1p13.2

HHF7,MCT,MCT1,MCT1D

Various cancers

MCT1/SLC16A1 has been described to be upregulated in a variety of tumours.

High grade glial neoplasms (Mathupala et al., 2004; Fang et al., 2006), colorectal (Koukourakis et al., 2006; Pinheiro et al., 2008), lung (Koukourakis et al., 2007), cervical (Pinheiro et al., 2008), and breast carcinomas (Pinheiro et al., in Press).

Breast cancer

In breast cancer, MCT1/SLC16A1 was found to be associated with poor prognostic variables such as basal-like subtype and high grade tumours (Pinheiro et al., in Press).

SLC16A1 is expressed in normal breast tissue, but is silenced in breast cancer due to gene methylation (Asada et al., 2003).

Gastric cancer

The prognostic value of CD147 (a MCT1/SLC16A1 and MCT4/SLC16A3 chaperone required for plasma membrane expression and activity) was associated with MCT1/SLC16A1 co-expression in gastric cancer cells (Pinheiro et al., 2009).

Co-expression of MCT1/SLC16A1 with CD147 was associated with advanced gastric carcinoma, Laurens intestinal type, TNM staging and lymph-node metastasis, in gastric cancer.

Colorectal carcinoma

MCT1/SLC16A1 has been described to be downregulated in colorectal carcinoma (Lamber et al., 2002).

Erythrocyte lactate transporter defect

Merezhinskaya et al. (2000) identified two heterozygous transitions in the SLC16A1 gene, in patients with erythrocyte lactate transporter defect: 610A-G transition (resulting in a lys204-to-glu (K204E) substitution in a highly conserved residue) and 1414G-A transition (resulting in a gly472-to-arg (G472R) substitution halfway along the cytoplasmic C-terminal chain). These substitutions are not conserved, but were not identified in 90 healthy control individuals. Erythrocyte lactate clearance in patients with these mutations was 40 to 50% that of normal control values.

Hyperinsulinemic hypoglycemia familial 7

Otonkoski et al. (2007) identified two heterozygotic alterations in the SLC16A1, in affected members of a Finnish family segregating autosomal dominant exercise-induced hyperinsulinemic hypoglycemia. First, a 163G-A transition in exon 1 located within a binding site for nuclear matrix protein-1 and predicted to disrupt the binding sites of 2 potential transcriptional repressors, and, secondly, a 25-bp insertion at nucleotide -24 introducing additional binding sites for the ubiquitous transcription factors SP1, USF and MZF1. The first variation leads to a 3-fold increase in transcription while the second variation leads to a 10-fold increase in transcription. These mutations were not found in 92 Finnish and German controls.