LOCUS       NM_000190               1505 bp    mRNA    linear   PRI 08-OCT-2024
DEFINITION  Homo sapiens hydroxymethylbilane synthase (HMBS), transcript
            variant 1, mRNA.
ACCESSION   NM_000190
VERSION     NM_000190.4
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 1505)
  AUTHORS   M,K., M,R., J,B., A,B.I., K,I.P., R,W., E,O., A,Z.K., R,S. and R,P.
  TITLE     Neurodevelopmental disorder in a patient with HMBS and SCN3A
            variants-A possibly blended phenotype further delineating autosomal
            recessive HMBS related disease
  JOURNAL   Am J Med Genet A 194 (8), e63617 (2024)
   PUBMED   38568055
  REMARK    GeneRIF: Neurodevelopmental disorder in a patient with HMBS and
            SCN3A variants-A possibly blended phenotype further delineating
            autosomal recessive HMBS related disease.
REFERENCE   2  (bases 1 to 1505)
  AUTHORS   Hu,Y., Li,W., Kang,N., Ma,L., Teng,Q., Mo,G., Wu,J., Wang,X., Bi,R.
            and Zhang,S.
  TITLE     Identification and molecular analysis of 17 novel variants of
            hydroxymethylbilane synthase in Chinese patients with acute
            intermittent porphyria
  JOURNAL   Clin Genet 101 (1), 116-121 (2022)
   PUBMED   34523126
  REMARK    GeneRIF: Identification and molecular analysis of 17 novel variants
            of hydroxymethylbilane synthase in Chinese patients with acute
            intermittent porphyria.
REFERENCE   3  (bases 1 to 1505)
  AUTHORS   Zhang,Y., Xiao,H., Xiong,Q., Wu,C. and Li,P.
  TITLE     Two Novel Hydroxymethylbilane Synthase Splicing Mutations
            Predispose to Acute Intermittent Porphyria
  JOURNAL   Int J Mol Sci 22 (20), 11008 (2021)
   PUBMED   34681668
  REMARK    GeneRIF: Two Novel Hydroxymethylbilane Synthase Splicing Mutations
            Predispose to Acute Intermittent Porphyria.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 1505)
  AUTHORS   Stutterd,C.A., Kidd,A., Florkowski,C., Janus,E., Fanjul,M.,
            Raizis,A., Wu,T.Y., Archer,J., Leventer,R.J., Amor,D.J., Lukic,V.,
            Bahlo,M., Gow,P., Lockhart,P.J., van der Knaap,M.S. and
            Delatycki,M.B.
  TITLE     Expanding the clinical and radiological phenotypes of
            leukoencephalopathy due to biallelic HMBS mutations
  JOURNAL   Am J Med Genet A 185 (10), 2941-2950 (2021)
   PUBMED   34089223
  REMARK    GeneRIF: Expanding the clinical and radiological phenotypes of
            leukoencephalopathy due to biallelic HMBS mutations.
REFERENCE   5  (bases 1 to 1505)
  AUTHORS   Jerico,D., Luis,E.O., Cusso,L., Fernandez-Seara,M.A., Morales,X.,
            Cordoba,K.M., Benito,M., Sampedro,A., Larriva,M., Ramirez,M.J., de
            Salamanca,R.E., Ortiz-de-Solorzano,C., Alegre,M., Prieto,J.,
            Lanciego,J.L., D'Avola,D., Gonzalez-Aseguinolaza,G., Pastor,M.A.,
            Desco,M. and Fontanellas,A.
  TITLE     Brain ventricular enlargement in human and murine acute
            intermittent porphyria
  JOURNAL   Hum Mol Genet 29 (19), 3211-3223 (2020)
   PUBMED   32916704
  REMARK    GeneRIF: Brain ventricular enlargement in human and murine acute
            intermittent porphyria.
REFERENCE   6  (bases 1 to 1505)
  AUTHORS   Sardh,E. and Barbaro,M.
  TITLE     Acute Intermittent Porphyria
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301372
REFERENCE   7  (bases 1 to 1505)
  AUTHORS   Gu,X.F., de Rooij,F., Voortman,G., Te Velde,K., Nordmann,Y. and
            Grandchamp,B.
  TITLE     High frequency of mutations in exon 10 of the porphobilinogen
            deaminase gene in patients with a CRIM-positive subtype of acute
            intermittent porphyria
  JOURNAL   Am J Hum Genet 51 (3), 660-665 (1992)
   PUBMED   1496994
REFERENCE   8  (bases 1 to 1505)
  AUTHORS   Mgone,C.S., Lanyon,W.G., Moore,M.R. and Connor,J.M.
  TITLE     Detection of seven point mutations in the porphobilinogen deaminase
            gene in patients with acute intermittent porphyria, by direct
            sequencing of in vitro amplified cDNA
  JOURNAL   Hum Genet 90 (1-2), 12-16 (1992)
   PUBMED   1427766
REFERENCE   9  (bases 1 to 1505)
  AUTHORS   Kauppinen,R., Peltonen,L., Pihlaja,H. and Mustajoki,P.
