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
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
109.20210514	current	GRCh38.p13 (GCF_000001405.39)	9	NC_000009.12 (128882133..128918042)
105.20201022	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: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
LRRC8A homohexameric channels poorly recapitulate VRAC regulation and pharmacology.
Title: LRRC8A homohexameric channels poorly recapitulate VRAC regulation and pharmacology.
LRRC8 family proteins within lysosomes regulate cellular osmoregulation and enhance cell survival to multiple physiological stresses.
Title: LRRC8 family proteins within lysosomes regulate cellular osmoregulation and enhance cell survival to multiple physiological stresses.
The LRRC8-mediated volume-regulated anion channel is altered in glaucoma.
Title: The LRRC8-mediated volume-regulated anion channel is altered in glaucoma.
LRRC8/VRAC channels exhibit a noncanonical permeability to glutathione, which modulates epithelial-to-mesenchymal transition (EMT).
Title: LRRC8/VRAC channels exhibit a noncanonical permeability to glutathione, which modulates epithelial-to-mesenchymal transition (EMT).
It discusses the recent molecular biological insights into the physiology of LRRC8A as the pore-forming components of volume-regulated anion channel (VRAC) in relation to its previously proposed roles.
Title: More than just a pressure relief valve: physiological roles of volume-regulated LRRC8 anion channels.
High LRRC8A expression is associated with Esophageal Squamous Cell Carcinoma.
Title: LRRC8A Expression Influences Growth of Esophageal Squamous Cell Carcinoma.
Non-vesicular release of glutamate through the glutamate-permeable volume-regulated anion channel (VRAC). Both cell swelling and receptor stimulation activated astrocytic VRAC, which requires its only obligatory subunit, Swell1.
Title: Glutamate-Releasing SWELL1 Channel in Astrocytes Modulates Synaptic Transmission and Promotes Brain Damage in Stroke.
Study revealed that LRRC8A-dependent volume-regulated anion channel (VRAC) function is essential for male germ cell survival, sperm motility and spermatogenesis and suggested that mutations in LRRC8A could be examined as a diagnostic target in human patients with coiled/deformed sperm tail morphology.
Title: Deficient LRRC8A-dependent volume-regulated anion channel activity is associated with male infertility in mice.

Submit: New GeneRIF Correction See all GeneRIFs (30)

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

Homology

Homologs of the LRRC8A gene: The LRRC8A gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 353 organisms have orthologs with human gene LRRC8A
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
contributes_to anion channel activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables cyclic-GMP-AMP transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables volume-sensitive anion channel activity	IDA Inferred from Direct Assay more info	PubMed
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 anion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in anion transmembrane transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in anion transmembrane transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in anion transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in aspartate transmembrane transport	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 cellular glucose homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in chloride transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in cyclic-GMP-AMP transmembrane import across plasma membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of insulin secretion	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of myoblast differentiation	ISS Inferred from Sequence or Structural Similarity 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	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to osmotic stress	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in spermatogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in taurine transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in integral component of lysosomal membrane	IDA Inferred from Direct Assay more info	PubMed
located_in integral component of membrane	IDA Inferred from Direct Assay more info	PubMed
located_in integral component of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in integral component of plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
part_of ion channel complex	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	HDA more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
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

Q8IWT6

UniProtKB/TrEMBL

A0A024R892, 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

Q8IWT6

UniProtKB/TrEMBL

A0A024R892

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

Q8IWT6

UniProtKB/TrEMBL

A0A024R892

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: Homo sapiens Updated Annotation Release 109.20210514

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

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000009.12 Reference GRCh38.p13 Primary Assembly

Range

128882133..128918042

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011518864.2 → 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

Q8IWT6

UniProtKB/TrEMBL

A0A024R892

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_005252095.2 → 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

Q8IWT6

UniProtKB/TrEMBL

A0A024R892

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_006717186.2 → 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

Q8IWT6

UniProtKB/TrEMBL

A0A024R892

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_011518863.1 → 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

Q8IWT6

UniProtKB/TrEMBL

A0A024R892

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_005252096.4 → 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

Q8IWT6

UniProtKB/TrEMBL

A0A024R892

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_011518865.2 → XP_011517167.1 volume-regulated anion channel subunit LRRC8A isoform X1

See identical proteins and their annotated locations for XP_011517167.1

UniProtKB/Swiss-Prot

Q8IWT6

UniProtKB/TrEMBL

A0A024R892

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