VDR

Summary

VDR (vitamin D receptor, HGNC:12679) is a protein-coding gene on chromosome 12q13.11, encoding Vitamin D3 receptor (P11473). Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action of this vitamin on cells.

This gene encodes vitamin D3 receptor, which is a member of the nuclear hormone receptor superfamily of ligand-inducible transcription factors. This receptor also functions as a receptor for the secondary bile acid, lithocholic acid. Downstream targets of vitamin D3 receptor are principally involved in mineral metabolism, though this receptor regulates a variety of other metabolic pathways, such as those involved in immune response and cancer. Mutations in this gene are associated with type II vitamin D-resistant rickets. A single nucleotide polymorphism in the initiation codon results in an alternate translation start site three codons downstream. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. A recent study provided evidence for translational readthrough in this gene, and expression of an additional C-terminally extended isoform via the use of an alternative in-frame translation termination codon.

Source: NCBI Gene 7421 — RefSeq curated summary.

At a glance

• Gene–disease (curated): vitamin D-dependent rickets, type 2A (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 10
• Clinical variants (ClinVar): 568 total — 25 pathogenic, 14 likely-pathogenic
• Phenotypes (HPO): 69
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• Transcription factor: yes — 165 downstream targets (CollecTRI)
• MANE Select transcript: NM_000376

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12679
Approved symbol	VDR
Name	vitamin D receptor
Location	12q13.11
Locus type	gene with protein product
Status	Approved
Aliases	NR1I1, PPP1R163
Ensembl gene	ENSG00000111424
Ensembl biotype	protein_coding
OMIM	601769
Entrez	7421

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 nonsense_mediated_decay

ENST00000229022, ENST00000395324, ENST00000546653, ENST00000547065, ENST00000548664, ENST00000549336, ENST00000550314, ENST00000550325, ENST00000891950

RefSeq mRNA: 6 — MANE Select: NM_000376 NM_000376, NM_001017535, NM_001017536, NM_001364085, NM_001374661, NM_001374662

CCDS: CCDS55820, CCDS8757, CCDS91689

Canonical transcript exons

ENST00000549336 — 10 exons

Exon	Start	End
ENSE00000000060	47904955	47904994
ENSE00003492058	47865047	47865177
ENSE00003519423	47855630	47855801
ENSE00003520661	47846335	47846451
ENSE00003576665	47857504	47857688
ENSE00003626343	47878968	47879115
ENSE00003647846	47857129	47857249
ENSE00003656760	47846657	47846808
ENSE00003678407	47882694	47882774
ENSE00003904119	47841537	47845005

Expression profiles

Bgee: expression breadth ubiquitous, 224 present calls, max score 97.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.3210 / max 311.8997, expressed in 1390 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130711	7.2183	1318
130710	3.5449	876
130704	0.9571	60
130702	0.2622	116
130705	0.1407	45
130706	0.0624	30
130707	0.0526	34
130703	0.0502	29
130708	0.0326	21

Top tissues by expression

274 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	97.43	gold quality
hair follicle	UBERON:0002073	96.74	gold quality
jejunal mucosa	UBERON:0000399	96.59	gold quality
colonic mucosa	UBERON:0000317	96.32	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.27	gold quality
duodenum	UBERON:0002114	95.40	gold quality
ileal mucosa	UBERON:0000331	94.12	gold quality
upper arm skin	UBERON:0004263	93.72	gold quality
mucosa of transverse colon	UBERON:0004991	93.08	gold quality
periodontal ligament	UBERON:0008266	92.56	gold quality
rectum	UBERON:0001052	91.50	gold quality
cervix squamous epithelium	UBERON:0006922	90.85	gold quality
squamous epithelium	UBERON:0006914	90.06	gold quality
trabecular bone tissue	UBERON:0002483	89.70	gold quality
esophagus squamous epithelium	UBERON:0006920	89.67	gold quality
gingiva	UBERON:0001828	89.48	gold quality
gingival epithelium	UBERON:0001949	89.38	gold quality
palpebral conjunctiva	UBERON:0001812	89.12	gold quality
epithelium of esophagus	UBERON:0001976	88.93	gold quality
nephron tubule	UBERON:0001231	87.72	gold quality
tongue squamous epithelium	UBERON:0006919	87.49	gold quality
mammary duct	UBERON:0001765	87.18	gold quality
epithelium of mammary gland	UBERON:0003244	87.17	gold quality
mammalian vulva	UBERON:0000997	87.13	gold quality
cervix epithelium	UBERON:0004801	87.08	gold quality
jejunum	UBERON:0002115	86.22	gold quality
zone of skin	UBERON:0000014	86.17	gold quality
upper leg skin	UBERON:0004262	86.06	gold quality
mucosa of urinary bladder	UBERON:0001259	85.89	gold quality
skin of abdomen	UBERON:0001416	85.74	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.42

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

165 targets.

Target	Regulation
ABCA12	Activation
ABCB1	Activation
ABCC3
ADAM2
AGT	Repression
AGTR1	Repression
ALOX5
AMH	Unknown
APOA1	Unknown
ARG1	Activation
ASAP2	Unknown
ATP6AP2	Repression
BAZ1B
BGLAP	Unknown
BHLHE40	Unknown
BMP2
BMP7
BRCA1	Activation
CA2	Unknown
CALB1	Activation
CAMP	Unknown
CASR
CCL2	Activation
CCND3
CCR10	Activation
CD14	Activation
CD44
CD8A
CDH1	Activation
CDKN1A	Unknown

JASPAR motifs

Motif	Name	Family
MA0074.1	RXRA::VDR	RXR-related receptors (NR2)::Thyroid hormone receptor-related factors (NR1)
MA0693.2	VDR	Thyroid hormone receptor-related factors (NR1)

JASPAR matrix evidence (PMIDs): PMID:8674817, PMID:8065900

Upstream regulators (CollecTRI, top): AR, BHLHE40, BHLHE41, CDX1, CDX2, CEBPA, CREM, CTBP1, DLX4, ESR1, ESR2, EZH2, FOS, GLI2, GRHL3, HDAC1, JUN, KLF4, MED1, MSX1, MYB, NCOA3, NR0B2, NR1H3, NR3C1, PGR, PIAS4, POU1F1, SMAD3, SNAI1, SNAI2, SNW1, SP1, SP7, SSRP1, STAT3, TCF3, TFAP2A, TP53, TP63

miRNA regulators (miRDB)

154 targeting VDR, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-6756-5P	99.82	67.97	2466

Literature-anchored findings (GeneRIF, showing 40)

• These data suggest that BsmI VDR polymorphism does not play an important role in the bone loss seen in hypercalciuric CSF patients. (PMID:11744805)
• critical role of helix 12 of the vitamin D3 receptor for the partial agonism of carboxylic ester antagonist, ZK159222 (PMID:11779241)
• transactivation modulated by a central dinucleotide within vitamin D response elements (PMID:11834737)
• Association of vitamin D receptor gene BsmI polymorphisms in Chinese patients with systemic lupus erythematosus. (PMID:11898916)
• Stat1-vitamin D receptor interactions antagonize 1,25-dihydroxyvitamin D transcriptional activity and enhance stat1-mediated transcription. (PMID:11909970)
• A clinically significant relationship between VDR and ER genotypes and biochemical markers of bone turnover or serum lipoproteins could not be demonstrated in healthy Danish postmenopausal women (PMID:11910656)
• Regulation of calbindin-D9k expression by 1,25-dihydroxyvitamin D(3) and parathyroid hormone in mouse primary renal tubular cells (PMID:11913978)
• polymorphism and risk of severe diabetic retinopathy. (PMID:11914750)
• data support the VDR gene as a quantitative trait locus(QTL)underlying spine bone mineral density variation (PMID:11918225)
• vitamin D receptor is required for the initiation of the postnatal hair follicular cycle (PMID:11918709)
• its genetic polymorphism determines bone mineral density (PMID:11979895)
• regulates expression of CYP3A4, CYP2B6, and CYP2C9 in hepatocytes (PMID:11991950)
• polymorphism in type 1 diabetics in a Romanian population (PMID:12003670)
• functions as a receptor for the secondary bile acid lithocholic acid (LCA) (PMID:12016314)
• results suggest that the vitamin D receptor Fok I start codon polymorphism is not related to patients with systemic lupus erythematosus in Taiwan (PMID:12064837)
• investigation of the genetic influence of Sp1 polymorphism on bone density in Irish women (PMID:12073153)
• levels in relation to vitamin D status, insulin secretory capacity, and VDR genotype in Bangladeshi Asians. (PMID:12086963)
• There is an association between genotype and age of onset in juvenile Japanese patients with type 1 diabetes. (PMID:12087029)
• The VDR genotype contributes to the liver dysfunction in patients with psoriasis, although no correlation was found between VDR genotype and the skin eruptions of psoriasis. (PMID:12111344)
• retinoid X receptor regulates vitamin D receptor functions in part by regulating subcellular localization (PMID:12145331)
• alteration of cellular phosphorylation state affects vitamin D receptor-mediated CYP3A4 mRNA induction in Caco-2 cells (PMID:12147248)
• expression is increased in ovarian carcinomas as compared to normal ovarian tissue (PMID:12174912)
• contribution of VDR genotypes to prostate cancer susceptibility might depend on the population studied and its geographic localization; VDR genotypes are important in the definition of the genetic risk profile of populations of southern Europe (PMID:12181642)
• This is the first report of an association between VDR gene polymorphism and psoriasis in a Caucasian population. (PMID:12192493)
• Tryptophan missense mutation in the ligand-binding domain of the vitamin D receptor causes severe resistance to 1,25-dihydroxyvitamin D. (PMID:12211444)
• removal of the insertion domain between helices 2 and 3 of the receptor does not markedly influence the functionality of the Vitamin d receptor. (PMID:12237325)
• Determination of VDR genotype by analysis of BsmI endonuclease gene polymorphism may predict both hemoglobin level and erythropoietin requirement in hemodialysis patients with anemia. (PMID:12324918)
• Despite a slight increase in the number of urinary tract infections among children with the BB genotype for the vitamin D receptor, there is no statistically significant correlation with genetic susceptibility. (PMID:12369133)
• the VDR genotype polymorphism affects bone density of renal transplant recipients via its effects on the severity of secondary hyperparathyroidism. (PMID:12369780)
• vitamin D receptor (VDR) gene polymorphism, which locates at the translation initiation site, matters in the adaptations of bone to long-term impact loading. (PMID:12391072)
• Association of vitamin D receptor gene polymorphism with renal cell carcinoma in Japanese. (PMID:12402975)
• A novel mutation in helix 12 of this receptor impairs coactivator interaction and causes hereditary 1,25-dihydroxyvitamin D-resistant rickets without alopecia. (PMID:12403843)
• Polymorphisms of VDR gene are associated with Japanese patients with psoriasis vulgaris. Allelic variance in the VDR gene or other genes in linkage disequilibrium with this gene might predispose to the development of psoriasis vulgaris. (PMID:12413773)
• associations between BsmI-polymorphism of the VDR gene and bone mineral density and bone metabolism in 24 premenopausal (aged 22-45 years) and 69 postmenopausal (aged 48-65 years) Finnish women (PMID:12434167)
• Novel mutation in the VDR, Q317X, is the molecular defect in a patient with 1,25-dihydroxyvitamin D resistant rickets (PMID:12468277)
• the FokI genotype of the vitamin D receptor gene is related to bone mass at the hip in Czech postmenopausal women, whereas the importance of remaining VDR genotypes was not evident. (PMID:12470203)
• VDR polymorphisms are associated with increased risk of type 1 diabetes in the Dalmatian population of South Croatia. (PMID:12482639)
• Data suggest that 1,25-dihydroxyvitamin D(3) actions on normal prostate cells may be mediated independently through androgen receptors and vitamin D receptors. (PMID:12532336)
• (Is this the right receptor?) Start codon polymorphism is an independent predictor of lumbar, but not femoral neck bone density. (PMID:12601576)
• The VDR genotype seems to slow the progression of secondary hyperparathyroidism needing parathyroidectomy in patients treated with hemodialysis. (PMID:12649542)

