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bone Paget disease

disease
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Also known as bone Paget's diseasefamilial Paget's disease of boneosseous Paget's diseaseosteitis deformansPaget disease of bonePaget's bone diseasePaget's disease of bonePaget's disease of the bonePagets disease (bone)

Summary

bone Paget disease (MONDO:0005382) is a disease (an umbrella term covering 5 Mondo subtypes) with 11 cohort genes (33 GWAS associations across 11 studies) and 14 clinical trials. Top therapeutic interventions include zoledronic acid anhydrous, alendronic acid, and calcium.

At a glance

  • Umbrella term: 5 Mondo subtypes
  • Cohort genes: 11
  • GWAS associations: 33
  • ClinVar variants: 2
  • Clinical trials: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namebone Paget disease
Mondo IDMONDO:0005382
EFOEFO:0004261
OMIM167250
Orphanet280110
DOIDDOID:5408
ICD-10-CMM88
NCITC3292
SNOMED CT2089002
UMLSC0029401
MedGen10493
Is cancer (heuristic)no

Also known as: bone Paget disease · bone Paget’s disease · familial Paget’s disease of bone · osseous Paget’s disease · osteitis deformans · Paget disease of bone · Paget’s bone disease · Paget’s disease of bone · Paget’s disease of the bone · Pagets disease (bone)

Data availability: 2 ClinVar variants · 33 GWAS associations (11 studies).

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone remodeling disease › hyperostosis › bone Paget disease

Related subtypes (8): exostosis, diffuse idiopathic skeletal hyperostosis, Caffey disease, autosomal dominant osteosclerosis, Worth type, craniodiaphyseal dysplasia, hyperostosis corticalis generalisata, X-linked calvarial hyperostosis, sclerosteosis

Subtypes (5): Paget disease of bone 3, juvenile Paget disease, Paget disease of bone 2, early-onset, paget disease of bone 4, Paget disease of bone 6

Genetics & variants

GWAS landscape

33 GWAS associations across 11 studies. Top hits map to 19 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs1048939412e-68SQSTM1, MRNIPC3.27
rs15615704e-38OPTNT1.67
rs104941127e-35GSTM5 - NDUFA5P10G1.72
rs4849595e-24NDUFA5P10 - LINC01768?1.82
rs30183628e-21TNFRSF11A - RPL17P44A1.45
rs24584137e-17DPYS, DCSTAMPA1.4
rs57429152e-14PMLC1.34
rs5488327684e-14SDK1G3.02
rs1138611181e-13OPTNC0.42
rs5454425066e-13CDCP1C4.31
rs5346899032e-12PLCE1C2.49
rs782562723e-12FCRL3, FCRL3-AS1G3.08
rs9698395364e-12TMPRSS11B - APOOP4G3.71
chr1:1103623577e-12T0.48
rs5658935308e-12RNA5SP279 - SMARCA2T2.66
rs5779921909e-12RPL5P35 - BRD1G3.53
rs5414827091e-11ADGRL3G3.26
rs3692505601e-11GALR1 - BDP1PG2.72
rs29571282e-11TNFRSF11A - RPL17P44A1.46
chr10:131591972e-11T0.45
rs3701747082e-11ZNF142C4
rs5285021042e-11BACE2C3.67
rs5284709852e-11EYA4A3.26
rs104986353e-11RIN3C1.44
rs5683405584e-11LINC01675 - FMO8PC3.49
rs42941348e-10NUP205G1.45
rs59105781e-07SLC25A43C1.34
rs13412394e-06CASC15T1.2

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90476246Verma A20241,392448,529Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST001086Albagha OM20117412,699Genome-wide association identifies three new susceptibility loci for Paget’s disease of bone.
GCST000672Albagha OM20106921,001Genome-wide association study identifies variants at CSF1, OPTN and TNFRSF11A as genetic risk factors for Paget’s disease of bone.
GCST90478967Verma A2024646120,803Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480526Verma A2024646120,803Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90476540Verma A2024495450,711Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90474145UK Biobank Whole-Genome Sequencing Consortium2025480457,960Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90480525Verma A2024373121,472Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90482410Verma A2024373121,472Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90436695Zhou W2018280391,041Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding3
Tier 2: splice/UTR0
Tier 3: regulatory1
Tier 4: intronic/intergenic24

