vitamin D deficiency

Summary

vitamin D deficiency (MONDO:0100471) is a disease with 1 cohort gene and 678 clinical trials. Top therapeutic interventions include cholecalciferol, ergocalciferol, and calcifediol anhydrous.

At a glance

• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 678

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	vitamin D deficiency
Mondo ID	MONDO:0100471
MeSH	D014808
DOID	DOID:10574
ICD-10-CM	E55
ICD-11	2080031371
NCIT	C114830
SNOMED CT	34713006
UMLS	C0042870
MedGen	12114
Is cancer (heuristic)	no

Also known as: avitaminosis D · avitaminosis D, NOS · DEFIC VITAMIN D · deficiencies, vitamin D · deficiency of vitamin D (disorder) · deficiency, vitamin D · VITAMIN D DEFIC · vitamin D deficiencies · vitamin D deficiency (disorder) · vitamin D deficiency, NOS · vitamin D insufficiency

Data availability: 1 ClinVar variant · 1 HPO phenotype.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › nutritional disorder › nutritional deficiency disease › vitamin deficiency disorder › vitamin D deficiency

Related subtypes (7): nutritional biotin deficiency, vitamin K deficiency hemorrhagic disease, inborn vitamin metabolic disorder, vitamin A deficiency, scurvy, vitamin B deficiency, vitamin deficiency related neuropathy

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
805882	NM_002335.4(LRP5):c.1618C>T (p.Leu540Phe)	LRP5	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 9 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LRP5	Orphanet:178377	Osteosclerosis-developmental delay-craniosynostosis syndrome
LRP5	Orphanet:2783	Autosomal dominant osteopetrosis type 1
LRP5	Orphanet:2788	Osteoporosis-pseudoglioma syndrome
LRP5	Orphanet:2790	Endosteal hyperostosis, Worth type
LRP5	Orphanet:2924	Isolated polycystic liver disease
LRP5	Orphanet:3416	Hyperostosis corticalis generalisata
LRP5	Orphanet:498481	LRP5-related primary osteoporosis
LRP5	Orphanet:891	Familial exudative vitreoretinopathy
LRP5	Orphanet:90050	Retinopathy of prematurity

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
LRP5	HGNC:6697	ENSG00000162337	O75197	Low-density lipoprotein receptor-related protein 5	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LRP5	Low-density lipoprotein receptor-related protein 5	Acts as a coreceptor with members of the frizzled family of seven-transmembrane spanning receptors to transduce signal by Wnt proteins.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LRP5	Other/Unknown	no		LDLR_classB_rpt, EGF, LDrepeatLR_classA_rpt

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ascending aorta	1
mucosa of transverse colon	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LRP5	224	ubiquitous	marker	right lobe of liver, mucosa of transverse colon, ascending aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LRP5	2,619

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LRP5	O75197	78.65

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signaling by LRP5 mutants	1	1631.4×	0.004	LRP5
Signaling by RNF43 mutants	1	1268.9×	0.004	LRP5
Negative regulation of TCF-dependent signaling by WNT ligand antagonists	1	713.8×	0.004	LRP5
Signaling by WNT in cancer	1	601.0×	0.004	LRP5
Regulation of FZD by ubiquitination	1	519.1×	0.004	LRP5
Disassembly of the destruction complex and recruitment of AXIN to the membrane	1	356.9×	0.005	LRP5
TCF dependent signaling in response to WNT	1	117.7×	0.012	LRP5
Signaling by WNT	1	112.0×	0.012	LRP5
Diseases of signal transduction by growth factor receptors and second messengers	1	56.8×	0.022	LRP5
Disease	1	13.1×	0.084	LRP5
Signal Transduction	1	10.2×	0.098	LRP5

