LRP5

Summary

LRP5 (LDL receptor related protein 5, HGNC:6697) is a protein-coding gene on chromosome 11q13.2, encoding Low-density lipoprotein receptor-related protein 5 (O75197). Acts as a coreceptor with members of the frizzled family of seven-transmembrane spanning receptors to transduce signal by Wnt proteins.

This gene encodes a transmembrane low-density lipoprotein receptor that binds and internalizes ligands in the process of receptor-mediated endocytosis. This protein also acts as a co-receptor with Frizzled protein family members for transducing signals by Wnt proteins and was originally cloned on the basis of its association with type 1 diabetes mellitus in humans. This protein plays a key role in skeletal homeostasis and many bone density related diseases are caused by mutations in this gene. Mutations in this gene also cause familial exudative vitreoretinopathy. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 4041 — RefSeq curated summary.

At a glance

• Gene–disease (curated): LRP5-related exudative vitreoretinopathy (Definitive, ClinGen) — +11 more curated relationships
• GWAS associations: 26
• Clinical variants (ClinVar): 2,496 total — 128 pathogenic, 78 likely-pathogenic
• Phenotypes (HPO): 175
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_002335

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6697
Approved symbol	LRP5
Name	LDL receptor related protein 5
Location	11q13.2
Locus type	gene with protein product
Status	Approved
Aliases	LR3, BMND1, HBM, OPS, OPTA1, VBCH2, EVR4
Ensembl gene	ENSG00000162337
Ensembl biotype	protein_coding
OMIM	603506
Entrez	4041

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 10 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000294304, ENST00000528714, ENST00000528890, ENST00000529481, ENST00000529702, ENST00000529993, ENST00000533695, ENST00000909989, ENST00000909990, ENST00000909991, ENST00000909992, ENST00000909993, ENST00000909994, ENST00000921488, ENST00000921489

RefSeq mRNA: 2 — MANE Select: NM_002335 NM_001291902, NM_002335

CCDS: CCDS8181

Canonical transcript exons

ENST00000294304 — 23 exons

Exon	Start	End
ENSE00000991969	68347847	68348243
ENSE00001166545	68365571	68365702
ENSE00001166549	68363747	68363943
ENSE00001166576	68357650	68357847
ENSE00001413096	68312591	68312805
ENSE00001642589	68386316	68386712
ENSE00001783344	68389881	68390052
ENSE00002193719	68448809	68449275
ENSE00003463688	68436889	68436999
ENSE00003508659	68403483	68403699
ENSE00003512210	68433602	68433838
ENSE00003518921	68425978	68426187
ENSE00003532926	68413689	68414012
ENSE00003542163	68423489	68423697
ENSE00003548518	68439777	68439916
ENSE00003564090	68409914	68410140
ENSE00003585836	68429575	68429700
ENSE00003598422	68425102	68425292
ENSE00003615328	68446436	68446533
ENSE00003623177	68411436	68411620
ENSE00003635169	68438446	68438682
ENSE00003642666	68406524	68406813
ENSE00003682021	68416328	68416527

Expression profiles

Bgee: expression breadth ubiquitous, 224 present calls, max score 98.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.4553 / max 150.1920, expressed in 1534 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115535	4.4981	1396
115534	2.3629	1194
115532	1.1063	760
115533	0.4880	286

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.20	gold quality
mucosa of transverse colon	UBERON:0004991	96.10	gold quality
ascending aorta	UBERON:0001496	95.78	gold quality
thoracic aorta	UBERON:0001515	95.69	gold quality
apex of heart	UBERON:0002098	95.24	gold quality
minor salivary gland	UBERON:0001830	95.20	gold quality
aorta	UBERON:0000947	95.00	gold quality
descending thoracic aorta	UBERON:0002345	94.90	gold quality
popliteal artery	UBERON:0002250	94.71	gold quality
tibial artery	UBERON:0007610	94.70	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.64	gold quality
right coronary artery	UBERON:0001625	94.29	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.29	gold quality
right lobe of thyroid gland	UBERON:0001119	94.24	gold quality
transverse colon	UBERON:0001157	94.08	gold quality
body of uterus	UBERON:0009853	94.06	gold quality
mucosa of stomach	UBERON:0001199	94.03	gold quality
left lobe of thyroid gland	UBERON:0001120	93.90	gold quality
endocervix	UBERON:0000458	93.69	gold quality
left coronary artery	UBERON:0001626	93.53	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.46	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.37	gold quality
body of stomach	UBERON:0001161	93.26	gold quality
left uterine tube	UBERON:0001303	93.24	gold quality
right atrium auricular region	UBERON:0006631	93.07	gold quality
body of pancreas	UBERON:0001150	92.83	gold quality
ectocervix	UBERON:0012249	92.76	gold quality
lower esophagus	UBERON:0013473	92.76	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.76	gold quality
left ovary	UBERON:0002119	92.46	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.99

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ELK1, FOXC1, KLF15, MSX2, RUNX2, SMAD1, SP1, VDR

miRNA regulators (miRDB)

16 targeting LRP5, 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-4668-3P	100.00	68.74	2635
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-5007-3P	99.51	68.14	1242
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-1206	99.30	69.32	1016
HSA-MIR-605-5P	98.79	68.24	1161
HSA-MIR-1279	97.83	67.50	1898
HSA-MIR-4733-5P	97.75	67.44	866

