Skip to main content
. 2020 Apr;72(2):466–485. doi: 10.1124/pr.119.018762

TABLE 4.

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
HHS Vulnerability Disclosure