LOCUS       NM_000551               4414 bp    mRNA    linear   PRI 12-FEB-2025
DEFINITION  Homo sapiens von Hippel-Lindau tumor suppressor (VHL), transcript
            variant 1, mRNA.
ACCESSION   NM_000551
VERSION     NM_000551.4
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 4414)
  AUTHORS   Dong,X., Zhang,D., Zhang,X., Liu,Y. and Liu,Y.
  TITLE     Network modeling links kidney developmental programs and the cancer
            type-specificity of VHL mutations
  JOURNAL   NPJ Syst Biol Appl 10 (1), 114 (2024)
   PUBMED   39362887
  REMARK    GeneRIF: Network modeling links kidney developmental programs and
            the cancer type-specificity of VHL mutations.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 4414)
  AUTHORS   Mabry,A.R., Singh,A., Mulrooney,B., Gorman,J., Thielbar,A.R.,
            Wolf,E.R. and Mayo,L.D.
  TITLE     Induction of the Mdm2 gene and protein by kinase signaling pathways
            is repressed by the pVHL tumor suppressor
  JOURNAL   Proc Natl Acad Sci U S A 121 (31), e2400935121 (2024)
   PUBMED   39047034
  REMARK    GeneRIF: Induction of the Mdm2 gene and protein by kinase signaling
            pathways is repressed by the pVHL tumor suppressor.
REFERENCE   3  (bases 1 to 4414)
  AUTHORS   Calderon-Garciduenas,A.L., Pina-Ballantyne,S.A.,
            Espinosa-Aguilar,E.J. and de Jesus Ramos-Sanchez,R.
  TITLE     Characterization of spinal hemangioblastomas in patients with and
            without von Hippel-Lindau, and YAP expression
  JOURNAL   Rev Esp Patol 57 (3), 160-168 (2024)
   PUBMED   38971615
  REMARK    GeneRIF: Characterization of spinal hemangioblastomas in patients
            with and without von Hippel-Lindau, and YAP expression.
REFERENCE   4  (bases 1 to 4414)
  AUTHORS   Mukhopadhyay,D., Chakraborty,B., Sarkar,S., Alam,N. and Panda,C.K.
  TITLE     Clinical implications of activation of the LIMD1-VHL-HIF1alpha
            pathway during head-&-neck squamous cell carcinoma development
  JOURNAL   Indian J Med Res 159 (5), 479-493 (2024)
   PUBMED   39382421
  REMARK    GeneRIF: Clinical implications of activation of the
            LIMD1-VHL-HIF1alpha pathway during head-&-neck squamous cell
            carcinoma development.
REFERENCE   5  (bases 1 to 4414)
  AUTHORS   Neumann,H.P., Eng,C., Mulligan,L.M., Glavac,D., Zauner,I.,
            Ponder,B.A., Crossey,P.A., Maher,E.R. and Brauch,H.
  TITLE     Consequences of direct genetic testing for germline mutations in
            the clinical management of families with multiple endocrine
            neoplasia, type II
  JOURNAL   JAMA 274 (14), 1149-1151 (1995)
   PUBMED   7563486
REFERENCE   6  (bases 1 to 4414)
  AUTHORS   Adams,M.D., Kerlavage,A.R., Fleischmann,R.D., Fuldner,R.A.,
            Bult,C.J., Lee,N.H., Kirkness,E.F., Weinstock,K.G., Gocayne,J.D.,
            White,O. et al.
  TITLE     Initial assessment of human gene diversity and expression patterns
            based upon 83 million nucleotides of cDNA sequence
  JOURNAL   Nature 377 (6547 Suppl), 3-174 (1995)
   PUBMED   7566098
REFERENCE   7  (bases 1 to 4414)
  AUTHORS   Duan,D.R., Humphrey,J.S., Chen,D.Y., Weng,Y., Sukegawa,J., Lee,S.,
            Gnarra,J.R., Linehan,W.M. and Klausner,R.D.
  TITLE     Characterization of the VHL tumor suppressor gene product:
            localization, complex formation, and the effect of natural
            inactivating mutations
  JOURNAL   Proc Natl Acad Sci U S A 92 (14), 6459-6463 (1995)
   PUBMED   7604013
REFERENCE   8  (bases 1 to 4414)
  AUTHORS   Latif,F., Tory,K., Gnarra,J., Yao,M., Duh,F.M., Orcutt,M.L.,
            Stackhouse,T., Kuzmin,I., Modi,W., Geil,L. et al.