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cell-cell signaling involved in mammary gland development	1	5617.3×	0.002	LRP5
mesodermal cell migration	1	3370.4×	0.002	LRP5
extracellular matrix-cell signaling	1	3370.4×	0.002	LRP5
anatomical structure regression	1	3370.4×	0.002	LRP5
Norrin signaling pathway	1	3370.4×	0.002	LRP5
apoptotic process involved in blood vessel morphogenesis	1	2808.7×	0.002	LRP5
establishment of blood-retinal barrier	1	2808.7×	0.002	LRP5
glucose catabolic process	1	2407.4×	0.002	LRP5
retinal blood vessel morphogenesis	1	2407.4×	0.002	LRP5
retina morphogenesis in camera-type eye	1	1872.4×	0.002	LRP5
cell migration involved in gastrulation	1	1532.0×	0.002	LRP5
bone marrow development	1	1532.0×	0.002	LRP5
osteoblast proliferation	1	1404.3×	0.002	LRP5
branching involved in mammary gland duct morphogenesis	1	1404.3×	0.002	LRP5
establishment of blood-brain barrier	1	1404.3×	0.002	LRP5
positive regulation of osteoblast proliferation	1	1203.7×	0.002	LRP5
osteoblast development	1	991.3×	0.002	LRP5
gastrulation with mouth forming second	1	936.2×	0.002	LRP5
bone remodeling	1	936.2×	0.002	LRP5
regulation of insulin secretion involved in cellular response to glucose stimulus	1	936.2×	0.002	LRP5
positive regulation of mesenchymal cell proliferation	1	601.9×	0.003	LRP5
bone morphogenesis	1	601.9×	0.003	LRP5
positive regulation of mitotic nuclear division	1	543.6×	0.004	LRP5
adipose tissue development	1	401.2×	0.004	LRP5
response to peptide hormone	1	391.9×	0.004	LRP5
amino acid transport	1	312.1×	0.005	LRP5
embryonic digit morphogenesis	1	300.9×	0.005	LRP5
positive regulation of fat cell differentiation	1	300.9×	0.005	LRP5
negative regulation of osteoblast differentiation	1	295.6×	0.005	LRP5
somatic stem cell population maintenance	1	247.8×	0.006	LRP5

Therapeutics

Drugs indicated for this disease

0 approved, 4 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Calcium Carbonate	Phase 3 (in late-stage trials)
Cholecalciferol	Phase 3 (in late-stage trials)
Ergocalciferol	Phase 3 (in late-stage trials)
Lactose, Anhydrous	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Aspirin.

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LRP5	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
LRP5	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	LRP5

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
LRP5	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 678.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	445
PHASE4	84
PHASE2	47
PHASE3	43
PHASE1	20
PHASE2/PHASE3	16
EARLY_PHASE1	14
PHASE1/PHASE2	9