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• mutation results in an autosomal dominant high-bone-mass trait (PMID:11741193)
• seven novel sequence variants/polymorphisms (PMID:11793484)
• The LRP5V171 mutation causes high bone density by impairing the action of a normal antagonist of the Wnt pathway and thus increasing Wnt signaling. These findings demonstrate the role of altered LRP5 function in high bone mass. (PMID:12015390)
• localization to chromosome 11q12-13 in autosomal dominant osteopetrosis type I (PMID:12054167)
• Six novel missense mutations in this gene shown in various conditions with an increased bone density and bone diseases. (PMID:12579474)
• disease association data, largely focused in the LRP5 region with 1,106 type 1 diabetes families, provided no further evidence for disease association at LRP5 or at D11S987 (PMID:12700977)
• G171V transgenic mice showed an increase in actively mineralizing bone surface and enhanced alkaline phosphatase staining in osteoblasts (PMID:12817748)
• LRP5 is a bone mineral density determinant and also contributes to a risk of osteoporosis (PMID:14727154)
• LRP5 has a role in neoplasm metastasis (PMID:14735475)
• Familial exudative vitreoretinopathy has mutations in a second gene at the EVR1 locus, low-density-lipoprotein receptor-related protein 5 (LRP5), a Wnt coreceptor (PMID:15024691)
• no association was found between a LRP5 polymorphism and peak bone mass in young men (PMID:15201508)
• LRP5 gene is a candidate for the genetic determinants of bone mineral density in postmenopausal women (PMID:15221492)
• Mutations in LRP5 can cause autosomal recessive or dominant Familial exudative vitreoretinopathy. (PMID:15346351)
• genetic variation in LRP5 seems to be of importance for regulation of bone mass and osteoporotic fractures (PMID:15777745)
• heterozygous mutations in the LRP5 gene can cause osteoporosis in both children and adults (PMID:15824851)
• a novel LRP5 mutation may be responsible for oropharyngeal skeletal disease (PMID:15824861)
• SOST antagonizes Wnt signaling by binding to the extracellular domain of the Wnt coreceptors LRP5 and LRP6 and disrupting Wnt-induced Frizzled-LRP complex formation. (PMID:15908424)
• These data suggest that HBM mutant proteins can transit to the cell surface in sufficient quantity to transduce Wnt signal and that the likely mechanism for the HBM mutations’ physiologic effects is via reduced affinity to and inhibition by DKK1. (PMID:15923613)
• mutations in the LRP5 and/or FZD4 genes may have roles in familial exudative vitreoretinopathy (PMID:15981244)
• These data indicate an association between LRP5 variants and idiopathic osteoporosis in males, pointing to a role of LRP5 in this disease. (PMID:16168727)
• Carrying an LRP5 mutation is a risk factor for idiopathic osteoporosis, but idiopathic osteoporosis in men is infrequently underlied by such a mutation. (PMID:16234968)
• active CKIepsilon generation may induce a negative feedback loop by phosphorylation of sites on LRP5/6 that modulate axin binding and hence beta-catenin degradation (PMID:16513652)
• Lrp5 locus was discovered to confer vitamin D response to a heterologous promoter when introduced into osteoblastic cells (PMID:16613987)
• LRP5 was increased in the calcified aortic valves by protein and gene expression. (PMID:16631011)
• observed mutations may affect the molecular interactions of LRP5 and so lead to the observed osteoporosis pseudoglioma syndrome phenotypes (PMID:16679074)
• The Q89R polymorphism is an independent factor for hypertension in Japanese females. (PMID:16754270)
• Splice forms of crucial genes of the Wnt-pathway, beta-Catenin, LRP5, GSK3beta, Axin-1 and CtBP1 are expressed in human colorectal tissue. (PMID:16772034)
• This study examined human LRP5 signaling and the effects of an intracellular domain single nucleotide polymorphism (SNP: p.V1525A) on osteoblast differentiation and mineralization. (PMID:16956801)
• functional interactions between Sost or Wise and LRP5 have the potential to regulate bone deposition by modulating Wnt signaling (PMID:17002572)
• SOST-LRP5 antagonistic interaction plays a central role in bone mass regulation and may represent a nodal point for therapeutic intervention for osteoporosis and other bone diseases (PMID:17052975)
• we found a relationship between the LRP5 genotype and serum follicle stimulating hormone but not luteinizing hormone levels (PMID:17087607)
• Wnt-LRP5 signalling may play a role in the adaptation of bone to mechanical load in humans, and may explain some gender-related differences in bone mass (PMID:17137849)
• In comparison with subjects with the AlaAla genotype (n=215), those with AlaVal genotype (n=20) had lower femoral neck BMC (P=0.029) and BMD (P=0.012), trochanter BMC (P=0.0067) and BMD (P=0.015), and total hip BMC (P=0.0044) and BMD (P=0.0089). (PMID:17223614)
• 1,25(OH)(2)D(3) can enhance the expression of a critical component of the Wnt signaling pathway which is known to impact osteogenesis (PMID:17229572)
• Results indicate the importance of LRP5 beta-propeller 1 for Dkk1 function and Wnt signaling. (PMID:17276019)
• genetic variations in LRP5 are important factors affecting BMD in adult women, and 1330 V may contribute to osteoporosis susceptibility, at least in Japanese (PMID:17306638)
• Premenopausal women drove the association as expected from the proposed role of LRP5 in peak bone mass (PMID:17307038)
• LRP5 polymorphism effect on bone mineral density is apparent in childhood (PMID:17505772)
• LRP5 mutations and the level of Wnt signaling determine differentiation fate of hMSCs into osteoblasts or adipocytes. (PMID:17680723)
• concludes that bone-derived prostate cell line that produces osteoblastic lesions induces new bone formation through Wnt canonical signaling, that LRP5 mediates this effect, and that DKK1 is involved in the balance between bone formation and resorption (PMID:17700537)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrp5	ENSDARG00000006921
mus_musculus	Lrp5	ENSMUSG00000024913
rattus_norvegicus	Lrp5	ENSRNOG00000015911

Paralogs (14): LRP6 (ENSG00000070018), LRP2 (ENSG00000081479), NID2 (ENSG00000087303), NID1 (ENSG00000116962), LRP1 (ENSG00000123384), LDLR (ENSG00000130164), LRP3 (ENSG00000130881), LRP4 (ENSG00000134569), EGF (ENSG00000138798), LRP12 (ENSG00000147650), VLDLR (ENSG00000147852), LRP8 (ENSG00000157193), LRP1B (ENSG00000168702), LRP10 (ENSG00000197324)

Protein

Protein identifiers

Low-density lipoprotein receptor-related protein 5 — O75197 (reviewed: O75197)

Alternative names: Low-density lipoprotein receptor-related protein 7

All UniProt accessions (3): E9PHY1, O75197, H0YE98

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a coreceptor with members of the frizzled family of seven-transmembrane spanning receptors to transduce signal by Wnt proteins. Activates the canonical Wnt signaling pathway that controls cell fate determination and self-renewal during embryonic development and adult tissue regeneration. In particular, may play an important role in the development of the posterior patterning of the epiblast during gastrulation. During bone development, regulates osteoblast proliferation and differentiation thus determining bone mass. Mechanistically, the formation of the signaling complex between Wnt ligand, frizzled receptor and LRP5 coreceptor promotes the recruitment of AXIN1 to LRP5, stabilizing beta-catenin/CTNNB1 and activating TCF/LEF-mediated transcriptional programs. Acts as a coreceptor for non-Wnt proteins, such as norrin/NDP. Binding of norrin/NDP to frizzled 4/FZD4-LRP5 receptor complex triggers beta-catenin/CTNNB1-dependent signaling known to be required for retinal vascular development. Plays a role in controlling postnatal vascular regression in retina via macrophage-induced endothelial cell apoptosis.

