LRRC8E

protein-coding

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

Gene summary

This gene encodes a member of a small, conserved family of proteins with similar structure, including a string of extracellular leucine-rich repeats. A related protein was shown to be involved in B-cell development. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jun 2012]

MANE transcript

NM_025061.6

Inheritance

—

ClinVar variants

U:163B:8

Top phenotype

Long QT syndrome

gnomAD constraint

pLI —, LoF o/e 0.55

Max pathogenic AF

—

Genomic locus

chr19:7,888,505-7,902,021

External References & Databases

Ensembl (ENSG00000171017)

Transcript & Mutation Effects

hg38 • Region Span ~13.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LRRC8E variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 168

not providedTotal: 3

Long QT syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_025061.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			163 clinvar	6 clinvar	2 clinvar	171
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	163	6	2	171

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_025061.6	RefSeq	NP_079337.2	2	MANE Select
ENST00000306708.11	Ensembl	ENSP00000306524.5	2	MANE Select
NM_001268284.3	RefSeq	NP_001255213.1	2	Standard
NM_001268285.3	RefSeq	NP_001255214.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Transport of small molecules
Miscellaneous transport and binding events

Biological Process

cell volume homeostasis
inorganic anion transport
aspartate transmembrane transport
transmembrane transport
cellular response to osmotic stress

Molecular Function

volume-sensitive anion channel activity
protein binding

Cellular Component

cytoplasm
endoplasmic reticulum membrane
plasma membrane
integral component of plasma membrane
ion channel complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000306708
Coding exons: 2
Length: 13512
Individuals with no LoFs: 125586
Homozygous LoFs: 0
Heterozygous LoFs: 162
Defined: 125748
p: 0.000644

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.368	466	489	0.953	0.0000322	5125
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00043	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0.00050	0.00050	rare
East Asian	0.00038	0.00038	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00094	0.00093	rare
South Asian	0.00075	0.00075	rare
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

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}.;

Intolerance Scores

LoFtool: 0.925
RVIS EVS: 0.41
RVIS percentile EVS: 76.51

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.362

Gene Damage Prediction

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