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Atlas / Disease / Bone fracture

Bone fracture

disease
On this page

Also known as fracturefracture of bonefracture(s)

Summary

Bone fracture (MONDO:0005315) is a disease (an umbrella term covering 7 Mondo subtypes) with 51 cohort genes (128 GWAS associations across 97 studies) and 258 clinical trials. The dominant Reactome pathway is TCF dependent signaling in response to WNT (7 cohort genes). Top therapeutic interventions include dibotermin alfa, ketorolac, and toremifene.

At a glance

  • Umbrella term: 7 Mondo subtypes
  • Cohort genes: 51
  • GWAS associations: 128
  • Clinical trials: 258

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namebone fracture
Mondo IDMONDO:0005315
EFOEFO:0003931
MeSHD050723
NCITC3046
SNOMED CT125605004
Is cancer (heuristic)no

Also known as: fracture · fracture of bone · fracture(s)

Data availability: 128 GWAS associations (97 studies).

Disease family

An umbrella term covering 7 Mondo subtypes.

Classification path: injury › bone fracture

Related subtypes (9): ischemia reperfusion injury, acute lung injury, spinal injury, radiation injury, burn, ankle injury, nervous system injury, frostbite, head injury

Subtypes (7): spinal fracture, humerus fracture, tibia fracture, ulna fracture, radius fracture, hip fracture, jaw fracture

Genetics & variants

GWAS landscape

128 GWAS associations across 97 studies. Top hits map to 19 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs29080072e-174CPED1 - WNT16A1.17
rs94827734e-71RSPO3G1.1
rs77410219e-65RSPO3A0.05
rs110030488e-58LNCARODC0.08
rs102766703e-55AQP1A0.06
rs359893998e-44PPP6R3 - GALC0.06
rs47930225e-41WHSC1L2P - SOSTG0.04
rs108247667e-39LNCARODT1.11
rs559832073e-37LINC01956T1.15
rs4779444e-35TMEM135A1.07
rs283627094e-33AQP1T1.08
rs110030471e-32LNCARODG1.09
rs801075516e-30WHSC1L2P - SOSTC1.11
rs47929098e-30WHSC1L2P - SOSTG1.06
rs44308171e-29FAM210AC1.06
rs28367898e-29ETS2-AS1 - LINC01700C0.04
rs18910023e-28CCDC170A1.07
rs104574875e-28RSPO3C1.05
rs47969952e-27FAM210AA0.03
rs5766797e-27TMEM135G0.03
rs69631348e-26SFRP4 - STARD3NLA0.03
rs27418563e-25WHSC1L2P - SOSTG1.1
rs785202973e-24FGFRL1T0.04
rs45057593e-24FGFRL1C1.06
rs48697422e-23CCDC170C0.03
rs110884582e-23LINC01700 - LINC02940G1.06
rs37362281e-21LRP5T1.06
rs11597983e-21LNCARODC1.06
rs624763384e-21CPED1 - WNT16C0.08
rs67268553e-20SLC8A1T1.06

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST006980Morris JA201853,184373,611An atlas of genetic influences on osteoporosis in humans and mice.
GCST90078951Backman JD202145,242383,540Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90043629Jiang L202143,921409,903A generalized linear mixed model association tool for biobank-scale data.
GCST006422Trajanoska K201837,857227,116Assessment of the genetic and clinical determinants of fracture risk: genome wide association and mendelian randomisation study.
GCST006423Trajanoska K201837,857227,116Assessment of the genetic and clinical determinants of fracture risk: genome wide association and mendelian randomisation study.
GCST90081484Backman JD202127,850328,502Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90078984Backman JD202126,80717,827Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90043713Jiang L202125,77317,546A generalized linear mixed model association tool for biobank-scale data.
GCST90079452Backman JD202124,62320,570Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90044358Jiang L202123,728430,096A generalized linear mixed model association tool for biobank-scale data.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding2
Tier 2: splice/UTR5
Tier 3: regulatory1
Tier 4: intronic/intergenic42