Subunit / interactions. Homodimer; disulfide-linked. Forms phosphorylated oligomer aggregates on Wnt-signaling. Component of a Wnt-signaling complex that contains a WNT protein, a FZD protein and LRP5 or LRP6. Interacts with FZD8; the interaction is formed on WNT-binding and signaling. Interacts (via the phosphorylated PPPSP motif domains) with AXIN1; the interaction prevents inhibition of beta-catenin phosphorylation and signaling and is enhanced in the presence of GSK3B and WNT1 or WNT3A. Interacts (via beta-propeller regions 3 and 4) with DKK1; the interaction, enhanced by MESD and/or KREMEN, inhibits beta-catenin signaling by preventing GSK3-mediated phosphorylation of the PPPSP motifs and subsequent, AXIN1 binding. Interacts with MESD; the interaction prevents the formation of LRP5 aggregates, targets LRP5 to the plasma membrane and, when complexed with KREMEN2, increases DKK1 binding. Interacts with CSNK1E. Interacts with SOST; the interaction antagonizes canonical Wnt signaling. Interacts with APCDD1. Interacts with CAPRIN2.

Subcellular location. Membrane. Endoplasmic reticulum.

Tissue specificity. Widely expressed, with the highest level of expression in the liver and in aorta.

Post-translational modifications. Phosphorylation of cytoplasmic PPPSP motifs regulates the signal transduction of the Wnt signaling pathway through acting as a docking site for AXIN1.

Disease relevance. Vitreoretinopathy, exudative 1 (EVR1) [MIM:133780] An autosomal dominant disorder of the retinal vasculature characterized by an abrupt cessation of growth of peripheral capillaries, leading to an avascular peripheral retina. This may lead to compensatory retinal neovascularization, which is thought to be induced by hypoxia from the initial avascular insult. New vessels are prone to leakage and rupture causing exudates and bleeding, followed by scarring, retinal detachment and blindness. Clinical features can be highly variable, even within the same family. Patients with mild forms of the disease are asymptomatic, and their only disease related abnormality is an arc of avascular retina in the extreme temporal periphery. In many ways the disease resembles retinopathy of prematurity but there is no evidence of prematurity or small birth weight in the patient history. The disease is caused by variants affecting the gene represented in this entry. Vitreoretinopathy, exudative 4 (EVR4) [MIM:601813] A disorder of the retinal vasculature characterized by an abrupt cessation of growth of peripheral capillaries, leading to an avascular peripheral retina. This may lead to compensatory retinal neovascularization, which is thought to be induced by hypoxia from the initial avascular insult. New vessels are prone to leakage and rupture causing exudates and bleeding, followed by scarring, retinal detachment and blindness. Clinical features can be highly variable, even within the same family. Patients with mild forms of the disease are asymptomatic, and their only disease related abnormality is an arc of avascular retina in the extreme temporal periphery. EVR4 inheritance can be autosomal dominant or autosomal recessive. The disease is caused by variants affecting the gene represented in this entry. Osteoporosis (OSTEOP) [MIM:166710] A systemic skeletal disorder characterized by decreased bone mass and deterioration of bone microarchitecture without alteration in the composition of bone. The result is fragile bones and an increased risk of fractures, even after minimal trauma. Osteoporosis is a chronic condition of multifactorial etiology and is usually clinically silent until a fracture occurs. Disease susceptibility is associated with variants affecting the gene represented in this entry. Osteoporosis-pseudoglioma syndrome (OPPG) [MIM:259770] A disease characterized by congenital or infancy-onset blindness and severe juvenile-onset osteoporosis and spontaneous fractures. Additional clinical manifestations may include microphthalmos, abnormalities of the iris, lens or vitreous, cataracts, short stature, microcephaly, ligamental laxity, intellectual disability and hypotonia. The disease is caused by variants affecting the gene represented in this entry. High bone mass trait (HBM) [MIM:601884] Rare phenotype characterized by exceptionally dense bones. HBM individuals show otherwise a completely normal skeletal structure and no other unusual clinical findings. The disease is caused by variants affecting the gene represented in this entry. Endosteal hyperostosis, Worth type (WENHY) [MIM:144750] An autosomal dominant sclerosing bone dysplasia clinically characterized by elongation of the mandible, increased gonial angle, flattened forehead, and the presence of a slowly enlarging osseous prominence of the hard palate (torus palatinus). Serum calcium, phosphorus and alkaline phosphatase levels are normal. Radiologically, it is characterized by early thickening of the endosteum of long bones, the skull and of the mandible. With advancing age, the trabeculae of the metaphysis become thickened. WENHY becomes clinically and radiologically evident by adolescence, does not cause deformity except in the skull and mandible, and is not associated with bone pain or fracture. Affected patients have normal height, proportion, intelligence and longevity. The disease is caused by variants affecting the gene represented in this entry. Osteopetrosis, autosomal dominant 1 (OPTA1) [MIM:607634] A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. OPTA1 is an autosomal dominant form characterized by generalized osteosclerosis most pronounced in the cranial vault. Patients are often asymptomatic, but some suffer from pain and hearing loss. It appears to be the only type of osteopetrosis not associated with an increased fracture rate. The disease is caused by variants affecting the gene represented in this entry. Van Buchem disease 2 (VBCH2) [MIM:607636] VBCH2 is an autosomal dominant sclerosing bone dysplasia characterized by cranial osteosclerosis, thickened calvaria and cortices of long bones, enlarged mandible and normal serum alkaline phosphatase levels. The disease is caused by variants affecting the gene represented in this entry. Polycystic liver disease 4 with or without kidney cysts (PCLD4) [MIM:617875] A form of polycystic liver disease, an autosomal dominant hepatobiliary disease characterized by overgrowth of biliary epithelium and supportive connective tissue, resulting in multiple liver cysts. PCLD4 patients may also develop kidney cysts that usually do not result in clinically significant renal disease. The disease is caused by variants affecting the gene represented in this entry. LRP5 variations may act as a disease modifier in autosomal dominant polycystic kidney disease (ADPKD) in patients who have causative mutations in PKD1. May contribute to the disease phenotype heterogeneity and hepatic cystogenesis.

Polymorphism. Genetic variations in LRP5 define the bone mineral density quantitative trait locus 1 (BMND1) [MIM:601884]. Variance in bone mineral density influences bone mass and contributes to size determination in the general population.

Similarity. Belongs to the LDLR family.

