MCT variants and MCT up/downregulation in disease

Health/Disease RelationReference
MCT1, 2, 4High expression in many cancer types, including breast, bone, colon, bladder, prostate, and renal cancersPark et al., 2018
MCT1Mutations in promoter region lead to exercise-induced hyperinsulinemiaOtonkoski et al., 2007
The missense mutation (1470T > A) results in an amino acid substitution leading to less efficient lactate transportOnali et al., 2018
Deficiency has also been associated with recurrent ketoacidosis in childrenFisel et al., 2018
Acute exercise-induced upregulation in skeletal muscleBickham et al., 2006
MCT2SNPs (rs10506398 and rs10506399) were associated with increased infertility in Korean menJones and Morris, 2016
Implicated as a potential biomarker and treatment of prostate cancerPertega-Gomes et al., 2013
MCT4Increased expression in obesity, followed by a decreased expression with weight lossFisel et al., 2018
Upregulation via hypoxia through a HIF-1α–dependent pathwayUllah et al., 2006
MCT3 and 4Wounded RPE results in a decrease in expression of MCT3, and an increase in the expression of MCT4Gallagher-Colombo et al., 2010
MCT5Gene expression was significantly upregulated in colorectal adenocarcinomaLiu et al., 2018
SNP (rs17025736) results in an intron variant of the human MCT5 gene, which is associated with adolescent idiopathic scoliosisBuniello et al., 2019
Enhancement of West Nile virus infection was demonstrated when MCT5 was silencedKrishnan et al., 2008; Fisel et al., 2018
MCT6Plays a role in the intestinal absorption of nateglinide, bumetanide’s brain penetrationKohyama et al., 2013; Romermann et al., 2017
Hypomethylation of MCT6, along with hypermethylation of a ZFN206, results in significantly prolonged event-free survival in neuroblastomasSugito et al., 2013
May play a role as a biomarker in Alzheimer’s disease riskBoada et al., 2014; Wei et al., 2019
Significant variant (rs4788863) resulted in a significant decrease in cisplatin-induced ototoxicity severity in testicular cancer patientsDrögemöller et al., 2017
MCT7Suggested to play a role in liver disease primarily from evidence gathered in preclinical modelsHugo et al., 2012; Kim et al., 2016; Karanth and Schlegel, 2019
MCT8Various mutations results in AHDS, which results in increased serum thyroid hormone: T3, due to the decrease in the cellular uptakeFriesema et al., 2003; Dumitrescu et al., 2004, 2006; Schwartz et al., 2005; Trajkovic et al., 2007; Wirth et al., 2009
MCT10A SNP in the gene was found to result in lower free plasma T3 concentrationsvan der Deure et al., 2007
Importance in maintaining circulating and liver aromatic amino acid concentrations in vivoMariotta et al., 2012
Functional role in aromatic amino acid transport and its relation to NASH due to the significant downregulation of gene expressionLake et al., 2015
MCT11Mutations in the gene encoding for MCT11 have been implicated in the risk of T2DWilliams 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 childrenMiranda-Lora et al., 2017
MCT12Mutation in the gene encoding for MCT12 was identified in a Swiss family with autosomal dominant juvenile cataracts, microcornea, as well as renal glucosuriaKloeckener-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 cataractsZuercher 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 basiginCastorino 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 eyeAbplanalp et al., 2013
Impacts the renal handling of creatinine transport and systemic concentrations of its precursor, guanidinoacetateDhayat et al., 2016
MCT13May also play a functional role in T2D riskRusu et al., 2017
MCT14Gene 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 AlcoholismMcClintick et al., 2019