LOCUS       NM_022139               1471 bp    mRNA    linear   PRI 09-JUN-2024
DEFINITION  Homo sapiens GDNF family receptor alpha 4 (GFRA4), transcript
            variant 1, mRNA.
ACCESSION   NM_022139
VERSION     NM_022139.4
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 1471)
  AUTHORS   Wang,G., Wang,H., Zhang,L., Guo,F., Wu,X. and Liu,Y.
  TITLE     MiR-195-5p inhibits proliferation and invasion of nerve cells in
            Hirschsprung disease by targeting GFRA4
  JOURNAL   Mol Cell Biochem 476 (5), 2061-2073 (2021)
   PUBMED   33515383
  REMARK    GeneRIF: MiR-195-5p inhibits proliferation and invasion of nerve
            cells in Hirschsprung disease by targeting GFRA4.
REFERENCE   2  (bases 1 to 1471)
  AUTHORS   Wang,G., Zhang,L., Wang,H., Cui,M., Liu,W., Liu,Y. and Wu,X.
  TITLE     Demethylation of GFRA4 Promotes Cell Proliferation and Invasion in
            Hirschsprung Disease
  JOURNAL   DNA Cell Biol 37 (4), 316-324 (2018)
   PUBMED   29634418
  REMARK    GeneRIF: Results support that aberrant CpG hypermethylation at
            least partly accounts for GFRA4 silencing in HSCR, which impairs
            its protective role in enteric nervous system.
REFERENCE   3  (bases 1 to 1471)
  AUTHORS   Wang,G., Guo,F., Wang,H., Liu,W., Zhang,L., Cui,M. and Wu,X.
  TITLE     Downregulation of microRNA-483-5p Promotes Cell Proliferation and
            Invasion by Targeting GFRA4 in Hirschsprung's Disease
  JOURNAL   DNA Cell Biol 36 (11), 930-937 (2017)
   PUBMED   29090971
  REMARK    GeneRIF: High GFRA4 expression is associated with Hirschsprung's
            Disease.
REFERENCE   4  (bases 1 to 1471)
  AUTHORS   Yang,J., Lindahl,M., Lindholm,P., Virtanen,H., Coffey,E.,
            Runeberg-Roos,P. and Saarma,M.
  TITLE     PSPN/GFRalpha4 has a significantly weaker capacity than
            GDNF/GFRalpha1 to recruit RET to rafts, but promotes neuronal
            survival and neurite outgrowth
  JOURNAL   FEBS Lett 569 (1-3), 267-271 (2004)
   PUBMED   15225646
  REMARK    GeneRIF: GDNF/GFRalpha1 is crucial for efficient signal
            transduction to recruit Ret protein into lipid rafts.
REFERENCE   5  (bases 1 to 1471)
  AUTHORS   Borrego,S., Fernandez,R.M., Dziema,H., Niess,A., Lopez-Alonso,M.,
            Antinolo,G. and Eng,C.
  TITLE     Investigation of germline GFRA4 mutations and evaluation of the
            involvement of GFRA1, GFRA2, GFRA3, and GFRA4 sequence variants in
            Hirschsprung disease
  JOURNAL   J Med Genet 40 (3), e18 (2003)
   PUBMED   12624147
  REMARK    GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
REFERENCE   6  (bases 1 to 1471)
  AUTHORS   Deloukas,P., Matthews,L.H., Ashurst,J., Burton,J., Gilbert,J.G.,
            Jones,M., Stavrides,G., Almeida,J.P., Babbage,A.K., Bagguley,C.L.,
            Bailey,J., Barlow,K.F., Bates,K.N., Beard,L.M., Beare,D.M.,
            Beasley,O.P., Bird,C.P., Blakey,S.E., Bridgeman,A.M., Brown,A.J.,
            Buck,D., Burrill,W., Butler,A.P., Carder,C., Carter,N.P.,
            Chapman,J.C., Clamp,M., Clark,G., Clark,L.N., Clark,S.Y.,
            Clee,C.M., Clegg,S., Cobley,V.E., Collier,R.E., Connor,R.,
            Corby,N.R., Coulson,A., Coville,G.J., Deadman,R., Dhami,P.,
            Dunn,M., Ellington,A.G., Frankland,J.A., Fraser,A., French,L.,
            Garner,P., Grafham,D.V., Griffiths,C., Griffiths,M.N., Gwilliam,R.,
            Hall,R.E., Hammond,S., Harley,J.L., Heath,P.D., Ho,S., Holden,J.L.,
            Howden,P.J., Huckle,E., Hunt,A.R., Hunt,S.E., Jekosch,K.,
            Johnson,C.M., Johnson,D., Kay,M.P., Kimberley,A.M., King,A.,
            Knights,A., Laird,G.K., Lawlor,S., Lehvaslaiho,M.H., Leversha,M.,
            Lloyd,C., Lloyd,D.M., Lovell,J.D., Marsh,V.L., Martin,S.L.,
            McConnachie,L.J., McLay,K., McMurray,A.A., Milne,S., Mistry,D.,
            Moore,M.J., Mullikin,J.C., Nickerson,T., Oliver,K., Parker,A.,
            Patel,R., Pearce,T.A., Peck,A.I., Phillimore,B.J.,
            Prathalingam,S.R., Plumb,R.W., Ramsay,H., Rice,C.M., Ross,M.T.,
            Scott,C.E., Sehra,H.K., Shownkeen,R., Sims,S., Skuce,C.D.,
            Smith,M.L., Soderlund,C., Steward,C.A., Sulston,J.E., Swann,M.,
            Sycamore,N., Taylor,R., Tee,L., Thomas,D.W., Thorpe,A., Tracey,A.,
            Tromans,A.C., Vaudin,M., Wall,M., Wallis,J.M., Whitehead,S.L.,
            Whittaker,P., Willey,D.L., Williams,L., Williams,S.A., Wilming,L.,
            Wray,P.W., Hubbard,T., Durbin,R.M., Bentley,D.R., Beck,S. and
            Rogers,J.
