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GeneE
50 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
VDR
vitamin D receptor
Chromosome 12 Β· 12q13.11
NCBI Gene: 7421Ensembl: ENSG00000111424.12HGNC: HGNC:12679UniProt: A0A5K1VW50
2,491PubMed Papers
21Diseases
18Drugs
40Pathogenic Variants
FUNCTIONAL ROLE
ReceptorTranscription Factor
RESEARCH IMPACT
Highly Studied
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
vitamin D receptor signaling pathwayDNA-binding transcription factor activityvitamin D response element bindingphosphate ion transmembrane transportHypocalcemic vitamin D-resistant ricketspsoriasischronic kidney diseaseosteoporosis
✦AI Summary

The vitamin D receptor (VDR) is a nuclear receptor that mediates calcitriol (active vitamin D3) signaling through a well-characterized mechanism 1. Upon vitamin D3 binding, VDR translocates to the nucleus and forms heterodimers with retinoid X receptor (RXR), enabling binding to vitamin D response elements and activation of target gene transcription 12. Beyond classical calcium homeostasis, VDR exhibits broader physiological roles. It functions as a receptor for secondary bile acid lithocholic acid and its metabolites 34. VDR expression is downregulated in pulmonary arterial hypertension, and calcitriol treatment restores expression while exerting antiproliferative effects in pulmonary artery smooth muscle cells through survivin and BMP signaling modulation 5. VDR polymorphisms associate with disease susceptibility: rs731236 and rs7975232 variants correlate with autism risk 6, while rs1989969 increases gastric cardiac adenocarcinoma risk in younger, alcohol-consuming populations 7. The rs1544410 BsmI polymorphism influences COVID-19 clinical severity 8. Conversely, in pancreatic cancer, elevated VDR expression paradoxically promotes tumor progression by upregulating CCL20, facilitating M2 macrophage polarization and recruitment 9. Additionally, VDR modulation through miR193a affects renin-angiotensin system activation and podocyte markers in kidney disease contexts 10.

Sources cited
1
VDR binds calcitriol, forms heterodimers with RXR, and activates vitamin D-responsive gene transcription
PMID: 28698609
2
VDR functions as a nuclear receptor activated by 1,25(OH)2D3 with structural mechanisms involving RXR heterodimer formation
PMID: 28257826
3
VDR functions as a receptor for secondary bile acids (lithocholic acid)
PMID: 12016314
4
VDR functions as a receptor for lithocholic acid metabolites
PMID: 32354638
5
VDR expression is downregulated in pulmonary arterial hypertension; calcitriol upregulates VDR and exerts antiproliferative effects via survivin and BMP signaling
PMID: 39523384
6
VDR rs731236 and rs7975232 polymorphisms are associated with autism risk
PMID: 31900887
7
VDR rs1989969 polymorphism increases gastric cardiac adenocarcinoma risk, particularly in younger and alcohol-consuming populations
PMID: 28489590
8
VDR BsmI rs1544410 polymorphism influences COVID-19 clinical severity and symptomatic presentation
PMID: 39075671
9
High VDR expression in pancreatic cancer promotes M2 macrophage polarization and recruitment through CCL20 upregulation, enhancing tumor progression
PMID: 38600588
10
VDR upregulates KCNK3, BIRC5 (survivin), and BMP4 gene expression in pulmonary artery smooth muscle cells
PMID: 39523384
11
VDR expression is modulated by miR193a and affects renin-angiotensin system activation and podocyte markers in kidney disease
PMID: 39766282
Disease Associationsβ“˜21
Hypocalcemic vitamin D-resistant ricketsOpen Targets
0.82Strong
psoriasisOpen Targets
0.63Moderate
chronic kidney diseaseOpen Targets
0.62Moderate
osteoporosisOpen Targets
0.61Moderate
vitamin D deficiencyOpen Targets
0.60Moderate
secondary hyperparathyroidismOpen Targets
0.60Moderate
psoriasis vulgarisOpen Targets
0.60Moderate
HypocalcemiaOpen Targets
0.60Moderate
hypoparathyroidismOpen Targets
0.58Moderate
postmenopausal osteoporosisOpen Targets
0.56Moderate
anemia (phenotype)Open Targets
0.51Moderate
parathyroid diseaseOpen Targets
0.50Moderate
hypertensionOpen Targets
0.47Moderate
hyperparathyroidismOpen Targets
0.45Moderate
vitamin D-dependent ricketsOpen Targets
0.42Moderate
breast cancerOpen Targets
0.41Moderate
COVID-19Open Targets
0.41Moderate
ricketsOpen Targets
0.40Weak
type 1 diabetes mellitusOpen Targets
0.39Weak
non-alcoholic fatty liver diseaseOpen Targets
0.38Weak
Rickets vitamin D-dependent 2AUniProt
Pathogenic Variants40
NM_000376.3(VDR):c.148C>T (p.Arg50Ter)Pathogenic
Vitamin D-dependent rickets type II with alopecia|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 50
NM_000376.3(VDR):c.218G>A (p.Arg73Gln)Pathogenic
Vitamin D-dependent rickets type II with alopecia|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 73
NM_000376.3(VDR):c.885C>A (p.Tyr295Ter)Pathogenic
