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Gene Review

TBC1D9  -  TBC1 domain family, member 9 (with GRAM...

Homo sapiens

Synonyms: KIAA0882, MDR1, TBC1 domain family member 9, TBC1 domain family member 9A, TBC1D9A
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Disease relevance of TBC1D9


Psychiatry related information on TBC1D9


High impact information on TBC1D9


Chemical compound and disease context of TBC1D9


Biological context of TBC1D9

  • Recently, several SNPs have been identified in the MDR1 gene, some of which can affect P-glycoprotein expression and function [16].
  • Genetic polymorphisms of the human MDR1 drug transporter [16].
  • We find that in vivo expression of the MDR1-containing operon is regulated by metal ion availability [17].
  • We have developed a preclinical model of MDR/CML uncomplicated by other mechanisms of drug resistance to evaluate the effects of MDR1 overexpression on cytodestructive and differentiation therapy and the ability of sensitizers to restore chemosensitivity in this disease [18].
  • CONCLUSIONS: The data indicate that overexpression of the MDR1 gene alone confers a multidrug-resistant phenotype, but it does not directly result in either cross-resistance to antiestrogens or a loss of steroid hormone receptor expression [12].

Anatomical context of TBC1D9


Associations of TBC1D9 with chemical compounds

  • Verapamil and quinidine lowered the IC50 values of doxorubicin for MDR1-positive cell lines [22].
  • Variability across the studies in the proportion of tumors expressing MDR1/gp170 was assessed by use of chi-squared tests of homogeneity, weighted means, and weighted linear regression [2].
  • Such data suggest that, at least for two distinct human cell line (SKOV3 and DU145), estramustine does not induce the overexpression of the MDR1 gene [23].
  • These findings together suggest an association between overexpression of the MDR1 gene and cross-resistance to progestin and antiestrogen therapies [12].
  • Other study results indicate that both progestins and triphenylethylene antiestrogens may be substrates for P-glycoprotein, the product of the MDR1 gene [12].

Other interactions of TBC1D9

  • AtrDp shows a particularly high degree of identity to the amino acid sequence of Afu Mdr1p, a previously characterized ABC transporter from the human pathogen A. fumigatus [24].
  • This finding suggests that drug-resistance may involve synergy between energy-dependent drug efflux pumps CDR1p and MDR1p in some but not all isolates [25].

Analytical, diagnostic and therapeutic context of TBC1D9

  • The human multidrug-resistance P-glycoprotein, encoded by the MDR1 gene, is also an ABC transporter, overexpression of which is one of the principal causes of resistance of human cancers to chemotherapy [26].
  • Expression of mdr1 messenger RNA (mRNA) was investigated using RT-PCR, and P-glycoprotein (Pgp) expression was determined by immunoflow cytometry with the monoclonal antibodies MRK16 and C219 [27].
  • METHODS: A sensitive assay based on the polymerase chain reaction (PCR) was used in a retrospective study to measure MDR1 mRNA in biopsy samples of 100 solid tumors, including 60 ovarian and 32 lung carcinomas [5].
  • RESULTS: Slot-blot analysis and immunocytochemistry showed that two cell lines expressed high levels of MDR1 mRNA, one expressed an intermediate level, and all others were low expressors [22].
  • The expression of MDR1 and GST-pi genes was assessed in the mRNA extracted from xenografts by Northern blot analysis [28].


