LRRC8A leucine rich repeat containing 8 VRAC subunit A [Homo sapiens (human)] - Gene

Summary

Official Symbol: LRRC8Aprovided by HGNC
Official Full Name: leucine rich repeat containing 8 VRAC subunit Aprovided by HGNC
Primary source: HGNC:HGNC:19027
See related: Ensembl:ENSG00000136802 MIM:608360; AllianceGenome:HGNC:19027
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: AGM5; LRRC8; SWELL1; HsLRRC8A
Summary: This gene encodes a protein belonging to the leucine-rich repeat family of proteins, which are involved in diverse biological processes, including cell adhesion, cellular trafficking, and hormone-receptor interactions. This family member is a putative four-pass transmembrane protein that plays a role in B cell development. Defects in this gene cause autosomal dominant non-Bruton type agammaglobulinemia, an immunodeficiency disease resulting from defects in B cell maturation. Multiple alternatively spliced transcript variants, which encode the same protein, have been identified for this gene. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in brain (RPKM 27.9), esophagus (RPKM 16.9) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 9q34.11

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	9	NC_000009.12 (128882133..128918039)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	9	NC_060933.1 (141086880..141122794)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	9	NC_000009.11 (131644412..131680318)

Chromosome 9 - NC_000009.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

LRRC8A as a central mediator promotes colon cancer metastasis by regulating PIP5K1B/PIP2 pathway.
Title: LRRC8A as a central mediator promotes colon cancer metastasis by regulating PIP5K1B/PIP2 pathway.
Physiological Functions of the Volume-Regulated Anion Channel VRAC/LRRC8 and the Proton-Activated Chloride Channel ASOR/TMEM206.
Title: Physiological Functions of the Volume-Regulated Anion Channel VRAC/LRRC8 and the Proton-Activated Chloride Channel ASOR/TMEM206.
Swell1 channel-mediated tonic GABA release from astrocytes modulates cocaine reward.
Title: Swell1 channel-mediated tonic GABA release from astrocytes modulates cocaine reward.
Structural insights into anion selectivity and activation mechanism of LRRC8 volume-regulated anion channels.
Title: Structural insights into anion selectivity and activation mechanism of LRRC8 volume-regulated anion channels.
LRRC8A is responsible for exosome biogenesis and volume regulation in colon cancer cells.
Title: LRRC8A is responsible for exosome biogenesis and volume regulation in colon cancer cells.
Small molecule SWELL1 complex induction improves glycemic control and nonalcoholic fatty liver disease in murine Type 2 diabetes.
Title: Small molecule SWELL1 complex induction improves glycemic control and nonalcoholic fatty liver disease in murine Type 2 diabetes.
LRRC8A influences the growth of gastric cancer cells via the p53 signaling pathway.
Title: LRRC8A influences the growth of gastric cancer cells via the p53 signaling pathway.
LRRC8A-containing chloride channel is crucial for cell volume recovery and survival under hypertonic conditions.
Title: LRRC8A-containing chloride channel is crucial for cell volume recovery and survival under hypertonic conditions.
Oxidant-resistant LRRC8A/C anion channels support superoxide production by NADPH oxidase 1.
Title: Oxidant-resistant LRRC8A/C anion channels support superoxide production by NADPH oxidase 1.
Volume-regulated chloride channel regulates cell proliferation and is involved in the possible interaction between TMEM16A and LRRC8A in human metastatic oral squamous cell carcinoma cells.
Title: Volume-regulated chloride channel regulates cell proliferation and is involved in the possible interaction between TMEM16A and LRRC8A in human metastatic oral squamous cell carcinoma cells.

Submit: New GeneRIF Correction See all GeneRIFs (38)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Agammaglobulinemia 5, autosomal dominant MedGen: C3150753 OMIM: 613506 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH102979 (e-PCR)
- UniSTS:97313