Cross-species orthologs

188 orthologs

Organism	Symbol	Gene ID
danio_rerio	vdrb	ENSDARG00000070721
danio_rerio	vdra	ENSDARG00000099483
danio_rerio	vdra	ENSDARG00000112923
mus_musculus	Vdr	ENSMUSG00000022479
rattus_norvegicus	Vdr	ENSRNOG00000054420
drosophila_melanogaster	EcR	FBGN0000546
drosophila_melanogaster	Hr96	FBGN0015240
caenorhabditis_elegans		WBGENE00001062
caenorhabditis_elegans	nhr-2	WBGENE00003601
caenorhabditis_elegans		WBGENE00003608
caenorhabditis_elegans		WBGENE00003611
caenorhabditis_elegans		WBGENE00003614
caenorhabditis_elegans		WBGENE00003615
caenorhabditis_elegans		WBGENE00003617
caenorhabditis_elegans		WBGENE00003618
caenorhabditis_elegans		WBGENE00003620
caenorhabditis_elegans		WBGENE00003624
caenorhabditis_elegans		WBGENE00003632
caenorhabditis_elegans		WBGENE00003634
caenorhabditis_elegans		WBGENE00003638
caenorhabditis_elegans		WBGENE00003640
caenorhabditis_elegans		WBGENE00003641
caenorhabditis_elegans		WBGENE00003642
caenorhabditis_elegans		WBGENE00003643
caenorhabditis_elegans		WBGENE00003644
caenorhabditis_elegans		WBGENE00003645
caenorhabditis_elegans		WBGENE00003646
caenorhabditis_elegans		WBGENE00003648
caenorhabditis_elegans		WBGENE00003649
caenorhabditis_elegans		WBGENE00003651
caenorhabditis_elegans		WBGENE00003653
caenorhabditis_elegans		WBGENE00003655
caenorhabditis_elegans		WBGENE00003658
caenorhabditis_elegans		WBGENE00003660
caenorhabditis_elegans		WBGENE00003662
caenorhabditis_elegans	nhr-73	WBGENE00003663
caenorhabditis_elegans	nhr-77	WBGENE00003667
caenorhabditis_elegans		WBGENE00003669
caenorhabditis_elegans	nhr-81	WBGENE00003671
caenorhabditis_elegans	nhr-82	WBGENE00003672
caenorhabditis_elegans		WBGENE00003676
caenorhabditis_elegans		WBGENE00003677
caenorhabditis_elegans		WBGENE00003680
caenorhabditis_elegans		WBGENE00003682
caenorhabditis_elegans		WBGENE00003684
caenorhabditis_elegans		WBGENE00003685
caenorhabditis_elegans		WBGENE00003686
caenorhabditis_elegans		WBGENE00003688
caenorhabditis_elegans		WBGENE00003689
caenorhabditis_elegans		WBGENE00003692
caenorhabditis_elegans		WBGENE00003693
caenorhabditis_elegans		WBGENE00003694
caenorhabditis_elegans		WBGENE00003696
caenorhabditis_elegans		WBGENE00003698
caenorhabditis_elegans		WBGENE00003699
caenorhabditis_elegans		WBGENE00003700
caenorhabditis_elegans		WBGENE00003702
caenorhabditis_elegans		WBGENE00003704
caenorhabditis_elegans		WBGENE00003705
caenorhabditis_elegans		WBGENE00003707
caenorhabditis_elegans		WBGENE00003708
caenorhabditis_elegans		WBGENE00003712
caenorhabditis_elegans		WBGENE00003713
caenorhabditis_elegans		WBGENE00003714
caenorhabditis_elegans		WBGENE00003715
caenorhabditis_elegans		WBGENE00003716
caenorhabditis_elegans		WBGENE00003717
caenorhabditis_elegans		WBGENE00003718
caenorhabditis_elegans		WBGENE00003720
caenorhabditis_elegans		WBGENE00003721
caenorhabditis_elegans		WBGENE00003722
caenorhabditis_elegans		WBGENE00003723
caenorhabditis_elegans		WBGENE00003724
caenorhabditis_elegans		WBGENE00003725
caenorhabditis_elegans		WBGENE00003728
caenorhabditis_elegans		WBGENE00006471
caenorhabditis_elegans	unc-55	WBGENE00006790
caenorhabditis_elegans		WBGENE00007367
caenorhabditis_elegans		WBGENE00008056
caenorhabditis_elegans	nhr-165	WBGENE00008158
caenorhabditis_elegans		WBGENE00008208
caenorhabditis_elegans	nhr-169	WBGENE00008289
caenorhabditis_elegans		WBGENE00008309
caenorhabditis_elegans	nhr-174	WBGENE00008474
caenorhabditis_elegans		WBGENE00008619
caenorhabditis_elegans		WBGENE00008630
caenorhabditis_elegans		WBGENE00008778
caenorhabditis_elegans		WBGENE00008830
caenorhabditis_elegans		WBGENE00008884
caenorhabditis_elegans		WBGENE00008901
caenorhabditis_elegans	nhr-265	WBGENE00009608
caenorhabditis_elegans		WBGENE00010017
caenorhabditis_elegans		WBGENE00010180
caenorhabditis_elegans		WBGENE00010186
caenorhabditis_elegans		WBGENE00010215
caenorhabditis_elegans		WBGENE00010410
caenorhabditis_elegans		WBGENE00010600
caenorhabditis_elegans		WBGENE00010601
caenorhabditis_elegans		WBGENE00010602
caenorhabditis_elegans		WBGENE00010603
caenorhabditis_elegans		WBGENE00010604
caenorhabditis_elegans		WBGENE00011002
caenorhabditis_elegans		WBGENE00011150
caenorhabditis_elegans		WBGENE00011396
caenorhabditis_elegans		WBGENE00011520
caenorhabditis_elegans		WBGENE00011565
caenorhabditis_elegans		WBGENE00011566
caenorhabditis_elegans		WBGENE00011568
caenorhabditis_elegans	nhr-217	WBGENE00011651
caenorhabditis_elegans		WBGENE00011750
caenorhabditis_elegans		WBGENE00012050
caenorhabditis_elegans		WBGENE00012056
caenorhabditis_elegans		WBGENE00012446
caenorhabditis_elegans		WBGENE00012449
caenorhabditis_elegans		WBGENE00012596
caenorhabditis_elegans		WBGENE00012703
caenorhabditis_elegans		WBGENE00013067
caenorhabditis_elegans		WBGENE00013483
caenorhabditis_elegans	nhr-276	WBGENE00013512
caenorhabditis_elegans		WBGENE00013584
caenorhabditis_elegans		WBGENE00013940
caenorhabditis_elegans		WBGENE00014068
caenorhabditis_elegans	nhr-245	WBGENE00014189
caenorhabditis_elegans		WBGENE00014193
caenorhabditis_elegans		WBGENE00015497
caenorhabditis_elegans		WBGENE00015758
caenorhabditis_elegans		WBGENE00015897
caenorhabditis_elegans		WBGENE00015900
caenorhabditis_elegans		WBGENE00015901
caenorhabditis_elegans		WBGENE00015902
caenorhabditis_elegans		WBGENE00016091
caenorhabditis_elegans		WBGENE00016233
caenorhabditis_elegans		WBGENE00016364
caenorhabditis_elegans		WBGENE00016365
caenorhabditis_elegans		WBGENE00016366
caenorhabditis_elegans		WBGENE00016367
caenorhabditis_elegans		WBGENE00016368
caenorhabditis_elegans		WBGENE00016517
caenorhabditis_elegans		WBGENE00016772
caenorhabditis_elegans		WBGENE00016926
caenorhabditis_elegans		WBGENE00016927
caenorhabditis_elegans		WBGENE00017503
caenorhabditis_elegans		WBGENE00017512
caenorhabditis_elegans		WBGENE00017961
caenorhabditis_elegans		WBGENE00018189
caenorhabditis_elegans		WBGENE00018265
caenorhabditis_elegans		WBGENE00018266
caenorhabditis_elegans		WBGENE00018404
caenorhabditis_elegans		WBGENE00018412
caenorhabditis_elegans		WBGENE00018415
caenorhabditis_elegans		WBGENE00018539
caenorhabditis_elegans		WBGENE00018541
caenorhabditis_elegans		WBGENE00018542
caenorhabditis_elegans		WBGENE00018544
caenorhabditis_elegans		WBGENE00018545
caenorhabditis_elegans		WBGENE00018622
caenorhabditis_elegans		WBGENE00019115
caenorhabditis_elegans		WBGENE00019116
caenorhabditis_elegans		WBGENE00019741
caenorhabditis_elegans		WBGENE00019742
caenorhabditis_elegans		WBGENE00019743
caenorhabditis_elegans		WBGENE00020015
caenorhabditis_elegans		WBGENE00020062
caenorhabditis_elegans		WBGENE00020152
caenorhabditis_elegans		WBGENE00020153
caenorhabditis_elegans		WBGENE00020385
caenorhabditis_elegans		WBGENE00020460
caenorhabditis_elegans		WBGENE00020555
caenorhabditis_elegans		WBGENE00020750
caenorhabditis_elegans		WBGENE00020849
caenorhabditis_elegans		WBGENE00020850
caenorhabditis_elegans		WBGENE00020851
caenorhabditis_elegans		WBGENE00020852
caenorhabditis_elegans		WBGENE00021163
caenorhabditis_elegans		WBGENE00021522
caenorhabditis_elegans		WBGENE00021610
caenorhabditis_elegans		WBGENE00021611
caenorhabditis_elegans		WBGENE00021617
caenorhabditis_elegans		WBGENE00022097
caenorhabditis_elegans		WBGENE00022637
caenorhabditis_elegans		WBGENE00022639
caenorhabditis_elegans		WBGENE00022640
caenorhabditis_elegans		WBGENE00022726
caenorhabditis_elegans		WBGENE00022756
caenorhabditis_elegans		WBGENE00022805
caenorhabditis_elegans		WBGENE00044353
caenorhabditis_elegans		WBGENE00044699
caenorhabditis_elegans		WBGENE00045515