Vitamin D-dependent rickets type II with alopecia|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 295
NM_000376.3(VDR):c.217C>T (p.Arg73Ter)Pathogenic
Vitamin D-dependent rickets type II with alopecia|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 73
NM_000376.3(VDR):c.88C>T (p.Arg30Ter)Pathogenic
Vitamin D-dependent rickets type II with alopecia|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 30
NM_000376.3(VDR):c.821G>A (p.Arg274His)Pathogenic
Vitamin D-dependent rickets type II with alopecia|not provided|Rickets
β˜…β˜…β˜†β˜†2024β†’ Residue 274
NM_000376.3(VDR):c.1027C>T (p.Arg343Cys)Likely pathogenic
not provided|Vitamin D-dependent rickets type II with alopecia
β˜…β˜…β˜†β˜†2024β†’ Residue 343
NM_000376.3(VDR):c.1036G>A (p.Val346Met)Likely pathogenic
Vitamin D-dependent rickets type II with alopecia|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 346
NM_000376.3(VDR):c.1172G>A (p.Arg391His)Pathogenic
not provided|Vitamin D-dependent rickets type II with alopecia
β˜…β˜…β˜†β˜†2023β†’ Residue 391
NM_000376.3(VDR):c.238C>T (p.Arg80Trp)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 80
NM_000376.3(VDR):c.907+1G>CLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_000376.3(VDR):c.937del (p.Leu313fs)Likely pathogenic
Vitamin D-dependent rickets type II with alopecia
β˜…β˜†β˜†β˜†2024β†’ Residue 313
NM_000376.3(VDR):c.1024+1G>ALikely pathogenic
Vitamin D-dependent rickets type II with alopecia
β˜…β˜†β˜†β˜†2024
NM_000376.3(VDR):c.1039C>T (p.Gln347Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 347
NM_000376.3(VDR):c.-2-1G>ALikely pathogenic
Vitamin D-dependent rickets type II with alopecia
β˜…β˜†β˜†β˜†2023
NM_000376.3(VDR):c.1181_*670del (p.Asn394_Ter428delinsXaa)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 394
NM_000376.3(VDR):c.334G>T (p.Glu112Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 112
NM_000376.3(VDR):c.1153C>T (p.Gln385Ter)Likely pathogenic
Vitamin D-dependent rickets type II with alopecia
β˜…β˜†β˜†β˜†2023β†’ Residue 385
NM_000376.3(VDR):c.560C>G (p.Ser187Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 187
NM_000376.3(VDR):c.249del (p.Cys84fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 84
View on ClinVar β†—
Drug Targets18
ALFACALCIDOLPhase III
Vitamin D receptor agonist
osteoporosis
BECOCALCIDIOLPhase II
Vitamin D receptor agonist
psoriasis
CALCIFEDIOLApproved
Vitamin D receptor agonist
chronic kidney disease
CALCIPOTRIENEApproved
Vitamin D receptor agonist
psoriasis vulgaris
CALCITRIOLApproved
Vitamin D receptor agonist
Hypocalcemia
CHOLECALCIFEROLApproved
Vitamin D receptor agonist
anemia (phenotype)
DIHYDROTACHYSTEROLApproved
Vitamin D receptor agonist
Hypocalcemia
DOXERCALCIFEROLApproved
Vitamin D receptor agonist
chronic kidney disease
DP001Phase II
Vitamin D receptor agonist
osteoporosis
ELDECALCITOLApproved
Vitamin D receptor agonist
osteoporosis
ELOCALCITOLPhase II
Vitamin D receptor agonist
Urinary incontinence
ERGOCALCIFEROLApproved
Vitamin D receptor agonist
hypophosphatemic rickets
ILX23-7553Phase I
Vitamin D receptor agonist
prostate disease
INECALCITOLPhase II
Vitamin D receptor agonist
acute myeloid leukemia by FAB classification
LUNACALCIPOLPhase II
Vitamin D receptor agonist
psoriasis vulgaris
PARICALCITOLApproved
Vitamin D receptor agonist
chronic kidney disease
PEFCALCITOLPhase III
Vitamin D receptor agonist
psoriasis vulgaris
SEOCALCITOLPhase III
Vitamin D receptor agonist
rickets
Related Genes
CYP2R1Protein interaction96%NCOA1Protein interaction92%GCProtein interaction90%PTHProtein interaction85%NCOA3Protein interaction84%NCOA2Protein interaction83%
Tissue Expression6 tissues
Lung
100%
Bone Marrow
30%
Liver
5%
Brain
4%
Ovary
3%
Heart
3%
Gene Interaction Network
Click a node to explore
VDRCYP2R1NCOA1GCPTHNCOA3NCOA2
PROTEIN STRUCTURE
Preparing viewer…
PDB3B0T Β· 1.30 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.71LoF Tolerant
pLIβ“˜
0.01Tolerant
Observed/Expected LoF0.49 [0.34–0.71]
RankingsWhere VDR stands among ~20K protein-coding genes
  • #35of 20,598
    Most Researched2,491 Β· top 1%
  • #165of 1,025
    FDA-Approved Drug Targets9 Β· top quartile
  • #1,528of 5,498
    Most Pathogenic Variants40
  • #5,486of 17,882
    Most Constrained (LOEUF)0.71
Genes detectedVDR
Sources retrieved50 papers
Response timeβ€”
πŸ“„ Sources
50β–Ό
1
VDR promotes pancreatic cancer progression in vivo by activating CCL20-mediated M2 polarization of tumor associated macrophage.
PMID: 38600588
Cell Commun Signal Β· 2024
1.00
2
PMID: 31752548
Immunol Invest Β· 2020
0.98
3
APOL1 Modulates Renin-Angiotensin System.
PMID: 39766282
Biomolecules Β· 2024
0.90
4
MiR193a Modulation and Podocyte Phenotype.
PMID: 32316697
Cells Β· 2020
0.90
5
Pharmacogenetics of bone treatments: the VDR and ERalpha gene story.
PMID: 18518851
Pharmacogenomics Β· 2008
0.82