.. _SLC22A18: SLC22A18 ^^^^^^^^ .. contents:: :local: General Information ******************* :Full gene name: solute carrier family 22, member 18 :Entrez Gene ID: 5002 :Location: 11p15.5 :Synonyms: HET, ITM, p45-BWR1A, BWSCR1A, ORCTL2, IMPT1, BWR1A, SLC22A1L, TSSC5 :Type: protein-coding User SNPs ********* SNPs given by the user that are near or inside this gene: +-----------+---------------+-----------+ | SNP | Distance (bp) | Direction | +===========+===============+===========+ | rs2237892 | 81200 | upstream | +-----------+---------------+-----------+ | rs231362 | 229480 | upstream | +-----------+---------------+-----------+ .. _SLC22A18 Gene summary: NCBI Summary ************ This gene is one of several tumor-suppressing subtransferable fragments located in the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. This gene is imprinted, with preferential expression from the maternal allele. Mutations in this gene have been found in Wilms' tumor and lung cancer. This protein may act as a transporter of organic cations, and have a role in the transport of chloroquine and quinidine-related compounds in kidney. Two alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Oct 2010] .. _OMIM ID 602631 : http://omim.org/entry/602631 .. _SLC22A18 OMIM Text: OMIM **** :OMIM ID: `OMIM ID 602631 `_ **Allelic Variants (Selected Examples)** .0001 BREAST CANCER, SOMATIC In the breast cancer (114480) cell line BT549, Schwienbacher et al. (1998) identified an insertion that introduced a stop codon in the BWR1A gene. The insertion consisted of 111 nucleotides between nucleotides 1295 and 1296 of the cDNA sequence. These nucleotides represented the junction between exon 8 and exon 9 of the BWR1A gene. Therefore, this inserted segment behaved like a new exon. Indeed, the newly added 111-nucleotide segment was found within intron 8, at 331 nucleotides from the 3-prime end of exon 8. The presence of the canonical splicing sites at the boundaries of the genomic sequence confirmed that the segment had been inserted in the normal BWR1A transcript by an mRNA splicing event. Though it did not introduce a frameshift, it did introduce an in-frame stop codon after 18 nucleotides, removing the last 136 amino acids at the normal polypeptide sequence. This result indicated that the mRNA was aberrant and not a product of alternative splicing. .0002 RHABDOMYOSARCOMA, SOMATIC In the rhabdomyosarcoma (268210) cell line TE125.5, Schwienbacher et al. (1998) found a G-to-A transition at nucleotide 688 that introduced an arginine in place of a cysteine in the product of the BWR1A gene. The change was present in a homozygous state, suggesting that loss of the normal allele occurred during the tumorigenic conversion. .0003 LUNG CANCER, SOMATIC In a lung cancer (211980), Lee et al. (1998) identified an apparent somatic mutation, a C-to-T transition at nucleotide 892 of the SLC22A1L gene, resulting in a ser233-to-phe substitution. They also found loss of heterozygosity in the lung cancer, suggesting that SLC22A1L may be a conventional tumor suppressor gene in the adult human lung and an imprinted tumor suppressor gene in the fetal kidney. .. _SLC22A18 Phenotype: NCBI Phenotypes *************** * Gene Reviews * Common variants in the calcium-sensing receptor gene are associated with total serum calcium levels. * Familial cancer of breast * GTR * Rhabdomyosarcoma 1 * OMIM * Genome-wide association meta-analysis for total serum bilirubin levels. * Lung cancer * NHGRI GWA Catalog .. _SLC22A18 GO Term: Gene Ontology ************* * nuclear envelope * symporter activity * apical plasma membrane * drug transmembrane transport * cytoplasmic part * transmembrane transport * excretion * drug transmembrane transporter activity * integral to membrane * drug transport * organic cation transport * ubiquitin protein ligase binding * plasma membrane .. _SLC22A18 Pathway: KEGG Pathways ************* No pathways found linked to this gene. .. _SLC22A18 GeneRIF: GeneRIFs ******** * Low expression of SLC22A18 was associated with tumor progression, recurrence and poor survival after breast surgery [`PMID 21144813`_] * Observational study and genome-wide association study of gene-disease association. (HuGE Navigator) [`PMID 20201924`_] * SLC22A18 gene is imprinted, with preferential expression from the maternal allele. [`PMID 9751628`_] * UbcH6-RING105 may define a novel ubiquitin-proteasome pathway that targets TSSC5 in mammalian cells [`PMID 16314844`_] * SLC22A18 