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Gene Review

TBC1D25  -  TBC1 domain family, member 25

Homo sapiens

Synonyms: MG81, OATL1, TBC1 domain family member 25
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Disease relevance of TBC1D25

  • The SSX1 gene involved in synovial sarcoma tumorigenesis and localized at the OATL1 cluster is also shown to be present in a minimum of five copies, all of which map to the aforementioned region [1].
  • Here we report the analysis of two additional tumors and demonstrate that again in these cases the chromosomal break occurs within the OATL1 cluster [2].

High impact information on TBC1D25

  • To define the interval containing the Xp11.2 break, we first performed FISH on ASPS cases using YAC probes for OATL1 (Xp11.23) and OATL2 (Xp11.21), and cosmid probes from the intervening genomic region [3].
  • In order to further specify the breakpoint, we subcloned the OATL1 YAC (no. 2) into cosmids [2].
  • In a previous study we localized the synovial sarcoma-associated t(X;18)(p11;q11) breakpoint within the ornithine aminotransferase-like 1 (OATL1) cluster on the X chromosome [2].
  • A yeast artificial chromosome (YAC) clone (OAT YAC2) which hybridizes to a human OAT cDNA probe and is known to contain part of the OATL1 cluster was selected and used to confirm these results both by fluorescence in situ hybridization on synovial sarcoma patient material and by hybridization of its end-clones to the der(X) containing hybrid cells [4].
  • Measurement of in vitro Rab-GAP activity revealed that OATL1 and Evi5-like actually possess significant Rab2A- and Rab10-GAP activity, respectively, but that FLJ12085 do not display Rab5A-GAP activity at all [5].

Biological context of TBC1D25

  • Because several retinal degenerative disorders map to this region, we used YAC2 (480 kb), which covers the most distal part of OATL1, as a probe to screen a retinal cDNA library [6].
  • We speculate that there seems to be a relationship between the occurrence of these breakpoint regions and the histologic phenotype of the tumors, with a predominance of OATL1-related breakpoints in the classical biphasic tumors and of OATL2-related breakpoints in the monophasic fibrous tumors [7].
  • To generate sequence-ready templates for the gene-rich Xp11.23 region, we have constructed a 1.5-Mb bacterial artificial chromosome (BAC) contig spanning the interval between the DNA markers OATL1 and DXS255 [8].
  • In this report two polymorphic dinucleotide repeats, DXS6949 and DXS6950, were isolated and characterized from the OATL1 locus [9].
  • Alone, the OATL1 ScaI RFLP system is expected to be informative in 48% of females [10].

Anatomical context of TBC1D25

  • Because the OATL1 ScaI RFLP is a relatively common polymorphism, this system should be useful for the identification of ND carriers and affected male fetuses and newborns [10].

Other interactions of TBC1D25

  • Long-range organization of reiterated sequences, including the SSX1 cDNA at the OATL1 cluster in Xp11.23 [1].
  • Preliminary observations indicated the potential correlation of OATL1-associated breakpoints with biphasic tumours and OATL2-associated breakpoints with monophasic fibrous tumours [11].
  • We have constructed a 1.8-Mb YAC contig in this region, confirming the link between TIMP and OATL1 reported by Knight et al [12].
  • In the proximal region below OATL1, we have isolated a pair of YACs from the GATA locus, B1026 and C01160 [9].
  • We had previously generated a YAC contig in this region extending from UBE1 to the OATL1 locus [9].

Analytical, diagnostic and therapeutic context of TBC1D25


  1. Long-range organization of reiterated sequences, including the SSX1 cDNA at the OATL1 cluster in Xp11.23. Chand, A., Clark, J., Cooper, C.S., Craig, I.W. Genomics (1995) [Pubmed]
  2. Sublocalization of the synovial sarcoma-associated t(X;18) chromosomal breakpoint in Xp11.2 using cosmid cloning and fluorescence in situ hybridization. de Leeuw, B., Suijkerbuijk, R.F., Balemans, M., Sinke, R.J., de Jong, B., Molenaar, W.M., Meloni, A.M., Sandberg, A.A., Geraghty, M., Hofker, M. Oncogene (1993) [Pubmed]
  3. The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25. Ladanyi, M., Lui, M.Y., Antonescu, C.R., Krause-Boehm, A., Meindl, A., Argani, P., Healey, J.H., Ueda, T., Yoshikawa, H., Meloni-Ehrig, A., Sorensen, P.H., Mertens, F., Mandahl, N., van den Berghe, H., Sciot, R., Cin, P.D., Bridge, J. Oncogene (2001) [Pubmed]
  4. Identification of a yeast artificial chromosome (YAC) spanning the synovial sarcoma-specific t(X;18)(p11.2;q11.2) breakpoint. de Leeuw, B., Berger, W., Sinke, R.J., Suijkerbuijk, R.F., Gilgenkrantz, S., Geraghty, M.T., Valle, D., Monaco, A.P., Lehrach, H., Ropers, H.H. Genes Chromosomes Cancer (1993) [Pubmed]
  5. Screening for target Rabs of TBC (Tre-2/Bub2/Cdc16) domain-containing proteins based on their Rab-binding activity. Itoh, T., Satoh, M., Kanno, E., Fukuda, M. Genes Cells (2006) [Pubmed]
  6. The isolation of cDNAs from OATL1 at Xp 11.2 using a 480-kb YAC. Geraghty, M.T., Brody, L.C., Martin, L.S., Marble, M., Kearns, W., Pearson, P., Monaco, A.P., Lehrach, H., Valle, D. Genomics (1993) [Pubmed]
  7. Distinct Xp11.2 breakpoint regions in synovial sarcoma revealed by metaphase and interphase FISH: relationship to histologic subtypes. de Leeuw, B., Suijkerbuijk, R.F., Olde Weghuis, D., Meloni, A.M., Stenman, G., Kindblom, L.G., Balemans, M., van den Berg, E., Molenaar, W.M., Sandberg, A.A. Cancer Genet. Cytogenet. (1994) [Pubmed]
  8. Construction of a 1.5-Mb bacterial artificial chromosome contig in Xp11.23, a region of high gene content. Boycott, K.M., Zahorchak, R.J., Summer, C.G., Boycott, N.P., Kotak, V., Russell, C.G., Bech-Hansen, N.T. Genomics (1998) [Pubmed]
  9. A high-resolution map of genes, microsatellite markers, and new dinucleotide repeats from UBE1 to the GATA locus in the region Xp11.23. Kwan, S.P., Hagemann, T.L., Blaese, R.M., Rosen, F.S. Genomics (1995) [Pubmed]
  10. Linkage analysis of Norrie disease with an X-chromosomal ornithine aminotransferase locus. Bateman, J.B., Kojis, T.L., Cantor, R.M., Heinzmann, C., Ngo, J.T., Spence, M.A., Inana, G., Kivlin, J.D., Curtis, D., Sparkes, R.S. Transactions of the American Ophthalmological Society. (1993) [Pubmed]
  11. Interphase cytogenetic analysis of distinct X-chromosomal translocation breakpoints in synovial sarcoma. Janz, M., De Leeuw, B., Weghuis, D.O., Werner, M., Nolte, M., Geurts Van Kessel, A., Nordheim, A., Hipskind, R.A. J. Pathol. (1995) [Pubmed]
  12. A 1.8-Mb YAC contig in Xp11.23: identification of CpG islands and physical mapping of CA repeats in a region of high gene density. Coleman, M.P., Németh, A.H., Campbell, L., Raut, C.P., Weissenbach, J., Davies, K.E. Genomics (1994) [Pubmed]
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