LOCUS       NM_019594               4334 bp    mRNA    linear   PRI 12-FEB-2025
DEFINITION  Homo sapiens leucine rich repeat containing 8 VRAC subunit A
            (LRRC8A), transcript variant 2, mRNA.
ACCESSION   NM_019594 XM_026998
VERSION     NM_019594.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 4334)
  AUTHORS   Zhang,H., Liu,R., Jing,Z., Li,C., Fan,W., Li,H., Li,H., Ren,J.,
            Cui,S., Zhao,W., Yu,L., Bai,Y., Liu,S., Fang,C., Yang,W., Wei,Y.,
            Li,L. and Peng,S.
  TITLE     LRRC8A as a central mediator promotes colon cancer metastasis by
            regulating PIP5K1B/PIP2 pathway
  JOURNAL   Biochim Biophys Acta Mol Basis Dis 1870 (4), 167066 (2024)
   PUBMED   38350542
  REMARK    GeneRIF: LRRC8A as a central mediator promotes colon cancer
            metastasis by regulating PIP5K1B/PIP2 pathway.
REFERENCE   2  (bases 1 to 4334)
  AUTHORS   Yang,J. and Qiu,Z.
  TITLE     Swell1 channel-mediated tonic GABA release from astrocytes
            modulates cocaine reward
  JOURNAL   Neuropsychopharmacology 49 (1), 327-328 (2024)
   PUBMED   37524750
  REMARK    GeneRIF: Swell1 channel-mediated tonic GABA release from astrocytes
            modulates cocaine reward.
REFERENCE   3  (bases 1 to 4334)
  AUTHORS   Kostritskaia,Y., Klussendorf,M., Pan,Y.E., Hassani Nia,F.,
            Kostova,S. and Stauber,T.
  TITLE     Physiological Functions of the Volume-Regulated Anion Channel
            VRAC/LRRC8 and the Proton-Activated Chloride Channel ASOR/TMEM206
  JOURNAL   Handb Exp Pharmacol 283, 181-218 (2024)
   PUBMED   37468723
  REMARK    GeneRIF: Physiological Functions of the Volume-Regulated Anion
            Channel VRAC/LRRC8 and the Proton-Activated Chloride Channel
            ASOR/TMEM206.
REFERENCE   4  (bases 1 to 4334)
  AUTHORS   Liu,H., Polovitskaya,M.M., Yang,L., Li,M., Li,H., Han,Z., Wu,J.,
            Zhang,Q., Jentsch,T.J. and Liao,J.
  TITLE     Structural insights into anion selectivity and activation mechanism
            of LRRC8 volume-regulated anion channels
  JOURNAL   Cell Rep 42 (8), 112926 (2023)
   PUBMED   37543949
  REMARK    GeneRIF: Structural insights into anion selectivity and activation
            mechanism of LRRC8 volume-regulated anion channels.
REFERENCE   5  (bases 1 to 4334)
  AUTHORS   Zhang,H., Cui,S., Jing,Z., Fu,G., Liu,R., Zhao,W., Xu,L., Yu,L.,
            Bai,Y., Lv,C., Wu,M., Wei,Y., Li,L. and Peng,S.
  TITLE     LRRC8A is responsible for exosome biogenesis and volume regulation
            in colon cancer cells
  JOURNAL   Biochem J 480 (9), 701-713 (2023)
   PUBMED   37129855
  REMARK    GeneRIF: LRRC8A is responsible for exosome biogenesis and volume
            regulation in colon cancer cells.
REFERENCE   6  (bases 1 to 4334)
  AUTHORS   Ghosh,D., Lippert,D., Krokhin,O., Cortens,J.P. and Wilkins,J.A.
  TITLE     Defining the membrane proteome of NK cells
  JOURNAL   J Mass Spectrom 45 (1), 1-25 (2010)
   PUBMED   19946888
REFERENCE   7  (bases 1 to 4334)
  AUTHORS   Smits,G. and Kajava,A.V.
  TITLE     LRRC8 extracellular domain is composed of 17 leucine-rich repeats
  JOURNAL   Mol Immunol 41 (5), 561-562 (2004)
   PUBMED   15183935
REFERENCE   8  (bases 1 to 4334)
  AUTHORS   Kubota,K., Kim,J.Y., Sawada,A., Tokimasa,S., Fujisaki,H.,
            Matsuda-Hashii,Y., Ozono,K. and Hara,J.
