Vitamin D Metabolism

Reduces CYP2R1 promoter activity and hepatic 25-hydroxylase expression, lowering circulating 25(OH)D independently of rs10741657

Intronic tag SNP at the CYP2R1/PDE3B locus on chromosome 11 that marks a haplotype associated with reduced vitamin D 25-hydroxylase activity and lower circulating 25-hydroxyvitamin D levels

Third independent intronic tag SNP in the vitamin D binding protein gene, influencing circulating 25-hydroxyvitamin D levels and supplementation response

Influences vitamin D synthesis by regulating how much 7-dehydrocholesterol is available for conversion to vitamin D3 in the skin

Upstream regulatory variant in CYP2R1 that tags a haplotype associated with reduced hepatic vitamin D 25-hydroxylation efficiency and lower circulating 25(OH)D levels

Intronic regulatory variant in CYP2R1 that reduces hepatic vitamin D 25-hydroxylase expression, lowering the rate of vitamin D activation and increasing susceptibility to vitamin D insufficiency

Upstream regulatory variant in CYP2R1 that reduces hepatic 25-hydroxylase expression, lowering the conversion of vitamin D3 to 25(OH)D and predisposing carriers to vitamin D insufficiency

Vitamin D receptor start codon variant — determines receptor protein length and transcriptional activity

Intronic DIO2 variant nominally associated with Graves' disease susceptibility and early-onset type 2 diabetes; may influence DIO2 expression in a gene carrying the key T4-to-T3 conversion enzyme

3' UTR regulatory variant in DIO2 that may alter local thyroid hormone availability, influencing how the body responds to levothyroxine therapy and how well inactive T4 is converted to active T3 in tissues

Intronic GWAS tag variant in the vitamin D binding protein gene, the strongest common genetic determinant of circulating 25-hydroxyvitamin D levels

Synonymous coding variant in CYP24A1 (vitamin D 24-hydroxylase) that tags functional haplotypes influencing vitamin D catabolism efficiency and cancer susceptibility

Intronic NADSYN1 variant at the DHCR7/NADSYN1 vitamin D locus; A allele was the top GWAS hit for lower circulating 25-hydroxyvitamin D in Ahn et al. 2010 (P = 3.4×10⁻⁹), reducing 7-dehydrocholesterol availability for skin vitamin D3 synthesis

Alters vitamin D binding protein affinity, affecting total and bioavailable 25-hydroxyvitamin D levels

Synonymous variant in vitamin D binding protein that tags distinct GC haplotypes, contributing to VDBP isoform diversity and influencing immune function, uveitis risk, and vitamin D bioavailability

Near-gene regulatory variant affecting vitamin D 24-hydroxylase expression — modulates the rate at which active vitamin D is degraded

Vitamin D binding protein variant that determines VDBP isoform, affecting vitamin D transport, bioavailability, and supplementation response

Intronic GC variant independently associated with vitamin D binding protein (VDBP) concentration; TT carriers have lower circulating VDBP and lower total 25(OH)D but may have normal or elevated free (bioavailable) vitamin D

Intronic variant in the primary hepatic vitamin D 25-hydroxylase gene associated with reduced CYP2R1 expression and lower circulating 25-hydroxyvitamin D concentrations

Intronic NADSYN1 variant in the DHCR7/NADSYN1 vitamin D locus; T allele tags the lower-vitamin-D haplotype, reducing 7-dehydrocholesterol availability for skin vitamin D3 synthesis

Near-gene intronic variant in the DHCR7/NADSYN1 locus on chromosome 11 that tags lower circulating vitamin D3 synthesis capacity; a near-perfect proxy for the canonical vitamin D synthesis SNP rs12785878

Intronic GC variant tagging a haplotype associated with lower circulating 25-hydroxyvitamin D and reduced response to vitamin D supplementation and UVB exposure