Paralogs (18): NR1H4 (ENSG00000012504), NR1H3 (ENSG00000025434), RORA (ENSG00000069667), RARB (ENSG00000077092), PPARD (ENSG00000112033), THRA (ENSG00000126351), NR1D1 (ENSG00000126368), NR1H2 (ENSG00000131408), RARA (ENSG00000131759), PPARG (ENSG00000132170), NR1I3 (ENSG00000143257), RORC (ENSG00000143365), NR1I2 (ENSG00000144852), THRB (ENSG00000151090), RARG (ENSG00000172819), NR1D2 (ENSG00000174738), PPARA (ENSG00000186951), RORB (ENSG00000198963)

Protein

Protein identifiers

Vitamin D3 receptor — P11473 (reviewed: P11473)

Alternative names: 1,25-dihydroxyvitamin D3 receptor, Nuclear receptor subfamily 1 group I member 1

All UniProt accessions (7): P11473, A0A5K1VW50, F1D8P8, F8VPF8, F8VRJ4, F8VVY8, F8VXQ9

UniProt curated annotations — full annotation on UniProt →

Function. Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action of this vitamin on cells. Enters the nucleus upon vitamin D3 binding where it forms heterodimers with the retinoid X receptor/RXR. The VDR-RXR heterodimers bind to specific response elements on DNA and activate the transcription of vitamin D3-responsive target genes. Plays a central role in calcium homeostasis. Also functions as a receptor for the secondary bile acid lithocholic acid (LCA) and its metabolites.

Subunit / interactions. Homodimer in the absence of bound vitamin D3. Heterodimer with RXRA after vitamin D3 binding. Interacts with MED1, NCOA1, NCOA2, NCOA3 and NCOA6 coactivators, leading to a strong increase of transcription of target genes. Interacts with the corepressor NCOR1. Interacts with SNW1. Interacts with IRX4, the interaction does not affect its transactivation activity. Interacts with CRY1. Interacts with CRY2 in a ligand-dependent manner.

Subcellular location. Nucleus. Cytoplasm.

Post-translational modifications. Ubiquitinated by UBR5, leading to its degradation: UBR5 specifically recognizes and binds ligand-bound VDR when it is not associated with coactivators (NCOAs). In presence of NCOAs, the UBR5-degron is not accessible, preventing its ubiquitination and degradation.

Disease relevance. Rickets vitamin D-dependent 2A (VDDR2A) [MIM:277440] A disorder of vitamin D metabolism resulting in severe rickets, hypocalcemia and secondary hyperparathyroidism. Most patients have total alopecia in addition to rickets. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.

Polymorphism. Genetic variations in VDR may determine Mycobacterium tuberculosis susceptibility [MIM:607948].

Similarity. Belongs to the nuclear hormone receptor family. NR1 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P11473-1	1	yes
P11473-2	2

RefSeq proteins (6): NP_000367, NP_001017535, NP_001017536, NP_001351014, NP_001361590, NP_001361591 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000324	VitD_rcpt	Family
IPR000536	Nucl_hrmn_rcpt_lig-bd	Domain
IPR001628	Znf_hrmn_rcpt	Domain
IPR001723	Nuclear_hrmn_rcpt	Family
IPR013088	Znf_NHR/GATA	Homologous_superfamily
IPR035500	NHR-like_dom_sf	Homologous_superfamily
IPR042153	DBD_VDR	Domain
IPR050234	Nuclear_hormone_rcpt_NR1	Family

Pfam: PF00104, PF00105

UniProt features (79 total): helix 20, sequence variant 17, binding site 14, turn 8, strand 6, mutagenesis site 3, region of interest 3, zinc finger region 2, chain 1, domain 1, DNA-binding region 1, splice variant 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

52 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
3B0T	X-RAY DIFFRACTION	1.3
3AZ3	X-RAY DIFFRACTION	1.36
1IE9	X-RAY DIFFRACTION	1.4
3A40	X-RAY DIFFRACTION	1.45
3AZ1	X-RAY DIFFRACTION	1.5
1IE8	X-RAY DIFFRACTION	1.52
7QPP	X-RAY DIFFRACTION	1.52
8IQN	X-RAY DIFFRACTION	1.64
3AZ2	X-RAY DIFFRACTION	1.69
3P8X	X-RAY DIFFRACTION	1.7
3A3Z	X-RAY DIFFRACTION	1.72
8IQT	X-RAY DIFFRACTION	1.75
3OGT	X-RAY DIFFRACTION	1.75
3TKC	X-RAY DIFFRACTION	1.75
1DB1	X-RAY DIFFRACTION	1.8
2HB7	X-RAY DIFFRACTION	1.8
3CS6	X-RAY DIFFRACTION	1.8
3M7R	X-RAY DIFFRACTION	1.8
3W0A	X-RAY DIFFRACTION	1.8
4G2I	X-RAY DIFFRACTION	1.8
5GT4	X-RAY DIFFRACTION	1.83
1TXI	X-RAY DIFFRACTION	1.9
2HAM	X-RAY DIFFRACTION	1.9
2HAR	X-RAY DIFFRACTION	1.9
3A78	X-RAY DIFFRACTION	1.9
3KPZ	X-RAY DIFFRACTION	1.9
3W0C	X-RAY DIFFRACTION	1.9
3X36	X-RAY DIFFRACTION	1.93
2HAS	X-RAY DIFFRACTION	1.96
3W0Y	X-RAY DIFFRACTION	1.98

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11473-F1	84.56	0.74

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (14): 24; 27; 41; 44; 60; 66; 76; 79; 143; 237; 274; 278 …

Mutagenesis-validated functional residues (3):

Position	Phenotype
47–48	abolishes nuclear export.
61–62	promotes heterodimerization with rxra; when associated with a-75.
75	promotes heterodimerization with rxra; when associated with a-61 and a-62.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-196791	Vitamin D (calciferol) metabolism
R-HSA-383280	Nuclear Receptor transcription pathway
R-HSA-4090294	SUMOylation of intracellular receptors

MSigDB gene sets: 595 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_DIGESTION, AP1_01, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MAMMARY_GLAND_MORPHOGENESIS, BENPORATH_ES_WITH_H3K27ME3, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, GOBP_GLAND_MORPHOGENESIS, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_KERATINOCYTE_DIFFERENTIATION, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_REGULATION_OF_EPIDERMIS_DEVELOPMENT

GO Biological Process (32): negative regulation of transcription by RNA polymerase II (GO:0000122), cell morphogenesis (GO:0000902), skeletal system development (GO:0001501), calcium ion transport (GO:0006816), intracellular calcium ion homeostasis (GO:0006874), lactation (GO:0007595), negative regulation of cell population proliferation (GO:0008285), positive regulation of gene expression (GO:0010628), negative regulation of keratinocyte proliferation (GO:0010839), cell differentiation (GO:0030154), positive regulation of bone mineralization (GO:0030501), intracellular receptor signaling pathway (GO:0030522), phosphate ion transmembrane transport (GO:0035435), nuclear receptor-mediated bile acid signaling pathway (GO:0038185), mRNA transcription by RNA polymerase II (GO:0042789), positive regulation of keratinocyte differentiation (GO:0045618), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), decidualization (GO:0046697), retinoic acid receptor signaling pathway (GO:0048384), intestinal absorption (GO:0050892), apoptotic process involved in mammary gland involution (GO:0060057), positive regulation of apoptotic process involved in mammary gland involution (GO:0060058), mammary gland branching involved in pregnancy (GO:0060745), vitamin D receptor signaling pathway (GO:0070561), positive regulation of vitamin D receptor signaling pathway (GO:0070564), response to bile acid (GO:1903412), regulation of DNA-templated transcription (GO:0006355), animal organ morphogenesis (GO:0009887), nuclear receptor-mediated steroid hormone signaling pathway (GO:0030518), cell-cell junction maintenance (GO:0045217), negative regulation of phosphate transmembrane transport (GO:2000186)

GO Molecular Function (16): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677), nuclear receptor activity (GO:0004879), vitamin D binding (GO:0005499), zinc ion binding (GO:0008270), bile acid nuclear receptor activity (GO:0038186), nuclear retinoid X receptor binding (GO:0046965), calcitriol binding (GO:1902098), lithocholic acid binding (GO:1902121), DNA-binding transcription factor activity (GO:0003700), nuclear steroid receptor activity (GO:0003707), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872), vitamin D response element binding (GO:0070644)