  TITLE     Identification of the von Hippel-Lindau disease tumor suppressor
            gene
  JOURNAL   Science 260 (5112), 1317-1320 (1993)
   PUBMED   8493574
REFERENCE   9  (bases 1 to 4414)
  AUTHORS   van Leeuwaarde,R.S., Ahmad,S., van Nesselrooij,B., Zandee,W. and
            Giles,R.H.
  TITLE     Von Hippel-Lindau Syndrome
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301636
REFERENCE   10 (bases 1 to 4414)
  AUTHORS   Neumann,H.P. and Wiestler,O.D.
  TITLE     Clustering of features of von Hippel-Lindau syndrome: evidence for
            a complex genetic locus
  JOURNAL   Lancet 337 (8749), 1052-1054 (1991)
   PUBMED   1673491
  REMARK    Review article
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC034193.5.
            
            On Nov 30, 2019 this sequence version replaced NM_000551.3.
            
            Summary: This gene encodes a component of a ubiquitination complex.
            The encoded protein is involved in the ubiquitination and
            degradation of hypoxia-inducible-factor (HIF), which is a
            transcription factor that plays a central role in the regulation of
            gene expression by oxygen. In addition to oxygen-related gene
            expression, this protein plays a role in many other cellular
            processes including cilia formation, cytokine signaling, regulation
            of senescence, and formation of the extracellular matrix. Variants
            of this gene are associated with von Hippel-Lindau syndrome,
            pheochromocytoma, erythrocytosis, renal cell carcinoma, and
            cerebellar hemangioblastoma. [provided by RefSeq, Jun 2022].
            
            Transcript Variant: This variant (1) encodes the longest isoform
            (1).
            
            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 :: SRR7346977.971511.1, L15409.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000256474.3/ ENSP00000256474.3
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-410               AC034193.5         21927-22336         c
            411-533             AC034193.5         17478-17600         c
            534-4414            AC034193.5         10447-14327         c
FEATURES             Location/Qualifiers
     source          1..4414
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="3"
                     /map="3p25.3"
     gene            1..4414
                     /gene="VHL"
                     /gene_synonym="HRCA1; pVHL; RCA1; VHL1"
                     /note="von Hippel-Lindau tumor suppressor"
                     /db_xref="GeneID:7428"
                     /db_xref="HGNC:HGNC:12687"
                     /db_xref="MIM:608537"
     exon            1..410
                     /gene="VHL"
                     /gene_synonym="HRCA1; pVHL; RCA1; VHL1"
                     /inference="alignment:Splign:2.1.0"
     CDS             71..712
                     /gene="VHL"
                     /gene_synonym="HRCA1; pVHL; RCA1; VHL1"
                     /note="isoform 1 is encoded by transcript variant 1;
                     elongin binding protein; von Hippel-Lindau disease tumor
                     suppressor; protein G7; von Hippel-Lindau tumor
                     suppressor, E3 ubiquitin protein ligase"
                     /codon_start=1
                     /product="von Hippel-Lindau disease tumor suppressor
                     isoform 1"