RefSeq proteins (2): NP_001278831, NP_002326* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000033	LDLR_classB_rpt	Repeat
IPR000742	EGF	Domain
IPR002172	LDrepeatLR_classA_rpt	Repeat
IPR011042	6-blade_b-propeller_TolB-like	Homologous_superfamily
IPR017049	LRP5/6	Family
IPR023415	LDLR_class-A_CS	Conserved_site
IPR036055	LDL_receptor-like_sf	Homologous_superfamily
IPR050778

Pfam: PF00057, PF00058, PF14670

UniProt features (169 total): sequence variant 86, repeat 31, disulfide bond 21, domain 7, region of interest 6, glycosylation site 6, short sequence motif 5, topological domain 2, signal peptide 1, chain 1, sequence conflict 1, transmembrane region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75197-F1	78.65	0.42

Functional residue map

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

Disulfide bonds (21): 299–310, 306–321, 323–336, 605–616, 612–625, 627–640, 906–917, 913–926, 928–941, 1217–1228, 1224–1238, 1240–1253, 1259–1273, 1266–1286, 1280–1295, 1298–1310, 1305–1323, 1317–1332, 1336–1348, 1343–1361 …

Glycosylation sites (6): 93, 138, 446, 499, 705, 878

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-201681	TCF dependent signaling in response to WNT
R-HSA-3772470	Negative regulation of TCF-dependent signaling by WNT ligand antagonists
R-HSA-4641262	Disassembly of the destruction complex and recruitment of AXIN to the membrane
R-HSA-4641263	Regulation of FZD by ubiquitination
R-HSA-5339717	Signaling by LRP5 mutants
R-HSA-5340588	Signaling by RNF43 mutants
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-195721	Signaling by WNT
R-HSA-4791275	Signaling by WNT in cancer
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers

MSigDB gene sets: 673 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_POSITIVE_REGULATION_OF_MITOTIC_NUCLEAR_DIVISION, GOBP_EPITHELIUM_DEVELOPMENT, YAATNRNNNYNATT_UNKNOWN, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_MAMMARY_GLAND_MORPHOGENESIS, FREAC2_01, GOBP_SOMATIC_STEM_CELL_POPULATION_MAINTENANCE, MYOGENIN_Q6, GOBP_GLAND_MORPHOGENESIS, HNF3ALPHA_Q6, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS

GO Biological Process (60): gastrulation with mouth forming second (GO:0001702), positive regulation of mesenchymal cell proliferation (GO:0002053), osteoblast development (GO:0002076), glucose catabolic process (GO:0006007), amino acid transport (GO:0006865), endocytosis (GO:0006897), nervous system development (GO:0007399), mesodermal cell migration (GO:0008078), cholesterol metabolic process (GO:0008203), regulation of blood pressure (GO:0008217), positive regulation of cell population proliferation (GO:0008284), anterior/posterior pattern specification (GO:0009952), gene expression (GO:0010467), osteoblast proliferation (GO:0033687), positive regulation of osteoblast proliferation (GO:0033690), somatic stem cell population maintenance (GO:0035019), extracellular matrix-cell signaling (GO:0035426), cell migration involved in gastrulation (GO:0042074), cholesterol homeostasis (GO:0042632), embryonic digit morphogenesis (GO:0042733), regulation of apoptotic process (GO:0042981), response to peptide hormone (GO:0043434), positive regulation of fat cell differentiation (GO:0045600), negative regulation of osteoblast differentiation (GO:0045668), positive regulation of osteoblast differentiation (GO:0045669), positive regulation of mitotic nuclear division (GO:0045840), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), bone remodeling (GO:0046849), bone marrow development (GO:0048539), anatomical structure regression (GO:0060033), retina morphogenesis in camera-type eye (GO:0060042), canonical Wnt signaling pathway (GO:0060070), bone morphogenesis (GO:0060349), branching involved in mammary gland duct morphogenesis (GO:0060444), adipose tissue development (GO:0060612), cell-cell signaling involved in mammary gland development (GO:0060764), establishment of blood-brain barrier (GO:0060856), regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0061178), retinal blood vessel morphogenesis (GO:0061304)

GO Molecular Function (4): coreceptor activity (GO:0015026), Wnt-protein binding (GO:0017147), Wnt receptor activity (GO:0042813), protein binding (GO:0005515)

GO Cellular Component (6): endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), signaling receptor complex (GO:0043235), Wnt-Frizzled-LRP5/6 complex (GO:1990851), Wnt signalosome (GO:1990909), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
TCF dependent signaling in response to WNT	3
Signaling by WNT in cancer	2
Signaling by WNT	1
Signal Transduction	1
Diseases of signal transduction by growth factor receptors and second messengers	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
gastrulation	2
positive regulation of cell population proliferation	2
ameboidal-type cell migration	2
cell population proliferation	2
protein-containing complex	2
mesenchymal cell proliferation	1
regulation of mesenchymal cell proliferation	1
osteoblast differentiation	1
cell development	1
glucose metabolic process	1
hexose catabolic process	1
transport	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
system development	1
sterol metabolic process	1
secondary alcohol metabolic process	1
blood circulation	1
regulation of biological quality	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
regionalization	1
macromolecule biosynthetic process	1
osteoblast proliferation	1
regulation of osteoblast proliferation	1
stem cell population maintenance	1
cell communication	1
signaling	1
sterol homeostasis	1
embryonic limb morphogenesis	1
embryonic morphogenesis	1
signaling receptor activity	1
protein binding	1
transmembrane signaling receptor activity	1
Wnt signaling pathway	1
Wnt-protein binding	1
binding	1
cytoplasm	1

Protein interactions and networks

STRING

2310 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRP5	AXIN1	O15169	999
LRP5	DKK1	O94907	999
LRP5	NDP	Q00604	999
LRP5	SOST	Q9BQB4	999
LRP5	FZD4	Q9ULV1	999
LRP5	WNT3A	P56704	998
LRP5	DKK2	Q9UBU2	998
LRP5	DKK4	Q9UBT3	997
LRP5	WNT1	P04628	997
LRP5	DVL1	O14640	997
LRP5	FZD1	Q9UP38	993
LRP5	WNT10B	O00744	992
LRP5	WNT7A	O00755	991
LRP5	APCDD1	Q8J025	988
LRP5	LRP6	O75581	987

IntAct

147 interactions, top by confidence:

A	B	Type	Score
CSNK1A1	FAM83G	psi-mi:“MI:0914”(association)	0.900
SOST	LRP4	psi-mi:“MI:0914”(association)	0.790
SOST	LRP5	psi-mi:“MI:0915”(physical association)	0.740
DKK1	LRP5	psi-mi:“MI:0914”(association)	0.640
TGIF2LY	PGP	psi-mi:“MI:0914”(association)	0.640
ETV6	LRP5	psi-mi:“MI:0914”(association)	0.640
POMK	LRP5	psi-mi:“MI:0914”(association)	0.640
MGAT4C	GXYLT2	psi-mi:“MI:0914”(association)	0.530
POMK	TMEM120B	psi-mi:“MI:0914”(association)	0.530
SCGB1D1	FAM234B	psi-mi:“MI:0914”(association)	0.530
ODAPH	TCAF2	psi-mi:“MI:0914”(association)	0.530
SOST	KPNA4	psi-mi:“MI:0914”(association)	0.530
RASD2	LRP5	psi-mi:“MI:0914”(association)	0.530
LRRC4C	DVL2	psi-mi:“MI:0914”(association)	0.530
FCGRT	GOLIM4	psi-mi:“MI:0914”(association)	0.530
PRSS37	MANBA	psi-mi:“MI:0914”(association)	0.530
SERPINA12	TSPAN6	psi-mi:“MI:0914”(association)	0.530
BRINP3	BUB1	psi-mi:“MI:0914”(association)	0.530
FAM3B	LRP5	psi-mi:“MI:0914”(association)	0.530
CHST9	LRP5	psi-mi:“MI:0914”(association)	0.530
LIPH	LRP5	psi-mi:“MI:0914”(association)	0.530
ADAM33	LRP5	psi-mi:“MI:0914”(association)	0.530
DKK4	LRP5	psi-mi:“MI:0914”(association)	0.530

BioGRID (162): LRP5 (Affinity Capture-MS), LRP5 (Affinity Capture-MS), LRP5 (Affinity Capture-MS), LRP5 (Affinity Capture-MS), LRP5 (Affinity Capture-MS), LRP5 (Affinity Capture-MS), LRP5 (Affinity Capture-MS), LRP5 (Affinity Capture-MS), LRP5 (Affinity Capture-MS), LRP5 (Affinity Capture-MS), LRP5 (Affinity Capture-MS), LRP5 (Affinity Capture-MS), LRP5 (Affinity Capture-MS), LRP5 (Affinity Capture-MS), LRP5 (Affinity Capture-MS)

ESM2 similar proteins: D3ZTD8, O18735, O60568, O75096, O75197, O75581, O88572, P00533, P04626, P06494, P21589, P21860, P31423, P35349, P52850, P55245, P70424, Q01279, Q08C93, Q14833, Q1EGL1, Q1ZZH0, Q2KHZ8, Q3TIW9, Q5E9T6, Q5EZ72, Q5I0K3, Q5NCH9, Q5R6K5, Q5R8E3, Q5RB22, Q5U367, Q60553, Q61526, Q62799, Q68EF4, Q6IS24, Q6UWV6, Q70KH2, Q7TT15

Diamond homologs: A2AR95, A2ARV4, A4IHY6, C0HL13, E9Q6D8, G3V928, O75074, O75197, O75581, O88204, O88307, O88572, P0DSP1, P13671, P35953, P56677, P61134, P61135, P86091, P98153, P98154, P98155, P98156, P98157, P98158, P98160, P98163, P98164, P98165, P98166, P98167, Q04833, Q06561, Q07954, Q0IIH7, Q14114, Q28832, Q29RU4, Q5HZW5, Q5R662

SIGNOR signaling

26 interactions.

A	Effect	B	Mechanism
WNT1	“up-regulates activity”	LRP5	binding
WNT10A	up-regulates	LRP5	binding
WNT10B	up-regulates	LRP5	binding
WNT2	up-regulates	LRP5	binding
WNT2B	up-regulates	LRP5	binding
WNT3A	“up-regulates activity”	LRP5	binding
WNT4	up-regulates	LRP5	binding
WNT5B	up-regulates	LRP5	binding
WNT6	up-regulates	LRP5	binding
WNT7A	“up-regulates activity”	LRP5	binding
WNT7B	up-regulates	LRP5	binding
WNT8A	up-regulates	LRP5	binding
WNT9A	up-regulates	LRP5	binding
WNT9B	up-regulates	LRP5	binding
FZD8	“up-regulates activity”	LRP5	binding
LRP5	“down-regulates quantity by destabilization”	GSK3B/Axin/APC	relocalization
LRP5	“form complex”	LPR5/6	binding
FZD4	“up-regulates activity”	LRP5	binding
FZD2	“up-regulates activity”	LRP5	binding
FZD5	“up-regulates activity”	LRP5	binding
LRP5	“up-regulates activity”	DVL1	binding
Wnt	up-regulates	LRP5	binding
LRP5	“down-regulates quantity”	AXIN1	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 146 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
Negative regulation of TCF-dependent signaling by WNT ligand antagonists	5	41.5×	4e-05
Class B/2 (Secretin family receptors)	6	13.3×	9e-04
TCF dependent signaling in response to WNT	8	10.9×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
non-canonical Wnt signaling pathway	5	22.9×	5e-04
hair follicle development	6	18.1×	2e-04
canonical Wnt signaling pathway	11	13.3×	5e-07
negative regulation of canonical Wnt signaling pathway	10	9.3×	5e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

2496 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	128
Likely pathogenic	78
Uncertain significance	1172
Likely benign	802
Benign	98

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1003536	NC_000011.9:g.(?68190957)(68216538_?)del	Pathogenic
1012805	NM_002335.4(LRP5):c.4349-1G>A	Pathogenic
1018700	NM_002335.4(LRP5):c.4453_4482del (p.Ser1485_Tyr1494del)	Pathogenic
1052278	NM_002335.4(LRP5):c.4087G>A (p.Asp1363Asn)	Pathogenic
1068481	NM_002335.4(LRP5):c.2270G>A (p.Trp757Ter)	Pathogenic
1074902	NM_002335.4(LRP5):c.2754dup (p.Ala919fs)	Pathogenic
1323251	NM_002335.4(LRP5):c.2831_2832dup (p.Thr945fs)	Pathogenic
1323252	NM_002335.4(LRP5):c.865C>T (p.Gln289Ter)	Pathogenic
1353581	NM_002335.4(LRP5):c.4670G>A (p.Trp1557Ter)	Pathogenic
1374334	NM_002335.4(LRP5):c.772del (p.Arg258fs)	Pathogenic
1375486	NM_002335.4(LRP5):c.4142del (p.Pro1381fs)	Pathogenic
1380194	NM_002335.4(LRP5):c.4488+2_4488+17del	Pathogenic
1407475	NM_002335.4(LRP5):c.480dup (p.Ala161fs)	Pathogenic
1409431	NM_002335.4(LRP5):c.346dup (p.Asp116fs)	Pathogenic
1419445	NM_002335.4(LRP5):c.999_1005dup (p.Cys336fs)	Pathogenic
1430505	NM_002335.4(LRP5):c.3344_3345dup (p.Ala1116fs)	Pathogenic
1441879	NM_002335.4(LRP5):c.2543C>T (p.Pro848Leu)	Pathogenic
1442774	NC_000011.9:g.(?68170931)(68171187_?)del	Pathogenic
1452372	NM_002335.4(LRP5):c.270del (p.Tyr91fs)	Pathogenic
1452942	NM_002335.4(LRP5):c.2247del (p.Gln750fs)	Pathogenic
1453158	NM_002335.4(LRP5):c.632G>A (p.Trp211Ter)	Pathogenic
1453204	NM_002335.4(LRP5):c.4781_4797del (p.Pro1594fs)	Pathogenic
1454811	NM_002335.4(LRP5):c.3742C>T (p.Gln1248Ter)	Pathogenic
1455445	NM_002335.4(LRP5):c.1564G>A (p.Ala522Thr)	Pathogenic
1456639	NM_002335.4(LRP5):c.3768_3819dup (p.Ile1274fs)	Pathogenic
1459887	NM_002335.4(LRP5):c.1375del (p.Asp459fs)	Pathogenic
1459979	NM_002335.4(LRP5):c.1275G>A (p.Trp425Ter)	Pathogenic
1526039	NM_002335.4(LRP5):c.1512G>A (p.Trp504Ter)	Pathogenic
162392	NM_002335.4(LRP5):c.4587G>C (p.Arg1529Ser)	Pathogenic
1702013	NM_002335.4(LRP5):c.209T>A (p.Phe70Tyr)	Pathogenic

