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Gene Review

SLC22A4  -  solute carrier family 22 (organic...

Homo sapiens

Synonyms: ET transporter, ETT, Ergothioneine transporter, MGC34546, OCTN1, ...
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Disease relevance of SLC22A4


Psychiatry related information on SLC22A4

  • METHODS: In a model we studied: 1) The influence on ETT-Res caused by different connectors and secretions; 2) Direct Trach-P measurements with a catheter (o.d. 2 mm, i.d. 0.9 mm) with either end or side hole, filled with either air or liquid, introduced through the ETT lumen and evaluated regarding response time and position [6].

High impact information on SLC22A4


Chemical compound and disease context of SLC22A4


Biological context of SLC22A4


Anatomical context of SLC22A4

  • The organic cation transporter OCTN1 (SLC22A4) is expressed ubiquitously, with strong expression in kidney, trachea, bone marrow, and fetal liver, and it mediates transport of organic cations in a pH-dependent manner [17].
  • OCTN1 (SLC22A4) transports cationic compounds such as tetraethylammonium in a pH-sensitive and sodium-independent manner in cultured cells, and is expressed in wide variety of tissues, including kidney, muscle, placenta, heart, and others [18].
  • The real-time PCR expression profile of human ETT, with strong expression in CD71+ cells, is consistent with a pivotal function of ET in erythrocytes [19].
  • By contrast, cells lacking ETT do not accumulate ET, because their plasma membrane is virtually impermeable for this compound [19].
  • Moreover, prominent expression of ETT in monocytes and SLC22A4 polymorphism associations suggest a protective role of ET in chronic inflammatory disorders [19].

Associations of SLC22A4 with chemical compounds


Physical interactions of SLC22A4


Regulatory relationships of SLC22A4

  • RESULTS: No statistically significant differences between patients with RA and healthy controls were observed when comparing the distribution of the genotypes or alleles of any of the SLC22A4 polymorphisms tested [26].

Other interactions of SLC22A4

  • There was no statistical evidence of interaction between CARD15 and either OCTN or IBD5 variants in susceptibility to IBD [2].
  • The SLC22A4 gene has also been associated with rheumatoid arthritis [27].
  • SLC22A4 is an organic cation transporter with unknown physiological function, and RUNX1 is a hematological transcriptional regulator that has been shown to be responsible for acute myelogenic leukemia [28].
  • Both carried a CARD15 R702W variant, but had normal alleles in TLR4 and OCTN [29].
  • Uptake of tetraethylammonium by OCTN1 was much higher in HEK293/PDZK1 cells, compared with that in the parent HEK293 cells, the uptake in HEK293/PDZK1-E195K cells showing middle range between the two values [30].

Analytical, diagnostic and therapeutic context of SLC22A4

  • We show that expression of SLC22A4 is specific to hematological and immunological tissues and that SLC22A4 is also highly expressed in the inflammatory joints of mice with collagen-induced arthritis [7].
  • Evidence for the association of the SLC22A4 and SLC22A5 genes with type 1 diabetes: a case control study [9].
  • Site-directed mutagenesis and introduction of residues nonconserved between OCTN1 and OCTN2 in the OCTN2 cDNA indicated that the R341A, L409W, L424Y, and T429I substitutions significantly decreased carnitine transport [31].
  • We demonstrate that the organic cation/carnitine transporters, OCTN1, OCTN2, and OCTN3, are expressed in sperm as three distinct proteins with an expected molecular mass of 63 kDa, using Western blot analysis and our transporter-specific antibodies [32].
  • After a short training programme 11 naval medical trainees inserted a laryngeal mask airway (LMA) and a tracheal tube (ETT) in random order in a total of 110 anaesthetised patients [33].


  1. Functional variants of OCTN cation transporter genes are associated with Crohn disease. Peltekova, V.D., Wintle, R.F., Rubin, L.A., Amos, C.I., Huang, Q., Gu, X., Newman, B., Van Oene, M., Cescon, D., Greenberg, G., Griffiths, A.M., St George-Hyslop, P.H., Siminovitch, K.A. Nat. Genet. (2004) [Pubmed]
  2. Evidence for association of OCTN genes and IBD5 with ulcerative colitis. Waller, S., Tremelling, M., Bredin, F., Godfrey, L., Howson, J., Parkes, M. Gut (2006) [Pubmed]
  3. Polymorphisms in the DLG5 and OCTN cation transporter genes in Crohn's disease. Török, H.P., Glas, J., Tonenchi, L., Lohse, P., Müller-Myhsok, B., Limbersky, O., Neugebauer, C., Schnitzler, F., Seiderer, J., Tillack, C., Brand, S., Brünnler, G., Jagiello, P., Epplen, J.T., Griga, T., Klein, W., Schiemann, U., Folwaczny, M., Ochsenkühn, T., Folwaczny, C. Gut (2005) [Pubmed]
  4. Analysis of the influence of OCTN1/2 variants within the IBD5 locus on disease susceptibility and growth indices in early onset inflammatory bowel disease. Russell, R.K., Drummond, H.E., Nimmo, E.R., Anderson, N.H., Noble, C.L., Wilson, D.C., Gillett, P.M., McGrogan, P., Hassan, K., Weaver, L.T., Bisset, W.M., Mahdi, G., Satsangi, J. Gut (2006) [Pubmed]
  5. Analysis of chromosome 5q31-32 and psoriasis: confirmation of a susceptibility locus but no association with SNPs within SLC22A4 and SLC22A5. Friberg, C., Björck, K., Nilsson, S., Inerot, A., Wahlström, J., Samuelsson, L. J. Invest. Dermatol. (2006) [Pubmed]
  6. Direct tracheal airway pressure measurements are essential for safe and accurate dynamic monitoring of respiratory mechanics. A laboratory study. Kárason, S., Søndergaard, S., Lundin, S., Wiklund, J., Stenqvist, O. Acta anaesthesiologica Scandinavica. (2001) [Pubmed]
  7. An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis. Tokuhiro, S., Yamada, R., Chang, X., Suzuki, A., Kochi, Y., Sawada, T., Suzuki, M., Nagasaki, M., Ohtsuki, M., Ono, M., Furukawa, H., Nagashima, M., Yoshino, S., Mabuchi, A., Sekine, A., Saito, S., Takahashi, A., Tsunoda, T., Nakamura, Y., Yamamoto, K. Nat. Genet. (2003) [Pubmed]
  8. The contribution of OCTN1/2 variants within the IBD5 locus to disease susceptibility and severity in Crohn's disease. Noble, C.L., Nimmo, E.R., Drummond, H., Ho, G.T., Tenesa, A., Smith, L., Anderson, N., Arnott, I.D., Satsangi, J. Gastroenterology (2005) [Pubmed]
  9. Evidence for the association of the SLC22A4 and SLC22A5 genes with type 1 diabetes: a case control study. Santiago, J.L., Martínez, A., de la Calle, H., Fernández-Arquero, M., Figueredo, M.A., de la Concha, E.G., Urcelay, E. BMC Med. Genet. (2006) [Pubmed]
  10. Characteristics of L-carnitine transport in cultured human hepatoma HLF cells. Yokogawa, K., Miya, K., Tamai, I., Higashi, Y., Nomura, M., Miyamoto, K., Tsuji, A. J. Pharm. Pharmacol. (1999) [Pubmed]
  11. Alkalinization of intra-cuff lidocaine and use of gel lubrication protect against tracheal tube-induced emergence phenomena. Estebe, J.P., Delahaye, S., Le Corre, P., Dollo, G., Le Naoures, A., Chevanne, F., Ecoffey, C. British journal of anaesthesia. (2004) [Pubmed]
  12. Factor analysis of laboratory and clinical measurements of dyspnea in patients with chronic obstructive pulmonary disease. Nguyen, H.Q., Altinger, J., Carrieri-Kohlman, V., Gormley, J.M., Stulbarg, M.S. Journal of pain and symptom management. (2003) [Pubmed]
  13. The efficiency of beta 2-agonist delivery through tracheal tubes with the metered-dose inhaler: an in vitro study. Takaya, T., Takeyama, K., Takiguchi, M. Journal of anesthesia. (2002) [Pubmed]
  14. Contribution of OCTN variants within the IBD5 locus to pediatric onset Crohn's disease. Babusukumar, U., Wang, T., McGuire, E., Broeckel, U., Kugathasan, S. Am. J. Gastroenterol. (2006) [Pubmed]
  15. Association of the organic cation transporter OCTN genes with Crohn's disease in the Spanish population. Martínez, A., Del Carmen Martín, M., Mendoza, J.L., Taxonera, C., Díaz-Rubio, M., de la Concha, E.G., Urcelay, E. Eur. J. Hum. Genet. (2006) [Pubmed]
  16. Polymorphisms in the organic cation transporter genes SLC22A4 and SLC22A5 and Crohn's disease in a New Zealand Caucasian cohort. Leung, E., Hong, J., Fraser, A.G., Merriman, T.R., Vishnu, P., Krissansen, G.W. Immunol. Cell Biol. (2006) [Pubmed]
  17. Functional characterization of human organic cation transporter OCTN1 single nucleotide polymorphisms in the Japanese population. Kawasaki, Y., Kato, Y., Sai, Y., Tsuji, A. Journal of pharmaceutical sciences. (2004) [Pubmed]
  18. Involvement of OCTN1 (SLC22A4) in pH-dependent transport of organic cations. Tamai, I., Nakanishi, T., Kobayashi, D., China, K., Kosugi, Y., Nezu, J., Sai, Y., Tsuji, A. Mol. Pharm. (2004) [Pubmed]
  19. Discovery of the ergothioneine transporter. Gründemann, D., Harlfinger, S., Golz, S., Geerts, A., Lazar, A., Berkels, R., Jung, N., Rubbert, A., Schömig, E. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  20. Cisplatin and Oxaliplatin, but Not Carboplatin and Nedaplatin, Are Substrates for Human Organic Cation Transporters (SLC22A1-3 and Multidrug and Toxin Extrusion Family). Yonezawa, A., Masuda, S., Yokoo, S., Katsura, T., Inui, K. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  21. Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. Yabuuchi, H., Tamai, I., Nezu, J., Sakamoto, K., Oku, A., Shimane, M., Sai, Y., Tsuji, A. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  22. Epitope shared by functional variant of organic cation/carnitine transporter, OCTN1, Campylobacter jejuni and Mycobacterium paratuberculosis may underlie susceptibility to Crohn's disease at 5q31. Lamhonwah, A.M., Ackerley, C., Onizuka, R., Tilups, A., Lamhonwah, D., Chung, C., Tao, K.S., Tellier, R., Tein, I. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  23. Association of rheumatoid arthritis with ergothioneine levels in red blood cells: a case control study. Taubert, D., Lazar, A., Grimberg, G., Jung, N., Rubbert, A., Delank, K.S., Perniok, A., Erdmann, E., Sch??mig, E. J. Rheumatol. (2006) [Pubmed]
  24. Functional effects of protein sequence polymorphisms in the organic cation/ergothioneine transporter OCTN1 (SLC22A4). Urban, T.J., Yang, C., Lagpacan, L.L., Brown, C., Castro, R.A., Taylor, T.R., Huang, C.C., Stryke, D., Johns, S.J., Kawamoto, M., Carlson, E.J., Ferrin, T.E., Burchard, E.G., Giacomini, K.M. Pharmacogenet. Genomics (2007) [Pubmed]
  25. Expression of organic cation transporter OCTN1 in hematopoietic cells during erythroid differentiation. Kobayashi, D., Aizawa, S., Maeda, T., Tsuboi, I., Yabuuchi, H., Nezu, J., Tsuji, A., Tamai, I. Exp. Hematol. (2004) [Pubmed]
  26. SLC22A4, RUNX1, and SUMO4 polymorphisms are not associated with rheumatoid arthritis: a case-control study in a Spanish population. Orozco, G., Sánchez, E., González-Gay, M.A., López-Nevot, M.A., Torres, B., Pascual-Salcedo, D., Balsa, A., Pablos, J.L., García, A., González-Escribano, M.F., Martín, J. J. Rheumatol. (2006) [Pubmed]
  27. Evidence for common genetic control in pathways of inflammation for Crohn's disease and psoriatic arthritis. Ho, P., Bruce, I.N., Silman, A., Symmons, D., Newman, B., Young, H., Griffiths, C.E., John, S., Worthington, J., Barton, A. Arthritis Rheum. (2005) [Pubmed]
  28. SLC22A4 and RUNX1: identification of RA susceptible genes. Yamada, R., Tokuhiro, S., Chang, X., Yamamoto, K. J. Mol. Med. (2004) [Pubmed]
  29. Genetic and environmental factors in monozygotic twins with Crohn's disease and their first-degree relatives: a case report. Vind, I., Jespersgaard, C., Hougs, L., Riis, L., Dinesen, L., Andersen, P.S., Locht, H., Jess, T., Munkholm, P. Digestion (2005) [Pubmed]
  30. Mutation in an Adaptor Protein PDZK1 Affects Transport Activity of Organic Cation Transporter OCTNs and Oligopeptide Transporter PEPT2. Sugiura, T., Kato, Y., Kubo, Y., Tsuji, A. Drug Metab. Pharmacokinet. (2006) [Pubmed]
  31. Functional domains in the carnitine transporter OCTN2, defective in primary carnitine deficiency. Amat di San Filippo, C., Wang, Y., Longo, N. J. Biol. Chem. (2003) [Pubmed]
  32. Characterization of organic cation/carnitine transporter family in human sperm. Xuan, W., Lamhonwah, A.M., Librach, C., Jarvi, K., Tein, I. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  33. Laryngeal mask airway and tracheal tube insertion by unskilled personnel. Davies, P.R., Tighe, S.Q., Greenslade, G.L., Evans, G.H. Lancet (1990) [Pubmed]
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