downregulation via promoter methylation is associated with the development and progression of glioma. [`PMID 21936894`_] * Mutational analysis of the two Sp1 sites suggested their requirement for the promoter activityof SLC22A18. [`PMID 18996451`_] * recent demonstration that the promoter of this gene is positively regulated by Sp1 [`PMID 18996451`_] * study reports the imprinting status of SLC22A18AS in breast tissue and breast cancer, and shows that gain of imprinting affects both the sense, and antisense transcripts at this locus [`PMID 16624517`_] * The expression level of SLC22A18 in non-small cell lung cancer was significantly higher than that in normal tissue. [`PMID 22237119`_] * Affinity Capture-MS [`PMID 21906983`_] * involved in the drug resistance mechanism of tumors [`PMID 11925925`_] * SLC22A18 functions as a tumor suppressor in glioma and represents a candidate biomarker for long-term survival in this disease. [`PMID 22153794`_] .. _PMID 21144813: http://www.ncbi.nlm.nih.gov/pubmed/21144813 .. _PMID 20201924: http://www.ncbi.nlm.nih.gov/pubmed/20201924 .. _PMID 9751628: http://www.ncbi.nlm.nih.gov/pubmed/9751628 .. _PMID 16314844: http://www.ncbi.nlm.nih.gov/pubmed/16314844 .. _PMID 21936894: http://www.ncbi.nlm.nih.gov/pubmed/21936894 .. _PMID 18996451: http://www.ncbi.nlm.nih.gov/pubmed/18996451 .. _PMID 16624517: http://www.ncbi.nlm.nih.gov/pubmed/16624517 .. _PMID 22237119: http://www.ncbi.nlm.nih.gov/pubmed/22237119 .. _PMID 21906983: http://www.ncbi.nlm.nih.gov/pubmed/21906983 .. _PMID 11925925: http://www.ncbi.nlm.nih.gov/pubmed/11925925 .. _PMID 22153794: http://www.ncbi.nlm.nih.gov/pubmed/22153794 .. _SLC22A18 Pubmed: PubMed Articles *************** *Recent articles:* * Lei M et al. "[Expression and its clinical significance of SLC22A18 in non-small cell lung cancer]." Zhongguo Fei Ai Za Zhi. 2012;15(1):17-20. `PMID 22237119`_ * Chu SH et al. "Correlation of low SLC22A18 expression with poor prognosis in patients with glioma." J Clin Neurosci. 2012 Jan;19(1):95-8. `PMID 22153794`_ * Kim W et al. "Systematic and quantitative assessment of the ubiquitin-modified proteome." Mol Cell. 2011 Oct 21;44(2):325-40. `PMID 21906983`_ * Wagner SA et al. "A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles." Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. `PMID 21890473`_ * Chu SH et al. "Promoter methylation and downregulation of SLC22A18 are associated with the development and progression of human glioma." J Transl Med. 2011 Sep 21;9:156. `PMID 21936894`_ * He H et al. "Low expression of SLC22A18 predicts poor survival outcome in patients with breast cancer after surgery." Cancer Epidemiol. 2011 Jun;35(3):279-85. `PMID 21144813`_ * O'Seaghdha CM et al. "Common variants in the calcium-sensing receptor gene are associated with total serum calcium levels." Hum Mol Genet. 2010 Nov 1;19(21):4296-303. `PMID 20705733`_ * Edenberg HJ et al. "Genome-wide association study of alcohol dependence implicates a region on chromosome 11." Alcohol Clin Exp Res. 2010 May;34(5):840-52. `PMID 20201924`_ * Petrucelli N et al. "BRCA1 and BRCA2 Hereditary Breast and Ovarian Cancer." None 1993;. `PMID 20301425`_ * Johnson AD et al. "Genome-wide association meta-analysis for total serum bilirubin levels." Hum Mol Genet. 2009 Jul 15;18(14):2700-10. `PMID 19414484`_ .. _PMID 21890473: http://www.ncbi.nlm.nih.gov/pubmed/21890473 .. _PMID 20705733: http://www.ncbi.nlm.nih.gov/pubmed/20705733 .. _PMID 21144813: http://www.ncbi.nlm.nih.gov/pubmed/21144813 .. _PMID 20201924: http://www.ncbi.nlm.nih.gov/pubmed/20201924 .. _PMID 20301425: http://www.ncbi.nlm.nih.gov/pubmed/20301425 .. _PMID 21936894: http://www.ncbi.nlm.nih.gov/pubmed/21936894 .. _PMID 19414484: http://www.ncbi.nlm.nih.gov/pubmed/19414484 .. _PMID 22237119: http://www.ncbi.nlm.nih.gov/pubmed/22237119 .. _PMID 21906983: http://www.ncbi.nlm.nih.gov/pubmed/21906983 .. _PMID 22153794: http://www.ncbi.nlm.nih.gov/pubmed/22153794 *Top Pubmed articles linked to gene SLC22A18 matching any search term:* * Sakatani T et al. "Epigenetic heterogeneity at imprinted loci in normal populations." Biochem Biophys Res Commun. 2001 May 25;283(5):1124-30. `PMID 11355889`_ * Onyango P et al. "Sequence and comparative analysis of the mouse 1-megabase region orthologous to the human 11p15 imprinted domain." Genome Res. 2000 Nov;10(11):1697-710. `PMID 11076855`_ .. _PMID 11355889: http://www.ncbi.nlm.nih.gov/pubmed/11355889 .. _PMID 11076855: http://www.ncbi.nlm.nih.gov/pubmed/11076855