LOCUS       NM_019863               2616 bp    mRNA    linear   PRI 13-OCT-2024
DEFINITION  Homo sapiens coagulation factor VIII (F8), transcript variant 2,
            mRNA.
ACCESSION   NM_019863
VERSION     NM_019863.3
KEYWORDS    RefSeq.
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 2616)
  AUTHORS   de Vries,P.S., Reventun,P., Brown,M.R., Heath,A.S., Huffman,J.E.,
            Le,N.Q., Bebo,A., Brody,J.A., Temprano-Sagrera,G., Raffield,L.M.,
            Ozel,A.B., Thibord,F., Jain,D., Lewis,J.P., Rodriguez,B.A.T.,
            Pankratz,N., Taylor,K.D., Polasek,O., Chen,M.H., Yanek,L.R.,
            Carrasquilla,G.D., Marioni,R.E., Kleber,M.E., Tregouet,D.A.,
            Yao,J., Li-Gao,R., Joshi,P.K., Trompet,S., Martinez-Perez,A.,
            Ghanbari,M., Howard,T.E., Reiner,A.P., Arvanitis,M., Ryan,K.A.,
            Bartz,T.M., Rudan,I., Faraday,N., Linneberg,A., Ekunwe,L.,
            Davies,G., Delgado,G.E., Suchon,P., Guo,X., Rosendaal,F.R.,
            Klaric,L., Noordam,R., van Rooij,F., Curran,J.E., Wheeler,M.M.,
            Osburn,W.O., O'Connell,J.R., Boerwinkle,E., Beswick,A., Psaty,B.M.,
            Kolcic,I., Souto,J.C., Becker,L.C., Hansen,T., Doyle,M.F.,
            Harris,S.E., Moissl,A.P., Deleuze,J.F., Rich,S.S., van Hylckama
            Vlieg,A., Campbell,H., Stott,D.J., Soria,J.M., de Maat,M.P.M.,
            Almasy,L., Brody,L.C., Auer,P.L., Mitchell,B.D., Ben-Shlomo,Y.,
            Fornage,M., Hayward,C., Mathias,R.A., Kilpelainen,T.O., Lange,L.A.,
            Cox,S.R., Marz,W., Morange,P.E., Rotter,J.I., Mook-Kanamori,D.O.,
            Wilson,J.F., van der Harst,P., Jukema,J.W., Ikram,M.A.,
            Blangero,J., Kooperberg,C., Desch,K.C., Johnson,A.D.,
            Sabater-Lleal,M., Lowenstein,C.J., Smith,N.L. and Morrison,A.C.
  TITLE     A genetic association study of circulating coagulation factor VIII
            and von Willebrand factor levels
  JOURNAL   Blood 143 (18), 1845-1855 (2024)
   PUBMED   38320121
  REMARK    GeneRIF: A genetic association study of circulating coagulation
            factor VIII and von Willebrand factor levels.
REFERENCE   2  (bases 1 to 2616)
  AUTHORS   Hopp,M.T., Ugurlar,D., Pezeshkpoor,B., Biswas,A., Ramoji,A.,
            Neugebauer,U., Oldenburg,J. and Imhof,D.
  TITLE     In-depth structure-function profiling of the complex formation
            between clotting factor VIII and heme
  JOURNAL   Thromb Res 237, 184-195 (2024)
   PUBMED   38631156
  REMARK    GeneRIF: In-depth structure-function profiling of the complex
            formation between clotting factor VIII and heme.
REFERENCE   3  (bases 1 to 2616)
  AUTHORS   Symington,E., Rangarajan,S., Lester,W., Madan,B., Pierce,G.F.,
            Raheja,P., Robinson,T.M., Osmond,D., Russell,C.B., Vettermann,C.,
            Agarwal,S.K., Li,M., Wong,W.Y. and Laffan,M.
  TITLE     Long-term safety and efficacy outcomes of valoctocogene
            roxaparvovec gene transfer up to 6 years post-treatment
  JOURNAL   Haemophilia 30 (2), 320-330 (2024)
   PUBMED   38317480
  REMARK    GeneRIF: Long-term safety and efficacy outcomes of valoctocogene
            roxaparvovec gene transfer up to 6 years post-treatment.