D13S1783 (e-PCR)
- UniSTS:474663

SGC34869 (e-PCR)
- UniSTS:21633

STS-D29325 (e-PCR)
- UniSTS:19334

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cyclic-GMP-AMP transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables cyclic-GMP-AMP transmembrane transporter activity	IEA Inferred from Electronic Annotation more info
enables identical protein binding	IEA Inferred from Electronic Annotation more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
contributes_to monoatomic anion channel activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables volume-sensitive anion channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables volume-sensitive anion channel activity	IDA Inferred from Direct Assay more info	PubMed
enables volume-sensitive anion channel activity	IEA Inferred from Electronic Annotation more info
enables volume-sensitive anion channel activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables volume-sensitive anion channel activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in aspartate transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in aspartate transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in cell volume homeostasis	IDA Inferred from Direct Assay more info	PubMed
involved_in cell volume homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in chloride transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in cyclic-GMP-AMP transmembrane import across plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
involved_in cyclic-GMP-AMP transmembrane import across plasma membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in cyclic-GMP-AMP transmembrane import across plasma membrane	IEA Inferred from Electronic Annotation more info
involved_in intracellular glucose homeostasis	IEA Inferred from Electronic Annotation more info
involved_in intracellular glucose homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in monoatomic anion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in monoatomic anion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in monoatomic anion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in monoatomic anion transmembrane transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in monoatomic anion transmembrane transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in monoatomic anion transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in monoatomic ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in monoatomic ion transport	IEA Inferred from Electronic Annotation more info
involved_in organic anion transport	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of insulin secretion	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of insulin secretion	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of myoblast differentiation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of myoblast differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in pre-B cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in pre-B cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein hexamerization	IDA Inferred from Direct Assay more info	PubMed
involved_in protein hexamerization	IEA Inferred from Electronic Annotation more info
involved_in protein hexamerization	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to osmotic stress	IEA Inferred from Electronic Annotation more info
involved_in response to osmotic stress	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in spermatogenesis	IEA Inferred from Electronic Annotation more info
involved_in spermatogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in taurine transmembrane transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in lysosomal membrane	IDA Inferred from Direct Assay more info	PubMed
located_in lysosomal membrane	IEA Inferred from Electronic Annotation more info
located_in lysosome	IEA Inferred from Electronic Annotation more info
located_in membrane	HDA more info	PubMed
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	IEA Inferred from Electronic Annotation more info
part_of monoatomic ion channel complex	IBA Inferred from Biological aspect of Ancestor more info
part_of monoatomic ion channel complex	IDA Inferred from Direct Assay more info	PubMed
part_of monoatomic ion channel complex	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: volume-regulated anion channel subunit LRRC8A

Names: leucine rich repeat containing 8 family member A; leucine-rich repeat-containing protein 8A; swelling protein 1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009630.1 RefSeqGene

Range

5001..40928

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_80

mRNA and Protein(s)

NM_001127244.2 → NP_001120716.1 volume-regulated anion channel subunit LRRC8A

See identical proteins and their annotated locations for NP_001120716.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript. All variants (1-3) encode the same protein.

Source sequence(s)

AL672142

Consensus CDS

CCDS35155.1

UniProtKB/Swiss-Prot

Q6UXM2, Q8IWT6, Q8NCI0, Q9P2B1

UniProtKB/TrEMBL

A8K1C7

Related

ENSP00000259324.5, ENST00000259324.5

Conserved Domains (4) summary

COG4886
Location:568 → 780

LRR; Leucine-rich repeat (LRR) protein [Transcription]

sd00033
Location:546 → 568

LRR_RI; leucine-rich repeat [structural motif]

NF033189
Location:379 → 713

internalin_A; class 1 internalin InlA

pfam12534
Location:1 → 340

Pannexin_like; Pannexin-like TM region of LRRC8
NM_001127245.2 → NP_001120717.1 volume-regulated anion channel subunit LRRC8A

See identical proteins and their annotated locations for NP_001120717.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. All variants (1-3) encode the same protein.

Source sequence(s)

AL672142

Consensus CDS

CCDS35155.1

UniProtKB/Swiss-Prot

Q6UXM2, Q8IWT6, Q8NCI0, Q9P2B1

UniProtKB/TrEMBL

A8K1C7

Related

ENSP00000361680.3, ENST00000372599.7

Conserved Domains (4) summary

COG4886
Location:568 → 780

LRR; Leucine-rich repeat (LRR) protein [Transcription]

sd00033
Location:546 → 568

LRR_RI; leucine-rich repeat [structural motif]

NF033189
Location:379 → 713

internalin_A; class 1 internalin InlA

pfam12534
Location:1 → 340

Pannexin_like; Pannexin-like TM region of LRRC8
NM_019594.4 → NP_062540.2 volume-regulated anion channel subunit LRRC8A

See identical proteins and their annotated locations for NP_062540.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. All variants (1-3) encode the same protein.