MAF distribution

BucketVariants
common (>=0.05)46
low_freq (0.01-0.05)4
rare (<0.01)0
unknown0

Functional consequences

ConsequenceCount
intron_variant29
intergenic_variant13
5_prime_UTR_variant4
missense_variant2
3_prime_UTR_variant1
regulatory_region_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs29080077121322110A>C,G,T0.372intergenic_variantCPED1 - WNT162e-174Tier 4: intronic/intergenic
rs94827736127138407G>C0.489intron_variantRSPO34e-71Tier 4: intronic/intergenic
rs77410216127147129A>C0.465intron_variantRSPO39e-65Tier 4: intronic/intergenic
rs110030481052674769C>G0.105intron_variantLNCAROD8e-58Tier 4: intronic/intergenic
rs10276670730916874A>G0.228intron_variantAQP13e-55Tier 4: intronic/intergenic
rs359893991168622433C>T0.156intergenic_variantPPP6R3 - GAL8e-44Tier 4: intronic/intergenic
rs47930221743721487G>C0.39intergenic_variantWHSC1L2P - SOST5e-41Tier 4: intronic/intergenic
rs108247661052668537C>A,T0.117intron_variantLNCAROD7e-39Tier 4: intronic/intergenic
rs559832072118772253T>C0.07intron_variantLINC019563e-37Tier 4: intronic/intergenic
rs4779441187149467G>A,C0.309intron_variantTMEM1354e-35Tier 4: intronic/intergenic
rs28362709730915924G>A,T0.207intron_variantAQP14e-33Tier 4: intronic/intergenic
rs110030471052674751T>G0.11intron_variantLNCAROD1e-32Tier 4: intronic/intergenic
rs801075511743731006C>T0.098intergenic_variantWHSC1L2P - SOST6e-30Tier 4: intronic/intergenic
rs47929091743721456G>T0.4intergenic_variantWHSC1L2P - SOST8e-30Tier 4: intronic/intergenic
rs44308171813682667G>A,C,T0.362intron_variantFAM210A1e-29Tier 4: intronic/intergenic
rs28367892138967069C>T0.284intergenic_variantETS2-AS1 - LINC017008e-29Tier 4: intronic/intergenic
rs18910026151578912T>A0.284intron_variantCCDC1703e-28Tier 4: intronic/intergenic
rs104574876127198089C>A0.493_prime_UTR_variantRSPO35e-28Tier 2: splice/UTR
rs47969951813708575A>G,T0.369intron_variantFAM210A2e-27Tier 4: intronic/intergenic
rs5766791187157029G>A,C,T0.315intron_variantTMEM1357e-27Tier 4: intronic/intergenic
rs6963134738105296A>C,G,T0.347intron_variantSFRP4 - STARD3NL8e-26Tier 4: intronic/intergenic
rs27418561743749471G>C,T0.08intergenic_variantWHSC1L2P - SOST3e-25Tier 4: intronic/intergenic
rs7852029741011076T>C0.1495_prime_UTR_variantFGFRL13e-24Tier 2: splice/UTR
rs450575941009234C>T0.2985_prime_UTR_variantFGFRL13e-24Tier 2: splice/UTR
rs48697426151586613C>A,G,T0.291intron_variantCCDC1702e-23Tier 4: intronic/intergenic
rs110884582138978194A>G,T0.294intron_variantLINC01700 - LINC029402e-23Tier 4: intronic/intergenic
rs37362281168433827C>T0.15missense_variantLRP51e-21Tier 1: coding
rs11597981052652733A>C0.227intron_variantLNCAROD3e-21Tier 4: intronic/intergenic
rs624763387121320217G>A,C,T0.369intergenic_variantCPED1 - WNT164e-21Tier 4: intronic/intergenic
rs6726855240409040G>C,T0.237intron_variantSLC8A13e-20Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 57 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