  TITLE     The DNA sequence and comparative analysis of human chromosome 20
  JOURNAL   Nature 414 (6866), 865-871 (2001)
   PUBMED   11780052
REFERENCE   7  (bases 1 to 1471)
  AUTHORS   Zhou,B., Bae,S.K., Malone,A.C., Levinson,B.B., Kuo,Y.M.,
            Cilio,M.R., Bertini,E., Hayflick,S.J. and Gitschier,J.M.
  TITLE     hGFRalpha-4: a new member of the GDNF receptor family and a
            candidate for NBIA
  JOURNAL   Pediatr Neurol 25 (2), 156-161 (2001)
   PUBMED   11551746
REFERENCE   8  (bases 1 to 1471)
  AUTHORS   Lindahl,M., Poteryaev,D., Yu,L., Arumae,U., Timmusk,T.,
            Bongarzone,I., Aiello,A., Pierotti,M.A., Airaksinen,M.S. and
            Saarma,M.
  TITLE     Human glial cell line-derived neurotrophic factor receptor alpha 4
            is the receptor for persephin and is predominantly expressed in
            normal and malignant thyroid medullary cells
  JOURNAL   J Biol Chem 276 (12), 9344-9351 (2001)
   PUBMED   11116144
REFERENCE   9  (bases 1 to 1471)
  AUTHORS   Masure,S., Cik,M., Hoefnagel,E., Nosrat,C.A., Van der Linden,I.,
            Scott,R., Van Gompel,P., Lesage,A.S., Verhasselt,P., Ibanez,C.F.
            and Gordon,R.D.
  TITLE     Mammalian GFRalpha -4, a divergent member of the GFRalpha family of
            coreceptors for glial cell line-derived neurotrophic factor family
            ligands, is a receptor for the neurotrophic factor persephin
  JOURNAL   J Biol Chem 275 (50), 39427-39434 (2000)
   PUBMED   10958791
REFERENCE   10 (bases 1 to 1471)
  AUTHORS   Enokido,Y., de Sauvage,F., Hongo,J.A., Ninkina,N., Rosenthal,A.,
            Buchman,V.L. and Davies,A.M.
  TITLE     GFR alpha-4 and the tyrosine kinase Ret form a functional receptor
            complex for persephin
  JOURNAL   Curr Biol 8 (18), 1019-1022 (1998)
   PUBMED   9740802
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AF253318.1 and AL356755.12.
            
            On May 20, 2020 this sequence version replaced NM_022139.3.
            
            Summary: The protein encoded by this gene is a member of the GDNF
            receptor family. It is a glycosylphosphatidylinositol(GPI)-linked
            cell surface receptor for persephin, and mediates activation of the
            RET tyrosine kinase receptor. This gene is a candidate gene for
            RET-associated diseases. Alternatively spliced transcript variants
            encoding different isoforms have been described for this gene.
            [provided by RefSeq, Jul 2008].
            
            Transcript Variant: This variant (1) encodes the predominant
            isoform (a).
