAC activity, leading to B-cell deficiency and antibody production defects. | ClinVar, OMIM |
| Hepatocellular carcinoma | Altered LRRC8C expression may contribute to tumor cell volume regulation and proliferation. | COSMIC, NCBI Gene |
| Colorectal cancer | Somatic mutations and expression changes in LRRC8C are observed, potentially affecting cell migration and apoptosis. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 12.5 | Medium |
| Brain | 8.3 | Low |
| Colon | 15.2 | Medium |
| Kidney | 18.7 | Medium |
| Liver | 14.1 | Medium |
| Lung | 10.6 | Medium |
| Spleen | 9.4 | Low |
| Testis | 20.3 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 16.5 | Embryonic kidney cells |
| HeLa | 12.8 | Cervical carcinoma cells |
| HepG2 | 14.2 | Hepatocellular carcinoma cells |
| K562 | 8.1 | Leukemia cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.130C>T (p.Arg44Trp) | Missense | <0.01% | Loss of VRAC function; associated with agammaglobulinemia |
| c.487G>A (p.Gly163Arg) | Missense | <0.01% | Impaired channel activity; reported in immunodeficiency |
| c.1021_1023del (p.Phe341del) | Deletion | <0.01% | Dominant-negative effect on VRAC assembly |
Mutation functional classification
Loss of Function (LOF)
Mutations such as p.Arg44Trp and p.Gly163Arg reduce or abolish VRAC channel activity, leading to defective volume regulation and immune cell dysfunction.
Gain of Function (GOF)
No gain-of-function mutations have been reported for LRRC8C.
Dominant Negative (DN)
The p.Phe341del mutation exerts a dominant-negative effect by disrupting heteromeric channel formation.
View complete mutation data：
Gene Ontology (GO)
| • volume-sensitive anion channel activity (GO:0005244) | • plasma membrane (GO:0005886) |
| • ion transport (GO:0006811) | • cell volume homeostasis (GO:0006884) |
| • chloride channel complex (GO:0034707) | • identical protein binding (GO:0042802) |
Pathways
• Volume-regulated anion channel (VRAC) pathway
• Ion transport by P-type ATPases
• Regulation of cell volume
Protein Summary
LRRC8C is a 803-amino acid transmembrane protein with four N-terminal transmembrane domains and a C-terminal leucine-rich repeat domain. It assembles with other LRRC8 family members (A, B, D, E) to form functional VRACs. The protein is critical for regulatory volume decrease and mediates efflux of chloride and organic osmolytes. Mutations in LRRC8C cause autosomal dominant agammaglobulinemia 5.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LRRC8C Knockout HEK293 Cell Line | EDJ-KQ10021 | Human | 84230 | Details Get a Quote |
| LRRC8C Knockout A-549 Cell Line | EDJ-KQ37009 | Human | 84230 | Details Get a Quote |
| LRRC8C Knockout HCT 116 Cell Line | EDJ-KQ37010 | Human | 84230 | Details Get a Quote |
| LRRC8C Knockout HeLa Cell Line | EDJ-KQ37011 | Human | 84230 | Details Get a Quote |
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