Review Article
Role of the Plasma Membrane Transporter of Organic Cations OCT1 and Its Genetic Variants in Modern Liver Pharmacology
Table 4
Genetic variants and functional consequences in human OCT1.
| Reference SNP | Amino acid change | Nucleotide variation | Exon | Protein domain | Transport activity compared with wild type | PML | MPP+ | TEA | Metformin | Others |
| rs34447885 | S14F | c.41C>T | 1 | NH2 terminus | ↑ [30] | = [3] | ↓ [36] | = Sorafenib [3] | | rs12208357 | R61C | c.181C>T | 1 | Large EL | ↓ [26, 30] | ↓ [3, 26] | ↓ [36] | ↓ Sorafenib [3] | NO [36] | NA | R61S fs*10 | c.181delCGinsT | 1 | Large EL | | ↓ [3] | | ↓ Sorafenib [3] | | rs35546288 | L85F | c.253C>G | 1 | Large El | = [30] | | | | NO [3] | rs55918055 | C88R | c.262T>C | 1 | Large EL | ↓ [26] | ↓ [3] | | ↓ Sorafenib [3] | NO [3] | NA | C88A fs*16 | c.262delT | 1 | Large EL | | ↓ [3] | | ↓ Sorafenib [3] | NO [3] | NA | Q97K | c.289C>A | 1 | Large EL | | | ↓ [35] | | YES [35] | NA | P117L | c.350C>T | 1 | Large EL | | | ↓ [35] | | YES [35] | rs683369 | L160F | c.480G>C | 2 | TMD2 | = [26, 30, 33] | = [3, 33] | = [36] | = Sorafenib [3] | YES [33] | rs34104736 | S189L | c.566C>T | 3 | TMD3 | = [30] | ↓ [3] | ↓ [36] | ↓ Sorafenib [3] | NO [3] | NA | P197S | c.589C>T | 3 | TMD3 | | = [3] | | = Sorafenib [3] | YES [3] | NA | R206C | c.616C>T | 3 | EL2 | | | ↓ [35] | | NO [35] | rs36103319 | G220V | c.659G>T | 3 | TMD4 | ↓ [30] | ↓ [3] | ↓ [36] | = Sorafenib [3] | | rs4646277 | P283L | c.848C>T | 5 | TMD6 | ↓
[33, 41] | ↓ [32, 33, 41] | = [41] | ↓ Lamivudine [41] | YES [33] | rs4646278 | R287G | c.859C>G | 5 | Large CL | ↓ [33] | ↓ [3, 32, 33] | | ↓ Sorafenib [3] | YES [33] | rs2282143 | P341L | c.1022C>T | 6 | Large CL | ↓ [30, 33, 41] | ↓ [32, 33, 41] | = [36, 41] | ↓ Lamivudine [41] | YES [33] | rs34205214 | R342H | c.1025G>A | 6 | Large CL | = [30] | | = [36] | | | rs34130495 | G401S | c.1201G>A | 7 | CL4 | ↓ [26, 30] | ↓ [26] = [3] | ↓ [36] | = Sorafenib [3] | | rs628031 | M408V | c.1222A>G | 7 | TMD9 | = [30] | | = [36] | | | rs20222080 | M420del | c.1258_1260delATG | 7 | TMD9 | = [26, 30] | | ↓ [36] | | | rs35956182 | M440I | c.1320G>A | 7 | TMD10 | = [30] | | | | | rs34295611 | V461I | c.1381G>A | 7 | CL5 | = [30] | | | | | rs34059508 | G465R | c.1393G>C | 8 | TMD11 | ↓ [30] | ↓ [3] | ↓ [36] | = Sorafenib [3] | YES [3] | rs35270274 | R488M | c.1463G>C | 8 | EL6 | = [30] | | = [36] | | YES [30] |
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EL: extracellular loop; CL: cytoplasmic loop; NA: not assigned; PML: plasma membrane localization; TMD: transmembrane domain; ↑: increased; ↓: decreased; =: unaltered.
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