SEM1Orphanet:2440Isolated split hand-split foot malformation
SLC40A1Orphanet:647834SLC40A1-related hemochromatosis
SLC40A1Orphanet:648562Ferroportin disease
SOX9Orphanet:140Campomelic dysplasia
SOX9Orphanet:213846,XX ovotesticular difference of sex development
SOX9Orphanet:24246,XY complete gonadal dysgenesis
SOX9Orphanet:25151046,XY partial gonadal dysgenesis
SOX9Orphanet:39346,XX testicular difference of sex development
SOX9Orphanet:718Isolated Pierre Robin sequence
SPTBN1Orphanet:528084Non-specific syndromic intellectual disability
TGFBR1Orphanet:284973Marfan syndrome type 2
TGFBR1Orphanet:60030Loeys-Dietz syndrome
TGFBR1Orphanet:65748Multiple self-healing squamous epithelioma
TGFBR1Orphanet:91387Familial thoracic aortic aneurysm and aortic dissection
VRK1Orphanet:2254Pontocerebellar hypoplasia type 1
VRK1Orphanet:423894Microcephaly-complex motor and sensory axonal neuropathy syndrome
SOSTOrphanet:1513Craniodiaphyseal dysplasia
SOSTOrphanet:3152Sclerosteosis
SOSTOrphanet:3416Hyperostosis corticalis generalisata
SUMF1Orphanet:585Multiple sulfatase deficiency
COL7A1Orphanet:158673Localized dystrophic epidermolysis bullosa, acral form
COL7A1Orphanet:158676Localized dystrophic epidermolysis bullosa, nails only
COL7A1Orphanet:231568Autosomal dominant generalized dystrophic epidermolysis bullosa
COL7A1Orphanet:79408Autosomal recessive generalized dystrophic epidermolysis bullosa, severe form
COL7A1Orphanet:79409Recessive dystrophic epidermolysis bullosa inversa
COL7A1Orphanet:79410Localized dystrophic epidermolysis bullosa, pretibial form
COL7A1Orphanet:79411Self-improving dystrophic epidermolysis bullosa
COL7A1Orphanet:89842Autosomal recessive generalized dystrophic epidermolysis bullosa, intermediate form
COL7A1Orphanet:89843Dystrophic epidermolysis bullosa pruriginosa
CTNNB1Orphanet:1501Adrenocortical carcinoma
CTNNB1Orphanet:210159Adult hepatocellular carcinoma
CTNNB1Orphanet:2780Osteopathia striata-cranial sclerosis syndrome
CTNNB1Orphanet:33402Pediatric hepatocellular carcinoma
CTNNB1Orphanet:404473Intellectual disability-eye abnormalities-microcephaly-peripheral spasticity syndrome
CTNNB1Orphanet:54595Craniopharyngioma
CTNNB1Orphanet:569248Microcystic stromal tumor
CTNNB1Orphanet:689430Adenoid ameloblastoma
CTNNB1Orphanet:873Desmoid tumor
CTNNB1Orphanet:891Familial exudative vitreoretinopathy
CTNNB1Orphanet:91414Pilomatrixoma
CTNNB1Orphanet:952Acrofacial dysostosis, Weyers type
NSMCE2Orphanet:436182Microcephalic primordial dwarfism-insulin resistance syndrome
NSMCE2Orphanet:808Seckel syndrome
DKK1Orphanet:268882Arnold-Chiari malformation type I
DKK1Orphanet:85193Idiopathic juvenile osteoporosis
ESR1Orphanet:785Estrogen resistance syndrome
GRB10Orphanet:96182Silver-Russell syndrome due to maternal uniparental disomy of chromosome 7
LRP5Orphanet:178377Osteosclerosis-developmental delay-craniosynostosis syndrome
LRP5Orphanet:2783Autosomal dominant osteopetrosis type 1
LRP5Orphanet:2788Osteoporosis-pseudoglioma syndrome

