LRRC8B

protein-coding

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

Gene summary

Contributes to volume-sensitive anion channel activity. Involved in monoatomic anion transmembrane transport. Located in cytoplasm and plasma membrane. Part of monoatomic ion channel complex. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001369817.2

Inheritance

—

ClinVar variants

U:67B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chr1:89,524,829-89,597,861

External References & Databases

Ensembl (ENSG00000197147)

Transcript & Mutation Effects

hg38 • Region Span ~73.0 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 LRRC8B variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 66

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001369817.2. 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			1 clinvar	1 clinvar	3 clinvar	5
missense			66 clinvar	1 clinvar	2 clinvar	69
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	67	2	5	74

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001369817.2	RefSeq	NP_001356746.1	2	MANE Select
ENST00000330947.7	Ensembl	ENSP00000332674.2	2	MANE Select
NM_001134476.2	RefSeq	NP_001127948.1	2	Standard
NM_001369819.2	RefSeq	NP_001356748.1	2	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
transmembrane transport
anion transmembrane transport

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: ENST00000330947
Coding exons: 2
Length: 73029
Individuals with no LoFs: 125714
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125737
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.54	267	412	0.648	0.0000218	5265
Missense (PolyPhen)		72	170.56	0.42213		2251
Synonymous	0.0790	170	171	0.992	0.00000938	1587
Loss of Function	4.29	2	25.3	0.0792	0.00000127	345

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.000033	0.000033	rare
Other	0.00016	0.00016	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. 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: 0.492
RVIS EVS: -1.35
RVIS percentile EVS: 4.58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.403

Gene Damage Prediction

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