SpliceAI

4870 predictions. Top by Δscore:

Variant	Effect	Δscore
11:68347842:CACAG:C	acceptor_loss	1.0000
11:68347843:ACAG:A	acceptor_loss	1.0000
11:68347844:CAGCC:C	acceptor_loss	1.0000
11:68347845:A:AG	acceptor_gain	1.0000
11:68347845:AG:A	acceptor_loss	1.0000
11:68347846:G:GC	acceptor_gain	1.0000
11:68347846:GCCTC:G	acceptor_gain	1.0000
11:68357645:CACA:C	acceptor_loss	1.0000
11:68357648:A:T	acceptor_loss	1.0000
11:68357649:G:GA	acceptor_loss	1.0000
11:68357845:CCGG:C	donor_loss	1.0000
11:68357848:G:GG	donor_gain	1.0000
11:68357849:T:A	donor_loss	1.0000
11:68363738:T:TA	acceptor_gain	1.0000
11:68363944:G:GA	donor_loss	1.0000
11:68363944:G:GG	donor_gain	1.0000
11:68363946:GAGT:G	donor_loss	1.0000
11:68365569:A:AG	acceptor_gain	1.0000
11:68365570:G:GG	acceptor_gain	1.0000
11:68365689:G:GT	donor_gain	1.0000
11:68386710:GGG:G	donor_gain	1.0000
11:68386711:GG:G	donor_gain	1.0000
11:68386711:GGG:G	donor_gain	1.0000
11:68386712:GG:G	donor_gain	1.0000
11:68403695:CGTCG:C	donor_loss	1.0000
11:68403696:GTCGG:G	donor_loss	1.0000
11:68403698:CGG:C	donor_loss	1.0000
11:68403700:G:A	donor_loss	1.0000
11:68403700:G:GG	donor_gain	1.0000
11:68403701:T:G	donor_loss	1.0000

AlphaMissense

10623 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:68347990:T:A	W79R	1.000
11:68347990:T:C	W79R	1.000
11:68348084:C:A	P110H	1.000
11:68348093:T:A	L113H	1.000
11:68348093:T:C	L113P	1.000
11:68348122:T:G	Y123D	1.000
11:68348125:T:A	W124R	1.000
11:68348125:T:C	W124R	1.000
11:68348147:G:C	R131P	1.000
11:68348158:G:C	A135P	1.000
11:68348216:G:T	R154M	1.000
11:68357660:T:A	W167R	1.000
11:68357660:T:C	W167R	1.000
11:68357669:T:A	W170R	1.000
11:68357669:T:C	W170R	1.000
11:68357671:G:C	W170C	1.000
11:68357671:G:T	W170C	1.000
11:68357751:C:A	P197H	1.000
11:68357757:G:A	G199E	1.000
11:68357792:T:A	W211R	1.000
11:68357792:T:C	W211R	1.000
11:68363781:T:C	F241L	1.000
11:68363782:T:G	F241C	1.000
11:68363783:C:A	F241L	1.000
11:68363783:C:G	F241L	1.000
11:68363814:T:A	W252R	1.000
11:68363814:T:C	W252R	1.000
11:68363825:G:C	W255C	1.000
11:68363825:G:T	W255C	1.000
11:68363835:T:C	S259P	1.000

dbSNP variants (sampled 300 via entrez): RS1000001961 (11:68316208 G>A), RS1000005386 (11:68354153 C>A,T), RS1000040667 (11:68335878 A>C), RS1000057974 (11:68345333 G>A,T), RS1000109698 (11:68345545 C>T), RS1000117966 (11:68375587 C>T), RS1000137023 (11:68324186 G>A), RS1000174807 (11:68368544 C>G), RS1000212305 (11:68440331 C>T), RS1000238269 (11:68370660 C>T), RS1000250412 (11:68299685 C>A,T), RS1000254215 (11:68375468 C>G), RS1000256860 (11:68416249 G>A,C,T), RS1000276290 (11:68360169 G>A), RS1000296899 (11:68411479 C>G,T)

Disease associations

OMIM: gene MIM:603506 | disease phenotypes: MIM:144750, MIM:607636, MIM:259770, MIM:601813, MIM:607634, MIM:617875, MIM:166710, MIM:133780, MIM:174050, MIM:166200, MIM:248200, MIM:204000, MIM:173900, MIM:131300

GenCC curated gene-disease

Disease	Classification	Inheritance
osteoporosis-pseudoglioma syndrome	Definitive	Autosomal recessive
exudative vitreoretinopathy 4	Definitive	Semidominant
bone mineral density quantitative trait locus 1	Definitive	Autosomal dominant
autosomal dominant osteopetrosis 1	Strong	Autosomal dominant
autosomal dominant osteosclerosis, Worth type	Strong	Autosomal dominant
polycystic liver disease 4 with or without kidney cysts	Strong	Autosomal dominant
LRP5-related exudative vitreoretinopathy	Strong	Autosomal dominant
osteosclerosis-developmental delay-craniosynostosis syndrome	Supportive	Autosomal dominant
polycystic liver disease 1	Supportive	Autosomal dominant
hyperostosis corticalis generalisata	Supportive	Autosomal dominant
exudative vitreoretinopathy	Supportive	Autosomal dominant
intellectual disability	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
LRP5-related exudative vitreoretinopathy	Definitive	AR
polycystic liver disease 4 with or without kidney cysts	Limited	AD

