LRRC8E

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

Basic information

Region (hg38): 19:7888504-7902021

Links

ENSG00000171017 ∙ NCBI:80131 ∙ OMIM:612891 ∙ HGNC:26272 ∙ Uniprot:Q6NSJ5 ∙ 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 LRRC8E gene.

• Inborn genetic diseases (48 variants)
• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LRRC8E 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			47	1	3	51
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	47	1	3

Variants in LRRC8E

This is a list of pathogenic ClinVar variants found in the LRRC8E region.

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

Position	Type	Phenotype	Significance	ClinVar
19-7895624-C-G		not specified	Uncertain significance (Jul 28, 2021)
19-7895688-G-A		not specified	Uncertain significance (Jun 11, 2021)
19-7898728-G-A		not specified	Uncertain significance (Dec 07, 2021)
19-7898751-A-C		not specified	Uncertain significance (Jan 08, 2024)
19-7898773-T-C		not specified	Uncertain significance (Oct 05, 2021)
19-7898878-C-T		not specified	Uncertain significance (May 17, 2023)
19-7898944-G-A		not specified	Uncertain significance (Mar 28, 2023)
19-7899010-C-T		not specified	Uncertain significance (Jan 17, 2024)
19-7899033-G-A		not specified	Uncertain significance (Sep 14, 2022)
19-7899067-G-A		not specified	Uncertain significance (Nov 18, 2022)
19-7899106-C-T		not specified	Uncertain significance (Aug 02, 2021)
19-7899122-G-T		not specified	Uncertain significance (Jun 27, 2023)
19-7899145-C-T		not specified	Likely benign (Jul 14, 2021)
19-7899155-G-T		not specified	Uncertain significance (Feb 21, 2024)
19-7899180-G-A		not specified	Uncertain significance (Apr 05, 2023)
19-7899267-G-A		not specified	Uncertain significance (May 17, 2023)
19-7899282-A-G		not specified	Uncertain significance (Feb 13, 2023)
19-7899349-A-G		not specified	Uncertain significance (Aug 20, 2023)
19-7899370-T-C		not specified	Uncertain significance (Oct 13, 2023)
19-7899421-G-C		not specified	Uncertain significance (Dec 12, 2023)
19-7899433-C-T		not specified	Uncertain significance (Dec 15, 2023)
19-7899499-C-A		not specified	Uncertain significance (Apr 05, 2023)
19-7899532-G-A		not specified	Uncertain significance (May 22, 2023)
19-7899628-T-C		not specified	Uncertain significance (Oct 17, 2023)
19-7899741-C-T		not specified	Uncertain significance (Sep 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LRRC8E	protein_coding	protein_coding	ENST00000306708	2	13512

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000174	0.969	125586	0	162	125748	0.000644

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.368	466	489	0.953	0.0000322	5125
Missense in Polyphen		217	235.72	0.92059		2690
Synonymous	0.312	228	234	0.974	0.0000169	1670
Loss of Function	2.01	13	23.5	0.553	0.00000116	266

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000664	0.000662
Ashkenazi Jewish	0.000497	0.000496
East Asian	0.000381	0.000381
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000936	0.000932
Middle Eastern	0.000381	0.000381
South Asian	0.000755	0.000752
Other	0.000654	0.000652

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:26824658, PubMed:28193731). The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine (PubMed:24790029, PubMed:26824658). Mediates 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:24790029, PubMed:26824658, PubMed:28193731). {ECO:0000269|PubMed:24790029, ECO:0000269|PubMed:26824658, ECO:0000269|PubMed:28193731}.
• Pathway: Transport of small molecules;Miscellaneous transport and binding events (Consensus)

Intolerance Scores

• loftool: 0.925
• rvis_EVS: 0.41
• rvis_percentile_EVS: 76.51

Haploinsufficiency Scores

• pHI: 0.204
• hipred: N
• hipred_score: 0.429
• ghis: 0.467

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.362

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lrrc8e

Gene ontology

• Biological process: cell volume homeostasis;inorganic anion 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;ion channel complex
• Molecular function: volume-sensitive anion channel activity;protein binding