MAF distribution

BucketVariants
common (>=0.05)14
low_freq (0.01-0.05)0
rare (<0.01)14
unknown0

Functional consequences

ConsequenceCount
intron_variant13
intergenic_variant9
missense_variant3
unknown2
regulatory_region_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs1048939415179836445C>G,T0.001missense_variantSQSTM1, MRNIP2e-68Tier 1: coding
rs15615701013113726T>C0.47intron_variantOPTN4e-38Tier 4: intronic/intergenic
rs104941121109809855A>G0.2intergenic_variantGSTM5 - NDUFA5P107e-35Tier 4: intronic/intergenic
rs4849591109823461T>A,C,G0.49intergenic_variantNDUFA5P10 - LINC017685e-24Tier 4: intronic/intergenic
rs30183621862414860A>C,G0.36intergenic_variantTNFRSF11A - RPL17P448e-21Tier 4: intronic/intergenic
rs24584138104347204C>A,G,T0.42intron_variantDPYS, DCSTAMP7e-17Tier 4: intronic/intergenic
rs57429151574044292T>C,G0.45missense_variantPML2e-14Tier 1: coding
rs54883276873883999G>A0.001intron_variantSDK14e-14Tier 4: intronic/intergenic
rs1138611181013126429C>T0.25intron_variantOPTN1e-13Tier 4: intronic/intergenic
rs545442506345140531C>A,G,T0.001intron_variantCDCP16e-13Tier 4: intronic/intergenic
rs5346899031094173701C>T0.001intron_variantPLCE12e-12Tier 4: intronic/intergenic
rs782562721157692869G>A0intron_variantFCRL3, FCRL3-AS13e-12Tier 4: intronic/intergenic
rs969839536468257636G>A,C0intergenic_variantTMPRSS11B - APOOP44e-12Tier 4: intronic/intergenic
chr1:1103623570.4817e-12Tier 4: intronic/intergenic
rs56589353091805105T>A,C,G0.001intergenic_variantRNA5SP279 - SMARCA28e-12Tier 4: intronic/intergenic
rs5779921902249767543G>A,T0.001regulatory_region_variantRPL5P35 - BRD19e-12Tier 3: regulatory
rs541482709461607533G>A0.002intron_variantADGRL31e-11Tier 4: intronic/intergenic
rs3692505601877310772G>A,T0intergenic_variantGALR1 - BDP1P1e-11Tier 4: intronic/intergenic
rs29571281862393502A>C,G0.38intergenic_variantTNFRSF11A - RPL17P442e-11Tier 4: intronic/intergenic
chr10:131591970.492e-11Tier 4: intronic/intergenic
rs3701747082218649070C>T0missense_variantZNF1422e-11Tier 1: coding
rs5285021042141248479C>T0.001intron_variantBACE22e-11Tier 4: intronic/intergenic
rs5284709856133246706A>G0intron_variantEYA42e-11Tier 4: intronic/intergenic
rs104986351492636964C>T0.18intron_variantRIN33e-11Tier 4: intronic/intergenic
rs5683405581166497886C>T0intergenic_variantLINC01675 - FMO8P4e-11Tier 4: intronic/intergenic
rs42941347135608380A>C,G,T0.16intron_variantNUP2058e-10Tier 4: intronic/intergenic
rs5910578X119433739T>A,C,G0.26intron_variantSLC25A431e-07Tier 4: intronic/intergenic
rs1341239622303975A>C,G,T0.38intergenic_variantCASC154e-06Tier 4: intronic/intergenic

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

2 conflicting classifications of pathogenicity

ClinVarVariant (HGVS)GeneClassificationReview
710944NM_020812.4(DOCK6):c.133G>A (p.Val45Ile)DOCK6Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
8108NM_003900.5(SQSTM1):c.1175C>T (p.Pro392Leu)SQSTM1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 13 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 1

