Vitamin D Receptor

The sun signal receptor.

VDR variants affect how cells respond to vitamin D. But the variants only matter when vitamin D is low.

What VDR does.

VDR is a nuclear receptor—a protein that sits in cells waiting for vitamin D. When vitamin D binds, VDR activates hundreds of genes.

VDR controls genes for:

Calcium & Bones

Regulates calcium absorption and bone mineralization

Immune Function

Activates antimicrobial peptides and modulates inflammation

Cell Growth

Regulates cell division and differentiation (cancer prevention)

Mood & Brain

Influences serotonin synthesis and neuroprotection

Key insight: VDR is found in almost every tissue—brain, immune cells, gut, skin, prostate, breast. Vitamin D signaling is systemic.

Common Variants

The main VDR polymorphisms.

Fok1 (rs2228570)

Affects the start codon—determines which version of VDR protein is made.

FF (CC)
Shorter, more active VDR protein
ff (TT)
Longer, less active protein

Bsm1 (rs1544410)

Located in an intron—affects mRNA stability and VDR expression levels.

BB (CC)
Lower VDR expression
bb (TT)
Higher VDR expression

Taq1 (rs731236)

Also affects mRNA stability. Often inherited together with Bsm1.

TT
Associated with higher bone density
tt
May need higher vitamin D levels

Variants only matter when vitamin D is low.

This is the crucial point. VDR variants are like having a slightly different shaped lock—but if you have enough keys (vitamin D), it still works.

Low vitamin D + VDR variant

  • • Weak signal through the receptor
  • • Gene activation is impaired
  • • Bone, immune, mood effects more likely
  • • Variant becomes clinically relevant

Optimal vitamin D + VDR variant

  • • Plenty of signal to activate VDR
  • • Gene activation proceeds normally
  • • Variant effect is minimized
  • • Clinically irrelevant for most people

Fix the vitamin D first. Then worry about the variant.

Reality Check

Genes don't act alone.

VDR doesn't determine your fate. It reveals where the system might need support.

Where it matters

VDR is expressed in almost every tissue—immune cells, brain, gut, bone, skin, prostate, breast. The same variant can have different effects depending on which tissue you're looking at and local vitamin D availability.

Expression depends on

  • • Nutrient availability
  • • Sunlight exposure
  • • Toxin burden
  • • Cell turnover rate
  • • Age and hormonal status

SNPs are throttles, not defects

Genetic variants often slow down pathways to protect the system from overwhelm. They reveal where you need to go slower, not that you're broken.

The real question

Not "what does this gene do?" but "what is this pathway already struggling with that makes this gene relevant?"

"Genes don't cause outcomes. They reveal where the system is already under pressure."

VDR Discussion