Cohort genes → proteins

51 cohort genes, 48 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only51

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
RNMTHGNC:10075ENSG00000101654O43148mRNA cap guanine-N(7) methyltransferasegwas
RPS6KA5HGNC:10434ENSG00000100784O75582Ribosomal protein S6 kinase alpha-5gwas
SETMARHGNC:10762ENSG00000170364Q53H47Histone-lysine N-methyltransferase SETMARgwas
SEM1HGNC:10845ENSG00000127922P6089626S proteasome complex subunit SEM1gwas
SLC40A1HGNC:10909ENSG00000138449Q9NP59Ferroportingwas
SLC8A1HGNC:11068ENSG00000183023P32418Sodium/calcium exchanger 1gwas
SOX9HGNC:11204ENSG00000125398P48436Transcription factor SOX-9gwas
SPTBN1HGNC:11275ENSG00000115306Q01082Spectrin beta chain, non-erythrocytic 1gwas
SVILHGNC:11480ENSG00000197321O95425Supervillingwas
PPP6R3HGNC:1173ENSG00000110075Q5H9R7Serine/threonine-protein phosphatase 6 regulatory subunit 3gwas
TGFBR1HGNC:11772ENSG00000106799P36897TGF-beta receptor type-1gwas
VRK1HGNC:12718ENSG00000100749Q99986Serine/threonine-protein kinase VRK1gwas
SOSTHGNC:13771ENSG00000167941Q9BQB4Sclerostingwas
HAGHLHGNC:14177ENSG00000103253Q6PII5Hydroxyacylglutathione hydrolase-like proteingwas
WNT16HGNC:16267ENSG00000002745Q9UBV4Protein Wnt-16gwas
NPLHGNC:16781ENSG00000135838Q9BXD5N-acetylneuraminate lyasegwas
TRIB1HGNC:16891ENSG00000173334Q96RU8Tribbles homolog 1gwas
STARD3NLHGNC:19169ENSG00000010270O95772STARD3 N-terminal-like proteingwas
SUMF1HGNC:20376ENSG00000144455Q8NBK3Formylglycine-generating enzymegwas
RSPO3HGNC:20866ENSG00000146374Q9BXY4R-spondin-3gwas
LRRN1HGNC:20980ENSG00000175928Q6UXK5Leucine-rich repeat neuronal protein 1gwas
CCDC170HGNC:21177ENSG00000120262Q8IYT3Coiled-coil domain-containing protein 170gwas
COL15A1HGNC:2192ENSG00000204291P39059Collagen alpha-1(XV) chaingwas
COL7A1HGNC:2214ENSG00000114270Q02388Collagen alpha-1(VII) chaingwas
COBLHGNC:22199ENSG00000106078O75128Protein cordon-bleugwas
LUZP2HGNC:23206ENSG00000187398Q86TE4Leucine zipper protein 2gwas
MOGAT2HGNC:23248ENSG00000166391Q3SYC22-acylglycerol O-acyltransferase 2gwas
PROSER2HGNC:23728ENSG00000148426Q86WR7Proline and serine-rich protein 2gwas
CTNNB1HGNC:2514ENSG00000168036P35222Catenin beta-1gwas
CPED1HGNC:26159ENSG00000106034A4D0V7Cadherin-like and PC-esterase domain-containing protein 1gwas
TMEM135HGNC:26167ENSG00000166575Q86UB9Transmembrane protein 135gwas
NSMCE2HGNC:26513ENSG00000156831Q96MF7E3 SUMO-protein ligase NSE2gwas
PROSER2-AS1HGNC:27343ENSG00000225778PROSER2 antisense RNA 1gwas
DOK6HGNC:28301ENSG00000206052Q6PKX4Docking protein 6gwas
MIMS1HGNC:28346ENSG00000177150Q96ND0Protein FAM210Agwas
DKK1HGNC:2891ENSG00000107984O94907Dickkopf-related protein 1gwas
DUSP3HGNC:3069ENSG00000108861P51452Dual specificity protein phosphatase 3gwas
ESR1HGNC:3467ENSG00000091831P03372Estrogen receptorgwas
ETS2HGNC:3489ENSG00000157557P15036Protein C-ets-2gwas
FGFRL1HGNC:3693ENSG00000127418Q8N441Fibroblast growth factor receptor-like 1gwas
FUBP3HGNC:4005ENSG00000107164Q96I24Far upstream element-binding protein 3gwas
GRB10HGNC:4564ENSG00000106070Q13322Growth factor receptor-bound protein 10gwas
SOX9-AS1HGNC:49321ENSG00000234899SOX9 antisense RNA 1gwas
LINC01700HGNC:52488ENSG00000232837long intergenic non-protein coding RNA 1700gwas
AQP1HGNC:633ENSG00000240583P29972Aquaporin-1gwas
LRP5HGNC:6697ENSG00000162337O75197Low-density lipoprotein receptor-related protein 5gwas
MBL2HGNC:6922ENSG00000165471P11226Mannose-binding protein Cgwas
MEOX1HGNC:7013ENSG00000005102P50221Homeobox protein MOX-1gwas
PLXNA4HGNC:9102ENSG00000221866Q9HCM2Plexin-A4gwas
PTERHGNC:9590ENSG00000165983Q96BW5N-acetyltaurine hydrolasegwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
RNMTmRNA cap guanine-N(7) methyltransferaseCatalytic subunit of the mRNA-capping methyltransferase RNMT:RAMAC complex that methylates the N7 position of the added guanosine to the 5’-cap structure of mRNAs.
RPS6KA5Ribosomal protein S6 kinase alpha-5Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factors RELA, STAT3 and ETV1/ER81, and that contribu…
SETMARHistone-lysine N-methyltransferase SETMARProtein derived from the fusion of a methylase with the transposase of an Hsmar1 transposon that plays a role in DNA double-strand break repair, stalled replication fork restart and DNA integration.
SEM126S proteasome complex subunit SEM1Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins.
SLC40A1FerroportinTransports Fe(2+) from the inside of a cell to the outside of the cell, playing a key role for maintaining systemic iron homeostasis.
SLC8A1Sodium/calcium exchanger 1Mediates the exchange of one Ca(2+) ion against three to four Na(+) ions across the cell membrane, and thereby contributes to the regulation of cytoplasmic Ca(2+) levels and Ca(2+)-dependent cellular processes.
SOX9Transcription factor SOX-9Transcription factor that plays a key role in chondrocytes differentiation and skeletal development.