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

GeneHGNCEvidence routes
TNFRSF11ATNFRSF11AGWAS, Orphanet

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
SQSTM1Orphanet:275864Behavioral variant of frontotemporal dementia
SQSTM1Orphanet:275872Frontotemporal dementia with motor neuron disease
SQSTM1Orphanet:603Distal myopathy, Welander type
SQSTM1Orphanet:803Amyotrophic lateral sclerosis
TNFRSF11AOrphanet:1782Dysosteosclerosis
TNFRSF11AOrphanet:178389Osteopetrosis-hypogammaglobulinemia syndrome
TNFRSF11AOrphanet:2801Juvenile Paget disease
TNFRSF11AOrphanet:391490Adult-onset myasthenia gravis
TNFRSF11AOrphanet:85195Familial expansile osteolysis
OPTNOrphanet:803Amyotrophic lateral sclerosis
NUP205Orphanet:656Hereditary steroid-resistant nephrotic syndrome
DOCK6Orphanet:974Adams-Oliver syndrome
PMLOrphanet:520Acute promyelocytic leukemia

Cohort genes → proteins

11 cohort genes, 11 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only9
multi_evidence2

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
SQSTM1HGNC:11280ENSG00000161011Q13501Sequestosome-1clinvar
TNFRSF11AHGNC:11908ENSG00000141655Q9Y6Q6Tumor necrosis factor receptor superfamily member 11Agwas
OPTNHGNC:17142ENSG00000123240Q96CV9Optineuringwas
DCSTAMPHGNC:18549ENSG00000164935Q9H295Dendritic cell-specific transmembrane proteingwas
NUP205HGNC:18658ENSG00000155561Q92621Nuclear pore complex protein Nup205gwas
RIN3HGNC:18751ENSG00000100599Q8TB24Ras and Rab interactor 3gwas
DOCK6HGNC:19189ENSG00000130158Q96HP0Dedicator of cytokinesis protein 6clinvar
CSF1HGNC:2432ENSG00000184371P09603Macrophage colony-stimulating factor 1gwas
SLC25A43HGNC:30557ENSG00000077713Q8WUT9Solute carrier family 25 member 43gwas
PMLHGNC:9113ENSG00000140464P29590Protein PMLgwas
PRLHGNC:9445ENSG00000172179P01236Prolactingwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
SQSTM1Sequestosome-1Molecular adapter required for selective macroautophagy (aggrephagy) by acting as a bridge between polyubiquitinated proteins and autophagosomes.
TNFRSF11ATumor necrosis factor receptor superfamily member 11AReceptor for TNFSF11/RANKL/TRANCE/OPGL; essential for RANKL-mediated osteoclastogenesis.
OPTNOptineurinPlays an important role in the maintenance of the Golgi complex, in membrane trafficking, in exocytosis, through its interaction with myosin VI and Rab8.
DCSTAMPDendritic cell-specific transmembrane proteinProbable cell surface receptor that plays several roles in cellular fusion, cell differentiation, bone and immune homeostasis.
NUP205Nuclear pore complex protein Nup205Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance.
RIN3Ras and Rab interactor 3Ras effector protein that functions as a guanine nucleotide exchange (GEF) for RAB5B and RAB31, by exchanging bound GDP for free GTP.
DOCK6Dedicator of cytokinesis protein 6Acts as a guanine nucleotide exchange factor (GEF) for CDC42 and RAC1 small GTPases.
CSF1Macrophage colony-stimulating factor 1Cytokine that plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes.
PMLProtein PMLFunctions via its association with PML-nuclear bodies (PML-NBs) in a wide range of important cellular processes, including tumor suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechani…
PRLProlactinProlactin acts primarily on the mammary gland by promoting lactation.

Protein-family classification

Druggable: 0 · Difficult: 3 · Unknown: 8 · 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.