REFERENCE   4  (bases 1 to 2616)
  AUTHORS   Tse,V., Chacaltana,G., Gutierrez,M., Forino,N.M., Jimenez,A.G.,
            Tao,H., Do,P.H., Oh,C., Chary,P., Quesada,I., Hamrick,A., Lee,S.,
            Stone,M.D. and Sanford,J.R.
  TITLE     An intronic RNA element modulates Factor VIII exon-16 splicing
  JOURNAL   Nucleic Acids Res 52 (1), 300-315 (2024)
   PUBMED   37962303
  REMARK    GeneRIF: An intronic RNA element modulates Factor VIII exon-16
            splicing.
REFERENCE   5  (bases 1 to 2616)
  AUTHORS   Nakajima,Y. and Nogami,K.
  TITLE     The role of proteolytic cleavage at Arg336 and Arg372 of the A1
            domain in factor VIIa/tissue factor-catalyzed reactions of B
            domain-deleted factor VIII
  JOURNAL   Biochim Biophys Acta Gen Subj 1868 (1), 130501 (2024)
   PUBMED   37925034
  REMARK    GeneRIF: The role of proteolytic cleavage at Arg[336] and Arg[372]
            of the A1 domain in factor VIIa/tissue factor-catalyzed reactions
            of B domain-deleted factor VIII.
REFERENCE   6  (bases 1 to 2616)
  AUTHORS   Konkle,B.A. and Nakaya Fletcher,S.
  TITLE     Hemophilia A
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301578
REFERENCE   7  (bases 1 to 2616)
  AUTHORS   Jonsdottir,S., Diamond,C., Levinson,B., Magnusson,S., Jensson,O.
            and Gitschier,J.
  TITLE     Missense mutations causing mild hemophilia A in Iceland detected by
            denaturing gradient gel electrophoresis
  JOURNAL   Hum Mutat 1 (6), 506-508 (1992)
   PUBMED   1301960
REFERENCE   8  (bases 1 to 2616)
  AUTHORS   Diamond,C., Kogan,S., Levinson,B. and Gitschier,J.
  TITLE     Amino acid substitutions in conserved domains of factor VIII and
            related proteins: study of patients with mild and moderately severe
            hemophilia A
  JOURNAL   Hum Mutat 1 (3), 248-257 (1992)
   PUBMED   1301932
REFERENCE   9  (bases 1 to 2616)
  AUTHORS   Nafa,K., Baudis,M., Deburgrave,N., Bardin,J.M., Sultan,Y.,
            Kaplan,J.C. and Delpech,M.
  TITLE     A novel mutation (Arg-->Leu in exon 18) in factor VIII gene
            responsible for moderate hemophilia A
  JOURNAL   Hum Mutat 1 (1), 77-78 (1992)
   PUBMED   1301194
REFERENCE   10 (bases 1 to 2616)
  AUTHORS   Zucker,M.B., Broekman,M.J. and Kaplan,K.L.
  TITLE     Factor VIII-related antigen in human blood platelets: localization
            and release by thrombin and collagen
  JOURNAL   J Lab Clin Med 94 (5), 675-682 (1979)
   PUBMED   501196
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BX842559.3 and AC109993.4.
            
            On Aug 14, 2020 this sequence version replaced NM_019863.2.
            
            Summary: This gene encodes coagulation factor VIII, which
            participates in the intrinsic pathway of blood coagulation; factor
            VIII is a cofactor for factor IXa which, in the presence of Ca+2
            and phospholipids, converts factor X to the activated form Xa.
            This gene produces two alternatively spliced transcripts.
            Transcript variant 1 encodes a large glycoprotein, isoform a, which
            circulates in plasma and associates with von Willebrand factor in a
            noncovalent complex. This protein undergoes multiple cleavage
            events. Transcript variant 2 encodes a putative small protein,
            isoform b, which consists primarily of the phospholipid binding
            domain of factor VIIIc. This binding domain is essential for
            coagulant activity. Defects in this gene results in hemophilia A, a
            common recessive X-linked coagulation disorder. [provided by
            RefSeq, Jul 2008].
            
            Transcript Variant: This variant (2) contains an unique 5' exon
            located within intron 22 of transcript variant 1. This exon codes
            for eight amino acids and is spliced to exons 23-26 maintaining the
            reading frame. The resulting isoform (b) is considerably shorter
            compared to isoform a, and includes the phospholipid binding
            domain.