Mondo (31): autosomal dominant osteosclerosis, Worth type (MONDO:0007764), osteoporosis-pseudoglioma syndrome (MONDO:0009820), exudative vitreoretinopathy 4 (MONDO:0011151), autosomal dominant osteopetrosis 1 (MONDO:0011877), polycystic liver disease 4 with or without kidney cysts (MONDO:0044327), osteoporosis (MONDO:0005298), exudative vitreoretinopathy 1 (MONDO:0007589), polycystic liver disease 1 (MONDO:0008265), osteogenesis imperfecta (MONDO:0019019), autosomal dominant polycystic liver disease (MONDO:0000447), severe early-childhood-onset retinal dystrophy (MONDO:0009549), postmenopausal osteoporosis (MONDO:0008159), LRP5-related primary osteoporosis (MONDO:0044675), inherited retinal dystrophy (MONDO:0019118), Leber congenital amaurosis (MONDO:0018998)

Orphanet (19): Autosomal dominant osteopetrosis type 1 (Orphanet:2783), Osteoporosis-pseudoglioma syndrome (Orphanet:2788), Endosteal hyperostosis, Worth type (Orphanet:2790), Familial exudative vitreoretinopathy (Orphanet:891), Retinopathy of prematurity (Orphanet:90050), Isolated polycystic liver disease (Orphanet:2924), Osteogenesis imperfecta (Orphanet:666), Severe early-childhood-onset retinal dystrophy (Orphanet:364055), Stargardt disease (Orphanet:827), Hyperostosis corticalis generalisata (Orphanet:3416), LRP5-related primary osteoporosis (Orphanet:498481), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Leber congenital amaurosis (Orphanet:65), Autosomal dominant polycystic kidney disease (Orphanet:730), Rare bone disease related to a common gene or pathway defect (Orphanet:364803)

HPO phenotypes

175 total (30 of 175 shown, HPO-id order):

HPO	Term
HP:0000002	Abnormality of body height
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000107	Renal cyst
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000337	Broad forehead
HP:0000348	High forehead
HP:0000365	Hearing impairment
HP:0000384	Preauricular skin tag
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000486	Strabismus
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000523	Subcapsular cataract
HP:0000533	Chorioretinal atrophy
HP:0000541	Retinal detachment
HP:0000545	Myopia
HP:0000555	Leukocoria
HP:0000565	Esotropia
HP:0000568	Microphthalmia
HP:0000592	Blue sclerae
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000646	Amblyopia

GWAS associations

26 associations (top):

Study	Trait	p-value
GCST000182_2	Bone mineral density	6.000000e-12
GCST000494_10	Bone mineral density (spine)	5.000000e-08
GCST001482_31	Lumbar spine bone mineral density	2.000000e-26
GCST002276_8	Bone mineral density	3.000000e-11
GCST002493_10	Bone mineral density (paediatric, skull)	2.000000e-10
GCST002493_9	Bone mineral density (paediatric, skull)	1.000000e-10
GCST003996_21	Monobrow	2.000000e-09
GCST004772_7	Bone mineral density (paediatric, total body less head)	1.000000e-09
GCST005795_34	Femoral neck bone mineral density	4.000000e-07
GCST005796_19	Lumbar spine bone mineral density	3.000000e-17
GCST006288_183	Heel bone mineral density	1.000000e-07
GCST006288_184	Heel bone mineral density	2.000000e-11
GCST006288_41	Heel bone mineral density	2.000000e-20
GCST006288_42	Heel bone mineral density	5.000000e-17
GCST006288_420	Heel bone mineral density	3.000000e-16
GCST006288_421	Heel bone mineral density	6.000000e-10
GCST006288_422	Heel bone mineral density	7.000000e-15
GCST006288_43	Heel bone mineral density	3.000000e-23
GCST006423_11	Fracture	1.000000e-21
GCST006979_405	Heel bone mineral density	2.000000e-73
GCST006979_406	Heel bone mineral density	4.000000e-11
GCST006979_407	Heel bone mineral density	2.000000e-35
GCST006979_408	Heel bone mineral density	2.000000e-54
GCST007641_1	Femoral neck section modulus	4.000000e-11
GCST007935_3	Medication use (drugs affecting bone structure and mineralization)	1.000000e-09
GCST90020026_507	Hip index	2.000000e-10

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0007906	synophrys measurement
EFO:0007785	femoral neck bone mineral density
EFO:0007701	spine bone mineral density
EFO:0009270	heel bone mineral density
EFO:0004511	femoral neck bone geometry
EFO:0009936	Drugs affecting bone structure and mineralization use measurement
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (17)

Descriptor	Name	Tree numbers
D001847	Bone Diseases	C05.116
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D057130	Leber Congenital Amaurosis	C11.270.516; C11.768.364
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D010013	Osteogenesis Imperfecta	C05.116.099.708.685; C16.320.737; C17.300.200.540
D010024	Osteoporosis	C05.116.198.579; C18.452.104.579
D015663	Osteoporosis, Postmenopausal	C05.116.198.579.610; C18.452.104.579.610
D016891	Polycystic Kidney, Autosomal Dominant	C12.050.351.968.419.403.875.500; C12.200.777.419.403.875.500; C12.950.419.403.875.500; C16.131.077.717.500; C16.320.184.625.500
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
D014808	Vitamin D Deficiency	C18.654.521.500.133.770
C566619	Exudative Vitreoretinopathy 4 (supp.)
C536382	Exudative vitreoretinopathy 1 (supp.)
C536056	Osteopetrosis autosomal dominant type 1 (supp.)
C536063	Osteoporosis-pseudoglioma syndrome (supp.)
C536326	Polycystic kidney disease, type 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295675 (SINGLE PROTEIN)

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2306862	LRP5		0.00	0
rs3736228	LRP5		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	6
Tobacco Smoke Pollution	decreases expression, decreases methylation, increases expression	3
Particulate Matter	increases abundance, increases expression	3
sodium arsenite	increases expression, decreases expression	2
Acetaminophen	decreases expression	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Valproic Acid	affects expression, increases methylation	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
dicrotophos	increases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	affects methylation	1
titanium dioxide	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
tanshinone	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
beta-methylcholine	affects expression	1
evodiamine	decreases expression	1
casticin	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Amiodarone	increases expression	1
Arbutin	decreases expression	1
Arsenic	affects methylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4221467	Binding	Inhibition of sclerostin binding to human ALP-fused LRP5 at 50 uM using alkaline phosphatase as substrate pretreated for 2 hrs followed by substrate addition measured after 25 mins by ELISA relative to control	In silico discovery of quinoxaline derivatives as novel LRP5/6-sclerostin interaction inhibitors. — Bioorg Med Chem Lett