  TITLE     CRIM-positive mutations of acute intermittent porphyria in Finland
  JOURNAL   Hum Mutat 1 (5), 392-396 (1992)
   PUBMED   1301948
REFERENCE   10 (bases 1 to 1505)
  AUTHORS   Delfau,M.H., Picat,C., De Rooij,F., Voortman,G., Deybach,J.C.,
            Nordmann,Y. and Grandchamp,B.
  TITLE     Molecular heterogeneity of acute intermittent porphyria:
            identification of four additional mutations resulting in the
            CRIM-negative subtype of the disease
  JOURNAL   Am J Hum Genet 49 (2), 421-428 (1991)
   PUBMED   1714233
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from CB128006.1, BC019323.1 and
            AW139390.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Aug 13, 2018 this sequence version replaced NM_000190.3.
            
            Summary: This gene encodes a member of the hydroxymethylbilane
            synthase superfamily. The encoded protein is the third enzyme of
            the heme biosynthetic pathway and catalyzes the head to tail
            condensation of four porphobilinogen molecules into the linear
            hydroxymethylbilane. Mutations in this gene are associated with the
            autosomal dominant disease acute intermittent porphyria.
            Alternatively spliced transcript variants encoding different
            isoforms have been described. [provided by RefSeq, Jul 2008].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer 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 :: AK290275.1, SRR1163655.660423.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000652429.1/ ENSP00000498786.1
            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
            1-2                 CB128006.1         16-17
            3-1503              BC019323.1         1-1501
            1504-1505           AW139390.1         18-19               c
FEATURES             Location/Qualifiers
     source          1..1505
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="11"
                     /map="11q23.3"
     gene            1..1505
                     /gene="HMBS"
                     /gene_synonym="ENCEP; LENCEP; PBG-D; PBGD; PORC; UPS"
                     /note="hydroxymethylbilane synthase"
                     /db_xref="GeneID:3145"
                     /db_xref="HGNC:HGNC:4982"
                     /db_xref="MIM:609806"
     exon            1..186
                     /gene="HMBS"
                     /gene_synonym="ENCEP; LENCEP; PBG-D; PBGD; PORC; UPS"
                     /inference="alignment:Splign:2.1.0"
     CDS             154..1239
                     /gene="HMBS"
                     /gene_synonym="ENCEP; LENCEP; PBG-D; PBGD; PORC; UPS"
                     /EC_number="2.5.1.61"
                     /note="isoform 1 is encoded by transcript variant 1;
                     porphyria, acute; Chester type; pre-uroporphyrinogen
                     synthase; uroporphyrinogen I synthase; uroporphyrinogen I
                     synthetase; porphobilinogen deaminase"
                     /codon_start=1
                     /product="porphobilinogen deaminase isoform 1"
                     /protein_id="NP_000181.2"
                     /db_xref="CCDS:CCDS8409.1"
                     /db_xref="GeneID:3145"
                     /db_xref="HGNC:HGNC:4982"
                     /db_xref="MIM:609806"
                     /translation="MSGNGNAAATAEENSPKMRVIRVGTRKSQLARIQTDSVVATLKA
                     SYPGLQFEIIAMSTTGDKILDTALSKIGEKSLFTKELEHALEKNEVDLVVHSLKDLPT
                     VLPPGFTIGAICKRENPHDAVVFHPKFVGKTLETLPEKSVVGTSSLRRAAQLQRKFPH
                     LEFRSIRGNLNTRLRKLDEQQEFSAIILATAGLQRMGWHNRVGQILHPEECMYAVGQG
                     ALGVEVRAKDQDILDLVGVLHDPETLLRCIAERAFLRHLEGGCSVPVAVHTAMKDGQL
                     YLTGGVWSLDGSDSIQETMQATIHVPAQHEDGPEDDPQLVGITARNIPRGPQLAAQNL
                     GISLANLLLSKGAKNILDVARQLNDAH"
     exon            187..240
                     /gene="HMBS"
                     /gene_synonym="ENCEP; LENCEP; PBG-D; PBGD; PORC; UPS"
                     /inference="alignment:Splign:2.1.0"
     exon            241..313
                     /gene="HMBS"
                     /gene_synonym="ENCEP; LENCEP; PBG-D; PBGD; PORC; UPS"
                     /inference="alignment:Splign:2.1.0"
     exon            314..363
                     /gene="HMBS"