FamilyGenesFoldFDR
Scaffold/PPI11.6×0.481
Transcription factor21.5×0.481
Other/Unknown81.3×0.481

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
SQSTM1Transcription factornoPB1_dom, Znf_ZZ, UBA-like_sf
TNFRSF11AOther/UnknownnoTNFR/NGFR_Cys_rich_reg, TNFR_11, TNFR_11A
OPTNOther/UnknownnoNEMO_N, CC2-LZ_dom, NEMO_ZF
DCSTAMPOther/UnknownnoDC_STAMP-like, CSR-E3_Ligase_Protein
NUP205Other/UnknownnoNup186/Nup192/Nup205
RIN3Scaffold/PPInoRA_dom, SH2, VPS9
DOCK6Other/UnknownnoDOCK_C/D_N, DOCK, C2_DOCK-type_domain
CSF1Other/UnknownnoMCSF-1, 4_helix_cytokine-like_core
SLC25A43Other/UnknownnoMCP, MCP_transmembrane, MCP_dom_sf
PMLTranscription factornoZnf_B-box, Znf_RING, Znf_RING/FYVE/PHD
PRLOther/UnknownnoSomatotropin/Prolactin, 4_helix_cytokine-like_core, Somatotropin_CS

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)11
unknown0

Top tissues across cohort

TissueCohort genes
jejunal mucosa2
omental fat pad2
peritoneum2
left adrenal gland1
right adrenal gland1
right adrenal gland cortex1
mucosa of sigmoid colon1
parotid gland1
amniotic fluid1
gastrocnemius1
muscle of leg1
amygdala1
buccal mucosa cell1
stromal cell of endometrium1
embryo1
ganglionic eminence1
ventricular zone1
granulocyte1
leukocyte1
monocyte1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
SQSTM1241ubiquitousmarkerright adrenal gland cortex, right adrenal gland, left adrenal gland
TNFRSF11A221broadmarkerparotid gland, mucosa of sigmoid colon, jejunal mucosa
OPTN302ubiquitousmarkeramniotic fluid, gastrocnemius, muscle of leg
DCSTAMP141broadyesstromal cell of endometrium, buccal mucosa cell, amygdala
NUP205265ubiquitousmarkerventricular zone, ganglionic eminence, embryo
RIN3210ubiquitousmarkergranulocyte, monocyte, leukocyte
DOCK6254ubiquitousmarkercolonic epithelium, right lung, apex of heart
CSF1223ubiquitousmarkeromental fat pad, peritoneum, adipose tissue of abdominal region
SLC25A43221ubiquitousmarkeresophagus squamous epithelium, lower esophagus mucosa, jejunal mucosa
PML253ubiquitousmarkeromental fat pad, peritoneum, body of uterus
PRL160tissue_specificmarkerpituitary gland, adenohypophysis, decidua

Protein interactions among cohort

Intra-cohort edges: 4.

Hub genes (top 10 by interactor count)

SymbolInteractor count
SQSTM17,269
PML3,704
OPTN3,505
CSF13,476
PRL2,957
NUP2052,881
RIN32,706
TNFRSF11A1,186
SLC25A431,062
DOCK61,018

Intra-cohort edges

ABSources
CSF1DCSTAMPstring_interaction
CSF1TNFRSF11Astring_interaction
OPTNSQSTM1string_interaction
SQSTM1TNFRSF11Astring_interaction

Structural data

PDB: 9 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
SQSTM1Q1350126
PMLP2959020
OPTNQ96CV914
PRLP0123612
CSF1P096038
DOCK6Q96HP07
NUP205Q926215
RIN3Q8TB242
TNFRSF11AQ9Y6Q61

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
SLC25A43Q8WUT988.76
DCSTAMPQ9H29582.44