                     /protein_id="NP_000542.1"
                     /db_xref="CCDS:CCDS2597.1"
                     /db_xref="GeneID:7428"
                     /db_xref="HGNC:HGNC:12687"
                     /db_xref="MIM:608537"
                     /translation="MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESG
                     PEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLP
                     PGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKE
                     RCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD"
     exon            411..533
                     /gene="VHL"
                     /gene_synonym="HRCA1; pVHL; RCA1; VHL1"
                     /inference="alignment:Splign:2.1.0"
     exon            534..4414
                     /gene="VHL"
                     /gene_synonym="HRCA1; pVHL; RCA1; VHL1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4390..4395
                     /regulatory_class="polyA_signal_sequence"
                     /gene="VHL"
                     /gene_synonym="HRCA1; pVHL; RCA1; VHL1"
                     /note="hexamer: ATTAAA"
     polyA_site      4414
                     /gene="VHL"
                     /gene_synonym="HRCA1; pVHL; RCA1; VHL1"
                     /note="major polyA site"
ORIGIN      
        1 gcagctccgc cccgcgtccg acccgcggat cccgcggcgt ccggcccggg tggtctggat
       61 cgcggaggga atgccccgga gggcggagaa ctgggacgag gccgaggtag gcgcggagga
      121 ggcaggcgtc gaagagtacg gccctgaaga agacggcggg gaggagtcgg gcgccgagga
      181 gtccggcccg gaagagtccg gcccggagga actgggcgcc gaggaggaga tggaggccgg
      241 gcggccgcgg cccgtgctgc gctcggtgaa ctcgcgcgag ccctcccagg tcatcttctg
      301 caatcgcagt ccgcgcgtcg tgctgcccgt atggctcaac ttcgacggcg agccgcagcc
      361 ctacccaacg ctgccgcctg gcacgggccg ccgcatccac agctaccgag gtcacctttg
      421 gctcttcaga gatgcaggga cacacgatgg gcttctggtt aaccaaactg aattatttgt
      481 gccatctctc aatgttgacg gacagcctat ttttgccaat atcacactgc cagtgtatac
      541 tctgaaagag cgatgcctcc aggttgtccg gagcctagtc aagcctgaga attacaggag
      601 actggacatc gtcaggtcgc tctacgaaga tctggaagac cacccaaatg tgcagaaaga
      661 cctggagcgg ctgacacagg agcgcattgc acatcaacgg atgggagatt gaagatttct
      721 gttgaaactt acactgtttc atctcagctt ttgatggtac tgatgagtct tgatctagat
      781 acaggactgg ttccttcctt agtttcaaag tgtctcattc tcagagtaaa ataggcacca
      841 ttgcttaaaa gaaagttaac tgacttcact aggcattgtg atgtttaggg gcaaacatca
      901 caaaatgtaa tttaatgcct gcccattaga gaagtattta tcaggagaag gtggtggcat
      961 ttttgcttcc tagtaagtca ggacagcttg tatgtaagga ggtttgtata agtaattcag
     1021 tgggaattgc agcatatcgt ttaattttaa gaaggcattg gcatctgctt ttaatggatg
     1081 tataatacat ccattctaca tccgtagcgg ttggtgactt gtctgcctcc tgctttggga
     1141 agactgaggc atccgtgagg cagggacaag tctttctcct ctttgagacc ccagtgcctg
     1201 cacatcatga gccttcagtc agggtttgtc agaggaacaa accaggggac actttgttag
     1261 aaagtgctta gaggttctgc ctctattttt gttggggggt gggagagggg accttaaaat
     1321 gtgtacagtg aacaaatgtc ttaaagggaa tcatttttgt aggaagcatt ttttataatt
     1381 ttctaagtcg tgcactttct cggtccactc ttgttgaagt gctgttttat tactgtttct
     1441 aaactaggat tgacattcta cagttgtgat aatagcattt ttgtaacttg ccatccgcac
     1501 agaaaatacg agaaaatctg catgtttgat tatagtatta atggacaaat aagtttttgc
     1561 taaatgtgag tatttctgtt cctttttgta aatatgtgac attcctgatt gatttgggtt
     1621 tttttgttgt tgttgttttg ttttgttttg tttttttgag atggagtctc actcttgtca