                     /gene_synonym="ENCEP; LENCEP; PBG-D; PBGD; PORC; UPS"
                     /inference="alignment:Splign:2.1.0"
     exon            364..419
                     /gene="HMBS"
                     /gene_synonym="ENCEP; LENCEP; PBG-D; PBGD; PORC; UPS"
                     /inference="alignment:Splign:2.1.0"
     exon            420..497
                     /gene="HMBS"
                     /gene_synonym="ENCEP; LENCEP; PBG-D; PBGD; PORC; UPS"
                     /inference="alignment:Splign:2.1.0"
     exon            498..575
                     /gene="HMBS"
                     /gene_synonym="ENCEP; LENCEP; PBG-D; PBGD; PORC; UPS"
                     /inference="alignment:Splign:2.1.0"
     exon            576..651
                     /gene="HMBS"
                     /gene_synonym="ENCEP; LENCEP; PBG-D; PBGD; PORC; UPS"
                     /inference="alignment:Splign:2.1.0"
     exon            652..765
                     /gene="HMBS"
                     /gene_synonym="ENCEP; LENCEP; PBG-D; PBGD; PORC; UPS"
                     /inference="alignment:Splign:2.1.0"
     exon            766..804
                     /gene="HMBS"
                     /gene_synonym="ENCEP; LENCEP; PBG-D; PBGD; PORC; UPS"
                     /inference="alignment:Splign:2.1.0"
     exon            805..924
                     /gene="HMBS"
                     /gene_synonym="ENCEP; LENCEP; PBG-D; PBGD; PORC; UPS"
                     /inference="alignment:Splign:2.1.0"
     exon            925..978
                     /gene="HMBS"
                     /gene_synonym="ENCEP; LENCEP; PBG-D; PBGD; PORC; UPS"
                     /inference="alignment:Splign:2.1.0"
     exon            979..1065
                     /gene="HMBS"
                     /gene_synonym="ENCEP; LENCEP; PBG-D; PBGD; PORC; UPS"
                     /inference="alignment:Splign:2.1.0"
     exon            1066..1505
                     /gene="HMBS"
                     /gene_synonym="ENCEP; LENCEP; PBG-D; PBGD; PORC; UPS"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1484..1489
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HMBS"
                     /gene_synonym="ENCEP; LENCEP; PBG-D; PBGD; PORC; UPS"
                     /note="hexamer: AATAAA"
     polyA_site      1504
                     /gene="HMBS"
                     /gene_synonym="ENCEP; LENCEP; PBG-D; PBGD; PORC; UPS"
                     /note="major polyA site"
ORIGIN      
        1 aagtgacgcg aggctctgcg gagaccagga gtcagactgt aggacgacct cgggtcccac
       61 gtgtccccgg tactcgccgg ccggagcccc cggcttcccg gggccggggg accttagcgg
      121 cacccacaca cagcctactt tccaagcgga gccatgtctg gtaacggcaa tgcggctgca
      181 acggcggaag aaaacagccc aaagatgaga gtgattcgcg tgggtacccg caagagccag
      241 cttgctcgca tacagacgga cagtgtggtg gcaacattga aagcctcgta ccctggcctg
      301 cagtttgaaa tcattgctat gtccaccaca ggggacaaga ttcttgatac tgcactctct
      361 aagattggag agaaaagcct gtttaccaag gagcttgaac atgccctgga gaagaatgaa
      421 gtggacctgg ttgttcactc cttgaaggac ctgcccactg tgcttcctcc tggcttcacc
      481 atcggagcca tctgcaagcg ggaaaaccct catgatgctg ttgtctttca cccaaaattt
      541 gttgggaaga ccctagaaac cctgccagag aagagtgtgg tgggaaccag ctccctgcga
      601 agagcagccc agctgcagag aaagttcccg catctggagt tcaggagtat tcggggaaac
      661 ctcaacaccc ggcttcggaa gctggacgag cagcaggagt tcagtgccat catcctggca
      721 acagctggcc tgcagcgcat gggctggcac aaccgggtgg ggcagatcct gcaccctgag
      781 gaatgcatgt atgctgtggg ccagggggcc ttgggcgtgg aagtgcgagc caaggaccag
      841 gacatcttgg atctggtggg tgtgctgcac gatcccgaga ctctgcttcg ctgcatcgct
      901 gaaagggcct tcctgaggca cctggaagga ggctgcagtg tgccagtagc cgtgcataca
      961 gctatgaagg atgggcaact gtacctgact ggaggagtct ggagtctaga cggctcagat
     1021 agcatacaag agaccatgca ggctaccatc catgtccctg cccagcatga agatggccct
     1081 gaggatgacc cacagttggt aggcatcact gctcgtaaca ttccacgagg gccccagttg
     1141 gctgcccaga acttgggcat cagcctggcc aacttgttgc tgagcaaagg agccaaaaac
     1201 atcctggatg ttgcacggca gcttaacgat gcccattaac tggtttgtgg ggcacagatg
     1261 cctgggttgc tgctgtccag tgcctacatc ccgggcctca gtgccccatt ctcactgcta
     1321 tctggggagt gattaccccg ggagactgaa ctgcagggtt caagccttcc agggatttgc
     1381 ctcaccttgg ggccttgatg actgccttgc ctcctcagta tgtgggggct tcatctcttt
     1441 agagaagtcc aagcaacagc ctttgaatgt aaccaatcct actaataaac cagttctgaa
     1501 ggtgt
//