  TITLE     LRRC8 involved in B cell development belongs to a novel family of
            leucine-rich repeat proteins
  JOURNAL   FEBS Lett 564 (1-2), 147-152 (2004)
   PUBMED   15094057
  REMARK    GeneRIF: identified four genes, named TA-LRRP, AD158, LRRC5, and
            FLJ23420, as unknown LRRC8-like genes
REFERENCE   9  (bases 1 to 4334)
  AUTHORS   Sawada,A., Takihara,Y., Kim,J.Y., Matsuda-Hashii,Y., Tokimasa,S.,
            Fujisaki,H., Kubota,K., Endo,H., Onodera,T., Ohta,H., Ozono,K. and
            Hara,J.
  TITLE     A congenital mutation of the novel gene LRRC8 causes
            agammaglobulinemia in humans
  JOURNAL   J Clin Invest 112 (11), 1707-1713 (2003)
   PUBMED   14660746
  REMARK    GeneRIF: LRRC8 is required for B cell development.
REFERENCE   10 (bases 1 to 4334)
  AUTHORS   Conley,M.E.
  TITLE     Genes required for B cell development
  JOURNAL   J Clin Invest 112 (11), 1636-1638 (2003)
   PUBMED   14660738
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL672142.9.
            
            On Feb 27, 2020 this sequence version replaced NM_019594.3.
            
            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].
            
            Transcript Variant: This variant (2) differs in the 5' UTR compared
            to variant 1. All variants (1-3) encode the same protein.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: BC051322.1, SRR11853567.30998.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1968189
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000372600.9/ ENSP00000361682.4
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-118               AL672142.9         18055-18172
            119-225             AL672142.9         21937-22043
            226-2390            AL672142.9         43079-45243
            2391-4334           AL672142.9         52018-53961
FEATURES             Location/Qualifiers
     source          1..4334
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="9"
                     /map="9q34.11"
     gene            1..4334
                     /gene="LRRC8A"
                     /gene_synonym="AGM5; HsLRRC8A; LRRC8; SWELL1"
                     /note="leucine rich repeat containing 8 VRAC subunit A"
                     /db_xref="GeneID:56262"
                     /db_xref="HGNC:HGNC:19027"
                     /db_xref="MIM:608360"
     exon            1..118
                     /gene="LRRC8A"
                     /gene_synonym="AGM5; HsLRRC8A; LRRC8; SWELL1"
                     /inference="alignment:Splign:2.1.0"
     exon            119..225
                     /gene="LRRC8A"
                     /gene_synonym="AGM5; HsLRRC8A; LRRC8; SWELL1"
                     /inference="alignment:Splign:2.1.0"
     exon            226..2390
                     /gene="LRRC8A"
                     /gene_synonym="AGM5; HsLRRC8A; LRRC8; SWELL1"
                     /inference="alignment:Splign:2.1.0"
     CDS             234..2666
                     /gene="LRRC8A"
                     /gene_synonym="AGM5; HsLRRC8A; LRRC8; SWELL1"
                     /note="swelling protein 1; leucine-rich repeat-containing
                     protein 8A; leucine rich repeat containing 8 family member
                     A"
                     /codon_start=1
                     /product="volume-regulated anion channel subunit LRRC8A"
                     /protein_id="NP_062540.2"
                     /db_xref="CCDS:CCDS35155.1"
                     /db_xref="GeneID:56262"
                     /db_xref="HGNC:HGNC:19027"
                     /db_xref="MIM:608360"