SPTBN1Spectrin beta chain, non-erythrocytic 1Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane.
SVILSupervillinForms a high-affinity link between the actin cytoskeleton and the membrane.
PPP6R3Serine/threonine-protein phosphatase 6 regulatory subunit 3Regulatory subunit of protein phosphatase 6 (PP6).
TGFBR1TGF-beta receptor type-1Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3.
VRK1Serine/threonine-protein kinase VRK1Serine/threonine kinase involved in the regulation of key cellular processes including the cell cycle, nuclear condensation, transcription regulation, and DNA damage response.
SOSTSclerostinNegative regulator of bone growth that acts through inhibition of Wnt signaling and bone formation.
HAGHLHydroxyacylglutathione hydrolase-like proteinHydrolase acting on ester bonds.
WNT16Protein Wnt-16Ligand for members of the frizzled family of seven transmembrane receptors.
NPLN-acetylneuraminate lyaseCatalyzes the cleavage of N-acetylneuraminic acid (sialic acid) to form pyruvate and N-acetylmannosamine via a Schiff base intermediate.
TRIB1Tribbles homolog 1Adapter protein involved in protein degradation by interacting with COP1 ubiquitin ligase.
STARD3NLSTARD3 N-terminal-like proteinTethering protein that creates contact site between the endoplasmic reticulum and late endosomes: localizes to late endosome membranes and contacts the endoplasmic reticulum via interaction with VAPA and VAPB.
SUMF1Formylglycine-generating enzymeOxidase that catalyzes the conversion of cysteine to 3-oxoalanine on target proteins, using molecular oxygen and an unidentified reducing agent. 3-oxoalanine modification, which is also named formylglycine (fGly), occurs in the maturation…
RSPO3R-spondin-3Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors, which acts as a key regulator of angiogenesis.
CCDC170Coiled-coil domain-containing protein 170Plays a role in Golgi-associated microtubules organization and stabilization.
COL15A1Collagen alpha-1(XV) chainStructural protein that stabilizes microvessels and muscle cells, both in heart and in skeletal muscle.
COL7A1Collagen alpha-1(VII) chainStratified squamous epithelial basement membrane protein that forms anchoring fibrils which may contribute to epithelial basement membrane organization and adherence by interacting with extracellular matrix (ECM) proteins such as type IV c…
COBLProtein cordon-bleuPlays an important role in the reorganization of the actin cytoskeleton.
MOGAT22-acylglycerol O-acyltransferase 2Involved in glycerolipid synthesis and lipid metabolism.
CTNNB1Catenin beta-1Key downstream component of the canonical Wnt signaling pathway.
TMEM135Transmembrane protein 135Involved in mitochondrial metabolism by regulating the balance between mitochondrial fusion and fission.
NSMCE2E3 SUMO-protein ligase NSE2E3 SUMO-protein ligase component of the SMC5-SMC6 complex, a complex involved in DNA double-strand break repair by homologous recombination.
DOK6Docking protein 6DOK proteins are enzymatically inert adaptor or scaffolding proteins.
MIMS1Protein FAM210AMay play a role in the structure and strength of both muscle and bone.
DKK1Dickkopf-related protein 1Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6.
DUSP3Dual specificity protein phosphatase 3Shows activity both for tyrosine-protein phosphate and serine-protein phosphate, but displays a strong preference toward phosphotyrosines.
ESR1Estrogen receptorNuclear hormone receptor.
ETS2Protein C-ets-2Transcription factor activating transcription.
FGFRL1Fibroblast growth factor receptor-like 1Has a negative effect on cell proliferation.
FUBP3Far upstream element-binding protein 3May interact with single-stranded DNA from the far-upstream element (FUSE).
GRB10Growth factor receptor-bound protein 10Adapter protein which modulates coupling of a number of cell surface receptor kinases with specific signaling pathways.
AQP1Aquaporin-1Forms a water channel that facilitates the transport of water across cell membranes, playing a crucial role in water homeostasis in various tissues.
LRP5Low-density lipoprotein receptor-related protein 5Acts as a coreceptor with members of the frizzled family of seven-transmembrane spanning receptors to transduce signal by Wnt proteins.
MBL2Mannose-binding protein CCalcium-dependent lectin, which acts as a pattern recognition receptor that initiates the lectin pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens t…
MEOX1Homeobox protein MOX-1Mesodermal transcription factor that plays a key role in somitogenesis and is specifically required for sclerotome development.
PLXNA4Plexin-A4Coreceptor for SEMA3A.
PTERN-acetyltaurine hydrolaseN-acetyltaurine hydrolase that regulates feeding by catalyzing the hydrolysis of N-acetyltaurine into taurine and acetate.
RAB31Ras-related protein Rab-31The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes.