Cellosaurus cell lines

10 cell lines: 8 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A7NI	2XSB	Cancer cell line	Female
CVCL_B3AA	Abcam HEK293T LRP5 KO	Transformed cell line	Female
CVCL_B8JV	Abcam HCT 116 LRP5 KO	Cancer cell line	Male
CVCL_B8YC	Abcam MCF-7 LRP5 KO	Cancer cell line	Female
CVCL_B9M4	Abcam A-549 LRP5 KO	Cancer cell line	Male
CVCL_D9IT	Ubigene HEK293 LRP5 KO	Transformed cell line	Female
CVCL_E0GQ	Ubigene HeLa LRP5 KO	Cancer cell line	Female
CVCL_SV88	HAP1 LRP5 (-) 1	Cancer cell line	Male
CVCL_SV89	HAP1 LRP5 (-) 2	Cancer cell line	Male
CVCL_SV90	HAP1 LRP5 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06520410	PHASE4	RECRUITING	Safety and Efficacy of 18 mm Short Vitrectomy Probe for Pediatric Vitreoretinal Surgeries
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00006180	PHASE4	COMPLETED	Bone Loss in Premenopausal Women With Depression
NCT00035256	PHASE4	COMPLETED	Sequential Use of Teriparatide and Raloxifene HCl in the Treatment of Postmenopausal Women With Osteoporosis
NCT00035971	PHASE4	COMPLETED	EVA: Evista Alendronate Comparison
NCT00114556	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Density in Liver Transplant Patients
NCT00130403	PHASE4	COMPLETED	OPTAMISE: Clinical Effectiveness of Teriparatide After Alendronate or Risedronate Therapy in Osteoporotic Postmenopausal Women
NCT00148915	PHASE4	COMPLETED	A Study To Assess the Quality and Strength of Bone in Women Participants With Osteoporosis Taking Oral Ibandronate Versus Placebo
NCT00157690	PHASE4	COMPLETED	Study of Alendronate to Prevent and Treat Osteoporosis in Cystic Fibrosis Patients
NCT00159419	PHASE4	COMPLETED	Bisphosphonate Therapy for Osteogenesis Imperfecta
NCT00165607	PHASE4	COMPLETED	Randomized, Open, Parallel, Active Controlled Study on Fracture Prevention in Antiosteoporosis Treatment (OF Study)
NCT00168909	PHASE4	COMPLETED	Influence of Alfacalcidol on Falls in Osteopenic/Osteoporotic Postmenopausal Women (ALFA Study)
NCT00182871	PHASE4	COMPLETED	Testosterone Effects on Bone and Frailty
NCT00191425	PHASE4	COMPLETED	2-Year Therapy With Teriparatide vs 1-yr Therapy Followed by 1-Year of Raloxifene or Calcium/Vit D in Severe Postmenopausal Osteoporosis
NCT00211211	PHASE4	COMPLETED	FREE Study - Fracture Reduction Evaluation
NCT00221299	PHASE4	COMPLETED	Risedronate and Parathyroid Hormone to Reverse Osteoporosis Caused by Chronic Steroid Use
NCT00252408	PHASE4	COMPLETED	Danish Osteoporosis Prevention Study
NCT00259298	PHASE4	COMPLETED	Evaluation of the Effects of Teriparatide on Skeleton Images in Postmenopausal Women With Osteoporosis
NCT00261625	PHASE4	COMPLETED	Can Alendronate Suppress Calcification and Improve Bone Density in Chronic Peritoneal Dialysis Patients?
NCT00271713	PHASE4	COMPLETED	Impact of Oral Ibandronate 150 mg Monthly on Structural Properties of Bone in Postmenopausal Osteoporosis (SPIMOS-3D)
NCT00294463	PHASE4	COMPLETED	Effects of Tibolone Treatment on the Endometrium
NCT00327990	PHASE4	COMPLETED	Evaluation Of Missed Osteoporosis Diagnoses, And Preference Between Once Monthly Ibandronate And Once Weekly Alendronate
NCT00357331	PHASE4	COMPLETED	The Effects of Potassium Citrate on Bone Metabolism
NCT00371956	PHASE4	COMPLETED	Raloxifene for Prevention of Bone Loss in Postmenopausal Patients Receiving Chronic Corticosteroid Therapy
NCT00372372	PHASE4	COMPLETED	The Efficacy of Risedronate in Prevention of Bone Loss in Patients Receiving High Dose Corticosteroid Treatment
NCT00376662	PHASE4	COMPLETED	HRT Versus Etidronate for Osteoporosis and Fractures in Asthmatics Receiving Glucocorticoids.
NCT00402441	PHASE4	COMPLETED	Risedronate in the Prevention of Osteoporosis in Postmenopausal Women
NCT00405392	PHASE4	COMPLETED	Study To Investigate Patient Preference On Dosing In Ibandronate And Risedronate In Korean Women With Postmenopausal Osteoporosis
NCT00431444	PHASE4	COMPLETED	Effects of Zoledronic Acid and Raloxifene on Bone Turnover Markers in Postmenopausal Women With Low Bone Mineral Density
NCT00446589	PHASE4	TERMINATED	The Effects of Ibandronate or Teriparatide Therapy on Bone Histology and Biochemical Indices in Patients on Hemodialysis With Low Bone Mineral Density
NCT00453492	PHASE4	COMPLETED	Risedronate Sodium in Post Menopausal Osteoporosis
NCT00460057	PHASE4	COMPLETED	The Change of Bone Markers After Low Dose Alendronate in Postmenopausal Women With Bone Loss
NCT00479037	PHASE4	COMPLETED	Effect of Full Length Parathyroid Hormone, PTH(1-84) or Strontium Ranelate on Bone Markers in Postmenopausal Women With Primary Osteoporosis (FP-006-IM)
NCT00485953	PHASE4	COMPLETED	Effect of Bisphosphonate on Bone Loss in Postmenopausal Women With Breast Cancer Initiating Aromatase Inhibitor Therapy
NCT00489424	PHASE4	COMPLETED	Acetaminophen or Fluvastatin Compared to Placebo on the Transient Post-Dose Symptoms (PDS) Following an Intravenous (i.v.) Infusion of a Single Dose of Zoledronic Acid 5mg, in Post-menopausal Women With Low Bone Mass
NCT00491920	PHASE4	COMPLETED	High Dosage Vitamin D and Osteoporosis
NCT00504166	PHASE4	COMPLETED	Alendronate Prevents Microarchitectural Deterioration of Trabecular Bone in Early Postmenopausal Women