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03621553	PHASE4	RECRUITING	Vitamin D Homeostasis in Sarcoidosis
NCT04482673	PHASE4	ACTIVE_NOT_RECRUITING	Vitamin D Supplementation in the Prevention and Mitigation of COVID-19 Infection
NCT05860270	PHASE4	RECRUITING	Oral Vitamin D Supplementation Prevent Peritoneal Dialysis-related Peritonitis
NCT06258850	PHASE4	NOT_YET_RECRUITING	REstoration of VItamin D in Pulmonary Arterial Hypertension
NCT07006714	PHASE4	ACTIVE_NOT_RECRUITING	Preoperative Correction of Vitamin D Deficiency in Total Joint Arthroplasty (TJA)
NCT00288873	PHASE4	COMPLETED	Characterization of Hyperparathyroidism and Vitamin D Deficiency in Obesity
NCT00497900	PHASE4	COMPLETED	The Effect of Calcium and Vitamin D in Patients With Heart Failure
NCT00581828	PHASE4	COMPLETED	Does Treatment of Hypovitaminosis D Increase Calcium Absorption?
NCT00752102	PHASE4	COMPLETED	Vitamin D and Coronary Calcification Study
NCT00882401	PHASE4	COMPLETED	Vitamin D, Chronic Kidney Disease (CKD) and the Microcirculation
NCT00933244	PHASE4	COMPLETED	Treatment of Vitamin D Insufficiency
NCT00974922	PHASE4	TERMINATED	Vitamin D Deficiency in Patients With Hypertension
NCT01016184	PHASE4	COMPLETED	Influence of Vitamin D Treatment on Multi-systemic Functions in Young Men With Vitamin D Deficiency Due to Work Conditions
NCT01025128	PHASE4	COMPLETED	Vitamin D Status in Males in Jerusalem Area and Its Correlation to Parathyroid Hormone (PTH) Level and Bone Mineral Density
NCT01037140	PHASE4	COMPLETED	Effects of Vitamin D Supplementation in Obesity
NCT01058720	PHASE4	COMPLETED	Efficacy of Daily Vitamin D3 Supplementation in Normal Weight Adolescents
NCT01112891	PHASE4	COMPLETED	Vitamin D in Pregnancy and Lactation
NCT01153243	PHASE4	UNKNOWN	Vitamin D and Inflammatory Markers of Cardiovascular Disease in African Americans With Type 2 Diabetes
NCT01187459	PHASE4	COMPLETED	Vitamin D in Pediatric Crohn’s Disease
NCT01295879	PHASE4	COMPLETED	Vitamin D Repletion in Stone Formers With Hypercalciuria
NCT01306656	PHASE4	COMPLETED	Vitamin D Repletion in Primary Hyperparathyroidism
NCT01312441	PHASE4	TERMINATED	Sustainability of Vitamin D Levels After Repletion With Ergocalciferol In Chronic Kidney Disease Stage 5D
NCT01417923	PHASE4	UNKNOWN	The Immune and Clinical Impacts of Vitamin D in Patients With Chronic Musculo-skeletal Pain
NCT01419119	PHASE4	COMPLETED	Vitamin Deficiency in Immigrants, a Treatment Study
NCT01436916	PHASE4	COMPLETED	Oral Cholecalciferol in Prevention of Type 2 Diabetes Mellitus
NCT01437696	PHASE4	COMPLETED	How Much Vitamin D is Required to be Protective Against Deficiency During the Winter Months?
NCT01497132	PHASE4	COMPLETED	Effects of Vitamin D on Beta Cell Function and Insulin Sensitivity in Pre-diabetes and Diabetes Mellitus Type 2
NCT01506557	PHASE4	COMPLETED	Vitamin D Supplementation of Lactating Mothers
NCT01596842	PHASE4	COMPLETED	Effect of Omega-3 Fatty Acid on Vitamin D Activation
NCT01633853	PHASE4	COMPLETED	Efficacy of Vitamin D2 to Treat Chronic Kidney Disease Mineral and Bone Disorder
NCT01721915	PHASE4	COMPLETED	Vitamin D Treatment, Pharmacogenetics and Glucose Metabolism
NCT01741181	PHASE4	COMPLETED	Vitamin D Supplementation in Patients With Diabetes Mellitus Type 2
NCT01784029	PHASE4	COMPLETED	Treatment Study of Vitamin D Deficiency in Adolescents
NCT01817699	PHASE4	TERMINATED	Correcting Anemia and Native Vitamin D Supplementation in Kidney Transplant Recipients
NCT01845142	PHASE4	COMPLETED	Immunologic Action of a Single Dose Cholecalciferol
NCT01924910	PHASE4	COMPLETED	A Single Wintertime Dose of Vitamin D3 to Prevent Winter Decline in Vitamin D Status in Healthy Adults
NCT01991054	PHASE4	COMPLETED	The Effects of Vitamin D Supplementation on Patients With Type 2 Diabetes and Vitamin D Deficiency
NCT01993537	PHASE4	COMPLETED	The Role of Vitamin D in the Pathophysiology of Chronic Failure
NCT02005302	PHASE4	UNKNOWN	Optimizing Treatment Programs for Chronic Kidney Disease-mineral and Bone Disorder and Malnutrition
NCT02136771	PHASE4	COMPLETED	Styrian Vitamin D Hypertension Trial

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CHOLECALCIFEROL	4	278
ERGOCALCIFEROL	4	28
CALCIFEDIOL ANHYDROUS	4	17
CALCITRIOL	4	4
PARICALCITOL	4	4
CALCIUM CARBONATE	4	3
CLOMIPHENE	4	3
OLIVE OIL	4	2
RETINOL	4	2
ALFACALCIDOL	4	1
ALISKIREN	4	1
CALCIUM	4	1
CYSTEINE	4	1
DESMOPRESSIN	4	1
DOXERCALCIFEROL	4	1
EZETIMIBE	4	1
FERRIC CARBOXYMALTOSE	4	1
MAGNESIUM CHLORIDE	4	1
MEDROXYPROGESTERONE ACETATE	4	1
PENICILLAMINE	4	1
TAMOXIFEN	4	1
VALSARTAN	4	1
LACTOSE, ANHYDROUS	3	2
25-HYDROXYERGOCALCIFEROL-	3	1
CALCIUM CITRATE	3	1
CREATININE	3	1
ENCLOMIPHENE	3	1
MINERAL OIL	3	1
PROPYLENE GLYCOL	3	1
SYRUP	3	1