Source sequence(s)

AL672142

Consensus CDS

CCDS35155.1

UniProtKB/Swiss-Prot

Q6UXM2, Q8IWT6, Q8NCI0, Q9P2B1

UniProtKB/TrEMBL

A8K1C7

Related

ENSP00000361682.4, ENST00000372600.9

Conserved Domains (4) summary

COG4886
Location:568 → 780

LRR; Leucine-rich repeat (LRR) protein [Transcription]

sd00033
Location:546 → 568

LRR_RI; leucine-rich repeat [structural motif]

NF033189
Location:379 → 713

internalin_A; class 1 internalin InlA

pfam12534
Location:1 → 340

Pannexin_like; Pannexin-like TM region of LRRC8

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000009.12 Reference GRCh38.p14 Primary Assembly

Range

128882133..128918039

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047423596.1 → XP_047279552.1 volume-regulated anion channel subunit LRRC8A isoform X1

UniProtKB/Swiss-Prot

Q6UXM2, Q8IWT6, Q8NCI0, Q9P2B1

UniProtKB/TrEMBL

A8K1C7
XM_047423597.1 → XP_047279553.1 volume-regulated anion channel subunit LRRC8A isoform X1

UniProtKB/Swiss-Prot

Q6UXM2, Q8IWT6, Q8NCI0, Q9P2B1

UniProtKB/TrEMBL

A8K1C7
XM_011518864.3 → XP_011517166.1 volume-regulated anion channel subunit LRRC8A isoform X1

See identical proteins and their annotated locations for XP_011517166.1

UniProtKB/Swiss-Prot

Q6UXM2, Q8IWT6, Q8NCI0, Q9P2B1

UniProtKB/TrEMBL

A8K1C7

Conserved Domains (4) summary

COG4886
Location:568 → 780

LRR; Leucine-rich repeat (LRR) protein [Transcription]

sd00033
Location:546 → 568

LRR_RI; leucine-rich repeat [structural motif]

NF033189
Location:379 → 713

internalin_A; class 1 internalin InlA

pfam12534
Location:1 → 340

Pannexin_like; Pannexin-like TM region of LRRC8
XM_005252096.5 → XP_005252153.1 volume-regulated anion channel subunit LRRC8A isoform X1

See identical proteins and their annotated locations for XP_005252153.1

UniProtKB/Swiss-Prot

Q6UXM2, Q8IWT6, Q8NCI0, Q9P2B1

UniProtKB/TrEMBL

A8K1C7

Conserved Domains (4) summary

COG4886
Location:568 → 780

LRR; Leucine-rich repeat (LRR) protein [Transcription]

sd00033
Location:546 → 568

LRR_RI; leucine-rich repeat [structural motif]

NF033189
Location:379 → 713

internalin_A; class 1 internalin InlA

pfam12534
Location:1 → 340

Pannexin_like; Pannexin-like TM region of LRRC8
XM_006717186.3 → XP_006717249.1 volume-regulated anion channel subunit LRRC8A isoform X1

See identical proteins and their annotated locations for XP_006717249.1

UniProtKB/Swiss-Prot

Q6UXM2, Q8IWT6, Q8NCI0, Q9P2B1

UniProtKB/TrEMBL

A8K1C7

Conserved Domains (4) summary

COG4886
Location:568 → 780

LRR; Leucine-rich repeat (LRR) protein [Transcription]

sd00033
Location:546 → 568

LRR_RI; leucine-rich repeat [structural motif]

NF033189
Location:379 → 713

internalin_A; class 1 internalin InlA

pfam12534
Location:1 → 340

Pannexin_like; Pannexin-like TM region of LRRC8
XM_047423601.1 → XP_047279557.1 volume-regulated anion channel subunit LRRC8A isoform X1

UniProtKB/Swiss-Prot

Q6UXM2, Q8IWT6, Q8NCI0, Q9P2B1

UniProtKB/TrEMBL

A8K1C7
XM_047423599.1 → XP_047279555.1 volume-regulated anion channel subunit LRRC8A isoform X1

UniProtKB/Swiss-Prot

Q6UXM2, Q8IWT6, Q8NCI0, Q9P2B1

UniProtKB/TrEMBL

A8K1C7
XM_005252095.3 → XP_005252152.1 volume-regulated anion channel subunit LRRC8A isoform X1

See identical proteins and their annotated locations for XP_005252152.1

UniProtKB/Swiss-Prot

Q6UXM2, Q8IWT6, Q8NCI0, Q9P2B1

UniProtKB/TrEMBL

A8K1C7

Conserved Domains (4) summary

COG4886
Location:568 → 780

LRR; Leucine-rich repeat (LRR) protein [Transcription]

sd00033
Location:546 → 568

LRR_RI; leucine-rich repeat [structural motif]

NF033189
Location:379 → 713

internalin_A; class 1 internalin InlA

pfam12534
Location:1 → 340

Pannexin_like; Pannexin-like TM region of LRRC8
XM_011518863.2 → XP_011517165.1 volume-regulated anion channel subunit LRRC8A isoform X1

See identical proteins and their annotated locations for XP_011517165.1

UniProtKB/Swiss-Prot

Q6UXM2, Q8IWT6, Q8NCI0, Q9P2B1

UniProtKB/TrEMBL

A8K1C7

Conserved Domains (4) summary

COG4886
Location:568 → 780

LRR; Leucine-rich repeat (LRR) protein [Transcription]

sd00033
Location:546 → 568

LRR_RI; leucine-rich repeat [structural motif]

