LRRC8C

leucine rich repeat containing 8 VRAC subunit C, the group of Volume regulated anion channel subunits

Basic information

Region (hg38): 1:89633072-89769903

Links

ENSG00000171488 ∙ NCBI:84230 ∙ OMIM:612889 ∙ HGNC:25075 ∙ Uniprot:Q8TDW0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Telangiectasia, impaired intellectual development, microcephaly, metaphyseal dysplasia, eye abnormalities, and short stature (TIMES syndrome)	AD	Hematologic	Individuals may be affected by telangiectasia involving the gastrointestinal tract, resulting in hemorrhage that has been described as requiring RBC transfusion, and awareness may allow prompt management	Cardiovascular; Craniofacial; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic	39623139

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LRRC8C gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LRRC8C gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	1	2
missense			39		1	40
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	39	1	2

Variants in LRRC8C

This is a list of pathogenic ClinVar variants found in the LRRC8C region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-89686482-C-T			Likely benign (Apr 16, 2018)
1-89686495-C-T		not specified	Uncertain significance (Dec 20, 2023)
1-89686505-C-G		not specified	Uncertain significance (Jul 05, 2023)
1-89686588-G-A		not specified	Uncertain significance (Aug 09, 2021)
1-89686591-G-A		not specified	Uncertain significance (Aug 28, 2024)
1-89686601-G-A		not specified	Uncertain significance (Apr 28, 2022)
1-89712744-A-C		not specified	Uncertain significance (Jun 22, 2021)
1-89712776-C-T		not specified	Uncertain significance (Aug 17, 2021)
1-89712779-A-G		not specified	Uncertain significance (Oct 04, 2024)
1-89712826-C-T		not specified	Uncertain significance (Jul 20, 2021)
1-89712874-G-T		not specified	Uncertain significance (Jun 10, 2024)
1-89712987-G-T		not specified	Uncertain significance (Apr 20, 2023)
1-89713039-C-A		not specified	Uncertain significance (Mar 07, 2025)
1-89713172-C-A		not specified	Uncertain significance (Jan 01, 2025)
1-89713361-G-A		not specified	Uncertain significance (Jan 02, 2025)
1-89713586-A-G		not specified	Uncertain significance (Feb 21, 2025)
1-89713738-G-C		Telangiectasia, impaired intellectual development, microcephaly, metaphyseal dysplasia, eye abnormalities, and short stature	Pathogenic (Jan 22, 2025)
1-89713764-C-CA		Telangiectasia, impaired intellectual development, microcephaly, metaphyseal dysplasia, eye abnormalities, and short stature	Pathogenic (Jan 22, 2025)
1-89713765-A-C		not specified	Uncertain significance (Dec 06, 2021)
1-89713792-G-A		not specified	Uncertain significance (Feb 28, 2023)
1-89713798-A-T		not specified	Uncertain significance (Oct 30, 2024)
1-89713861-A-G		not specified	Uncertain significance (Mar 07, 2025)
1-89713911-A-G			Benign (Apr 16, 2018)
1-89713939-G-T		not specified	Uncertain significance (Nov 19, 2024)
1-89713948-C-T		not specified	Uncertain significance (Oct 20, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LRRC8C	protein_coding	protein_coding	ENST00000370454	2	136832

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000785	0.999	125716	0	31	125747	0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.58	277	427	0.649	0.0000223	5324
Missense in Polyphen		65	168.37	0.38604		2225
Synonymous	0.823	154	168	0.919	0.00000863	1572
Loss of Function	2.97	10	26.5	0.377	0.00000168	308

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000210	0.000210
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000220	0.000220
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 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. The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine. Plays a redundant role in the efflux of amino acids, such as aspartate and glutamate, in response to osmotic stress. Channel activity requires LRRC8A plus at least one other family member (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel characteristics depend on the precise subunit composition. {ECO:0000269|PubMed:24790029, ECO:0000269|PubMed:26824658, ECO:0000269|PubMed:28193731}.
• Pathway: Transport of small molecules;Miscellaneous transport and binding events (Consensus)

Recessive Scores

• pRec: 0.110

Intolerance Scores

• loftool: 0.642
• rvis_EVS: 0.09
• rvis_percentile_EVS: 60.65

Haploinsufficiency Scores

• pHI: 0.514
• hipred: Y
• hipred_score: 0.639
• ghis: 0.492

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.147

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Lrrc8c
• Phenotype: growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype; liver/biliary system phenotype

Gene ontology

• Biological process: cell volume homeostasis;inorganic anion transport;taurine transport;aspartate transmembrane transport;protein hexamerization;fat cell differentiation;transmembrane transport;cellular response to osmotic stress;anion transmembrane transport
• Cellular component: cytoplasm;endoplasmic reticulum membrane;plasma membrane;integral component of plasma membrane;membrane;ion channel complex
• Molecular function: volume-sensitive anion channel activity;protein binding