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

    Gene ID: 56262, updated on 18-May-2023

    Summary

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    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

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    See LRRC8A in Genome Data Viewer
    Location:
    9q34.11
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2023_03 current GRCh38.p14 (GCF_000001405.40) 9 NC_000009.12 (128882133..128918039)
    RS_2023_03 current T2T-CHM13v2.0 (GCF_009914755.1) 9 NC_060933.1 (141086880..141122794)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (131644412..131680318)

    Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene KYAT1-SPOUT1 readthrough Neighboring gene kynurenine aminotransferase 1 Neighboring gene Sharpr-MPRA regulatory region 9337 Neighboring gene Sharpr-MPRA regulatory region 7409 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:131647725-131648487 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:131654523-131655130 Neighboring gene uncharacterized LOC101929291 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:131672021-131672804 Neighboring gene Sharpr-MPRA regulatory region 12425 Neighboring gene phytanoyl-CoA dioxygenase domain containing 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:131708642-131709204 Neighboring gene dolichol kinase

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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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    Related articles in PubMed

    1. LRRC8A-containing chloride channel is crucial for cell volume recovery and survival under hypertonic conditions. Serra SA, et al. Proc Natl Acad Sci U S A, 2021 Jun 8. PMID 34083438, Free PMC Article
    2. Oxidant-resistant LRRC8A/C anion channels support superoxide production by NADPH oxidase 1. Choi H, et al. J Physiol, 2021 Jun. PMID 33932953, Free PMC Article
    3. LRRC8A homohexameric channels poorly recapitulate VRAC regulation and pharmacology. Yamada T, et al. Am J Physiol Cell Physiol, 2021 Mar 1. PMID 33356947, Free PMC Article
    4. LRRC8A Expression Influences Growth of Esophageal Squamous Cell Carcinoma. Konishi T, et al. Am J Pathol, 2019 Oct. PMID 31323188
    5. Inhibition of angiotensin II-induced cerebrovascular smooth muscle cell proliferation by LRRC8A downregulation through suppressing PI3K/AKT activation. Lu J, et al. Hum Cell, 2019 Jul. PMID 31127489

    See all (69) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. 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.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. LRRC8A homohexameric channels poorly recapitulate VRAC regulation and pharmacology.
      Title: LRRC8A homohexameric channels poorly recapitulate VRAC regulation and pharmacology.
    7. 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.
    8. The LRRC8-mediated volume-regulated anion channel is altered in glaucoma.
      Title: The LRRC8-mediated volume-regulated anion channel is altered in glaucoma.
    9. 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).
    10. 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.
    Submit: New GeneRIF Correction See all GeneRIFs (33)

    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)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ10337, FLJ41617, KIAA1437

    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 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 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 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 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 intracellular glucose homeostasis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in monoatomic anion transmembrane transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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 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 signal transduction IBA
    Inferred from Biological aspect of Ancestor
    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 lysosomal membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in membrane HDA PubMed 
    located_in membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of monoatomic ion channel complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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

    1. NG_009630.1 RefSeqGene

      Range
      5001..40928
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_80

    mRNA and Protein(s)

    1. 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, Q9P2B1
      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

    2. 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, Q9P2B1
      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

    3. 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, Q9P2B1
      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: GCF_000001405.40-RS_2023_03

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000009.12 Reference GRCh38.p14 Primary Assembly

      Range
      128882133..128918039
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

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

      UniProtKB/Swiss-Prot
      Q9P2B1
      UniProtKB/TrEMBL
      A0A024R892

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

      UniProtKB/Swiss-Prot
      Q9P2B1
      UniProtKB/TrEMBL
      A0A024R892

    3. 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
      Q8IWT6, Q9P2B1
      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

    4. 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
      Q8IWT6, Q9P2B1
      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

    5. 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
      Q8IWT6, Q9P2B1
      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

    6. XM_047423601.1 → XP_047279557.1  volume-regulated anion channel subunit LRRC8A isoform X1

      UniProtKB/Swiss-Prot
      Q9P2B1
      UniProtKB/TrEMBL
      A0A024R892

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

      UniProtKB/Swiss-Prot
      Q9P2B1
      UniProtKB/TrEMBL
      A0A024R892

    8. 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
      Q8IWT6, Q9P2B1
      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

    9. 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
      Q8IWT6, Q9P2B1
      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

    10. XM_047423598.1 → XP_047279554.1  volume-regulated anion channel subunit LRRC8A isoform X1

      UniProtKB/Swiss-Prot
      Q9P2B1
      UniProtKB/TrEMBL
      A0A024R892

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

      UniProtKB/Swiss-Prot
      Q9P2B1
      UniProtKB/TrEMBL
      A0A024R892

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

      UniProtKB/Swiss-Prot
      Q9P2B1
      UniProtKB/TrEMBL
      A0A024R892

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060933.1 Alternate T2T-CHM13v2.0

      Range
      141086880..141122794
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

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

      UniProtKB/Swiss-Prot
      Q9P2B1
      UniProtKB/TrEMBL
      A0A024R892

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

      UniProtKB/Swiss-Prot
      Q9P2B1
      UniProtKB/TrEMBL
      A0A024R892

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

      UniProtKB/Swiss-Prot
      Q9P2B1
      UniProtKB/TrEMBL
      A0A024R892

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

      UniProtKB/Swiss-Prot
      Q9P2B1
      UniProtKB/TrEMBL
      A0A024R892

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

      UniProtKB/Swiss-Prot
      Q9P2B1
      UniProtKB/TrEMBL
      A0A024R892

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

      UniProtKB/Swiss-Prot
      Q9P2B1
      UniProtKB/TrEMBL
      A0A024R892

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

      UniProtKB/Swiss-Prot
      Q9P2B1
      UniProtKB/TrEMBL
      A0A024R892

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

      UniProtKB/Swiss-Prot
      Q9P2B1
      UniProtKB/TrEMBL
      A0A024R892

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

      UniProtKB/Swiss-Prot
      Q9P2B1
      UniProtKB/TrEMBL
      A0A024R892

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

      UniProtKB/Swiss-Prot
      Q9P2B1
      UniProtKB/TrEMBL
      A0A024R892

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

      UniProtKB/Swiss-Prot
      Q9P2B1
      UniProtKB/TrEMBL
      A0A024R892

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

      UniProtKB/Swiss-Prot
      Q9P2B1
      UniProtKB/TrEMBL
      A0A024R892
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8IWT6.1 GenPept UniProtKB/Swiss-Prot:Q8IWT6

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