                     /translation="MIPVTELRYFADTQPAYRILKPWWDVFTDYISIVMLMIAVFGGT
                     LQVTQDKMICLPCKWVTKDSCNDSFRGWAAPGPEPTYPNSTILPTPDTGPTGIKYDLD
                     RHQYNYVDAVCYENRLHWFAKYFPYLVLLHTLIFLACSNFWFKFPRTSSKLEHFVSIL
                     LKCFDSPWTTRALSETVVEESDPKPAFSKMNGSMDKKSSTVSEDVEATVPMLQRTKSR
                     IEQGIVDRSETGVLDKKEGEQAKALFEKVKKFRTHVEEGDIVYRLYMRQTIIKVIKFI
                     LIICYTVYYVHNIKFDVDCTVDIESLTGYRTYRCAHPLATLFKILASFYISLVIFYGL
                     ICMYTLWWMLRRSLKKYSFESIREESSYSDIPDVKNDFAFMLHLIDQYDPLYSKRFAV
                     FLSEVSENKLRQLNLNNEWTLDKLRQRLTKNAQDKLELHLFMLSGIPDTVFDLVELEV
                     LKLELIPDVTIPPSIAQLTGLKELWLYHTAAKIEAPALAFLRENLRALHIKFTDIKEI
                     PLWIYSLKTLEELHLTGNLSAENNRYIVIDGLRELKRLKVLRLKSNLSKLPQVVTDVG
                     VHLQKLSINNEGTKLIVLNSLKKMANLTELELIRCDLERIPHSIFSLHNLQEIDLKDN
                     NLKTIEEIISFQHLHRLTCLKLWYNHIAYIPIQIGNLTNLERLYLNRNKIEKIPTQLF
                     YCRKLRYLDLSHNNLTFLPADIGLLQNLQNLAITANRIETLPPELFQCRKLRALHLGN
                     NVLQSLPSRVGELTNLTQIELRGNRLECLPVELGECPLLKRSGLVVEEDLFNTLPPEV
                     KERLWRADKEQA"
     exon            2391..4334
                     /gene="LRRC8A"
                     /gene_synonym="AGM5; HsLRRC8A; LRRC8; SWELL1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4315..4320
                     /regulatory_class="polyA_signal_sequence"
                     /gene="LRRC8A"
                     /gene_synonym="AGM5; HsLRRC8A; LRRC8; SWELL1"
                     /note="hexamer: AATAAA"
     polyA_site      4334
                     /gene="LRRC8A"
                     /gene_synonym="AGM5; HsLRRC8A; LRRC8; SWELL1"
                     /note="major polyA site"
ORIGIN      
        1 gagtggtgca gtgagggaca aacaaaagga ggcgccggag cagcgctgcg gccggcggcg
       61 ggacggagcg gccggggcct ggggctgcct gccgggcggc cgggcgcggc gagcccaggg
      121 aggcagcgtc catggagcaa aaggaatgcc aggatcctgc acaggcagac gcgggccagc
      181 ctcagcaccg acagccgacg cgcagatagc agagccatcc ttggggttga accatgattc
      241 cggtgacaga gctccgctac tttgcggaca cgcagccagc ataccggatc ctgaagccgt
      301 ggtgggatgt gttcacagac tacatctcta tcgtcatgct gatgattgcc gtcttcgggg
      361 ggacgctgca ggtcacccaa gacaagatga tctgcctgcc ttgtaagtgg gtcaccaagg
      421 actcctgcaa tgattcgttc cggggctggg cagcccctgg cccggagccc acctacccca
      481 actccaccat tctgccgacc cctgacacgg gccccacagg catcaagtat gacctggacc
      541 ggcaccagta caactacgtg gacgctgtgt gctatgagaa ccgactgcac tggtttgcca
      601 agtacttccc ctacctggtg cttctgcaca cgctcatctt cctggcctgc agcaacttct
      661 ggttcaaatt cccgcgcacc agctcgaagc tggagcactt tgtgtctatc ctgctgaagt
      721 gcttcgactc gccctggacc acgagggccc tgtcggagac agtggtggag gagagcgacc
      781 ccaagccggc cttcagcaag atgaatgggt ccatggacaa aaagtcatcg accgtcagtg
      841 aggacgtgga ggccaccgtg cccatgctgc agcggaccaa gtcacggatc gagcagggta
      901 tcgtggaccg ctcagagacg ggcgtgctgg acaagaagga gggggagcaa gccaaggcgc
      961 tgtttgagaa ggtgaagaag ttccggaccc atgtggagga gggggacatt gtgtaccgcc
     1021 tctacatgcg gcagaccatc atcaaggtga tcaagttcat cctcatcatc tgctacaccg
     1081 tctactacgt gcacaacatc aagttcgacg tggactgcac cgtggacatt gagagcctga
     1141 cgggctaccg cacctaccgc tgtgcccacc ccctggccac actcttcaag atcctggcgt
     1201 ccttctacat cagcctagtc atcttctacg gcctcatctg catgtataca ctgtggtgga
     1261 tgctacggcg ctccctcaag aagtactcgt ttgagtcgat ccgtgaggag agcagctaca
     1321 gcgacatccc cgacgtcaag aacgacttcg ccttcatgct gcacctcatt gaccaatacg
     1381 acccgctcta ctccaagcgc ttcgccgtct tcctgtcgga ggtgagtgag aacaagctgc
     1441 ggcagctgaa cctcaacaac gagtggacgc tggacaagct ccggcagcgg ctcaccaaga