Protein-family classification

Druggable: 16 · Difficult: 6 · Unknown: 29 · Druggable fraction: 0.31

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
Kinase52.7×0.325
Nuclear receptor17.6×0.372
Antibody/Immunoglobulin42.3×0.372
Phosphatase11.6×0.703
Transporter11.5×0.703
Other/Unknown291.0×0.703
Scaffold/PPI31.0×0.703
Enzyme (other)40.9×0.703
Transcription factor30.5×0.956

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
RNMTEnzyme (other)yes2.1.1.56mRNA_G-N7_MeTrfase_dom, mRNA_G-N7_MeTrfase_euk, SAM-dependent_MTases_sf
RPS6KA5KinaseyesProt_kinase_dom, AGC-kinase_C, Ser/Thr_kinase_AS
SETMAREnzyme (other)yes2.1.1.357SET_dom, Transposase_1, Post-SET_dom
SEM1Other/UnknownnoDSS1_SEM1, DUF5543
SLC40A1TransporteryesFerroportin-1, MFS_trans_sf
SLC8A1Other/UnknownnoDnaJ_domain, NaCa_exhngr1, Calx_beta
SOX9Transcription factornoHMG_box_dom, Sox_N, HMG_box_dom_sf
SPTBN1Scaffold/PPInoActinin_actin-bd_CS, PH_dom-spectrin-type, CH_dom
SVILOther/UnknownnoVillin_headpiece, Villin/Gelsolin, Gelsolin-like_dom
PPP6R3Other/UnknownnoSAPS, ARM-type_fold
TGFBR1Kinaseyes2.7.10.2TGFB_receptor, Activin_recp, Prot_kinase_dom
VRK1KinaseyesProt_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
SOSTOther/UnknownnoCys_knot_C, Sclerostin/SOSTDC1, Cystine-knot_cytokine
HAGHLOther/UnknownnoMetallo-B-lactamas, Clx_II_MBL, RibonucZ/Hydroxyglut_hydro
WNT16Other/UnknownnoWnt, Wnt16, Wnt_CS
NPLEnzyme (other)yes4.1.3.3DapA-like, NanA, Aldolase_TIM
TRIB1KinaseyesProt_kinase_dom, Kinase-like_dom_sf, Tribbles/Ser_Thr_kinase_40
STARD3NLOther/UnknownnoMENTAL, STARD3
SUMF1Kinaseyes1.8.3.7SUMF_dom, CTDL_fold, SUMF_sf
RSPO3Other/UnknownnoTSP1_rpt, Furin_repeat, Growth_fac_rcpt_cys_sf
LRRN1Antibody/ImmunoglobulinyesCys-rich_flank_reg_C, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp
CCDC170Other/UnknownnoCCDC170-like
COL15A1Other/UnknownnoCollagen, Collagenase_NC10/endostatin, ConA-like_dom_sf
COL7A1Antibody/ImmunoglobulinyesVWF_A, Kunitz_BPTI, FN3_dom
COBLOther/UnknownnoWH2_dom, Cordon-bleu_ubiquitin_domain, COBL-like
LUZP2Other/UnknownnoLuzp2
MOGAT2Enzyme (other)yes2.3.1.22DAGAT
PROSER2Other/Unknownno
CTNNB1Other/UnknownnoArmadillo, ARM-like, Beta-catenin
CPED1Other/UnknownnoCadherin-like_domain, NXPE4_C
TMEM135Other/UnknownnoTmem135, TMEM135_N
NSMCE2Transcription factornoZnf_MIZ, Znf_RING/FYVE/PHD, Nse2(Mms21)
PROSER2-AS1Other/Unknownno
DOK6Scaffold/PPInoPH_domain, IRS_PTB, PH-like_dom_sf
MIMS1Other/UnknownnoFAM210A/B-like_dom, FAM210A/B-like
DKK1Other/UnknownnoDickkopf_N, DKK1-4, Dkk1_Cys2
DUSP3Phosphataseyes3.1.3.16Dual-sp_phosphatase_cat-dom, Tyr_Pase_dom, Tyr_Pase_AS
ESR1Nuclear receptoryesNucl_hrmn_rcpt_lig-bd, Estr_rcpt, Znf_hrmn_rcpt
ETS2Other/UnknownnoEts_dom, Pointed_dom, SAM/pointed_sf
FGFRL1Antibody/ImmunoglobulinyesIg_sub2, Ig_sub, Ig-like_dom
FUBP3Other/UnknownnoKH_dom, KH_dom_type_1, KH_dom_type_1_sf
GRB10Scaffold/PPInoRA_dom, SH2, PH_domain
SOX9-AS1Other/Unknownno
LINC01700Other/Unknownno
AQP1Other/UnknownnoMIP, MIP_CS, Aquaporin-like
LRP5Other/UnknownnoLDLR_classB_rpt, EGF, LDrepeatLR_classA_rpt
MBL2Other/UnknownnoC-type_lectin-like, Collagen, C-type_lectin-like/link_sf
MEOX1Transcription factornoHD, Homeodomain-like_sf, Homeobox_CS
PLXNA4Antibody/ImmunoglobulinyesSemap_dom, Plexin_repeat, IPT_dom
PTEROther/UnknownnoPhosphotriesterase, AryldialkylPase_Zn-BS, Metal_Hydrolase

Expression context

Cohort genes with no expression data: 0.

49 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)1
broad (>20)50
unknown0

Top tissues across cohort

TissueCohort genes
male germ line stem cell (sensu Vertebrata) in testis5
adrenal tissue5
ventricular zone4
right lobe of liver4
amniotic fluid3
cauda epididymis3
secondary oocyte3
calcaneal tendon3
pancreatic ductal cell3
skin of hip3
visceral pleura3
oocyte3
body of uterus2
tendon2
tendon of biceps brachii2
epithelial cell of pancreas2
oviduct epithelium2
endothelial cell2
heart right ventricle2
skeletal muscle tissue of rectus abdominis2