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 94. Enrichment computed across 11 evidence-associated genes (10 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 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
PINK1-PRKN Mediated Mitophagy271.4×0.024SQSTM1, OPTN
SUMOylation of ubiquitinylation proteins258.6×0.024NUP205, PML
SUMOylation of DNA damage response and repair proteins229.3×0.063NUP205, PML
p75NTR signals via NF-kB1190.3×0.070SQSTM1
CREB3 factors activate genes1126.9×0.070DCSTAMP
Mitophagy1103.8×0.070SQSTM1
Regulation of PTEN localization1103.8×0.070PML
Pexophagy195.2×0.070SQSTM1
Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation195.2×0.070OPTN
p75NTR recruits signalling complexes187.8×0.070SQSTM1
NF-kB is activated and signals survival187.8×0.070SQSTM1
TICAM1-dependent activation of IRF3/IRF7181.6×0.070OPTN
Prolactin receptor signaling176.1×0.070PRL
Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7176.1×0.070OPTN
NRIF signals cell death from the nucleus171.4×0.070SQSTM1
TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway167.2×0.070TNFRSF11A
Regulation of RUNX1 Expression and Activity167.2×0.070PML
Developmental Lineage of Mammary Gland Alveolar Cells163.4×0.070PRL
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)160.1×0.070OPTN
Other interleukin signaling147.6×0.070CSF1
Growth hormone receptor signaling147.6×0.070PRL
Regulation of TP53 Activity through Acetylation145.7×0.070PML
TNFR1-induced proapoptotic signaling143.9×0.070OPTN
Postmitotic nuclear pore complex (NPC) reformation140.8×0.070NUP205
IPs transport between nucleus and cytosol138.1×0.070NUP205
IP3 and IP4 transport between cytosol and nucleus138.1×0.070NUP205
IP6 and IP7 transport between cytosol and nucleus138.1×0.070NUP205
Transport of Ribonucleoproteins into the Host Nucleus135.7×0.070NUP205
Regulation of Glucokinase by Glucokinase Regulatory Protein135.7×0.070NUP205
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)135.7×0.070NUP205

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 11 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
osteoclast differentiation393.8×7e-04TNFRSF11A, DCSTAMP, CSF1
positive regulation of monocyte differentiation2278.6×0.002DCSTAMP, CSF1
branching involved in mammary gland duct morphogenesis2255.3×0.002CSF1, PML
positive regulation of bone resorption2180.2×0.003TNFRSF11A, DCSTAMP
cellular response to interleukin-42117.8×0.005DCSTAMP, PML
positive regulation of osteoclast differentiation2105.7×0.005TNFRSF11A, CSF1
regulation of canonical NF-kappaB signal transduction287.5×0.006SQSTM1, OPTN
regulation of calcium ion transport into cytosol11532.0×0.010PML
regulation of macrophage derived foam cell differentiation11532.0×0.010CSF1
negative regulation of translation in response to oxidative stress11532.0×0.010PML
mammary gland fat development11532.0×0.010CSF1
negative regulation of mast cell chemotaxis11532.0×0.010RIN3
positive regulation of macrophage colony-stimulating factor signaling pathway11532.0×0.010CSF1
response to ischemia245.7×0.012SQSTM1, CSF1
prolactin signaling pathway1766.0×0.013PRL
positive regulation of odontogenesis of dentin-containing tooth1766.0×0.013CSF1
positive regulation of fever generation by positive regulation of prostaglandin secretion1766.0×0.013TNFRSF11A
positive regulation of lactation1766.0×0.013PRL
monocyte homeostasis1510.7×0.013CSF1
macrophage colony-stimulating factor signaling pathway1510.7×0.013CSF1
circadian temperature homeostasis1510.7×0.013TNFRSF11A
mammary duct terminal end bud growth1510.7×0.013CSF1
macrophage homeostasis1510.7×0.013CSF1
brown fat cell proliferation1510.7×0.013SQSTM1
protein targeting to vacuole involved in autophagy1510.7×0.013SQSTM1
multinuclear osteoclast differentiation1510.7×0.013TNFRSF11A
positive regulation of protein localization to chromosome, telomeric region1510.7×0.013PML
positive regulation of macrophage migration1510.7×0.013CSF1
positive regulation of autophagy237.8×0.013SQSTM1, OPTN
negative regulation of angiogenesis230.6×0.013PML, PRL

Therapeutics

Drugs indicated for this disease

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

DrugDevelopment status
Calcitonin SalmonApproved (phase 4)
Alendronic AcidPhase 3 (in late-stage trials)
CalciumPhase 3 (in late-stage trials)
Risedronic AcidPhase 3 (in late-stage trials)

