LRRC8C

Chr 1p22.2

leucine rich repeat containing 8 VRAC subunit C

Aliases:: AD158
MANE:: ENST00000370454.9

OMIM: 612889 ↗NCBI: 84230 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

LRRC8C · Q8TDW0

v62025-08-01

Predicted Aligned Error matrix for LRRC8C — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

83.4/ 100

Confident

803 residues

Confidence breakdown

Very high(≥ 90)50%
Confident(70–90)35%
Low(50–70)5%
Very low(< 50)10%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Moderate Evidence (Amber)

Fetal anomalies
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic short stature
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Optic neuropathy
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe microcephaly
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Disease associations (Open Targets)

telangiectasia, impaired intellectual development, microcephaly, metaphyseal dysplasia, eye abnormalities, and short stature
0.48
IMAGe syndrome
0.03
immune system disorder
0.02
liver cancer
0.02
gastric cancer
0.02
neoplasm
0.01
pancreatic adenocarcinoma
0.01
idiopathic pulmonary fibrosis
0.01
melanoma
0.01
cystic fibrosis
0.01

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Volume-regulated anion channel subunit LRRC8C

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:26824658, PubMed:28193731, PubMed:36897307, PubMed:39623139). 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 and glutamate, in response to osmotic stress (PubMed:24790029, PubMed:26824658, PubMed:28193731). The VRAC channel also mediates transport of immunoreactive cyclic dinucleotide GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytosol (PubMed:33171122). 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:24790029, PubMed:26824658, PubMed:28193731)