Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders
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Vitamin D receptor

Mutations of this vitamin D sensing transcription factor lead to rickets and osteoporosis.


A defective vitamin D receptor is rare. But polymorphisms are frequent: Apa I 37% (homozygous lacking), 43% (heterozygous), 20% (homozygous present); Bsm I 24%, 46%, 30% (respectively); Fok I 44%, 50%, 6% (respectively); Taq I 30%, 45%, 25% (respectively).

Gene Structure

The gene (VDR) is about 65kb in size. It is localized in chromosome 12 (12q12-14) in proximity to 25-hydroxyvitamin D3 1-alpha-hydroxylase. The gene forms 10 exons but only 8 of them are translated.


The symptoms of vitamin D deficiency are similar: growth retardation, muscular weakness and bone deformities. The lack of improvement of the symptoms under physiological doses of calcitriol is important for differential diagnoses. Sometimes depending on the mutation pharmacological doses of calcitriol can be successfully used for therapy. In some cases alopecia is an additional symptom. Some polymorphisms are describe with connection to osteoporosis.


The vitamin D receptor is an intracellular receptor to calcitriol and acts as a transcription factor. For this function two important domains can be distinguished a DNA binding domain (DBD) and a ligand binding domain (LBD). The protein forms a homodimer or a heterodimer with one of three retinoid X receptors. The DNA portion that binds to the receptor is called vitamin D response element (VDRE). Several cofactors are necessary for transactivation.

Test Strategy

Family consulting is the main reason for this investigation. The determination of the risk of osteoporosis is an other intention.


The genetic test is important for confirmation of a suspected diagnosis. Missense mutations in LBD are still susceptible to pharmacological dose of calcitriol. On the other hand mutation in DBD result in severe clinical pictures. A lot of studies connecting osteoporosis to polymorphisms exist. The results are still controversial. This is because of to small patient populations and parameters of osteoporosis that are difficult to compare.


Clinic Method Carrier testing
Turnaround 5 days
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25 days
Specimen type genomic DNA
Clinic Method Genomic sequencing of the entire coding region
Turnaround 20 days
Specimen type genomic DNA
Clinic Method Target mutation analysis
Turnaround 20 days
Specimen type genomic DNA

Related Diseases:

Osteoporosis/renal Osteodystrophy
Vitamin D-dependent rickets, type 2A



Rothe H et al. (2017) Ecto-5' -Nucleotidase CD73 (NT5E), vitamin D receptor and FGF23 gene polymorphisms may play a role in the development of calcific uremic arteriolopathy in dialysis patients - Data from the German Calciphylaxis Registry.

external link

Kato S et al. (2002) Molecular genetics of vitamin D- dependent hereditary rickets.

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Uitterlinden AG et al. (2004) Genetics and biology of vitamin D receptor polymorphisms.

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Orphanet article

Orphanet ID 120464 external link

NCBI article

NCBI 7421 external link

OMIM.ORG article

Omim 601769 external link

Wikipedia article

Wikipedia EN (Calcitriol_receptor) external link
Update: Aug. 14, 2020
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