     1681 cccaggctgg agtgcagtgg cgccatctcg gctcactgca acctctgcct cctgggttca
     1741 cgtaatcctc ctgagtagct gggattacag gcgcctgcca ccacgctggc caatttttgt
     1801 acttttagta gagacagtgt ttcgtcatgt tggccaggct ggtttcaaac tcctgacctc
     1861 aggtgatccg cccacctcag cctcccaaaa tggtgggatt acaggtgtgt gggccaccgt
     1921 gcctggctga ttcagcattt tttatcaggc aggaccaggt ggcacttcca cctccagcct
     1981 ctggtcctac caatggattc atggagtagc ctggactgtt tcatagtttt ctaaatgtac
     2041 aaattcttat aggctagact tagattcatt aactcaaatt caatgcttct atcagactca
     2101 gttttttgta actaatagat ttttttttcc acttttgttc tactccttcc ctaatagctt
     2161 tttaaaaaaa tctccccagt agagaaacat ttggaaaaga cagaaaacta aaaaggaaga
     2221 aaaaagatcc ctattagata cacttcttaa atacaatcac attaacattt tgagctattt
     2281 ccttccagcc tttttagggc agattttggt tggtttttac atagttgaga ttgtactgtt
     2341 catacagttt tatacccttt ttcatttaac tttataactt aaatattgct ctatgttagt
     2401 ataagctttt cacaaacatt agtatagtct cccttttata attaatgttt gtgggtattt
     2461 cttggcatgc atctttaatt ccttatccta gcctttgggc acaattcctg tgctcaaaaa
     2521 tgagagtgac ggctggcatg gtggctcccg cctgtaatcc cagtactttg gaaagccaag
     2581 gtaagaggat tgcttgagcc cagaacttca agatgagcct gggctcatag tgagaaccca
     2641 tctatacaaa aaatttttaa aaattagcat ggcggcacac atctgtaatc ctagctactt
     2701 ggcaggctga ggtgagaaga tcattggagt ttaggaattg gaggctgcag tgagccatga
     2761 gtatgccact gcactccagc ctgggggaca gagcaagacc ctgcctcaaa aaaaaaaaaa
     2821 aaaaaaaaat caggccgggc atggtggctc acgcctgtaa tcccagcact ttgggaggtc
     2881 gaggtgggca gatcacctga ggtcaggagt tcgagaccag cctggccaac atggtaaaac
     2941 cccatttcta ctaaaaaata caagaattag ctgggtgtgg tggcgcatgc ctgtaatcct
     3001 agctactcag gaggctgagg caggagaatc acttgaaccc aggaggcgaa gattgcagtg
     3061 agctgatatc gcaccattgt actccagcct gtgtgacaga gcaatactct tgtctcaaaa
     3121 aaaaaaaaaa attcaaatca gagtgaagtg aatgagacac tccagttttc cttctactcc
     3181 gaatttcaac tgattttagc tcctcctttc aacattcaac aaatagtctt tttttttttt
     3241 tttttttttt tttttttgag atggagtctc actctgttgc ccaggctgga gtgcagtggt
     3301 gcgatctctg ctcactacaa gctctgcctc ccgagttcaa gtgattctcc tggctcaccc
     3361 tcctgagtag ctgggattac aggcgcctgc caccatgcct ggctaatttt gtgtttttag
     3421 tggagacggg gtttcaccat gttgtccagg atggtcttga tctcctgacc ttgtgatcca
     3481 cccacctcag cctcccaaag tgctgggatt acaggtgtga gccaccgcgt ccagccagct
     3541 ttattatttt ttttaagctg tctttgtgtc aaaatgatag ttcatgctcc tcttgttaaa
     3601 acctgcaggc cgagcacagt ggctcatgcc tgtaatccca gcattttggg agaccaaggc
     3661 ggatggatca cctgaggtca ggagctgaag accagcctgg ctaacatggt gaaacctcat
     3721 ctccacttaa aatacaaaaa ttgccggccg cggcggctca tgcctgtaat cccagcactt
     3781 tgggaggcct aggcgggtgg atcacgaggt caggaaatcg agaccatcct ggctaacacg
     3841 ggtgaaaccc cgtctctatt aaaaaataga aaaaattagg cgggcgtggt ggtgagcgcc
     3901 tgtagtccca gctactcgag agcctgaggc aggagaatgg catgaacctg gaaggcggag
     3961 cttgcagtga gctgagatgg tgccactgca ctctaacctg ggcgacagag tgagacaccg
     4021 tctcaaaaaa aaaaacaaaa aacaaaaatt atccaggtgt ggcggtgggc gcctgtgagg
     4081 caggcgaatc tcttgaaccc gggaggcgga ggttgcagtg agccaagatc acaccattgc
     4141 actccagcct gggcaacaag agtgaaattc catctcaaaa agaaaccaaa aaaacaaaaa
     4201 aaaaacatgc cgtttgagta ctgtgttttt ggtgttgtcc aaggaaaatt aaaaacctgt
     4261 agcatgaata atgtttgttt ttcatttcga atcttgtgaa tgtattaaat atatcgctct
     4321 taagagacgg tgaagttcct atttcaagtt tttttttttt tttttttttt taaagctgtt
     4381 ttttaataca ttaaatggtg ctgagtaaag gaaa
//