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
RNMT293ubiquitousmarkermale germ line stem cell (sensu Vertebrata) in testis, amniotic fluid, lateral nuclear group of thalamus
RPS6KA5283ubiquitousmarkersecondary oocyte, cauda epididymis, nipple
SETMAR250ubiquitousmarkerbody of uterus, popliteal artery, tibial artery
SEM1285ubiquitousmarkercalcaneal tendon, tendon, tendon of biceps brachii
SLC40A1260ubiquitousmarkerpancreatic ductal cell, epithelial cell of pancreas, oviduct epithelium
SLC8A1249ubiquitousmarkerheart right ventricle, adrenal tissue, endothelial cell
SOX9274ubiquitousmarkerventricular zone, cranial nerve II, hair follicle
SPTBN1295ubiquitousmarkerendothelial cell, trigeminal ganglion, skin of hip
SVIL276ubiquitousmarkergluteal muscle, skeletal muscle tissue of rectus abdominis, vastus lateralis
PPP6R3285ubiquitousmarkercalcaneal tendon, adrenal tissue, sural nerve
TGFBR1269ubiquitousmarkersaphenous vein, tibia, visceral pleura
VRK1286ubiquitousmarkeroocyte, bone marrow, secondary oocyte
SOST73broadmarkertrabecular bone tissue, descending thoracic aorta, male germ line stem cell (sensu Vertebrata) in testis
HAGHL230ubiquitousmarkerpancreatic ductal cell, right uterine tube, C1 segment of cervical spinal cord
WNT16137broadmarkermale germ line stem cell (sensu Vertebrata) in testis, skin of hip, upper leg skin
NPL244ubiquitousmarkermonocyte, mononuclear cell, leukocyte
TRIB1280ubiquitousmarkermucosa of urinary bladder, mucosa of sigmoid colon, visceral pleura
STARD3NL258ubiquitousmarkersecondary oocyte, oocyte, epithelial cell of pancreas
SUMF1258ubiquitousmarkerkidney epithelium, renal medulla, upper arm skin
RSPO3218broadmarkermucosa of stomach, cauda epididymis, caput epididymis
LRRN1209broadmarkerventricular zone, ganglionic eminence, dorsal root ganglion
CCDC170182broadmarkerbronchial epithelial cell, epithelium of bronchus, bronchus
COL15A1249broadmarkerskin of hip, placenta, synovial joint
COL7A1267ubiquitousmarkerstromal cell of endometrium, skin of abdomen, skin of leg
COBL255broadmarkerinferior vagus X ganglion, parotid gland, lateral globus pallidus
LUZP2153broadmarkeradrenal tissue, hypothalamus, C1 segment of cervical spinal cord
MOGAT290tissue_specificmarkerileal mucosa, mucosa of transverse colon, right lobe of liver
PROSER2204ubiquitousmarkerpancreatic ductal cell, amniotic fluid, right lobe of liver
CTNNB1295ubiquitousmarkeradrenal tissue, ventricular zone, periodontal ligament
CPED1245ubiquitousmarkercauda epididymis, saphenous vein, superficial temporal artery

Protein interactions among cohort

Intra-cohort edges: 30.

Hub genes (top 10 by interactor count)

SymbolInteractor count
CTNNB115,668
ESR112,382
SOX94,935
TGFBR14,828
AQP14,259
DKK13,058
VRK13,022
LRP52,619
SPTBN12,432
SOST2,417

Intra-cohort edges

ABSources
AQP1SLC40A1intact
CCDC170ESR1string_interaction
CCDC170TMEM135string_interaction
COBLGRB10string_interaction
CPED1MIMS1string_interaction
CPED1PPP6R3string_interaction
CPED1STARD3NLstring_interaction
CPED1WNT16string_interaction
CTNNB1DKK1biogrid_interaction, string_interaction
CTNNB1RSPO3string_interaction
CTNNB1SOSTstring_interaction
CTNNB1SOX9string_interaction
CTNNB1WNT16string_interaction
DKK1LRP5biogrid_interaction, intact, string_interaction
DKK1SOSTstring_interaction
DKK1WNT16string_interaction
DUSP3MEOX1intact
ESR1ETS2string_interaction
ESR1LUZP2intact
LRP5SOSTbiogrid_interaction, intact, string_interaction
LRP5WNT16string_interaction
LRRN1SETMARstring_interaction
LRRN1SUMF1string_interaction
MEOX1SOSTstring_interaction
MIMS1SPTBN1string_interaction
MIMS1STARD3NLstring_interaction
MIMS1WNT16string_interaction
SETMARSUMF1string_interaction
SOSTWNT16string_interaction
TMEM135WNT16string_interaction

Structural data

PDB: 28 · AlphaFold-only: 20 · No structure: 3

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
ESR1P03372478
SEM1P60896129
CTNNB1P3522250
TGFBR1P3689744
VRK1Q9998626
SUMF1Q8NBK318
AQP1P2997210
DUSP3P514529
RNMTO431488
RPS6KA5O755828
SLC40A1Q9NP598
SETMARQ53H475
SLC8A1P324185
TRIB1Q96RU85
DKK1O949075
SPTBN1Q010823
SOSTQ9BQB43
NSMCE2Q96MF73
SVILO954252
ETS2P150362
GRB10Q133222
SOX9P484361
NPLQ9BXD51
COL15A1P390591
COBLO751281
MBL2P112261
PLXNA4Q9HCM21
RAB31Q136361

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
PTERQ96BW597.60
MOGAT2Q3SYC294.86
WNT16Q9UBV488.67
TMEM135Q86UB986.37
CCDC170Q8IYT382.06
LRRN1Q6UXK582.05
LRP5O7519778.65
RSPO3Q9BXY478.27
HAGHLQ6PII577.27
DOK6Q6PKX474.63
LUZP2Q86TE473.61
CPED1A4D0V773.08
FGFRL1Q8N44172.04
PPP6R3Q5H9R768.31
FUBP3Q96I2466.40
MIMS1Q96ND064.73
MEOX1P5022164.33
STARD3NLO9577262.78
PROSER2Q86WR758.50
COL7A1Q02388

