Functional characterization of the reveals its role in vitamin D biosynthesis.

Vitamin D deficiency poses a widespread health challenge, shaped by environmental and genetic determinants. A recent discovery identified a genetic regulator, rs11542462, in the gene, though its biological implications remain largely unexplored. Our bioinformatic assessments revealed pronounced expression in skin keratinocytes and the analogous HaCaT human keratinocyte cell lines, prompting us to select the latter as an experimental model. Employing CRISPR/Cas9 gene-editing technology and multi-omics approach, we discovered that depleting showed a 1.6-fold disruption in steroid biosynthesis pathway (-value = 0.03), considerably affecting crucial vitamin D biosynthesis regulators. Notably, (-value = 2.17 × 10), (-value = 2.46 × 10), and (-value = 8.03 × 10) elevated by ∼2-3 fold, while (-value <2.2 × 10), (-value = 1.96 × 10), and (-value = 1.06 × 10) downregulated by ∼1.5-3 fold. These alterations resulted in accumulation of 7-dehydrocholesterol precursor and reduction of vitamin D production, as evidenced by the drug enrichment (-value = 4.39 × 10) and total vitamin D quantification (R = 0.935, -value = 0.0016) analyses. Our investigation unveils 's significance in vitamin D homeostasis, emphasizing the potential of precision medicine in addressing vitamin D deficiency through understanding its genetic basis.