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Gene Review

F8A1  -  coagulation factor VIII-associated 1

Homo sapiens

Synonyms: DXS522E, F8A, HAP40
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Disease relevance of F8A1


Psychiatry related information on F8A1


High impact information on F8A1


Chemical compound and disease context of F8A1


Biological context of F8A1

  • P&Q is specific for 5' and 3' flanking regions of F8A1 respectively [17].
  • HAP40 is encoded by the open reading frame factor VIII-associated gene A (F8A) located within intron 22 of the factor VIII gene [6].
  • In this study, we have identified Htt-associated protein 40 (HAP40) as a novel effector of the small guanosine triphosphatase Rab5, a key regulator of endocytosis [18].
  • A region of intron 22 of the factor VIII gene, which contains factor VIII-associated gene A (F8A), is repeated twice more nearer the Xq telomere [19].
  • The observed heterozygosity for the flanking marker DXS 52 (TaqI/St14 RFLP) in combination with intragenic BclI/F8A polymorphism was 0.94 [20].

Anatomical context of F8A1

  • Remarkably, endogenous HAP40 was up-regulated in fibroblasts and brain tissue from human patients affected by Huntington's disease (HD) as well as in STHdhQ(111) striatal cells established from a HD mouse model [18].
  • These cells consistently displayed altered endosome motility and endocytic activity, which was restored by the ablation of HAP40 [18].
  • HAP40 overexpression caused a drastic reduction of early endosomal motility through their displacement from microtubules and preferential association with actin filaments [18].
  • We identified aberrant methylation in the CpG island of SOCS-1 that correlated with its transcription silencing in HCC cell lines [21].
  • We report that CpG island methylation, an epigenetic modification of DNA known to correlate closely with silencing of gene transcription, appears in the oestrogen receptor (ER) gene in a subpopulation of cells which increases as a direct function of age in human colonic mucosa [22].

Associations of F8A1 with chemical compounds


Physical interactions of F8A1


Enzymatic interactions of F8A1


Regulatory relationships of F8A1


Other interactions of F8A1

  • We investigated the presence of a recombinant event between the F8A gene located in intron 22 of the factor VIII gene and the two additional copies of F8A lying 500 Kb upstream of FVIII in severe hemophilic patients [1].
  • The higher expression of firefly luciferase in the embryonal F9 cells by the use of SCA2 promoter, rather than by the use of CMV promoter may be related with the origin of the nonmethylated CpG island during the early embryogenesis [41].
  • A lod score of 3.61 (theta = 0) was obtained with multipoint linkage analysis of F8A and DXS15 [42].
  • These results indicate that DNMT1 is necessary and sufficient to maintain global methylation and aberrant CpG island methylation in human cancer cells [43].
  • The most studied change of DNA methylation in neoplasms is the silencing of tumor suppressor genes by CpG island promoter hypermethylation, which targets genes such as p16(INK4a), BRCA1, and hMLH1 [44].

Analytical, diagnostic and therapeutic context of F8A1

  • DNA from HeA patients and related at-risk women has been analyzed by Southern blotting with two probes: the intragenic F8A and the extragenic St14 [20].
  • The results obtained from a comparative analysis between phenotypic bioassays as the ratio of factor VIII: C clotting activity to factor VIII: C-related antigen, and DNA haplotypes from RFLP's TaqI/St14 and BclI/F8A in 12 hemophilia A (HeA) families are described [20].
  • Here we report the use of RNA expression arrays and CpG-island DNA arrays to identify and characterize human PRC2/3 target genes [45].
  • Isolating human transcription factor targets by coupling chromatin immunoprecipitation and CpG island microarray analysis [46].
  • We describe a new method, MSP (methylation-specific PCR), which can rapidly assess the methylation status of virtually any group of CpG sites within a CpG island, independent of the use of methylation-sensitive restriction enzymes [47].