            
            ##Evidence-Data-START##
            Transcript exon combination :: AF253318.1, AJ291673.1 [ECO:0000332]
            RNAseq introns              :: partial sample support SAMEA2144120,
                                           SAMEA2148874 [ECO:0000350]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000290417.7/ ENSP00000290417.2
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            ##RefSeq-Attributes-END##
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-859               AF253318.1         1-859
            860-1427            AL356755.12        7157-7724           c
            1428-1471           AL356755.12        7113-7156           c
FEATURES             Location/Qualifiers
     source          1..1471
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="20"
                     /map="20p13"
     gene            1..1471
                     /gene="GFRA4"
                     /note="GDNF family receptor alpha 4"
                     /db_xref="GeneID:64096"
                     /db_xref="HGNC:HGNC:13821"
                     /db_xref="MIM:618679"
     CDS             1..810
                     /gene="GFRA4"
                     /note="isoform a precursor is encoded by transcript
                     variant 1; persephin receptor; GFR receptor alpha 4;
                     GFR-alpha-4; GDNFR-alpha-4; GDNF receptor alpha-4"
                     /codon_start=1
                     /product="GDNF family receptor alpha-4 isoform a
                     precursor"
                     /protein_id="NP_071422.1"
                     /db_xref="CCDS:CCDS13055.1"
                     /db_xref="GeneID:64096"
                     /db_xref="HGNC:HGNC:13821"
                     /db_xref="MIM:618679"
                     /translation="MVRCLGPALLLLLLLGSASSVGGNRCVDAAEACTADARCQRLRS
                     EYVAQCLGRAAQGGCPRARCRRALRRFFARGPPALTHALLFCPCAGPACAERRRQTFV
                     PSCAFSGPGPAPPSCLEPLNFCERSRVCRPRLLAFQVSCTPAPSAPDGCLLDQGARCL
                     RAYAGLVGTAVTPNYVDNVSARVAPWCDCGASGNRREDCEAFRGLFTRNRCLDGAIQA
                     FASGWPPVLLDQLNPQGDPEHSLLQVSSTGRALERRSLLSILPVLALPALL"
     exon            1..46
                     /gene="GFRA4"
                     /inference="alignment:Splign:2.1.0"
     exon            47..392
                     /gene="GFRA4"
                     /inference="alignment:Splign:2.1.0"
     exon            393..502
                     /gene="GFRA4"
                     /inference="alignment:Splign:2.1.0"
     exon            503..637
                     /gene="GFRA4"
                     /inference="alignment:Splign:2.1.0"
     exon            638..729
                     /gene="GFRA4"
                     /inference="alignment:Splign:2.1.0"
     exon            730..1471
                     /gene="GFRA4"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1447..1452
                     /regulatory_class="polyA_signal_sequence"
                     /gene="GFRA4"
                     /note="hexamer: ATTAAA"
     polyA_site      1471
                     /gene="GFRA4"
                     /note="major polyA site"
ORIGIN      
        1 atggtccgct gcctggggcc tgcgctgctg ctgctgctgt tactggggtc ggcgagctcg
       61 gtcggaggga accgatgtgt ggacgcggcc gaagcctgca cggcggacgc gcggtgccag
      121 cgtttgcgct ccgagtatgt ggcgcagtgc ctgggccggg ctgcgcaggg gggctgtccc
      181 cgcgcccgct gccgccgggc cctgcgccgc ttcttcgccc gcgggccgcc cgcgctcacc
      241 cacgcactgc tcttctgccc gtgcgcgggc cccgcgtgcg ccgagcgtcg gcgccagacc
      301 ttcgtgccct cctgcgcctt ttcggggccc ggccccgcgc cgccctcctg ccttgagccc
      361 ttaaacttct gcgagcgcag ccgggtctgc aggcctcgcc tcctggcctt tcaggtctcg
      421 tgcaccccag cgcccagcgc ccccgacggc tgcctgctgg accagggcgc ccgctgcctg
      481 cgcgcctacg cgggcctcgt gggcaccgcc gtcaccccta actacgtgga caacgtgagc
      541 gcgcgcgtgg cgccctggtg cgactgcgga gccagcggga accggcgtga ggactgcgaa
      601 gccttccggg ggctctttac caggaaccgc tgcttggatg gtgccattca ggcctttgcc
      661 agcgggtggc ccccagtcct gctggaccag ctgaaccccc agggagaccc ggagcacagc
      721 ctcctgcagg tgtcctccac aggcagggcc ctggagagac gctccctgct ctccatactt
      781 cctgtcctgg ctctcccggc cctgctctga ttaggacagc gacctcggat agcacagcca
      841 gctactccac cctgcctgcc tgggccgcct ctgtggccta ctggcccctt gagaaggggc
      901 tggcttaccc cccaagccgg ccctggtgct ttcactccgc tgccctttgt aggtttggac
      961 accctgtgtg ccgtcccctg gggcaaggga tgtaggctgg ggcctgactg taaagccccc
     1021 gtctccctgt caggaggcat cttggttgta agtcccttta ttcacagacc ttgagaccac
     1081 tggggtctcc cacaaggtgg ggtcaggaga gggtcacttt tgtagctgag acctctctgg
     1141 agacccagat cccctagagc aggtcagaga ccatccagaa tcccagaatt ctaggaaatt
     1201 gtatcagcct cccaagcata taacccccta aggaatccat cggacaagac cccgtctaac
     1261 actgcatcct cccaactggg cattacccac cattgtagcc acctgtgcgc catgaccatg
     1321 ctggcagagt ctttcctgtt ccccatatgc tgcttgaggg gccccaccct gtgccctgcc
     1381 tggcattggc cctgtggcca tcttccccct ggtttcctgc agctgtagga ataacataca
     1441 gtgcttatta aatctgtgtg ctgagactga c
//