            
            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 :: BC064380.1, M90707.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1968540
                                           [ECO:0000348]
            ##Evidence-Data-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-184               BX842559.3         23618-23801         c
            185-329             AC109993.4         177066-177210       c
            330-478             AC109993.4         175701-175849       c
            479-655             AC109993.4         174415-174591       c
            656-2616            AC109993.4         149775-151735       c
FEATURES             Location/Qualifiers
     source          1..2616
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="X"
                     /map="Xq28"
     gene            1..2616
                     /gene="F8"
                     /gene_synonym="AHF; DXS1253E; F8B; F8C; FVIII; HEMA;
                     THPH13"
                     /note="coagulation factor VIII"
                     /db_xref="GeneID:2157"
                     /db_xref="HGNC:HGNC:3546"
                     /db_xref="MIM:300841"
     exon            1..184
                     /gene="F8"
                     /gene_synonym="AHF; DXS1253E; F8B; F8C; FVIII; HEMA;
                     THPH13"
                     /inference="alignment:Splign:2.1.0"
     CDS             161..811
                     /gene="F8"
                     /gene_synonym="AHF; DXS1253E; F8B; F8C; FVIII; HEMA;
                     THPH13"
                     /note="isoform b is encoded by transcript variant 2;
                     factor VIII F8B; coagulation factor VIIIc; antihemophilic
                     factor; coagulation factor VIII, procoagulant component;
                     coagulation factor VIII C2 domain; coagulation factor VIII
                     A1 domain"
                     /codon_start=1
                     /product="coagulation factor VIII isoform b"
                     /protein_id="NP_063916.1"
                     /db_xref="CCDS:CCDS44026.1"
                     /db_xref="GeneID:2157"
                     /db_xref="HGNC:HGNC:3546"
                     /db_xref="MIM:300841"
                     /translation="MRIQDPGKVFFGNVDSSGIKHNIFNPPIIARYIRLHPTHYSIRS
                     TLRMELMGCDLNSCSMPLGMESKAISDAQITASSYFTNMFATWSPSKARLHLQGRSNA
                     WRPQVNNPKEWLQVDFQKTMKVTGVTTQGVKSLLTSMYVKEFLISSSQDGHQWTLFFQ
                     NGKVKVFQGNQDSFTPVVNSLDPPLLTRYLRIHPQSWVHQIALRMEVLGCEAQDLY"
     exon            185..329
                     /gene="F8"
                     /gene_synonym="AHF; DXS1253E; F8B; F8C; FVIII; HEMA;
                     THPH13"
                     /inference="alignment:Splign:2.1.0"
     exon            330..478
                     /gene="F8"
                     /gene_synonym="AHF; DXS1253E; F8B; F8C; FVIII; HEMA;
                     THPH13"
                     /inference="alignment:Splign:2.1.0"
     exon            479..655
                     /gene="F8"
                     /gene_synonym="AHF; DXS1253E; F8B; F8C; FVIII; HEMA;
                     THPH13"
                     /inference="alignment:Splign:2.1.0"
     exon            656..2616
                     /gene="F8"
                     /gene_synonym="AHF; DXS1253E; F8B; F8C; FVIII; HEMA;
                     THPH13"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2594..2599
                     /regulatory_class="polyA_signal_sequence"
                     /gene="F8"
                     /gene_synonym="AHF; DXS1253E; F8B; F8C; FVIII; HEMA;