  1. Inversion mutation as a major cause of severe hemophilia A in Italian patients. Mori, P.G., Caprino, D., Bicocchi, M.P., Valetto, A., Bottini, F., Aquila, M. Haematologica (1997) [Pubmed]
  2. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Weisenberger, D.J., Siegmund, K.D., Campan, M., Young, J., Long, T.I., Faasse, M.A., Kang, G.H., Widschwendter, M., Weener, D., Buchanan, D., Koh, H., Simms, L., Barker, M., Leggett, B., Levine, J., Kim, M., French, A.J., Thibodeau, S.N., Jass, J., Haile, R., Laird, P.W. Nat. Genet. (2006) [Pubmed]
  3. CpG island hypermethylation is maintained in human colorectal cancer cells after RNAi-mediated depletion of DNMT1. Ting, A.H., Jair, K.W., Suzuki, H., Yen, R.W., Baylin, S.B., Schuebel, K.E. Nat. Genet. (2004) [Pubmed]
  4. The full mutation in the FMR-1 gene of male fragile X patients is absent in their sperm. Reyniers, E., Vits, L., De Boulle, K., Van Roy, B., Van Velzen, D., de Graaff, E., Verkerk, A.J., Jorens, H.Z., Darby, J.K., Oostra, B. Nat. Genet. (1993) [Pubmed]
  5. Pathological and molecular aspects of prostate cancer. DeMarzo, A.M., Nelson, W.G., Isaacs, W.B., Epstein, J.I. Lancet (2003) [Pubmed]
  6. Isolation of a 40-kDa Huntingtin-associated protein. Peters, M.F., Ross, C.A. J. Biol. Chem. (2001) [Pubmed]
  7. Trinucleotide repeat amplification and hypermethylation of a CpG island in FRAXE mental retardation. Knight, S.J., Flannery, A.V., Hirst, M.C., Campbell, L., Christodoulou, Z., Phelps, S.R., Pointon, J., Middleton-Price, H.R., Barnicoat, A., Pembrey, M.E. Cell (1993) [Pubmed]
  8. Transcription of tissue-specific genes in human preimplantation embryos. Daniels, R., Lowell, S., Bolton, V., Monk, M. Hum. Reprod. (1997) [Pubmed]
  9. Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Weber, M., Hellmann, I., Stadler, M.B., Ramos, L., Pääbo, S., Rebhan, M., Schübeler, D. Nat. Genet. (2007) [Pubmed]
  10. A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing. Ohm, J.E., McGarvey, K.M., Yu, X., Cheng, L., Schuebel, K.E., Cope, L., Mohammad, H.P., Chen, W., Daniel, V.C., Yu, W., Berman, D.M., Jenuwein, T., Pruitt, K., Sharkis, S.J., Watkins, D.N., Herman, J.G., Baylin, S.B. Nat. Genet. (2007) [Pubmed]
  11. Evidence for an instructive mechanism of de novo methylation in cancer cells. Keshet, I., Schlesinger, Y., Farkash, S., Rand, E., Hecht, M., Segal, E., Pikarski, E., Young, R.A., Niveleau, A., Cedar, H., Simon, I. Nat. Genet. (2006) [Pubmed]
  12. A point mutation in the FMR-1 gene associated with fragile X mental retardation. De Boulle, K., Verkerk, A.J., Reyniers, E., Vits, L., Hendrickx, J., Van Roy, B., Van den Bos, F., de Graaff, E., Oostra, B.A., Willems, P.J. Nat. Genet. (1993) [Pubmed]
  13. MYO18B, a candidate tumor suppressor gene at chromosome 22q12.1, deleted, mutated, and methylated in human lung cancer. Nishioka, M., Kohno, T., Tani, M., Yanaihara, N., Tomizawa, Y., Otsuka, A., Sasaki, S., Kobayashi, K., Niki, T., Maeshima, A., Sekido, Y., Minna, J.D., Sone, S., Yokota, J. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  14. Transcriptional silencing of Polo-like kinase 2 (SNK/PLK2) is a frequent event in B-cell malignancies. Syed, N., Smith, P., Sullivan, A., Spender, L.C., Dyer, M., Karran, L., O'Nions, J., Allday, M., Hoffmann, I., Crawford, D., Griffin, B., Farrell, P.J., Crook, T. Blood (2006) [Pubmed]
  15. p15(INK4B) CpG island methylation in primary acute leukemia is heterogeneous and suggests density as a critical factor for transcriptional silencing. Cameron, E.E., Baylin, S.B., Herman, J.G. Blood (1999) [Pubmed]
