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The exact association between the position of mutation and clinical phenotypes is yet unknown, as a biallelic loss-of-function mutation in any part of the protein results in extreme enzyme deficiency

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Under the control of the biological clock system, the heterodimer CLOCK/BMAL1 and a series of other transcription factors are responsible for the circadian oscillation of gene expression ( PER1 , PER2 , and PER3 ), and Cryptochromes ( CRY1 and CRY2 )