NF033189
Location:379 → 713

internalin_A; class 1 internalin InlA

pfam12534
Location:1 → 340

Pannexin_like; Pannexin-like TM region of LRRC8
XM_047423598.1 → XP_047279554.1 volume-regulated anion channel subunit LRRC8A isoform X1

UniProtKB/Swiss-Prot

Q6UXM2, Q8IWT6, Q8NCI0, Q9P2B1

UniProtKB/TrEMBL

A8K1C7
XM_047423595.1 → XP_047279551.1 volume-regulated anion channel subunit LRRC8A isoform X1

UniProtKB/Swiss-Prot

Q6UXM2, Q8IWT6, Q8NCI0, Q9P2B1

UniProtKB/TrEMBL

A8K1C7
XM_047423600.1 → XP_047279556.1 volume-regulated anion channel subunit LRRC8A isoform X1

UniProtKB/Swiss-Prot

Q6UXM2, Q8IWT6, Q8NCI0, Q9P2B1

UniProtKB/TrEMBL

A8K1C7

Alternate T2T-CHM13v2.0

Genomic

NC_060933.1 Alternate T2T-CHM13v2.0

Range

141086880..141122794

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054363296.1 → XP_054219271.1 volume-regulated anion channel subunit LRRC8A isoform X1

UniProtKB/Swiss-Prot

Q6UXM2, Q8IWT6, Q8NCI0, Q9P2B1

UniProtKB/TrEMBL

A8K1C7
XM_054363297.1 → XP_054219272.1 volume-regulated anion channel subunit LRRC8A isoform X1

UniProtKB/Swiss-Prot

Q6UXM2, Q8IWT6, Q8NCI0, Q9P2B1

UniProtKB/TrEMBL

A8K1C7
XM_054363295.1 → XP_054219270.1 volume-regulated anion channel subunit LRRC8A isoform X1

UniProtKB/Swiss-Prot

Q6UXM2, Q8IWT6, Q8NCI0, Q9P2B1

UniProtKB/TrEMBL

A8K1C7
XM_054363290.1 → XP_054219265.1 volume-regulated anion channel subunit LRRC8A isoform X1

UniProtKB/Swiss-Prot

Q6UXM2, Q8IWT6, Q8NCI0, Q9P2B1

UniProtKB/TrEMBL

A8K1C7
XM_054363294.1 → XP_054219269.1 volume-regulated anion channel subunit LRRC8A isoform X1

UniProtKB/Swiss-Prot

Q6UXM2, Q8IWT6, Q8NCI0, Q9P2B1

UniProtKB/TrEMBL

A8K1C7
XM_054363293.1 → XP_054219268.1 volume-regulated anion channel subunit LRRC8A isoform X1

UniProtKB/Swiss-Prot

Q6UXM2, Q8IWT6, Q8NCI0, Q9P2B1

UniProtKB/TrEMBL

A8K1C7
XM_054363301.1 → XP_054219276.1 volume-regulated anion channel subunit LRRC8A isoform X1

UniProtKB/Swiss-Prot

Q6UXM2, Q8IWT6, Q8NCI0, Q9P2B1

UniProtKB/TrEMBL

A8K1C7
XM_054363299.1 → XP_054219274.1 volume-regulated anion channel subunit LRRC8A isoform X1

UniProtKB/Swiss-Prot

Q6UXM2, Q8IWT6, Q8NCI0, Q9P2B1

UniProtKB/TrEMBL

A8K1C7
XM_054363292.1 → XP_054219267.1 volume-regulated anion channel subunit LRRC8A isoform X1

UniProtKB/Swiss-Prot

Q6UXM2, Q8IWT6, Q8NCI0, Q9P2B1

UniProtKB/TrEMBL

A8K1C7
XM_054363298.1 → XP_054219273.1 volume-regulated anion channel subunit LRRC8A isoform X1

UniProtKB/Swiss-Prot

Q6UXM2, Q8IWT6, Q8NCI0, Q9P2B1

UniProtKB/TrEMBL

A8K1C7
XM_054363291.1 → XP_054219266.1 volume-regulated anion channel subunit LRRC8A isoform X1

UniProtKB/Swiss-Prot

Q6UXM2, Q8IWT6, Q8NCI0, Q9P2B1

UniProtKB/TrEMBL

A8K1C7
XM_054363300.1 → XP_054219275.1 volume-regulated anion channel subunit LRRC8A isoform X1

UniProtKB/Swiss-Prot

Q6UXM2, Q8IWT6, Q8NCI0, Q9P2B1

UniProtKB/TrEMBL

A8K1C7