  16. Shared epigenetic mechanisms in human and mouse gliomas inactivate expression of the growth suppressor SLC5A8. Hong, C., Maunakea, A., Jun, P., Bollen, A.W., Hodgson, J.G., Goldenberg, D.D., Weiss, W.A., Costello, J.F. Cancer Res. (2005) [Pubmed]
  17. PCR assay for the inversion causing severe Hemophilia A and its application. Liu, J., Liu, Q., Liang, Y., Wang, L., Nozary, G., Xiao, B., Zhu, Z., Zhou, Y., Liu, L., Guan, Y., Zhang, J., Sommer, S.S. Chin. Med. J. (1999) [Pubmed]
  18. Huntingtin-HAP40 complex is a novel Rab5 effector that regulates early endosome motility and is up-regulated in Huntington's disease. Pal, A., Severin, F., Lommer, B., Shevchenko, A., Zerial, M. J. Cell Biol. (2006) [Pubmed]
  19. Investigation of the factor VIII intron 22 repeated region (int22h) and the associated inversion junctions. Naylor, J.A., Buck, D., Green, P., Williamson, H., Bentley, D., Giannelli, F. Hum. Mol. Genet. (1995) [Pubmed]
  20. Carrier detection for prenatal diagnosis of hemophilia A in Italian families. Cappello, N., Restagno, G., Garnerone, S., Gennaro, C., Perugini, L., Rendine, S., Piazza, A., Carbonara, A. Haematologica (1992) [Pubmed]
  21. SOCS-1, a negative regulator of the JAK/STAT pathway, is silenced by methylation in human hepatocellular carcinoma and shows growth-suppression activity. Yoshikawa, H., Matsubara, K., Qian, G.S., Jackson, P., Groopman, J.D., Manning, J.E., Harris, C.C., Herman, J.G. Nat. Genet. (2001) [Pubmed]
  22. Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon. Issa, J.P., Ottaviano, Y.L., Celano, P., Hamilton, S.R., Davidson, N.E., Baylin, S.B. Nat. Genet. (1994) [Pubmed]
  23. Evidence for a third transcript from the human factor VIII gene. Levinson, B., Kenwrick, S., Gamel, P., Fisher, K., Gitschier, J. Genomics (1992) [Pubmed]
  24. Disruption of the Fanconi anemia-BRCA pathway in cisplatin-sensitive ovarian tumors. Taniguchi, T., Tischkowitz, M., Ameziane, N., Hodgson, S.V., Mathew, C.G., Joenje, H., Mok, S.C., D'Andrea, A.D. Nat. Med. (2003) [Pubmed]
  25. Instability of a 550-base pair DNA segment and abnormal methylation in fragile X syndrome. Oberlé, I., Rousseau, F., Heitz, D., Kretz, C., Devys, D., Hanauer, A., Boué, J., Bertheas, M.F., Mandel, J.L. Science (1991) [Pubmed]
  26. Dynamic DNA methylation change in the CpG island region of p15 during human myeloid development. Sakashita, K., Koike, K., Kinoshita, T., Shiohara, M., Kamijo, T., Taniguchi, S., Kubota, T. J. Clin. Invest. (2001) [Pubmed]
  27. HPP1: a transmembrane protein-encoding gene commonly methylated in colorectal polyps and cancers. Young, J., Biden, K.G., Simms, L.A., Huggard, P., Karamatic, R., Eyre, H.J., Sutherland, G.R., Herath, N., Barker, M., Anderson, G.J., Fitzpatrick, D.R., Ramm, G.A., Jass, J.R., Leggett, B.A. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  28. Tandem arrangement of human genes for interleukin-4 and interleukin-13: resemblance in their organization. Smirnov, D.V., Smirnova, M.G., Korobko, V.G., Frolova, E.I. Gene (1995) [Pubmed]
  29. Elevated mRNA levels of DNA methyltransferase-1 as an independent prognostic factor in primary nonsmall cell lung cancer. Kim, H., Kwon, Y.M., Kim, J.S., Han, J., Shim, Y.M., Park, J., Kim, D.H. Cancer (2006) [Pubmed]
  30. Differentiation and injury-repair signals modulate the interaction of E2F and pRB proteins with novel target genes in keratinocytes. Chang, W.Y., Andrews, J., Carter, D.E., Dagnino, L. Cell Cycle (2006) [Pubmed]
  31. The endothelin receptor B (EDNRB) promoter displays heterogeneous, site specific methylation patterns in normal and tumor cells. Pao, M.M., Tsutsumi, M., Liang, G., Uzvolgyi, E., Gonzales, F.A., Jones, P.A. Hum. Mol. Genet. (2001) [Pubmed]