  1. Human multidrug-resistant cell lines: increased mdr1 expression can precede gene amplification. Shen, D.W., Fojo, A., Chin, J.E., Roninson, I.B., Richert, N., Pastan, I., Gottesman, M.M. Science (1986) [Pubmed]
  2. Multidrug resistance in breast cancer: a meta-analysis of MDR1/gp170 expression and its possible functional significance. Trock, B.J., Leonessa, F., Clarke, R. J. Natl. Cancer Inst. (1997) [Pubmed]
  3. MDR1 gene expression and treatment outcome in acute myeloid leukemia. Pirker, R., Wallner, J., Geissler, K., Linkesch, W., Haas, O.A., Bettelheim, P., Hopfner, M., Scherrer, R., Valent, P., Havelec, L. J. Natl. Cancer Inst. (1991) [Pubmed]
  4. Expression of a multidrug resistance gene in human cancers. Goldstein, L.J., Galski, H., Fojo, A., Willingham, M., Lai, S.L., Gazdar, A., Pirker, R., Green, A., Crist, W., Brodeur, G.M. J. Natl. Cancer Inst. (1989) [Pubmed]
  5. Clinical correlates of MDR1 (P-glycoprotein) gene expression in ovarian and small-cell lung carcinomas. Holzmayer, T.A., Hilsenbeck, S., Von Hoff, D.D., Roninson, I.B. J. Natl. Cancer Inst. (1992) [Pubmed]
  6. Allele frequency of three functionally active polymorphisms of the MDR-1 gene in high-risk HIV-negative and HIV-positive Caucasians. Ifergan, I., Bernard, N.F., Bruneau, J., Alary, M., Tsoukas, C.M., Roger, M. AIDS (2002) [Pubmed]
  7. Psychological stress induces chemoresistance in breast cancer by upregulating mdr1. Su, F., Ouyang, N., Zhu, P., Ouyang, N., Jia, W., Gong, C., Ma, X., Xu, H., Song, E. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  8. Chimerism of the transplanted heart. Quaini, F., Urbanek, K., Beltrami, A.P., Finato, N., Beltrami, C.A., Nadal-Ginard, B., Kajstura, J., Leri, A., Anversa, P. N. Engl. J. Med. (2002) [Pubmed]
  9. Dominant effector genetics in mammalian cells. Xu, X., Leo, C., Jang, Y., Chan, E., Padilla, D., Huang, B.C., Lin, T., Gururaja, T., Hitoshi, Y., Lorens, J.B., Anderson, D.C., Sikic, B., Luo, Y., Payan, D.G., Nolan, G.P. Nat. Genet. (2001) [Pubmed]
  10. The yeast STE6 gene encodes a homologue of the mammalian multidrug resistance P-glycoprotein. McGrath, J.P., Varshavsky, A. Nature (1989) [Pubmed]
  11. Reversal of multidrug resistance in human colon cancer cells expressing the human MDR1 gene by liposomes in combination with monoclonal antibody or verapamil. Sela, S., Husain, S.R., Pearson, J.W., Longo, D.L., Rahman, A. J. Natl. Cancer Inst. (1995) [Pubmed]
  12. Effect of P-glycoprotein expression on sensitivity to hormones in MCF-7 human breast cancer cells. Clarke, R., Currier, S., Kaplan, O., Lovelace, E., Boulay, V., Gottesman, M.M., Dickson, R.B. J. Natl. Cancer Inst. (1992) [Pubmed]
  13. Decreased expression of the amplified mdr1 gene in revertants of multidrug-resistant human myelogenous leukemia K562 occurs without loss of amplified DNA. Sugimoto, Y., Roninson, I.B., Tsuruo, T. Mol. Cell. Biol. (1987) [Pubmed]
  14. The value of the MDR1 reversal agent PSC-833 in addition to daunorubicin and cytarabine in the treatment of elderly patients with previously untreated acute myeloid leukemia (AML), in relation to MDR1 status at diagnosis. van der Holt, B., Löwenberg, B., Burnett, A.K., Knauf, W.U., Shepherd, J., Piccaluga, P.P., Ossenkoppele, G.J., Verhoef, G.E., Ferrant, A., Crump, M., Selleslag, D., Theobald, M., Fey, M.F., Vellenga, E., Dugan, M., Sonneveld, P. Blood (2005) [Pubmed]
  15. Action of gossypol and rhodamine 123 on wild type and multidrug-resistant MCF-7 human breast cancer cells: 31P nuclear magnetic resonance and toxicity studies. Jaroszewski, J.W., Kaplan, O., Cohen, J.S. Cancer Res. (1990) [Pubmed]
  16. Genetic polymorphisms of the human MDR1 drug transporter. Schwab, M., Eichelbaum, M., Fromm, M.F. Annu. Rev. Pharmacol. Toxicol. (2003) [Pubmed]
  17. Transcriptional regulation of an archaeal operon in vivo and in vitro. Bell, S.D., Cairns, S.S., Robson, R.L., Jackson, S.P. Mol. Cell (1999) [Pubmed]
  18. Sensitivity of K562 human chronic myelogenous leukemia blast cells transfected with a human multidrug resistance cDNA to cytotoxic drugs and differentiating agents. Hait, W.N., Choudhury, S., Srimatkandada, S., Murren, J.R. J. Clin. Invest. (1993) [Pubmed]
  19. Modulation of multidrug-resistant multiple myeloma by cyclosporin. The Leukaemia Group of the EORTC and the HOVON. Sonneveld, P., Durie, B.G., Lokhorst, H.M., Marie, J.P., Solbu, G., Suciu, S., Zittoun, R., Löwenberg, B., Nooter, K. Lancet (1992) [Pubmed]
  20. Functional expression of human mdr1 in the yeast Saccharomyces cerevisiae. Kuchler, K., Thorner, J. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  21. Results of MDR-1 vector modification trial indicate that granulocyte/macrophage colony-forming unit cells do not contribute to posttransplant hematopoietic recovery following intensive systemic therapy. Hanania, E.G., Giles, R.E., Kavanagh, J., Fu, S.Q., Ellerson, D., Zu, Z., Wang, T., Su, Y., Kudelka, A., Rahman, Z., Holmes, F., Hortobagyi, G., Claxton, D., Bachier, C., Thall, P., Cheng, S., Hester, J., Ostrove, J.M., Bird, R.E., Chang, A., Korbling, M., Seong, D., Cote, R., Holzmayer, T., Deisseroth, A.B. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  22. MDR1 gene expression: its effect on drug resistance to doxorubicin in human hepatocellular carcinoma cell lines. Park, J.G., Lee, S.K., Hong, I.G., Kim, H.S., Lim, K.H., Choe, K.J., Kim, W.H., Kim, Y.I., Tsuruo, T., Gottesman, M.M. J. Natl. Cancer Inst. (1994) [Pubmed]
  23. P-glycoprotein binding and modulation of the multidrug-resistant phenotype by estramustine. Speicher, L.A., Barone, L.R., Chapman, A.E., Hudes, G.R., Laing, N., Smith, C.D., Tew, K.D. J. Natl. Cancer Inst. (1994) [Pubmed]
  24. The role of ABC transporters from Aspergillus nidulans in protection against cytotoxic agents and in antibiotic production. Andrade, A.C., Van Nistelrooy, J.G., Peery, R.B., Skatrud, P.L., De Waard, M.A. Mol. Gen. Genet. (2000) [Pubmed]
  25. Increased expression and hotspot mutations of the multidrug efflux transporter, CDR1 in azole-resistant Candida albicans isolates from vaginitis patients. Looi, C.Y., D' Silva, E.C., Seow, H.F., Rosli, R., Ng, K.P., Chong, P.P. FEMS Microbiol. Lett. (2005) [Pubmed]
  26. A bacterial antibiotic-resistance gene that complements the human multidrug-resistance P-glycoprotein gene. van Veen, H.W., Callaghan, R., Soceneantu, L., Sardini, A., Konings, W.N., Higgins, C.F. Nature (1998) [Pubmed]
  27. Reversal of multidrug resistance by transduction of cytokine genes into human colon carcinoma cells. Stein, U., Walther, W., Shoemaker, R.H. J. Natl. Cancer Inst. (1996) [Pubmed]
  28. Response of small-cell lung cancer xenografts to chemotherapy: multidrug resistance and direct clinical correlates. Poupon, M.F., Arvelo, F., Goguel, A.F., Bourgeois, Y., Jacrot, M., Hanania, N., Arriagada, R., Le Chevalier, T. J. Natl. Cancer Inst. (1993) [Pubmed]
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