Three Nonsynonymous Single Nucleotide Polymorphisms in the RhitH Gene Cause Reduction of the Repression Activity That Leads to Upregulation of M-LPH, a Participant in Mitochondrial Function

Human Mpv17-like protein (M-LPH) has been suggested to play a role in mitochondrial function. In this study, we identified a RhitH (human regulator of heat-induced transcription) binding site in intron 1 of the M-LPH gene. Tissue distribution analysis showed that M-LPH was specifically distributed in tissues with high mitochondrial metabolism. Functional and genetic analyses of nonsynonymous single nucleotide polymorphisms (SNPs) in the RhitH gene revealed that p.Cys461Ser, p.Thr465Ala, and p.Leu495Gln, corresponding to substitutions in the zinc fingers, cause reductions in the repression activity that lead to upregulation of M-LPH expression. The analyses also showed that the minor allele frequencies of these SNPs are extremely low in worldwide populations.