GO Cellular Component (7): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), signaling receptor complex (GO:0043235), RNA polymerase II transcription regulator complex (GO:0090575), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of steroids	1
Generic Transcription Pathway	1
SUMO E3 ligases SUMOylate target proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
nuclear receptor-mediated signaling pathway	2
regulation of DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
steroid binding	2
nuclear receptor activity	2
bile acid binding	2
negative regulation of DNA-templated transcription	1
anatomical structure morphogenesis	1
system development	1
metal ion transport	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
body fluid secretion	1
mammary gland development	1
milk ejection reflex	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
regulation of keratinocyte proliferation	1
keratinocyte proliferation	1
negative regulation of epithelial cell proliferation	1
cellular developmental process	1
bone mineralization	1
regulation of bone mineralization	1
positive regulation of ossification	1
positive regulation of biomineral tissue development	1
intracellular signal transduction	1
phosphate ion transport	1
transmembrane transport	1
bile acid signaling pathway	1
bile acid nuclear receptor activity	1
mRNA transcription	1
keratinocyte differentiation	1
positive regulation of epidermal cell differentiation	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

85 interactions, top by confidence:

A	B	Type	Score
RXRA	VDR	psi-mi:“MI:0407”(direct interaction)	0.790
RXRA	VDR	psi-mi:“MI:0915”(physical association)	0.790
VDR	RXRA	psi-mi:“MI:0407”(direct interaction)	0.790
MED1	VDR	psi-mi:“MI:0915”(physical association)	0.740
VDR	MED1	psi-mi:“MI:0915”(physical association)	0.740
SNW1	VDR	psi-mi:“MI:0915”(physical association)	0.670
VDR	SNW1	psi-mi:“MI:0915”(physical association)	0.670
VDR	SNW1	psi-mi:“MI:0403”(colocalization)	0.670
NCOA1	VDR	psi-mi:“MI:0915”(physical association)	0.660
VDR	NCOA1	psi-mi:“MI:0915”(physical association)	0.660
VDR	SQSTM1	psi-mi:“MI:0915”(physical association)	0.590
SQSTM1	VDR	psi-mi:“MI:0407”(direct interaction)	0.590
VDR	Rxra	psi-mi:“MI:0914”(association)	0.580
VDR	Rxra	psi-mi:“MI:0915”(physical association)	0.580
VDR	TRIP13	psi-mi:“MI:0915”(physical association)	0.560
VDR	MEOX2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (269): RXRA (Two-hybrid), VDR (Reconstituted Complex), VDR (Affinity Capture-Western), VDR (Co-crystal Structure), RXRA (Reconstituted Complex), NCOA3 (Reconstituted Complex), PSMC5 (Two-hybrid), NCOA1 (Two-hybrid), VDR (Reconstituted Complex), NCOA1 (Two-hybrid), NCOA1 (Reconstituted Complex), MDM2 (Affinity Capture-Western), VDR (Affinity Capture-Western), MEOX2 (Two-hybrid), TRIP13 (Two-hybrid)

ESM2 similar proteins: A2T7D9, A3RGC1, O35627, O42295, O42450, O54915, O57606, O75469, P04625, P11473, P15204, P18113, P18115, P18117, P18119, P37242, P48281, P55055, P62044, P62045, P68305, P68306, Q02777, Q02965, Q13133, Q14994, Q1L673, Q28037, Q28570, Q28571, Q5E9B6, Q60644, Q62685, Q62755, Q8MIM3, Q8SQ01, Q90382, Q91241, Q91279, Q91424

Diamond homologs: A2T7D9, A2T928, A3RGC1, G5EFF5, O00482, O13124, O18531, O35627, O42101, O42295, O42392, O42450, O54915, O57606, O75469, O97716, P03373, P04625, P10276, P10827, P10828, P11416, P11473, P13053, P13631, P15204, P18113, P18115, P18117, P18119, P18514, P18911, P22448, P33242, P33244, P37242, P41235, P48281, P49700, P49701

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
CSNK2A1	up-regulates	VDR	phosphorylation
SNAI2	“down-regulates quantity by repression”	VDR	“transcriptional regulation”
CTBP1	“down-regulates quantity by repression”	VDR	“transcriptional regulation”
HDAC1	“down-regulates quantity by repression”	VDR	“transcriptional regulation”
VDR	“down-regulates quantity by repression”	CYP24A1	“transcriptional regulation”
VDR	“up-regulates quantity by expression”	CYP3A4	“transcriptional regulation”
ZEB2	“up-regulates quantity by expression”	VDR	“transcriptional regulation”
VDR	“up-regulates quantity by expression”	HLA-DRB1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 33 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
R-HSA-1368082	5	127.5×	4e-08
RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression	6	87.4×	2e-08
BMAL1:CLOCK,NPAS2 activates circadian expression	5	75.5×	3e-07
Expression of BMAL (ARNTL), CLOCK, and NPAS2	6	62.8×	4e-08
R-HSA-400253	5	61.8×	6e-07
Regulation of cholesterol biosynthesis by SREBP (SREBF)	5	56.6×	7e-07
Activation of gene expression by SREBF (SREBP)	5	46.4×	2e-06
Heme signaling	6	46.2×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
mRNA transcription by RNA polymerase II	5	53.3×	5e-06
positive regulation of gene expression	6	7.5×	4e-03
negative regulation of apoptotic process	6	6.7×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

568 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	25
Likely pathogenic	14
Uncertain significance	222
Likely benign	227
Benign	35

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1343092	NM_000376.3(VDR):c.148C>T (p.Arg50Ter)	Pathogenic
1686293	NM_000376.3(VDR):c.217C>T (p.Arg73Ter)	Pathogenic
2024664	NM_000376.3(VDR):c.755+1G>C	Pathogenic
2137319	NM_000376.3(VDR):c.1172G>A (p.Arg391His)	Pathogenic
2506489	NM_000376.3(VDR):c.856T>C (p.Trp286Arg)	Pathogenic
264696	NM_000376.3(VDR):c.1171C>A (p.Arg391Ser)	Pathogenic
264697	NM_000376.3(VDR):c.1190A>C (p.His397Pro)	Pathogenic
2696150	NM_000376.3(VDR):c.334G>T (p.Glu112Ter)	Pathogenic
2697799	NM_000376.3(VDR):c.1181_*670del (p.Asn394_Ter428delinsXaa)	Pathogenic
2704201	NM_000376.3(VDR):c.1039C>T (p.Gln347Ter)	Pathogenic
2727171	NM_000376.3(VDR):c.560C>G (p.Ser187Ter)	Pathogenic
2839317	NM_000376.3(VDR):c.249del (p.Cys84fs)	Pathogenic
3244360	NC_000012.11:g.(?48249393)(48251491_?)del	Pathogenic
7745	NM_000376.3(VDR):c.98G>A (p.Gly33Asp)	Pathogenic
7747	NM_000376.3(VDR):c.885C>A (p.Tyr295Ter)	Pathogenic
7748	NM_000376.3(VDR):c.985G>A (p.Glu329Lys)	Pathogenic
7750	NM_000376.3(VDR):c.149G>A (p.Arg50Gln)	Pathogenic
7751	NM_000376.3(VDR):c.454C>T (p.Gln152Ter)	Pathogenic
7752	NM_000376.3(VDR):c.821G>T (p.Arg274Leu)	Pathogenic
7753	NM_000376.3(VDR):c.137G>A (p.Gly46Asp)	Pathogenic
7754	NM_000376.3(VDR):c.915C>G (p.His305Gln)	Pathogenic
7756	NM_000376.3(VDR):c.1171C>T (p.Arg391Cys)	Pathogenic
7757	NM_000376.3(VDR):c.88C>T (p.Arg30Ter)	Pathogenic
7758	NM_000376.3(VDR):c.366del (p.Lys123fs)	Pathogenic
944287	NM_000376.3(VDR):c.832_833insA (p.Ser278fs)	Pathogenic
1338550	NM_000376.3(VDR):c.910G>A (p.Gly304Arg)	Likely pathogenic
1343093	NM_000376.3(VDR):c.-45A>G	Likely pathogenic
2137321	NM_000376.3(VDR):c.76G>A (p.Val26Met)	Likely pathogenic
2434513	NM_000376.3(VDR):c.146+1G>T	Likely pathogenic
2691486	NM_000376.3(VDR):c.-2-1G>A	Likely pathogenic

SpliceAI

1690 predictions. Top by Δscore:

Variant	Effect	Δscore
12:47845002:CGAT:C	acceptor_gain	1.0000
12:47845003:GAT:G	acceptor_gain	1.0000
12:47845006:C:CC	acceptor_gain	1.0000
12:47845007:T:C	acceptor_loss	1.0000
12:47845013:C:CT	acceptor_gain	1.0000
12:47845015:C:CT	acceptor_gain	1.0000
12:47845016:G:T	acceptor_gain	1.0000
12:47845020:A:AC	acceptor_gain	1.0000
12:47846329:CCATA:C	donor_loss	1.0000
12:47846330:CATA:C	donor_loss	1.0000
12:47846331:ATAC:A	donor_loss	1.0000
12:47846332:TACCT:T	donor_loss	1.0000
12:47846333:ACC:A	donor_loss	1.0000
12:47846447:TCCGG:T	acceptor_gain	1.0000
12:47846448:CCGG:C	acceptor_gain	1.0000
12:47846448:CCGGC:C	acceptor_gain	1.0000
12:47846449:CGG:C	acceptor_gain	1.0000
12:47846449:CGGC:C	acceptor_gain	1.0000
12:47846451:GC:G	acceptor_loss	1.0000
12:47846452:C:CC	acceptor_gain	1.0000
12:47846452:C:G	acceptor_loss	1.0000
12:47846453:T:G	acceptor_loss	1.0000
12:47846652:CATAC:C	donor_loss	1.0000
12:47846653:ATACC:A	donor_loss	1.0000
12:47846654:TA:T	donor_loss	1.0000
12:47846655:A:AC	donor_gain	1.0000
12:47846655:AC:A	donor_gain	1.0000
12:47846656:C:CC	donor_gain	1.0000
12:47846656:CC:C	donor_gain	1.0000
12:47846656:CCT:C	donor_gain	1.0000

AlphaMissense

2843 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:47844861:A:G	L390P	1.000
12:47857657:C:A	K103N	1.000
12:47857657:C:G	K103N	1.000
12:47857682:A:G	L95P	1.000
12:47857685:A:T	I94N	1.000
12:47865057:C:A	M89I	1.000
12:47865057:C:G	M89I	1.000
12:47865057:C:T	M89I	1.000
12:47865058:A:G	M89T	1.000
12:47865072:A:C	C84W	1.000
12:47865073:C:A	C84F	1.000
12:47865073:C:G	C84S	1.000
12:47865073:C:T	C84Y	1.000
12:47865074:A:G	C84R	1.000
12:47865074:A:T	C84S	1.000
12:47865082:A:G	L81P	1.000
12:47865086:G:A	R80W	1.000
12:47865086:G:C	R80G	1.000
12:47865087:G:C	C79W	1.000
12:47865088:C:A	C79F	1.000
12:47865088:C:G	C79S	1.000
12:47865088:C:T	C79Y	1.000
12:47865089:A:G	C79R	1.000
12:47865089:A:T	C79S	1.000
12:47865096:G:C	C76W	1.000
12:47865097:C:A	C76F	1.000
12:47865097:C:G	C76S	1.000
12:47865097:C:T	C76Y	1.000
12:47865098:A:G	C76R	1.000
12:47865098:A:T	C76S	1.000

dbSNP variants (sampled 300 via entrez): RS1000015145 (12:47860677 T>C), RS1000121954 (12:47897163 C>T), RS1000183206 (12:47891525 G>A), RS1000213154 (12:47846216 A>G), RS1000241434 (12:47855566 A>G,T), RS1000249956 (12:47896160 T>A,G), RS1000258821 (12:47849747 T>C), RS1000315114 (12:47884566 C>A), RS1000343072 (12:47874013 T>A), RS1000375144 (12:47850024 T>C), RS1000472915 (12:47896758 C>T), RS1000508418 (12:47880277 G>A), RS1000514615 (12:47868569 TC>T), RS1000661107 (12:47875560 A>C), RS1000665453 (12:47885732 T>C)

Disease associations

OMIM: gene MIM:601769 | disease phenotypes: MIM:277440, MIM:608456, MIM:114550, MIM:606963

GenCC curated gene-disease

Disease	Classification	Inheritance
vitamin D-dependent rickets, type 2A	Definitive	Autosomal recessive
vitamin D-dependent rickets, type 2	Supportive	Autosomal recessive

Mondo (7): vitamin D-dependent rickets, type 2A (MONDO:0010186), familial adenomatous polyposis 2 (MONDO:0012041), periodontitis (MONDO:0005076), hepatocellular carcinoma (MONDO:0007256), chronic obstructive pulmonary disease (MONDO:0005002), rickets (MONDO:0005520), vitamin D-dependent rickets, type 2 (MONDO:0019642)

Orphanet (4): Hypocalcemic vitamin D-resistant rickets (Orphanet:93160), Attenuated familial adenomatous polyposis (Orphanet:220460), MUTYH-related polyposis (Orphanet:247798), Hepatocellular carcinoma (Orphanet:88673)

HPO phenotypes

69 total (30 of 69 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000164	Abnormality of the dentition
HP:0000268	Dolichocephaly
HP:0000286	Epicanthus
HP:0000365	Hearing impairment
HP:0000431	Wide nasal bridge
HP:0000670	Carious teeth
HP:0000684	Delayed eruption of teeth
HP:0000737	Irritability
HP:0000765	Abnormal thorax morphology
HP:0000787	Nephrolithiasis
HP:0000843	Hyperparathyroidism
HP:0000867	Secondary hyperparathyroidism
HP:0000886	Deformed rib cage
HP:0000893	Bulging of the costochondral junction
HP:0000944	Abnormal metaphysis morphology
HP:0000951	Abnormality of the skin
HP:0001252	Hypotonia
HP:0001270	Motor delay
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001373	Joint dislocation
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001538	Protuberant abdomen
HP:0001596	Alopecia
HP:0002007	Frontal bossing
HP:0002148	Hypophosphatemia
HP:0002199	Hypocalcemic seizures
HP:0002289	Alopecia universalis

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001356_9	Gout	1.000000e-07
GCST001725_18	Inflammatory bowel disease	8.000000e-09
GCST002541_92	Menarche (age at onset)	1.000000e-08
GCST003876_10	Gut microbiota (beta diversity)	5.000000e-08
GCST007928_20	Medication use (diuretics)	4.000000e-09
GCST007929_78	Medication use (calcium channel blockers)	3.000000e-08
GCST007993_17	Asthma (adult onset)	2.000000e-10
GCST010146_36	Serum immune biomarker levels	9.000000e-13
GCST90002382_310	Eosinophil percentage of white cells	1.000000e-09
GCST90013410_28	Basal cell carcinoma	6.000000e-09

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0007874	gut microbiome measurement
EFO:0009928	Diuretic use measurement
EFO:0009930	Calcium channel blocker use measurement
EFO:1002011	adult onset asthma
EFO:0004869	YKL40 measurement
EFO:0004872	inflammatory biomarker measurement
EFO:0007991	eosinophil percentage of leukocytes

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D006528	Carcinoma, Hepatocellular	C04.557.470.200.025.255; C04.588.274.623.160; C06.301.623.160; C06.552.697.160
D010518	Periodontitis	C07.465.714.533
D029424	Pulmonary Disease, Chronic Obstructive	C08.381.495.389; C23.550.291.500.875
D012279	Rickets	C05.116.198.816; C18.452.104.816; C18.452.174.845; C18.654.521.500.133.770.734
C563924	Colorectal Adenomatous Polyposis, Autosomal Recessive (supp.)
C562794	Vitamin D-Dependent Rickets, Type 2A (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL1977 (SINGLE PROTEIN), CHEMBL3885632 (PROTEIN COMPLEX), CHEMBL4748225 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

10 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 237,922 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1042	CHOLECALCIFEROL	4	64,162
CHEMBL1200666	CALCIPOTRIENE	4	21,689
CHEMBL1200810	DOXERCALCIFEROL	4	951
CHEMBL2105611	TACALCITOL	4	2,309
CHEMBL846	CALCITRIOL	4	29,522
CHEMBL140	CURCUMIN	3	93,882
CHEMBL1908376	SEOCALCITOL	3	163
CHEMBL333950	MAXACALCITOL	3	1,797
CHEMBL408701	TAUROLITHOCHOLIC ACID	3	1,133
CHEMBL99	TRICHOSTATIN	1	22,314

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

18 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11168292	Dosage	3	warfarin
rs11168293	Dosage	3	warfarin
rs11568820	Metabolism/PK	3	midazolam
rs11574077	Metabolism/PK	3	irinotecan	Colorectal Neoplasms
rs1540339	Efficacy	3	selective beta-2-adrenoreceptor agonists	Asthma
rs1544410	Toxicity	3	peginterferon alfa-2a;ribavirin	Hepatitis C virus infection
rs1544410	Efficacy	3	conjugated estrogens;medroxyprogesterone
rs1544410	Efficacy	3	deferasirox	Beta-thalassemia and related diseases
rs1544410	Efficacy	3	clodronate
rs1544410	Efficacy	3	alendronate	Osteoporosis
rs1544410	Metabolism/PK	3	midazolam
rs2228570	Efficacy	3	peginterferon alfa-2b;ribavirin	Chronic hepatitis C virus infection
rs2239179	Efficacy	3	selective beta-2-adrenoreceptor agonists	Asthma
rs4516035	Metabolism/PK	3	midazolam
rs4760658	Dosage	3	warfarin
rs731236	Efficacy	3	clodronate	Osteitis Deformans
rs731236	Efficacy	3	calcium
rs731236	Efficacy	3	deferasirox	Beta-thalassemia and related diseases

PharmGKB variants

19 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs731236	VDR	3	2.75	3	clodronate;calcium;deferasirox
rs1540339	VDR	3	2.50	1	selective beta-2-adrenoreceptor agonists
rs1544410	VDR	3	3.75	6	alendronate;peginterferon alfa-2a;ribavirin;conjugated estrogens;medroxyprogesterone;midazolam;deferasirox;clodronate
rs2228570	VDR	3	6.00	1	peginterferon alfa-2b;ribavirin
rs2239179	VDR	3	3.00	1	selective beta-2-adrenoreceptor agonists
rs2239185	VDR		0.00	0
rs3782905	VDR		0.00	0
rs4516035	VDR	3	1.25	1	midazolam
rs7975232	VDR		0.00	0
rs11568820	VDR	3	1.25	1	midazolam
rs4760658	VDR	3	3.00	1	warfarin
rs11168292	VDR	3	3.00	1	warfarin
rs11168293	VDR	3	3.00	1	warfarin
rs11168287	VDR		0.00	0
rs11574026	VDR		0.00	0
rs12717991	VDR		0.00	0
rs11574077	VDR	3	1.75	1	irinotecan
rs4760648	VDR		0.00	0
rs2853564	VDR		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: nhr — 1I. Vitamin D receptor-like receptors

Most potent curated ligand interactions (18 total), top 18:

Ligand	Action	Affinity	Parameter
lexacalcitol	Agonist	10.1	pKd
2MD	Agonist	10.0	pEC50
seocalcitol	Agonist	9.6	pKd
calcipotriol	Agonist	9.3	pKd
inecalcitol	Agonist	9.28	pKd
1,25-dihydroxyvitamin D3	Agonist	9.2	pKd
falecalcitriol	Agonist	8.8	pKd
tacalcitol	Agonist	8.5	pKd
gemini	Agonist	8.5	pKd
maxacalcitol	Agonist	8.21	pEC50
elocalcitol	Agonist	8.21	pIC50
TEI-9647	Antagonist	8.2	pIC50
eldecalcitol	Agonist	8.0	pKd
calcitriol-26,23-lactone	Agonist	7.5	pKd
ZK159222	Antagonist	7.5	pIC50
LG190178	Agonist	6.82	pKi
3-keto-lithocholic acid	Agonist	6.54	pKi
lithocholic acid	Agonist	5.1	pKi

Binding affinities (BindingDB)

102 measured of 111 human assays (111 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(24R)-24-Adamantyl-1r,24-dihydroxy-2-methylene-22,23-didehydro-19,25,26,27-tetranorvitamin D3	EC50	0.02 nM
Vitamin D analog, 15	KI	0.1 nM
ethyl N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]carbamate	KI	0.2 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
Vitamin D analog, 6	KI	0.2 nM
Vitamin D analog, 17	KI	0.2 nM
Vitamin D analog, 8	KI	0.3 nM
Vitamin D analog, 9	KI	0.3 nM
Vitamin D analog, 7	KI	0.3 nM
CHEMBL3263871	IC50	0.5 nM
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]-1H-pyrrole-2-carboxamide	KI	0.52 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
phenyl N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]carbamate	KI	0.58 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]-5-chloro-1-benzothiophene-2-sulfonamide	KI	0.79 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
benzyl N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]carbamate	KI	0.79 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]-5-methoxy-1-benzothiophene-2-sulfonamide	KI	0.97 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
ethyl N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]carbamate	KI	0.97 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]-2-thiophen-2-ylacetamide	KI	0.98 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
(25R)-25-Adamantyl-1alpha,25-dihydroxy-2-methylene-22,23-didehydro-19,26,27-trinor-20-epivitamin D3	EC50	1 nM
Vitamin D analog, 14	KI	1 nM
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]-1H-indole-2-sulfonamide	KI	1.01 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]thiophene-2-carboxamide	KI	1.1 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
methyl N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]carbamate	KI	1.14 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]thiophene-2-sulfonamide	KI	1.14 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]furan-2-carboxamide	KI	1.3 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]furan-2-carboxamide	KI	1.37 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]-1-benzofuran-2-sulfonamide	KI	1.69 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
cyclohexyl N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]carbamate	KI	1.69 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]-5-methyl-1-benzothiophene-2-sulfonamide	KI	1.76 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
thiophen-2-ylmethyl N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]carbamate	KI	1.76 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
2-methylpropyl N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]carbamate	KI	1.79 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
1-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]-3-pyridin-3-ylurea	KI	1.79 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]-1H-indole-2-carboxamide	KI	1.9 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]-5-isocyano-1-benzothiophene-2-sulfonamide	KI	1.99 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
Vitamin D analog, 16	KI	2 nM
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]-5-methylfuran-2-sulfonamide	KI	2.02 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]-5-isocyanofuran-2-sulfonamide	KI	2.1 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]-5-methylfuran-2-sulfonamide	KI	2.1 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]thiophene-2-sulfonamide	KI	2.14 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
benzyl N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]carbamate	KI	2.14 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
3-[4-[2-[4-(2,3-dichlorophenyl)piperazin-1-yl]ethyl]cyclohexyl]-1,1-dimethylurea	KI	2.16 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]furan-2-sulfonamide	KI	2.54 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
methyl N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]carbamate	KI	2.55 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]-5-methyl-1H-pyrrole-2-carboxamide	KI	2.57 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
1-benzofuran-2-ylmethyl N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]carbamate	KI	2.63 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
cyclopropyl N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]carbamate	KI	2.64 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
1-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]-3-(furan-2-yl)urea	KI	2.64 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]-3-methylthiophene-2-carboxamide	KI	2.84 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]furan-2-sulfonamide	KI	2.87 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
(4-chlorophenyl) N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]carbamate	KI	2.88 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
1-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]-3-(3-methoxyphenyl)urea	KI	2.88 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]-1H-pyrrole-2-sulfonamide	KI	2.94 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia

ChEMBL bioactivities

708 potent at pChembl≥5 of 851 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	EC50	0.01	nM	CHEMBL2407821
10.97	EC50	0.0106	nM	CALCITRIOL
10.96	EC50	0.011	nM	CALCITRIOL
10.85	EC50	0.014	nM	CHEMBL4794075
10.70	EC50	0.02	nM	CHEMBL467212
10.59	EC50	0.026	nM	CALCITRIOL
10.54	IC50	0.029	nM	CHEMBL2058272
10.52	EC50	0.03	nM	CHEMBL4159525
10.52	ED50	0.03	nM	CHEMBL578780
10.40	IC50	0.04	nM	CALCITRIOL
10.40	EC50	0.04	nM	CHEMBL272304
10.40	EC50	0.0396	nM	CHEMBL272304
10.36	EC50	0.044	nM	CHEMBL2407824
10.30	IC50	0.05	nM	CALCITRIOL
10.22	IC50	0.06	nM	CALCITRIOL
10.22	EC50	0.06	nM	CHEMBL1834893
10.19	Kd	0.065	nM	CALCITRIOL
10.15	EC50	0.07	nM	CHEMBL3263871
10.15	EC50	0.07	nM	CALCITRIOL
10.15	EC50	0.07	nM	CHEMBL226380
10.14	Kd	0.073	nM	CHEMBL318267
10.10	IC50	0.08	nM	CALCITRIOL
10.05	IC50	0.09	nM	CHEMBL3745849
10.05	IC50	0.09	nM	CHEMBL4159525
10.05	Kd	0.089	nM	CHEMBL318617
10.02	IC50	0.0953	nM	CALCITRIOL
10.00	IC50	0.1	nM	CALCITRIOL
10.00	EC50	0.1	nM	CALCITRIOL
9.92	IC50	0.12	nM	CHEMBL3264162
9.92	EC50	0.12	nM	CALCITRIOL
9.92	ED50	0.12	nM	CHEMBL583232
9.85	EC50	0.14	nM	CHEMBL4159525
9.82	EC50	0.15	nM	CHEMBL2407823
9.82	EC50	0.15	nM	CHEMBL4776651
9.80	IC50	0.16	nM	CALCITRIOL
9.74	EC50	0.18	nM	CHEMBL299680
9.70	EC50	0.2	nM	CHEMBL375811
9.68	EC50	0.21	nM	CHEMBL2407825
9.68	EC50	0.21	nM	CHOLECALCIFEROL
9.68	IC50	0.21	nM	CHEMBL3629552
9.62	IC50	0.24	nM	CHEMBL4159525
9.62	EC50	0.24	nM	CHEMBL4794075
9.59	IC50	0.26	nM	CHEMBL3264160
9.54	EC50	0.29	nM	CHEMBL2407822
9.54	IC50	0.29	nM	CHEMBL3264166
9.52	EC50	0.3	nM	CALCITRIOL
9.51	Kd	0.31	nM	CALCIPOTRIENE
9.46	IC50	0.35	nM	CALCITRIOL
9.46	EC50	0.35	nM	CHEMBL2112315
9.42	IC50	0.38	nM	CHEMBL2058273

PubChem BioAssay actives

677 with measured affinity, of 2894 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(4R)-4-[(3S,5R,8R,9S,10S,13R,14S,17R)-3-(2-hydroxy-2-methylpropyl)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid	1744120: Agonist activity at human VDR expressed in HEK293 cells expressing mouse osteopontin VDRE assessed as induction of receptor transactivation incubated for 16 hrs by luciferase reporter gene assay	ec50	<0.0001	uM
trans-(1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R,6S)-6-(1-adamantyl)-6-hydroxyhex-4-yn-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol	1506103: Transactivation of VDR (unknown origin) expressed in HEK293 cells harboring TK-Spp X 3-LUC reporter plasmid after 24 hrs by luciferase reporter gene assay	ec50	<0.0001	uM
trans-(1R,3R)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(E,2R,5R)-5-(1-adamantyl)-5-hydroxypent-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol	362894: Agonist activity at VDR assessed as receptor transactivation by transient transcription assay	ec50	<0.0001	uM
(2S)-3-[4-[3-[4-[(2R)-2-hydroxy-3,3-dimethylbutoxy]-3-methylphenyl]pentan-3-yl]-2-methylphenoxy]propane-1,2-diol	1585399: Agonist activity at human VDR expressed in HOS cells co-expressing human RXR by Dual-Glo luciferase reporter gene assay	ec50	<0.0001	uM
trans-(1R,3S,5Z)-5-[(2E)-2-[(1R,7aR)-1-[(2S,3R)-6-hydroxy-3,6-dimethylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol	280115: Induction of transactivation of human VDR responsive gene in COS7 cells by rat osteopontin luciferase reporter gene assay	ec50	<0.0001	uM
trans-(1R,3S,5Z)-5-[(2E)-2-[(1R,7aR)-1-[(2S,3R)-3-ethyl-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol	280115: Induction of transactivation of human VDR responsive gene in COS7 cells by rat osteopontin luciferase reporter gene assay	ec50	<0.0001	uM
Calcitriol	1505674: Displacement of [3H]-1,25D3 from C-terminal GST-tagged human recombinant VDR LBD expressed in Escherichia coli BL21 (DE3) after 16 hrs by radioligand binding assay	ic50	<0.0001	uM
trans-(1R,3R)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R)-5-ethyl-5-hydroxyheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol	673011: Displacement of [3H]1alpha,25-dihydroxyvitamin D3 from human recombinant GST-tagged vitamin D3 receptor LBD expressed in Escherichia coli BL21 after 16 hrs	ic50	<0.0001	uM
(1R,2S,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R)-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidene-2-[2-(tetrazol-2-yl)ethyl]cyclohexane-1,3-diol	760217: Transactivation of VDR-mediated osteocalcin promoter in human HOS/SF cells after 24 hrs by luciferase reporter gene assay	ec50	<0.0001	uM
(1R,2S,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R)-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidene-2-[2-(triazol-2-yl)ethyl]cyclohexane-1,3-diol	760217: Transactivation of VDR-mediated osteocalcin promoter in human HOS/SF cells after 24 hrs by luciferase reporter gene assay	ec50	<0.0001	uM
trans-(1R,3R)-5-[(2E)-2-[(1S,3aS,7aS)-1-[(5S)-5-(1-adamantyl)-5-hydroxypenta-1,3-diynyl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol	1267646: Agonist activity at VDR (unknown origin) expressed in HEK293 cells cotransfected with NCoR assessed as decrease in NCoR recruitment by two-hybrid assay	ic50	0.0001	uM
(4R)-4-[(3R,5R,8R,9S,10S,13R,14S,17R)-3-(2-hydroxy-2-methylpropyl)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid	1744120: Agonist activity at human VDR expressed in HEK293 cells expressing mouse osteopontin VDRE assessed as induction of receptor transactivation incubated for 16 hrs by luciferase reporter gene assay	ec50	0.0001	uM
trans-(1R,3S,5Z)-5-[(2E)-2-[(3aS,7aR)-1-[(2R)-1-[4-(2-hydroxypropan-2-yl)phenyl]sulfanylpropan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol	217167: Binding affinity to VDR receptor	kd	0.0001	uM
trans-(1R,3S,5Z)-5-[(2E)-2-[(3aS,7aR)-1-[(2R)-1-[4-(2-hydroxypropan-2-yl)phenoxy]propan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol	217167: Binding affinity to VDR receptor	kd	0.0001	uM
trans-(1R,3R)-2-(2-fluoroethylidene)-5-[(2E)-2-[1-[(2S)-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]cyclohexane-1,3-diol	287170: Inhibition of human VDR induced-transcriptional transactivation of luciferase reporter gene in COS7 cells after 24 hrs	ec50	0.0001	uM
(2R)-2-[4-[3-[4-[(2R)-2-hydroxy-3,3-dimethylbutoxy]-3-methylphenyl]pentan-3-yl]-2-methylphenoxy]butane-1,4-diol	622098: Activity at human VDR expressed in human HOS cells transfected with pGL3-hOc, pCDNA-hVDR and phRL-TK assessed as assessed as transcriptional activation measured 24 hrs post infection by luciferase reporter gene assay	ec50	0.0001	uM
trans-(1R,3R)-5-[(2E)-2-[(7aR)-1-[(2S)-6-hydroxyhexan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylcyclohexane-1,3-diol	1799878: VDR Binding Assay from Article 10.1016/j.bioorg.2013.01.001: “26- and 27-Methyl groups of 2-substituted, 19-nor-1a,25-dihydroxylated vitamin D compounds are essential for calcium mobilization in vivo.”	ki	0.0001	uM
trans-(1R,3R)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R,6S)-6-(1-adamantyl)-6-hydroxyhex-4-yn-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol	1142108: Transactivation of human VDR expressed in HEK293 cells cotransfected with mouse VDRE, Tk-Sppx3-LUC reporter plasmid measured after 24 hrs by luciferase reporter assay	ec50	0.0001	uM
(1R,2S,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R)-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidene-2-[2-(1,2,4-triazol-1-yl)ethyl]cyclohexane-1,3-diol	760217: Transactivation of VDR-mediated osteocalcin promoter in human HOS/SF cells after 24 hrs by luciferase reporter gene assay	ec50	0.0001	uM
trans-(1R,3R)-5-[(2E)-2-[(1S,3aS,7aS)-1-[(1R)-1-[(2S)-3-hydroxy-2,3-dimethylbutoxy]ethyl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol	775185: Agonist activity at VDR ligand binding domain (unknown origin) by reporter gene assay	ec50	0.0001	uM
trans-(1R,3R)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R,3R)-3-(2-hydroxy-2-methylpropyl)heptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol	1140744: Displacement of [3H]-1-alpha,25-dihydroxyvitamin D3 from N-terminal GST-tagged human recombinant VDR LBD expressed in Escherichia coli Rosetta2 (DE3) after 16 hrs	ic50	0.0001	uM
trans-(1R,3R)-5-[(2E)-2-[(7aR)-1-[(2S)-hexan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylcyclohexane-1,3-diol	1799878: VDR Binding Assay from Article 10.1016/j.bioorg.2013.01.001: “26- and 27-Methyl groups of 2-substituted, 19-nor-1a,25-dihydroxylated vitamin D compounds are essential for calcium mobilization in vivo.”	ki	0.0002	uM
trans-(1R,3S,5E)-5-[(2Z)-2-[(3aS,7aR)-1-[(2R)-6-hydroxy-6-methylheptan-2-yl]-3a,7a-dimethyl-1,2,3,5,6,7-hexahydroinden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol	216995: Effective concentration required for inhibition of Vitamin D3 receptor	ec50	0.0002	uM
trans-(1R,3S,5Z)-5-[(2E)-2-[(1R,7aR)-1-[(2S,3R)-3-butyl-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol	280115: Induction of transactivation of human VDR responsive gene in COS7 cells by rat osteopontin luciferase reporter gene assay	ec50	0.0002	uM
cholecalciferol	1168708: Agonist activity at human VDR expressed in HEK293 cells by luciferase reporter gene assay	ec50	0.0002	uM
trans-(1R,3R)-5-[(2E)-2-[(7aR)-1-[(2R)-6-hydroxyhexan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol	1799878: VDR Binding Assay from Article 10.1016/j.bioorg.2013.01.001: “26- and 27-Methyl groups of 2-substituted, 19-nor-1a,25-dihydroxylated vitamin D compounds are essential for calcium mobilization in vivo.”	ki	0.0002	uM
(1R,2S,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R)-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidene-2-[2-(triazol-1-yl)ethyl]cyclohexane-1,3-diol	760217: Transactivation of VDR-mediated osteocalcin promoter in human HOS/SF cells after 24 hrs by luciferase reporter gene assay	ec50	0.0002	uM
trans-(1R,3R)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R,3S)-3-(2-hydroxyethyl)nonan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol	1254251: Displacement of [3H]-1alpha,25-dihydroxyvitamin D3 from recombinant human VDR LBD expressed in Escherichia coli BL21 (DE3) pLysS after 16 hrs	ic50	0.0002	uM
calcipotriene	217167: Binding affinity to VDR receptor	kd	0.0003	uM
trans-(1R,3R)-5-[(2E)-2-[(7aR)-1-[(2S)-hexan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol	1799878: VDR Binding Assay from Article 10.1016/j.bioorg.2013.01.001: “26- and 27-Methyl groups of 2-substituted, 19-nor-1a,25-dihydroxylated vitamin D compounds are essential for calcium mobilization in vivo.”	ki	0.0003	uM
trans-(1R,3R)-5-[(2E)-2-[(7aR)-1-[(2R)-hexan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol	1799878: VDR Binding Assay from Article 10.1016/j.bioorg.2013.01.001: “26- and 27-Methyl groups of 2-substituted, 19-nor-1a,25-dihydroxylated vitamin D compounds are essential for calcium mobilization in vivo.”	ki	0.0003	uM
trans-(1R,3R)-5-[(2E)-2-[(7aR)-1-[(2S)-6-hydroxyhexan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol	1799878: VDR Binding Assay from Article 10.1016/j.bioorg.2013.01.001: “26- and 27-Methyl groups of 2-substituted, 19-nor-1a,25-dihydroxylated vitamin D compounds are essential for calcium mobilization in vivo.”	ki	0.0003	uM
(1R,2S,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R)-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidene-2-[2-(tetrazol-1-yl)ethyl]cyclohexane-1,3-diol	760217: Transactivation of VDR-mediated osteocalcin promoter in human HOS/SF cells after 24 hrs by luciferase reporter gene assay	ec50	0.0003	uM
trans-(1R,3R)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R,3R)-3-butyl-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol	1140744: Displacement of [3H]-1-alpha,25-dihydroxyvitamin D3 from N-terminal GST-tagged human recombinant VDR LBD expressed in Escherichia coli Rosetta2 (DE3) after 16 hrs	ic50	0.0003	uM
trans-(1R,3R)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R,3R)-3-(2-hydroxyethyl)heptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol	1140744: Displacement of [3H]-1-alpha,25-dihydroxyvitamin D3 from N-terminal GST-tagged human recombinant VDR LBD expressed in Escherichia coli Rosetta2 (DE3) after 16 hrs	ic50	0.0003	uM
ethyl (E)-3-[1-[(E,1R,4R)-4-[(1R,3aS,4E,7aR)-4-[(2Z)-2-[(3S,5R)-3,5-dihydroxy-2-methylidenecyclohexylidene]ethylidene]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-1-yl]-1-hydroxypent-2-enyl]cyclopropyl]prop-2-enoate	216995: Effective concentration required for inhibition of Vitamin D3 receptor	ec50	0.0003	uM
trans-(1R,3R)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R,3S)-3,5-diethyl-5-hydroxyheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol	673011: Displacement of [3H]1alpha,25-dihydroxyvitamin D3 from human recombinant GST-tagged vitamin D3 receptor LBD expressed in Escherichia coli BL21 after 16 hrs	ic50	0.0004	uM
trans-(1R,3R)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R,3S)-3-butyl-5-ethyl-5-hydroxyheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol	673011: Displacement of [3H]1alpha,25-dihydroxyvitamin D3 from human recombinant GST-tagged vitamin D3 receptor LBD expressed in Escherichia coli BL21 after 16 hrs	ic50	0.0004	uM
butyl 1-[(E,1R,4R)-4-[(1R,3aS,4E,7aR)-4-[(2Z)-2-[(3S,5R)-3,5-dihydroxy-2-methylidenecyclohexylidene]ethylidene]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-1-yl]-1-hydroxypent-2-enyl]cyclopropane-1-carboxylate	216995: Effective concentration required for inhibition of Vitamin D3 receptor	ec50	0.0004	uM
trans-(1R,3R)-2-(2-fluoroethylidene)-5-[(2E)-2-[1-[(2R)-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]cyclohexane-1,3-diol	287170: Inhibition of human VDR induced-transcriptional transactivation of luciferase reporter gene in COS7 cells after 24 hrs	ec50	0.0005	uM
6-[5-[(E,3Z)-3-[(3S,5S)-3,5-dimethyl-2-methylidenecyclohexylidene]prop-1-enyl]-7a-methyl-1,2,3,3a,4,5,6,7-octahydroinden-1-yl]-2-methylheptan-2-ol	1799452: VDR Ligand-Binding Assay from Article 10.1016/S1074-5521(99)80072-6: “Novel nonsecosteroidal vitamin D mimics exert VDR-modulating activities with less calcium mobilization than 1,25-dihydroxyvitamin D3.”	ki	0.0005	uM
3-[4-[5-[2-[3,4-bis(hydroxymethyl)phenyl]ethyl]-2-methylphenyl]-3-propylphenyl]pentan-3-ol	702757: Transactivation of full length human VDR expressed in human HeLa cells assessed as increase in CYP24 transcription after 18 hrs by luciferase reporter gene assay	ec50	0.0005	uM
trans-(1R,3S,5Z)-5-[(2E)-2-[(3aS,7aS)-1-[1-(4-hydroxy-4-methylpentyl)cyclopropyl]-7a-methyl-3a,5,6,7-tetrahydro-3H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol	414864: Activation of VDR in human THP1 cells assessed as increase in 25-hydroxyvitamin D-24-hydroxylase mRNA expression by RT-PCR	ec50	0.0007	uM
1-[1-[(3aS,4E,7aS)-4-[(2Z)-2-[(3S,5R)-3,5-dihydroxy-2-methylidenecyclohexylidene]ethylidene]-7a-methyl-3a,5,6,7-tetrahydro-3H-inden-1-yl]cyclopropyl]-4-hydroxy-4-methylpentan-3-one	414864: Activation of VDR in human THP1 cells assessed as increase in 25-hydroxyvitamin D-24-hydroxylase mRNA expression by RT-PCR	ec50	0.0007	uM
(1R,2S,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R)-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-(2-imidazol-1-ylethyl)-4-methylidenecyclohexane-1,3-diol	760217: Transactivation of VDR-mediated osteocalcin promoter in human HOS/SF cells after 24 hrs by luciferase reporter gene assay	ec50	0.0007	uM
trans-(1R,3R)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R,6S)-7-(1-adamantyl)-6-hydroxyhept-4-yn-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol	1142112: Activation of human VDR expressed in HEK293 cells cotransfected CMX-GAL4-RXRalpha and 4-tk-LUC assessed as heterodimerization with RXRalpha by mammalian two-hybrid assay	ec50	0.0008	uM
(2S,3S)-3-[4-[3-[4-[(2R)-2-hydroxy-3,3-dimethylbutoxy]-3-methylphenyl]pentan-3-yl]-2-methylphenoxy]butane-1,2,4-triol	622098: Activity at human VDR expressed in human HOS cells transfected with pGL3-hOc, pCDNA-hVDR and phRL-TK assessed as assessed as transcriptional activation measured 24 hrs post infection by luciferase reporter gene assay	ec50	0.0009	uM
trans-(1R,3S,5Z)-5-[(2E)-2-[(1S,3aS,7aS)-1-[(1S)-1-(3-hydroxy-3-methylbutoxy)ethyl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol	1309800: Activation of VDR in human Jurkat cells expressing lentiviral VDRE-luciferase vector assessed as VDRE-mediated transcriptional activity measured after 24 hrs by luciferase transcriptional reporter assay	ec50	0.0009	uM
trans-(1R,3R)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R,3R)-3-(3-hydroxypropyl)heptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol	1140744: Displacement of [3H]-1-alpha,25-dihydroxyvitamin D3 from N-terminal GST-tagged human recombinant VDR LBD expressed in Escherichia coli Rosetta2 (DE3) after 16 hrs	ic50	0.0009	uM
trans-(1R,3R)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(E,2S,6R)-6-(1-adamantyl)-6-hydroxyhex-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol	362894: Agonist activity at VDR assessed as receptor transactivation by transient transcription assay	ec50	0.0010	uM

CTD chemical–gene interactions

183 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Calcitriol	affects binding, increases reaction, decreases expression, affects reaction, increases activity (+13 more)	71
Lithocholic Acid	decreases expression, increases localization, affects cotreatment, increases phosphorylation, affects reaction (+7 more)	23
Lead	affects abundance, affects response to substance, affects cotreatment, increases response to substance	9
Valproic Acid	affects reaction, increases expression, affects cotreatment, affects expression, increases reaction (+1 more)	9
sodium arsenite	increases expression, affects reaction, decreases expression, increases abundance	7
Estradiol	increases expression, affects cotreatment, affects binding, increases reaction, decreases expression (+1 more)	6
1,25-dihydroxyvitamin D	affects cotreatment, increases activity, increases expression, affects binding, increases reaction (+5 more)	5
U 0126	affects cotreatment, increases expression, affects activity, decreases reaction, increases phosphorylation (+2 more)	5
lithocholic acid acetate	decreases reaction, increases activity, decreases expression, increases expression, affects cotreatment (+4 more)	5
Tretinoin	affects binding, affects cotreatment, increases reaction, increases expression	5
Vitamin D	increases expression, decreases reaction, increases activity, affects binding, increases reaction (+2 more)	5
Resveratrol	affects reaction, increases activity, decreases reaction, affects cotreatment, increases expression	4
Benzo(a)pyrene	increases expression, affects cotreatment, affects binding, decreases reaction, increases reaction (+2 more)	4
Calcifediol	increases reaction, decreases degradation, increases activity, decreases reaction, affects binding (+4 more)	4
Cholecalciferol	affects cotreatment, increases reaction, affects reaction, affects binding, affects localization (+3 more)	4
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	4
Aflatoxin B1	affects response to substance, affects localization, decreases reaction, increases expression, affects binding (+1 more)	4
trichostatin A	affects expression, affects cotreatment, increases expression, decreases reaction, increases activity	3
calcipotriene	affects binding, affects reaction, affects expression, decreases reaction, increases expression (+1 more)	3
paricalcitol	increases localization, affects activity, affects binding, affects cotreatment, increases expression	3
Fulvestrant	decreases expression, decreases reaction, increases expression	3
Alitretinoin	affects activity, affects binding, affects cotreatment, increases stability, increases reaction (+1 more)	3
Arsenic	increases abundance, increases expression	3
Calcium	affects response to substance, affects metabolic processing	3
Doxorubicin	decreases activity, decreases expression, increases expression	3
Etoposide	increases expression, increases response to substance, affects reaction, affects response to substance	3
Tetradecanoylphorbol Acetate	increases expression, increases reaction	3
Cadmium Chloride	increases reaction, decreases expression, increases abundance, affects binding	3
Genistein	decreases reaction, increases expression, increases reaction, affects binding	3
alfacalcidol	affects binding, increases reaction, increases activity	2

ChEMBL screening assays

561 unique, capped per target: 459 binding, 99 functional, 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1007256	Binding	Binding affinity to VDR relative to 1,25-Dihydroxyvitamin D3	Crystal structures of rat vitamin D receptor bound to adamantyl vitamin D analogs: structural basis for vitamin D receptor antagonism and partial agonism. — J Med Chem
CHEMBL1007257	Functional	Agonist activity at VDR assessed as receptor transactivation by transient transcription assay	Crystal structures of rat vitamin D receptor bound to adamantyl vitamin D analogs: structural basis for vitamin D receptor antagonism and partial agonism. — J Med Chem
CHEMBL2066209	ADMET	Binding affinity to full length human VDR by fluorescence polarization-based competitive assay	Probing the structural requirements for vitamin D3 inhibition of the hedgehog signaling pathway. — Bioorg Med Chem Lett

Cellosaurus cell lines

11 cell lines: 7 cancer cell line, 3 embryonic stem cell, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A7T6	SEES3-1V human VDR, clone1	Embryonic stem cell	Male
CVCL_A7T7	SEES3-1V human VDR, clone2	Embryonic stem cell	Male
CVCL_A7T8	SEES3-1V human VDR, clone3	Embryonic stem cell	Male
CVCL_B2L0	Abcam HeLa VDR KO	Cancer cell line	Female
CVCL_B6Q1	WM164 VDR KO	Cancer cell line	Male
CVCL_B8RL	Abcam HCT 116 VDR KO	Cancer cell line	Male
CVCL_B9U1	Abcam A-549 VDR KO	Cancer cell line	Male
CVCL_D2HM	Abcam MCF-7 VDR KO	Cancer cell line	Female
CVCL_E0ST	Ubigene HeLa VDR KO	Cancer cell line	Female
CVCL_LF57	GeneBLAzer VDR-UAS-bla HEK 293T	Transformed cell line	Female

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00296881	PHASE4	UNKNOWN	SRP in Combination With PERIOWAVE in Comparison to SRP Alone in Chronic Periodontitis
NCT00297518	PHASE4	COMPLETED	Study of Scaling and Root Planing (SRP) With PerioWave vs. SRP Alone in Chronic Periodontitis
NCT00297531	PHASE4	UNKNOWN	Study of Scaling and Root Planing With PerioWave Versus Scaling and Root Planing Alone in Chronic Periodontitis
NCT00668746	PHASE4	COMPLETED	Long-term Safety of Minocycline in Patients With Gum Disease
NCT00707369	PHASE4	COMPLETED	Adjunctive Antimicrobial Therapy of Periodontitis: Long-Term Effects on Disease Progression and Oral Microbiological Colonization
NCT01030666	PHASE4	TERMINATED	Effect of Postsurgical Systemic Doxycycline After Regenerative Periodontal Therapy
NCT01538927	PHASE4	COMPLETED	Effect of Fibrin Sealant on Early Wound Healing
NCT01548469	PHASE4	COMPLETED	Study to Evaluate Clinical Efficacy and Safety of Bio Mineral Toothpaste in Patients With Mild Periodontitis
NCT01593540	PHASE4	COMPLETED	Clinical Examination of Metal Free Interdental Brushes
NCT01806974	PHASE4	TERMINATED	Consequences of Anti-interleukin 6 Immunotherapy Treatment for Rheumatoid Arthritis on Periodontium
NCT02030470	PHASE4	COMPLETED	Evaluation of Photodynamic Treatment FOTOSAN® Efficacy in Periodontology
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NCT02215473	PHASE4	COMPLETED	Bacteremia in Periodontal Patients
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NCT03103204	PHASE4	COMPLETED	Treatment of Periodontitis in Obese Individuals
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NCT03176537	PHASE4	WITHDRAWN	Periodontal Profile of Hypogonadic Men
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NCT04044417	PHASE4	COMPLETED	Curcumin-Simvastatin-EDTA in the Treatment of Periodontitis
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NCT04223076	PHASE4	UNKNOWN	Clinical Effect of Chlorhexidine Mouthwash After Periodontal Surgery
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