Defective SLC22A18 does not exchange extracellular organic cations for cytosolic H+

Stable Identifier
R-HSA-5625574
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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The human gene SLC22A18 (aka TSSC5) encodes organic cation transporter-like protein 2 (ORCTL2). It is expressed at high levels in kidney, liver and colon and at lower levels in heart, brain and lung. ORCTL2 can transport organic cations such as chloroquine and quinidine with the antiport of protons.

Mutations and/or reduced expression of SLC22A18 have been found in certain tumors such as lung cancer (LNCR; MIM:211980) (Lee et al. 1998) and embryonal rhabdomyosarcoma 1 (RMSE1; MIM:268210) (Schwienbacher et al. 1998). How SLC22A18 might be involved in growth regulation is poorly understood. There is speculation that it may be involved in resistance to chemotherapy drugs and/or in the export of genotoxic substances whose retention may increase the risk of tumor formation. A mutation implicated in LNCR is S233F (Lee et al. 1998). A mutation implicated in RMSE1 is R286H (Schwienbacher et al. 1998; paper incorrectly deciphered it to be a C to R change).

Literature References
PubMed ID Title Journal Year
9751628 Somatic mutation of TSSC5, a novel imprinted gene from human chromosome 11p15.5

Lee, MP, Reeves, C, Schmitt, A, Su, K, Connors, TD, Hu, RJ, Brandenburg, S, Lee, MJ, Miller, G, Feinberg, AP

Cancer Res. 1998
9520460 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, CM, Negrini, M

Proc Natl Acad Sci U S A 1998
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
solute:proton antiporter activity of SLC22A18 mutants [plasma membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
rhabdomyosarcoma 3247 Rhabdomyosarcoma NOS (morphologic abnormality), rhabdomyosarcoma, Rhabdomyosarcoma, no subtype (morphologic abnormality), rhabdomyoblastoma, Rhabdomyosarcoma (disorder)
lung cancer 1324
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