MCT variants and MCT up/downregulation in disease
| Health/Disease Relation | Reference | |
|---|---|---|
| MCT1, 2, 4 | High expression in many cancer types, including breast, bone, colon, bladder, prostate, and renal cancers | Park et al., 2018 |
| MCT1 | Mutations in promoter region lead to exercise-induced hyperinsulinemia | Otonkoski et al., 2007 |
| The missense mutation (1470T > A) results in an amino acid substitution leading to less efficient lactate transport | Onali et al., 2018 | |
| Deficiency has also been associated with recurrent ketoacidosis in children | Fisel et al., 2018 | |
| Acute exercise-induced upregulation in skeletal muscle | Bickham et al., 2006 | |
| MCT2 | SNPs (rs10506398 and rs10506399) were associated with increased infertility in Korean men | Jones and Morris, 2016 |
| Implicated as a potential biomarker and treatment of prostate cancer | Pertega-Gomes et al., 2013 | |
| MCT4 | Increased expression in obesity, followed by a decreased expression with weight loss | Fisel et al., 2018 |
| Upregulation via hypoxia through a HIF-1α–dependent pathway | Ullah et al., 2006 | |
| MCT3 and 4 | Wounded RPE results in a decrease in expression of MCT3, and an increase in the expression of MCT4 | Gallagher-Colombo et al., 2010 |
| MCT5 | Gene expression was significantly upregulated in colorectal adenocarcinoma | Liu et al., 2018 |
| SNP (rs17025736) results in an intron variant of the human MCT5 gene, which is associated with adolescent idiopathic scoliosis | Buniello et al., 2019 | |
| Enhancement of West Nile virus infection was demonstrated when MCT5 was silenced | Krishnan et al., 2008; Fisel et al., 2018 | |
| MCT6 | Plays a role in the intestinal absorption of nateglinide, bumetanide’s brain penetration | Kohyama et al., 2013; Romermann et al., 2017 |
| Hypomethylation of MCT6, along with hypermethylation of a ZFN206, results in significantly prolonged event-free survival in neuroblastomas | Sugito et al., 2013 | |
| May play a role as a biomarker in Alzheimer’s disease risk | Boada et al., 2014; Wei et al., 2019 | |
| Significant variant (rs4788863) resulted in a significant decrease in cisplatin-induced ototoxicity severity in testicular cancer patients | Drögemöller et al., 2017 | |
| MCT7 | Suggested to play a role in liver disease primarily from evidence gathered in preclinical models | Hugo et al., 2012; Kim et al., 2016; Karanth and Schlegel, 2019 |
| MCT8 | Various mutations results in AHDS, which results in increased serum thyroid hormone: T3, due to the decrease in the cellular uptake | Friesema et al., 2003; Dumitrescu et al., 2004, 2006; Schwartz et al., 2005; Trajkovic et al., 2007; Wirth et al., 2009 |
| MCT10 | A SNP in the gene was found to result in lower free plasma T3 concentrations | van der Deure et al., 2007 |
| Importance in maintaining circulating and liver aromatic amino acid concentrations in vivo | Mariotta et al., 2012 | |
| Functional role in aromatic amino acid transport and its relation to NASH due to the significant downregulation of gene expression | Lake et al., 2015 | |
| MCT11 | Mutations in the gene encoding for MCT11 have been implicated in the risk of T2D | Williams et al., 2014; Rusu et al., 2017; Kimura et al., 2018 |
| SNP (rs13342232) was found to be significantly associated with the occurrence of T2D in adults and children | Miranda-Lora et al., 2017 | |
| MCT12 | Mutation in the gene encoding for MCT12 was identified in a Swiss family with autosomal dominant juvenile cataracts, microcornea, as well as renal glucosuria | Kloeckener-Gruissem et al., 2008 |
| A SNP was identified in the 5′UTR of MCT12, which provided evidence for its role in regulation of translational efficiency that could potentially be associated with age-related cataracts | Zuercher et al., 2010 | |
| Mutation in MCT12’s coding region of exon 6 yielded evidence that suggested that the variant most likely impacts correct protein folding and trafficking with basigin | Castorino et al., 2011b | |
| In vitro and in vivo evidence for MCT12’s role in creatinine transporter, which supported a plausible mechanism by which MCT12 mutations lead to perturbations in the eye | Abplanalp et al., 2013 | |
| Impacts the renal handling of creatinine transport and systemic concentrations of its precursor, guanidinoacetate | Dhayat et al., 2016 | |
| MCT13 | May also play a functional role in T2D risk | Rusu et al., 2017 |
| MCT14 | Gene expression was shown to increase 2.1-fold following treatment with ethanol for 48 hours vs. no treatment in immortalized lymphoblastoid cells originally isolated from subjects enrolled in the Collaborative Study on the Genetics of Alcoholism | McClintick et al., 2019 |