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Gene Review

SLC22A18  -  solute carrier family 22, member 18

Homo sapiens

Synonyms: BWR1A, BWSCR1A, Beckwith-Wiedemann syndrome chromosomal region 1 candidate gene A protein, Efflux transporter-like protein, HET, ...
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Disease relevance of SLC22A18


Psychiatry related information on SLC22A18

  • Depending on the operant conditioning training procedure used the learning can be consolidated into intermediate term (ITM) or long-term memory (LTM) [5].

High impact information on SLC22A18

  • The three additional genes were designated BWR1A, BWR1B, and BWR1C [6].
  • Transcriptional map of 170-kb region at chromosome 11p15.5: identification and mutational analysis of the BWR1A gene reveals the presence of mutations in tumor samples [6].
  • PURPOSE: Recent reports by European investigators suggest that sentinel lymphadenectomy (SLND), a mainstay of melanoma diagnosis and treatment planning, increases the risk of in-transit metastasis (ITM) and should be abandoned [7].
  • This study compared the incidence of ITM after wide local excision (WLE), WLE plus SLND (SLND), or WLE plus elective lymphadenectomy (ELND) for primary melanoma [7].
  • Sequence analysis suggests that TSSC5 is a membrane protein with 10 transmembrane segments, and it is located between two imprinted genes, p57KIP2 and TSSC3 [2].

Biological context of SLC22A18

  • SLC22AI8 DNA-PCR-RFLP analysis using NlaIII restriction digestion identified SLC22A18 heterozygotes within this breast tissue cohort (n = 89) [1].
  • Somatic mutation of TSSC5, a novel imprinted gene from human chromosome 11p15.5 [2].
  • Reverse transcription-PCR analysis of TSSC5 revealed frequent occurrence of aberrant RNA splicing, which deleted exons 4, 5, and 6 in Wilms' tumors [2].
  • Altered methylation of TSSC5 and LIT1 was observed in only 6% and 8% of HCCs, respectively, compared with 89% at the IGF2 locus, suggesting that these loci were not concomitantly dysregulated [8].
  • However, PCR and restriction fragment length polymorphism analysis based on M. ulcerans-specific insertion sequence IS2404 showed the presence of this element in a low copy number in isolate ITM 00-1026 [9].

Anatomical context of SLC22A18

  • The impact of ILP was clearly on the occurrence-as first site of progression - of in-transit metastases (ITM), which were reduced from 6.6% to 3.3%, and of regional lymph node (RLN) metastases, with a reduction from 16.7% to 12.6% [10].
  • We have previously described HAP, a novel hnRNP protein that is identical both to SAF-B, a component of the nuclear scaffold, and to HET, a transcriptional regulator of the gene for heat shock protein 27 [11].
  • We therefore screened 62 HBs, 3 HB cell lines and 1 pediatric hepatocellular carcinoma for BWR1A mutations using single-strand conformation polymorphism analysis [12].
  • Other projections were to the frontal eye field (FEF), a more ventral region of frontal cortex (FV), and a medial division of inferior temporal cortex, ITM, on the ventral surface of the temporal lobe [13].
  • METHODS AND RESULTS: Intensity-modulated PT methods (IMPT) for spot scanning were applied to create and deliver a donut-shaped high-dose configuration with protons, allowing treating > 75% of the target with at least 95% of the prescribed dose of 72.8 CGE, whilst restricting dose to the cauda equina to 60-65 CGE [14].

Associations of SLC22A18 with chemical compounds

  • These results suggest that ORCTL2 may play a role in the transport of chloroquine and quinidine related compounds in the kidney [15].
  • We have previously identified a transcript at 11p15.5 which encodes a putative membrane transport protein, designated organic cation transporter-like 2 (ORCTL2), that shares homology with tetracycline resistance proteins and bacterial multidrug resistance proteins [15].
  • These regions were named by location: ITC (the caudal subdivision of inferior temporal cortex), ITR (the rostral subdivision of inferior temporal cortex), ITP (the polar subdivision of inferior temporal cortex), and ITM (the medial subdivision of inferior temporal cortex) [13].
  • The injection of a translation blocker, Anisomycin, 2.5 h before training prevents the establishment of both ITM and LTM [16].
  • On the other hand, injection of the transcription blocker Actinomycin D, 2.5 h before training, did not prevent the establishment of ITM, but did, however, prevent LTM formation [16].

Regulatory relationships of SLC22A18

  • The allelic expression of small nuclear ribonucleoprotein N (SNRPN) was stringently regulated while that of multimembrane-spanning polyspecific transporter-like gene 1 (IMPT1) showed a large degree of variation [17].

Other interactions of SLC22A18

  • In contrast, other maternal imprinted genes in this region, including p57(KIP2), IMPT1, and IPL exhibited almost normal expression in these samples, although some samples expressed IGF2 biallelically [18].
  • Here, we present evidences indicating that RING105, a novel conserved RING-finger protein with a PA (protease-associated) domain and a PEST sequence, is a ubiquitin ligase for TSSC5 that can function in concert with the ubiquitin-conjugating enzyme UbcH6 [19].
  • However, similar to the putative 11p15.5 tumor suppressor H19, BWR1A appears to be reduced in expression [12].

Analytical, diagnostic and therapeutic context of SLC22A18

  • Random hexamer-primed cDNA synthesis, SLC22A18/SLC22A18AS-specific PCR, and imprinting evaluation by commercial sequencing demonstrated that SLC22A18AS displays a nonimprinted profile in reduction mastectomies (n = 6) [1].
  • Immunohistochemistry analyses performed with anti-ORCTL2 polyclonal antibodies on human renal sections indicate that ORCTL2 is localized on the apical membrane surface of the proximal tubules [15].
  • BWR1A mRNA expression was determined in 14 HBs by differential RT-PCR of matched cDNA samples from tumor and normal liver [12].
  • 5. By Western blot analysis, all 4 tumors and matching liver samples displayed a 48-51 kd band corresponding to BWR1A [12].
  • PT was administered after function-preserving surgery, using a gantry and spot scanning, without or with intensity modulation (IMPT; 6 patients), and/or photon-based radiotherapy (RT, 6 patients) [20].


  1. Gain of imprinting of SLC22A18 sense and antisense transcripts in human breast cancer. Gallagher, E., Mc Goldrick, A., Chung, W.Y., Mc Cormack, O., Harrison, M., Kerin, M., Dervan, P.A., Mc Cann, A. Genomics (2006) [Pubmed]
  2. Somatic mutation of TSSC5, a novel imprinted gene from human chromosome 11p15.5. Lee, M.P., Reeves, C., Schmitt, A., Su, K., Connors, T.D., Hu, R.J., Brandenburg, S., Lee, M.J., Miller, G., Feinberg, A.P. Cancer Res. (1998) [Pubmed]
  3. Intraductal papillary-mucinous tumors of the pancreas: clinicopathologic features, outcome, and nomenclature. Members of the Pancreas Clinic, and Pancreatic Surgeons of Mayo Clinic. Loftus, E.V., Olivares-Pakzad, B.A., Batts, K.P., Adkins, M.C., Stephens, D.H., Sarr, M.G., DiMagno, E.P. Gastroenterology (1996) [Pubmed]
  4. Gain of imprinting at chromosome 11p15: A pathogenetic mechanism identified in human hepatocarcinomas. Schwienbacher, C., Gramantieri, L., Scelfo, R., Veronese, A., Calin, G.A., Bolondi, L., Croce, C.M., Barbanti-Brodano, G., Negrini, M. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  5. A molluscan model system in the search for the engram. Lukowiak, K., Sangha, S., Scheibenstock, A., Parvez, K., McComb, C., Rosenegger, D., Varshney, N., Sadamoto, H. J. Physiol. Paris (2003) [Pubmed]
  6. Transcriptional map of 170-kb region at chromosome 11p15.5: identification and mutational analysis of the BWR1A gene reveals the presence of mutations in tumor samples. Schwienbacher, C., Sabbioni, S., Campi, M., Veronese, A., Bernardi, G., Menegatti, A., Hatada, I., Mukai, T., Ohashi, H., Barbanti-Brodano, G., Croce, C.M., Negrini, M. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  7. Sentinel lymphadenectomy does not increase the incidence of in-transit metastases in primary melanoma. Kang, J.C., Wanek, L.A., Essner, R., Faries, M.B., Foshag, L.J., Morton, D.L. J. Clin. Oncol. (2005) [Pubmed]
  8. Loss of parental-specific methylation at the IGF2 locus in human hepatocellular carcinoma. Poirier, K., Chalas, C., Tissier, F., Couvert, P., Mallet, V., Carrié, A., Marchio, A., Sarli, D., Gicquel, C., Chaussade, S., Beljord, C., Chelly, J., Kerjean, A., Terris, B. J. Pathol. (2003) [Pubmed]
  9. Characterization of an unusual Mycobacterium: a possible missing link between Mycobacterium marinum and Mycobacterium ulcerans. Chemlal, K., Huys, G., Laval, F., Vincent, V., Savage, C., Gutierrez, C., Laneelle, M.A., Swings, J., Meyers, W.M., Daffe, M., Portaels, F. J. Clin. Microbiol. (2002) [Pubmed]
  10. Prophylactic isolated limb perfusion for localized, high-risk limb melanoma: results of a multicenter randomized phase III trial. European Organization for Research and Treatment of Cancer Malignant Melanoma Cooperative Group Protocol 18832, the World Health Organization Melanoma Program Trial 15, and the North American Perfusion Group Southwest Oncology Group-8593. Koops, H.S., Vaglini, M., Suciu, S., Kroon, B.B., Thompson, J.F., Göhl, J., Eggermont, A.M., Di Filippo, F., Krementz, E.T., Ruiter, D., Lejeune, F.J. J. Clin. Oncol. (1998) [Pubmed]
  11. Structure and dynamics of hnRNP-labelled nuclear bodies induced by stress treatments. Chiodi, I., Biggiogera, M., Denegri, M., Corioni, M., Weighardt, F., Cobianchi, F., Riva, S., Biamonti, G. J. Cell. Sci. (2000) [Pubmed]
  12. Allelic loss but absence of mutations in the polyspecific transporter gene BWR1A on 11p15.5 in hepatoblastoma. Albrecht, S., Hartmann, W., Houshdaran, F., Koch, A., Gärtner, B., Prawitt, D., Zabel, B.U., Russo, P., Von Schweinitz, D., Pietsch, T. Int. J. Cancer (2004) [Pubmed]
  13. Subdivisions and connections of inferior temporal cortex in owl monkeys. Weller, R.E., Kaas, J.H. J. Comp. Neurol. (1987) [Pubmed]
  14. Donut-shaped high-dose configuration for proton beam radiation therapy. Rutz, H.P., Lomax, A.J. Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al]. (2005) [Pubmed]
  15. Functional characterization of ORCTL2--an organic cation transporter expressed in the renal proximal tubules. Reece, M., Prawitt, D., Landers, J., Kast, C., Gros, P., Housman, D., Zabel, B.U., Pelletier, J. FEBS Lett. (1998) [Pubmed]
  16. Intermediate and long-term memories of associative learning are differentially affected by transcription versus translation blockers in Lymnaea. Sangha, S., Scheibenstock, A., McComb, C., Lukowiak, K. J. Exp. Biol. (2003) [Pubmed]
  17. Epigenetic heterogeneity at imprinted loci in normal populations. Sakatani, T., Wei, M., Katoh, M., Okita, C., Wada, D., Mitsuya, K., Meguro, M., Ikeguchi, M., Ito, H., Tycko, B., Oshimura, M. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  18. A novel imprinted gene, KCNQ1DN, within the WT2 critical region of human chromosome 11p15.5 and its reduced expression in Wilms' tumors. Xin, Z., Soejima, H., Higashimoto, K., Yatsuki, H., Zhu, X., Satoh, Y., Masaki, Z., Kaneko, Y., Jinno, Y., Fukuzawa, R., Hata, J., Mukai, T. J. Biochem. (2000) [Pubmed]
  19. Tumor suppressor candidate TSSC5 is regulated by UbcH6 and a novel ubiquitin ligase RING105. Yamada, H.Y., Gorbsky, G.J. Oncogene (2006) [Pubmed]
  20. Extracranial chordoma: Outcome in patients treated with function-preserving surgery followed by spot-scanning proton beam irradiation. Rutz, H.P., Weber, D.C., Sugahara, S., Timmermann, B., Lomax, A.J., Bolsi, A., Pedroni, E., Coray, A., Jermann, M., Goitein, G. Int. J. Radiat. Oncol. Biol. Phys. (2007) [Pubmed]
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