                     THPH13"
                     /note="hexamer: AATAAA"
     polyA_site      2616
                     /gene="F8"
                     /gene_synonym="AHF; DXS1253E; F8B; F8C; FVIII; HEMA;
                     THPH13"
                     /note="major polyA site"
ORIGIN      
        1 ggggcgacgt gccctgcgtc cccctcggcg ggctgccgcc gtgcccgcgc cggctcccca
       61 gcccgagcct gccccttgcc ctgatgaggt gcaaagagcg ggatcggagg cggggcctgg
      121 ccgggctgtg agcggcgtat gcaaatcgag ggtctcgggg atgcggatcc aagaccctgg
      181 gaaggtcttc tttggcaatg tggattcatc tgggataaaa cacaatattt ttaaccctcc
      241 aattattgct cgatacatcc gtttgcaccc aactcattat agcattcgca gcactcttcg
      301 catggagttg atgggctgtg atttaaatag ttgcagcatg ccattgggaa tggagagtaa
      361 agcaatatca gatgcacaga ttactgcttc atcctacttt accaatatgt ttgccacctg
      421 gtctccttca aaagctcgac ttcacctcca agggaggagt aatgcctgga gacctcaggt
      481 gaataatcca aaagagtggc tgcaagtgga cttccagaag acaatgaaag tcacaggagt
      541 aactactcag ggagtaaaat ctctgcttac cagcatgtat gtgaaggagt tcctcatctc
      601 cagcagtcaa gatggccatc agtggactct cttttttcag aatggcaaag taaaggtttt
      661 tcagggaaat caagactcct tcacacctgt ggtgaactct ctagacccac cgttactgac
      721 tcgctacctt cgaattcacc cccagagttg ggtgcaccag attgccctga ggatggaggt
      781 tctgggctgc gaggcacagg acctctactg agggtggcca ctgcagcacc tgccactgcc
      841 gtcacctctc cctcctcagc tccagggcag tgtccctccc tggcttgcct tctacctttg
      901 tgctaaatcc tagcagacac tgccttgaag cctcctgaat taactatcat cagtcctgca
      961 tttctttggt ggggggccag gagggtgcat ccaatttaac ttaactctta cctattttct
     1021 gcagctgctc ccagattact ccttccttcc aatataacta ggcaaaaaga agtgaggaga
     1081 aacctgcatg aaagcattct tccctgaaaa gttaggcctc tcagagtcac cacttcctct
     1141 gttgtagaaa aactatgtga tgaaactttg aaaaagatat ttatgatgtt aacatttcag
     1201 gttaagcctc atacgtttaa aataaaactc tcagttgttt attatcctga tcaagcatgg
     1261 aacaaagcat gtttcaggat cagatcaata caatcttgga gtcaaaaggc aaatcatttg
     1321 gacaatctgc aaaatggaga gaatacaata actactacag taaagtctgt ttctgcttcc
     1381 ttacacatag atataattat gttatttagt cattatgagg ggcacattct tatctccaaa
     1441 actagcattc ttaaactgag aattatagat ggggttcaag aatccctaag tcccctgaaa
     1501 ttatataagg cattctgtat aaatgcaaat gtgcattttt ctgacgagtg tccatagata
     1561 taaagccatt tggtcttaat tctgaccaat aaaaaaataa gtcaggagga tgcaattgtt
     1621 gaaagctttg aaataaaata acaatgtctt cttgaaattt gtgatggcca agaaagaaaa
     1681 tgatgatgac attaggcttc taaaggacat acatttaata tttctgtgga aatatgagga
     1741 aaatccatgg ttatctgaga taggagatac aaactttgta attctaataa tgcactcagt
     1801 ttactctctc cctctactaa tttcctgctg aaaataacac aacaaaaatg taacagggga
     1861 aattatatac cgtgactgaa aactagagtc ctacttacat agttgaaata tcaaggaggt
     1921 cagaagaaaa ttggactggt gaaaacagaa aaaacactcc agtctgccat atcaccacac
     1981 aataggatcc cccttcttgc cctccacccc cataagattg tgaagggttt actgctcctt
     2041 ccatctgcct gaccccttca ctatgactac acagaatctc ctgatagtaa agggggctgg
     2101 agacaaggat aagttataga gcagttggag gaagcatcca aagattgcaa cccagggcaa
     2161 atggaaaaca ggagatccta atatgaaaga aaaatggatc ccaatctgag aaaaggcaaa
     2221 agaatggcta cttttttcta tgctggagta ttttctaata atcctgcttg acccttatct
     2281 gacctctttg gaaactataa catagctgtc acagtatagt cacaatccac aaatgatgca
     2341 ggtgcaaatg gtttatagcc ctgtgaagtt cttaaagttt agaggctaac ttacagaaat
     2401 gaataagttg ttttgtttta tagcccggta gaggagttaa ccccaaaggt gatatggttt
     2461 tatttcctgt tatgtttaac ttgataatct tattttggca ttcttttccc attgactata
     2521 tacatctcta tttctcaaat gttcatggaa ctagctcttt tattttcctg ctggtttctt
     2581 cagtaatgag ttaaataaaa cattgacaca tacaaa
//