     1501 acgcgcagga caagctggag ctgcacctgt tcatgctcag tggcatccct gacactgtgt
     1561 ttgacctggt ggagctggag gtcctcaagc tggagctgat ccccgacgtg accatcccgc
     1621 ccagcattgc ccagctcacg ggcctcaagg agctgtggct ctaccacaca gcggccaaga
     1681 ttgaagcgcc cgcgctggcc ttcctgcgtg agaacctgcg ggcgctgcac atcaagttca
     1741 ccgacatcaa ggagatcccg ctgtggatct atagcctgaa gacactggag gagctgcacc
     1801 tgacgggcaa cctgagcgcg gagaacaacc gctacatcgt catcgacggg ctgcgggagc
     1861 tcaaacgcct caaggtgctg cggctcaaga gcaacctaag caagctgcca caggtggtca
     1921 cagatgtggg cgtgcacctg cagaagctgt ccatcaacaa tgagggcacc aagctcatcg
     1981 tcctcaacag cctcaagaag atggcgaacc tgactgagct ggagctgatc cgctgtgacc
     2041 tggagcgcat cccccactcc atcttcagcc tccacaacct gcaggagatt gacctcaagg
     2101 acaacaacct caagaccatc gaggagatca tcagcttcca gcacctgcac cgcctcacct
     2161 gccttaagct gtggtacaac cacatcgcct acatccccat ccagatcggc aacctcacca
     2221 acctggagcg cctctacctg aaccgcaaca agatcgagaa gatccccacc cagctcttct
     2281 actgccgcaa gctgcgctac ctggacctca gccacaacaa cctgaccttc ctccctgccg
     2341 acatcggcct cctgcagaac ctccagaacc tagccatcac ggccaaccgg atcgagacgc
     2401 tccctccgga gctcttccag tgccggaagc tgcgggccct gcacctgggc aacaacgtgc
     2461 tgcagtcact gccctccagg gtgggcgagc tgaccaacct gacgcagatc gagctgcggg
     2521 gcaaccggct ggagtgcctg cctgtggagc tgggcgagtg cccactgctc aagcgcagcg
     2581 gcttggtggt ggaggaggac ctgttcaaca cactgccacc cgaggtgaag gagcggctgt
     2641 ggagggctga caaggagcag gcctgagcga ggccggccca gcacagcaag cagcaggacc
     2701 gctgcccagt cctcaggccc ggaggggcag gcctagcttc tcccagaact cccggacagc
     2761 caggacagcc tcgtggctgg gcaggagcct ggggccgctt gtgagtcagg ccagagcgag
     2821 aggacagtat ctgtggggct ggcccctttt ctccctctga gactcacgtc ccccagggca
     2881 agtgcttgtg gaggagagca agtctcaaga gcgcagtatt tggataatca gggtctcctc
     2941 cctggaggcc agctctgccc caggggctga gctgccacca gaggtcctgg gaccctcact
     3001 ttagttcttg gtatttattt ttctccatct cccacctcct tcatccagat aacttataca
     3061 ttcccaagaa agttcagccc agatggaagg tgttcaggga aaggtgggct gccttttccc
     3121 cttgtcctta tttagcgatg ccgccgggca tttaacaccc acctggactt cagcagagtg
     3181 gtccggggcg aaccagccat gggacggtca cccagcagtg ccgggctggg ctctgcggtg
     3241 cggtccacgg gagagcaggc ctccagctgg aaaggccagg cctggagctt gcctcttcag
     3301 tatttgtggc agttttagtt ttttgttttt ttttttttaa tcaaaaaaca atttttttaa
     3361 aaaaaaagct ttgaaaatgg atggtttggg tattaaaaag aaaaaaaaaa cttaaaaaaa
     3421 aaaagacact aacggccagt gagttggagt ctcagggcag ggtggcagtt tcccttgagc
     3481 aaagcagcca gacgttgaac tgtgtttcct ttccctgggc gcagggtgca gggtgtcttc
     3541 cggatctggt gtgaccttgg tccaggagtt ctatttgttc ctggggaggg aggttttttt
     3601 gtttgttttt tgggtttttt tggtgtcttg ttttctttct cctccatgtg tcttggcagg
     3661 cactcatttc tgtggctgtc ggccagaggg aatgttctgg agctgccaag gagggaggag
     3721 actcgggttg gctaatcccc ggatgaacgg tgctccattc gcacctcccc tcctcgtgcc
     3781 tgccctgcct ctccacgcac agtgttaagg agccaagagg agccacttcg cccagacttt
     3841 gtttccccac cgcctgcggc atgggtgtgt ccagtgccac cgctggcctc cgctgcttcc
     3901 atcagccctg tcaccacctg gtccttcatg aagagcagac acttagaggc tggtcgggaa
     3961 tggggaggtc gcccctggga gggcaggcgt tggttccaag ccggttcccg tccctggcgc
     4021 ctggagtgca cacagcccag tcggcacctg gtggctggaa gccaccctgc tttagatcac
     4081 tcgggtcccc accttagaag ggtccccgcc ttagatcaat cacgtggaca ctaaggcacg
     4141 ttttagagtc tcttgtctta atgattatgt ccatccgtct gtccgtccat ttgtgttttc
     4201 tgcgtcgtgt cattggatat aatcctcaga aataatgcac actagcctct gacaaccatg
     4261 aagcaaaaat ccgttacatg tgggtctgaa cttgtagact cggtcacagt atcaaataaa
     4321 atctataaca gaaa
//
