LRRC8D

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

Basic information

Region (hg38): 1:89821014-89936611

Previous symbols: [ "LRRC5" ]

Links

ENSG00000171492 ∙ NCBI:55144 ∙ OMIM:612890 ∙ HGNC:16992 ∙ Uniprot:Q7L1W4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LRRC8D gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LRRC8D 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						0
missense			21	2		23
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	21	2	0

Variants in LRRC8D

This is a list of pathogenic ClinVar variants found in the LRRC8D region.

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

Position	Type	Phenotype	Significance	ClinVar
1-89933145-T-C		not specified	Uncertain significance (Dec 14, 2023)
1-89933280-G-A		not specified	Uncertain significance (Jun 22, 2024)
1-89933291-G-A		not specified	Uncertain significance (May 27, 2022)
1-89933301-A-G		not specified	Uncertain significance (Jul 22, 2022)
1-89933357-G-A		not specified	Uncertain significance (Mar 25, 2024)
1-89933372-A-G		not specified	Likely benign (Oct 10, 2023)
1-89933429-G-A		not specified	Likely benign (Mar 17, 2023)
1-89933589-T-G		not specified	Uncertain significance (Feb 17, 2022)
1-89933728-C-A		not specified	Uncertain significance (Sep 20, 2023)
1-89933765-A-G		not specified	Uncertain significance (Mar 21, 2023)
1-89933800-A-C		not specified	Uncertain significance (May 15, 2024)
1-89934062-G-A		not specified	Uncertain significance (Dec 07, 2021)
1-89934178-A-G		not specified	Uncertain significance (Dec 07, 2021)
1-89934464-C-T		not specified	Uncertain significance (Mar 01, 2023)
1-89934518-G-A		not specified	Uncertain significance (Dec 17, 2023)
1-89934609-A-G		not specified	Uncertain significance (Jan 17, 2024)
1-89934707-A-G		not specified	Uncertain significance (Feb 05, 2024)
1-89934777-A-G		not specified	Uncertain significance (Jun 14, 2023)
1-89934795-A-G		not specified	Uncertain significance (Sep 20, 2023)
1-89934924-A-G		not specified	Uncertain significance (Jan 06, 2023)
1-89935076-A-T		not specified	Uncertain significance (May 16, 2022)
1-89935151-A-C		not specified	Uncertain significance (Dec 28, 2023)
1-89935409-A-C		not specified	Uncertain significance (Jan 03, 2022)
1-89935503-G-A		not specified	Uncertain significance (Nov 05, 2021)
1-89935529-C-G		not specified	Uncertain significance (Dec 18, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LRRC8D	protein_coding	protein_coding	ENST00000337338	1	115598

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.978	0.0225	125737	0	10	125747	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.20	267	460	0.580	0.0000238	5722
Missense in Polyphen		62	166.49	0.37239		2259
Synonymous	1.08	158	176	0.897	0.00000969	1642
Loss of Function	4.06	3	24.9	0.121	0.00000136	334

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000868	0.0000868
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000265	0.0000264
Middle Eastern	0.000109	0.000109
South Asian	0.0000327	0.0000327
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 (PubMed:24790029, PubMed:26530471, PubMed:26824658, PubMed:28193731). 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). 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). LRRC8A and LRRC8D are required for the uptake of the drug cisplatin (PubMed:26530471). Mediates the import of the antibiotic blasticidin-S into the cell (PubMed:24782309). {ECO:0000269|PubMed:24782309, ECO:0000269|PubMed:24790029, ECO:0000269|PubMed:26530471, ECO:0000269|PubMed:26824658, ECO:0000269|PubMed:28193731}.
• Pathway: Transport of small molecules;Miscellaneous transport and binding events (Consensus)

Recessive Scores

• pRec: 0.113

Intolerance Scores

• loftool: 0.334
• rvis_EVS: -0.78
• rvis_percentile_EVS: 12.97

Haploinsufficiency Scores

• pHI: 0.299
• hipred: Y
• hipred_score: 0.728
• ghis: 0.447

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.118

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lrrc8d

Gene ontology

• Biological process: cell volume homeostasis;inorganic anion transport;taurine transport;aspartate transmembrane transport;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