  32. De novo CpG island methylation in human cancer cells. Jair, K.W., Bachman, K.E., Suzuki, H., Ting, A.H., Rhee, I., Yen, R.W., Baylin, S.B., Schuebel, K.E. Cancer Res. (2006) [Pubmed]
  33. Hypomethylation of the synuclein gamma gene CpG island promotes its aberrant expression in breast carcinoma and ovarian carcinoma. Gupta, A., Godwin, A.K., Vanderveer, L., Lu, A., Liu, J. Cancer Res. (2003) [Pubmed]
  34. 5-Azacytidine-induced reactivation of the human X chromosome-linked PGK1 gene is associated with a large region of cytosine demethylation in the 5' CpG island. Hansen, R.S., Gartler, S.M. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  35. Methylation of the HIC-1 candidate tumor suppressor gene in human breast cancer. Fujii, H., Biel, M.A., Zhou, W., Weitzman, S.A., Baylin, S.B., Gabrielson, E. Oncogene (1998) [Pubmed]
  36. The human ARF cell cycle regulatory gene promoter is a CpG island which can be silenced by DNA methylation and down-regulated by wild-type p53. Robertson, K.D., Jones, P.A. Mol. Cell. Biol. (1998) [Pubmed]
  37. Frequent epigenetic inactivation of the SLIT2 gene in gliomas. Dallol, A., Krex, D., Hesson, L., Eng, C., Maher, E.R., Latif, F. Oncogene (2003) [Pubmed]
  38. Hypermethylation of NAD(P)H: quinone oxidoreductase 1 (NQO1) gene in human hepatocellular carcinoma. Tada, M., Yokosuka, O., Fukai, K., Chiba, T., Imazeki, F., Tokuhisa, T., Saisho, H. J. Hepatol. (2005) [Pubmed]
  39. Methylation status and expression of human telomerase reverse transcriptase mRNA in relation to hypermethylation of the p16 gene in colorectal cancers as analyzed by bisulfite PCR-SSCP. Nomoto, K., Maekawa, M., Sugano, K., Ushiama, M., Fukayama, N., Fujita, S., Kakizoe, T. Jpn. J. Clin. Oncol. (2002) [Pubmed]
  40. A novel p16INK4A transcript. Mao, L., Merlo, A., Bedi, G., Shapiro, G.I., Edwards, C.D., Rollins, B.J., Sidransky, D. Cancer Res. (1995) [Pubmed]
  41. Identification of the physiological promoter for spinocerebellar ataxia 2 gene reveals a CpG island for promoter activity situated into the exon 1 of this gene and provides data about the origin of the nonmethylated state of these types of islands. Aguiar, J., Santurlidis, S., Nowok, J., Alexander, C., Rudnicki, D., Gispert, S., Schulz, W., Auburger, G. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  42. Localization of the gene for X-linked nephrogenic diabetes insipidus to Xq28. Kambouris, M., Dlouhy, S.R., Trofatter, J.A., Conneally, P.M., Hodes, M.E. Am. J. Med. Genet. (1988) [Pubmed]
  43. DNMT1 is required to maintain CpG methylation and aberrant gene silencing in human cancer cells. Robert, M.F., Morin, S., Beaulieu, N., Gauthier, F., Chute, I.C., Barsalou, A., MacLeod, A.R. Nat. Genet. (2003) [Pubmed]
  44. Aberrant DNA methylation as a cancer-inducing mechanism. Esteller, M. Annu. Rev. Pharmacol. Toxicol. (2005) [Pubmed]
  45. Silencing of human polycomb target genes is associated with methylation of histone H3 Lys 27. Kirmizis, A., Bartley, S.M., Kuzmichev, A., Margueron, R., Reinberg, D., Green, R., Farnham, P.J. Genes Dev. (2004) [Pubmed]
  46. Isolating human transcription factor targets by coupling chromatin immunoprecipitation and CpG island microarray analysis. Weinmann, A.S., Yan, P.S., Oberley, M.J., Huang, T.H., Farnham, P.J. Genes Dev. (2002) [Pubmed]
  47. Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Herman, J.G., Graff, J.R., Myöhänen, S., Nelkin, B.D., Baylin, S.B. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
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