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 2 · Undrugged: 9

Druggability breadth: 4 of 11 evidence-associated genes (36%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

SymbolMoleculesMax phase
NUP20512
PML12
SQSTM100
TNFRSF11A00
OPTN00
DCSTAMP00
RIN300
DOCK600
CSF100
SLC25A4300

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
MOLIBRESIB2NUP205, PML

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

SymbolAssaysType breakdown
PML34Binding:34
SQSTM120Binding:20
NUP2057Binding:7

Pharmacogenomics

Cohort genes with a PharmGKB record: 11; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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.

CompoundMax phaseCohort target (bioactivity)
MOLIBRESIB2NUP205, PML

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)0
BPhased (≥1) drug, not yet approved2NUP205, PML
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug9SQSTM1, TNFRSF11A, OPTN, DCSTAMP, RIN3, DOCK6, CSF1, SLC25A43, PRL

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
SQSTM120—
TNFRSF11A0—
OPTN0—
DCSTAMP0—
RIN30—
DOCK60—
CSF10—
SLC25A430—
PRL0—

Clinical trials & evidence

Clinical trials

Clinical trials: 14.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified7
PHASE44
PHASE33

Top trials by phase / activity

NCTPhaseStatusTitle
NCT00159419PHASE4COMPLETEDBisphosphonate Therapy for Osteogenesis Imperfecta
NCT00668200PHASE4COMPLETEDImpact on Reducing the Incidence of Low Serum Calcium by Providing Educational Materials on the Need to Take Daily Supplemental Calcium and Vitamin D to Patients With Paget’s Disease Treated With Reclast®
NCT00740129PHASE4COMPLETEDRe-treatment of Participants With Paget’s Disease Using Zoledronic Acid
NCT00774020PHASE4COMPLETEDEfficacy and Safety of Single Dose of 5 mg Zoledronic Acid in Chinese Patients With Paget’s Disease of Bone (PDB)
NCT00051636PHASE3COMPLETEDSafety and Efficacy Trial With Zoledronic Acid for the Treatment of Paget’s Disease of Bone, Including an Extended Observation Period
NCT00103740PHASE3COMPLETEDSafety and Efficacy Trial With Zoledronic Acid for the Treatment of Paget’s Disease of Bone, Including an Extended Observation Period
NCT00480662PHASE3COMPLETEDA Research Study to Test the Effectiveness of MK0217 in Patients With Paget’s Bone Disease (0217-206)(COMPLETED)
NCT01353430Not specifiedRECRUITINGCharacterization of Inclusion Body Myopathy Associated With Paget’s Disease of Bone and Frontotemporal Dementia (IBMPFD)
NCT05309954Not specifiedACTIVE_NOT_RECRUITINGGenetic Analysis to Predict the Development of Paget’s Disease
NCT00306046Not specifiedCOMPLETED18F-Fluoride Positron Emission Tomography (PET) in Paget’s Disease of Bone
NCT00403598Not specifiedUNKNOWNPreliminary Study for Identification of Calcium-Binding Proteins in the Serum in Various Metabolic Bone Disorders
NCT00747994Not specifiedCOMPLETEDGenetic Study of Families Affected by Paget’s Disease of Bone
NCT02106455Not specifiedCOMPLETEDSodium Risedronate Tablets - Special Drug Use Surveillance in Patients With Osseous Paget’s Disease (All-case Surveillance) -48-week Surveillance -
NCT02802384Not specifiedCOMPLETEDPathophysiology of Paget’s Disease of Bone

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
ZOLEDRONIC ACID ANHYDROUS413
ALENDRONIC ACID46
CALCIUM43
RISEDRONIC ACID43
CHOLECALCIFEROL41
ERGOCALCIFEROL41
PAMIDRONIC ACID41
MEDRONIC ACID31
CHEMBL507282603

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 71

This page pulls from 71 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncicd10cmintactinterpromedgenmeshmimmondomondochildmondoparentncitorphanetpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot