VDR

vitamin D receptor, the group of Nuclear receptor subfamily 1 group I|Protein phosphatase 1 regulatory subunits

Basic information

Region (hg38): 12:47841537-47943048

Links

ENSG00000111424 ∙ NCBI:7421 ∙ OMIM:601769 ∙ HGNC:12679 ∙ Uniprot:P11473 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• vitamin D-dependent rickets, type 2A (Definitive), mode of inheritance: AR
• vitamin D-dependent rickets, type 2 (Supportive), mode of inheritance: AR
• vitamin D-dependent rickets, type 2A (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Vitamin D-dependent rickets, type 2A	AD/AR	Endocrine	Treatment of manifestations such as rickets (eg, with vitamin D3, calcium, phosphate) can be beneficial in some individuals, though not all individuals have been reported as demonstrating clinical or laboratory-based response to treatments	Dermatologic; Endocrine; Musculoskeletal	205789; 233695; 221630; 6102232; 7318845; 3009551; 3024987; 3040300; 2849209; 2551693; 9005998; 17970811; 19815438; 19921089; 21073129; 21424181; 21590741; 21812032; 21860566; 22145479; 22145480; 23026218

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VDR gene.

• not provided (11 variants)
• Vitamin D-dependent rickets type II with alopecia (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VDR gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	104	5	110
missense	3	6	94	3		106
nonsense	6					6
start loss			1		1	2
frameshift	2					2
inframe indel						0
splice donor/acceptor (+/-2bp)	1	3				4
splice region			4	20	3	27
non coding			75	87	29	191
Total	12	9	171	194	35

Highest pathogenic variant AF is 0.0000394

Variants in VDR

This is a list of pathogenic ClinVar variants found in the VDR region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-47841772-T-A		Vitamin D-dependent rickets type II with alopecia	Likely benign (Jan 13, 2018)
12-47841773-C-T		Vitamin D-dependent rickets type II with alopecia	Uncertain significance (Jan 13, 2018)
12-47841846-T-G		Vitamin D-dependent rickets type II with alopecia	Uncertain significance (Jan 12, 2018)
12-47841868-T-C		Vitamin D-dependent rickets type II with alopecia	Uncertain significance (Jan 12, 2018)
12-47841914-G-A		Vitamin D-dependent rickets type II with alopecia	Uncertain significance (Jan 12, 2018)
12-47841919-T-C		Vitamin D-dependent rickets type II with alopecia	Likely benign (Jan 13, 2018)
12-47841955-C-T		Vitamin D-dependent rickets type II with alopecia	Benign (Jan 12, 2018)
12-47842087-T-TC		Vitamin D-dependent rickets	Uncertain significance (Jun 14, 2016)
12-47842153-T-C		Vitamin D-dependent rickets type II with alopecia	Likely benign (Jan 12, 2018)
12-47842201-C-A		Vitamin D-dependent rickets type II with alopecia	Uncertain significance (Jan 12, 2018)
12-47842217-C-T		Vitamin D-dependent rickets type II with alopecia	Uncertain significance (Jan 13, 2018)
12-47842255-T-G		Vitamin D-dependent rickets type II with alopecia	Uncertain significance (Jan 13, 2018)
12-47842282-G-C		Vitamin D-dependent rickets type II with alopecia	Uncertain significance (Jan 13, 2018)
12-47842290-G-A		Vitamin D-dependent rickets type II with alopecia	Uncertain significance (Jan 13, 2018)
12-47842300-C-T		Vitamin D-dependent rickets type II with alopecia	Uncertain significance (Jan 12, 2018)
12-47842333-C-G		Vitamin D-dependent rickets type II with alopecia	Uncertain significance (Jan 13, 2018)
12-47842355-G-C		Vitamin D-dependent rickets	Uncertain significance (Jun 14, 2016)
12-47842387-G-T		Vitamin D-dependent rickets type II with alopecia	Uncertain significance (Jan 13, 2018)
12-47842418-G-C		Vitamin D-dependent rickets type II with alopecia	Uncertain significance (Jan 12, 2018)
12-47842437-G-A		Vitamin D-dependent rickets type II with alopecia	Uncertain significance (Jan 12, 2018)
12-47842450-A-G		Vitamin D-dependent rickets type II with alopecia	Uncertain significance (Jan 12, 2018)
12-47842483-C-T		Vitamin D-dependent rickets type II with alopecia	Uncertain significance (Jan 13, 2018)
12-47842519-C-T		Vitamin D-dependent rickets type II with alopecia	Uncertain significance (Jan 13, 2018)
12-47842520-G-A		Vitamin D-dependent rickets type II with alopecia	Uncertain significance (Jan 13, 2018)
12-47842578-C-G		Vitamin D-dependent rickets type II with alopecia	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VDR	protein_coding	protein_coding	ENST00000550325	10	101512

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000168	0.970	125738	0	10	125748	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.06	232	282	0.823	0.0000183	3146
Missense in Polyphen		67	105.67	0.63407		1149
Synonymous	-0.995	121	108	1.12	0.00000667	925
Loss of Function	1.98	11	20.7	0.530	0.00000116	245

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000532	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: 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. Recruited to promoters via its interaction with BAZ1B/WSTF which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis. {ECO:0000269|PubMed:10678179, ECO:0000269|PubMed:15728261, ECO:0000269|PubMed:16252006, ECO:0000269|PubMed:16913708, ECO:0000269|PubMed:28698609}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:1652893, ECO:0000269|PubMed:17970811, ECO:0000269|PubMed:2177843, ECO:0000269|PubMed:2849209, ECO:0000269|PubMed:28698609, ECO:0000269|PubMed:7828346, ECO:0000269|PubMed:8106618, ECO:0000269|PubMed:8381803, ECO:0000269|PubMed:8392085, ECO:0000269|PubMed:8675579, ECO:0000269|PubMed:8961271, ECO:0000269|PubMed:9005998}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Endocrine and other factor-regulated calcium reabsorption - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Mineral absorption - Homo sapiens (human);Etoposide Pathway, Pharmacokinetics/Pharmacodynamics;NHR;Vitamin D Metabolism;Nuclear Receptors;Drug Induction of Bile Acid Pathway;Vitamin D Receptor Pathway;Nuclear Receptors Meta-Pathway;Nuclear Receptors in Lipid Metabolism and Toxicity;Ovarian Infertility Genes;PI3K-AKT-mTOR - VitD3 Signalling;Gene expression (Transcription);Generic Transcription Pathway;Metabolism of lipids;Nuclear Receptor transcription pathway;RNA Polymerase II Transcription;Metabolism;Metabolism of steroids;TGF_beta_Receptor;Vitamin D (calciferol) metabolism;Validated transcriptional targets of TAp63 isoforms;RXR and RAR heterodimerization with other nuclear receptor;Direct p53 effectors;Retinoic acid receptors-mediated signaling;Validated transcriptional targets of deltaNp63 isoforms;Regulation of nuclear SMAD2/3 signaling;Steroid hormones (Consensus)

Recessive Scores

• pRec: 0.772

Intolerance Scores

• loftool: 0.0311
• rvis_EVS: -0.62
• rvis_percentile_EVS: 17.31

Haploinsufficiency Scores

• pHI: 0.286
• hipred: Y
• hipred_score: 0.786
• ghis: 0.574

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.951

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Vdr
• Phenotype: hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system phenotype; skeleton phenotype; immune system phenotype; muscle phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype

Zebrafish Information Network

• Gene name: vdrb
• Affected structure: macula saccule
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;cell morphogenesis;skeletal system development;transcription initiation from RNA polymerase II promoter;calcium ion transport;cellular calcium ion homeostasis;signal transduction;multicellular organism development;lactation;negative regulation of cell population proliferation;animal organ morphogenesis;positive regulation of gene expression;negative regulation of keratinocyte proliferation;positive regulation of vitamin D 24-hydroxylase activity;cell differentiation;bile acid signaling pathway;vitamin D metabolic process;steroid hormone mediated signaling pathway;positive regulation of keratinocyte differentiation;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;decidualization;intestinal absorption;positive regulation of apoptotic process involved in mammary gland involution;regulation of calcidiol 1-monooxygenase activity;mammary gland branching involved in pregnancy;vitamin D receptor signaling pathway
• Cellular component: nucleus;nucleoplasm;cytoplasm;receptor complex;RNA polymerase II transcription factor complex
• Molecular function: transcription regulatory region sequence-specific DNA binding;RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;steroid hormone receptor activity;nuclear receptor activity;vitamin D binding;protein binding;transcription factor binding;zinc ion binding;nuclear receptor transcription coactivator activity;signaling receptor activity;lithocholic acid receptor activity;retinoid X receptor binding;vitamin D response element binding;calcitriol binding;lithocholic acid binding