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 398. Enrichment computed across 51 evidence-associated genes (34 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 34 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
TCF dependent signaling in response to WNT724.2×5e-06SEM1, SOX9, SOST, RSPO3, CTNNB1, DKK1, LRP5
Negative regulation of TCF-dependent signaling by WNT ligand antagonists363.0×0.002SOST, DKK1, LRP5
Signaling by WNT516.5×0.002SEM1, SOX9, SOST, RSPO3, LRP5
RUNX1 regulates transcription of genes involved in WNT signaling2112.0×0.013RSPO3, ESR1
Signaling by LRP5 mutants296.0×0.014DKK1, LRP5
Regulation of FZD by ubiquitination230.5×0.127RSPO3, LRP5
Defective SLC40A1 causes hemochromatosis 4 (HFE4) (macrophages)1167.9×0.152SLC40A1
Defective CP causes aceruloplasminemia (ACERULOP)1167.9×0.152SLC40A1
Defective SLC40A1 causes hemochromatosis 4 (HFE4) (duodenum)1167.9×0.152SLC40A1
Loss of Function of TGFBR2 in Cancer1112.0×0.152TGFBR1
TGFBR2 Kinase Domain Mutants in Cancer1112.0×0.152TGFBR1
Impaired BRCA2 translocation to the nucleus1112.0×0.152SEM1
Impaired BRCA2 binding to SEM1 (DSS1)1112.0×0.152SEM1
TGFBR1 LBD Mutants in Cancer184.0×0.152TGFBR1
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production167.2×0.152CTNNB1
Loss of Function of TGFBR1 in Cancer167.2×0.152TGFBR1
R-HSA-69610167.2×0.152SEM1
p53-Independent G1/S DNA Damage Checkpoint167.2×0.152SEM1
IRS activation167.2×0.152GRB10
Creation of C4 and C2 activators156.0×0.152MBL2
Regulation of Apoptosis156.0×0.152SEM1
Loss of Function of SMAD2/3 in Cancer156.0×0.152TGFBR1
Signaling by TGF-beta Receptor Complex in Cancer156.0×0.152TGFBR1
SMAD2/3 Phosphorylation Motif Mutants in Cancer156.0×0.152TGFBR1
TGFBR1 KD Mutants in Cancer156.0×0.152TGFBR1
RUNX1 regulates estrogen receptor mediated transcription156.0×0.152ESR1
Formation of paraxial mesoderm224.0×0.152SEM1, CTNNB1
Disassembly of the destruction complex and recruitment of AXIN to the membrane221.0×0.152CTNNB1, LRP5
NCAM signaling for neurite out-growth216.0×0.152RPS6KA5, SPTBN1
RET signaling215.3×0.152DOK6, GRB10

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 43 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
canonical Wnt signaling pathway724.9×8e-06SOX9, SOST, WNT16, RSPO3, CTNNB1, DKK1, LRP5
negative regulation of chondrocyte differentiation347.0×0.009SOX9, TGFBR1, CTNNB1
negative regulation of ossification343.5×0.009SOX9, SOST, DKK1
positive regulation of mesenchymal cell proliferation342.0×0.009SOX9, CTNNB1, LRP5
somite specification2156.8×0.009COBL, MEOX1
establishment of blood-retinal barrier2130.6×0.011CTNNB1, LRP5
embryonic axis specification2112.0×0.013COBL, CTNNB1
heart valve morphogenesis287.1×0.016SOX9, FGFRL1
positive regulation of extracellular matrix assembly287.1×0.016SOX9, TGFBR1
positive regulation of Wnt signaling pathway, planar cell polarity pathway287.1×0.016RSPO3, DKK1
notochord development278.4×0.016SOX9, COBL
epithelial cell development271.3×0.016CTNNB1, ESR1
heart valve development271.3×0.016SOX9, DKK1
regulation of epithelial to mesenchymal transition271.3×0.016TGFBR1, CTNNB1
negative regulation of Wnt signaling pathway324.0×0.016SOST, DKK1, GRB10
epithelial to mesenchymal transition321.8×0.016SOX9, TGFBR1, CTNNB1
skeletal system development411.7×0.016SOX9, TGFBR1, ETS2, FGFRL1
establishment of blood-brain barrier265.3×0.016CTNNB1, LRP5
negative regulation of canonical Wnt signaling pathway411.0×0.018SOX9, SOST, CTNNB1, DKK1
cardiac epithelial to mesenchymal transition256.0×0.020TGFBR1, WNT16
positive regulation of gene expression65.4×0.025SOX9, TGFBR1, WNT16, CTNNB1, DKK1, FUBP3
positive regulation of DNA-templated transcription74.5×0.025SOX9, TGFBR1, SOST, CTNNB1, ESR1, FUBP3, LRP5
gastrulation with mouth forming second243.5×0.028CTNNB1, LRP5
bone remodeling243.5×0.028WNT16, LRP5
regulation of protein ubiquitination241.2×0.030TGFBR1, CTNNB1
epithelial tube branching involved in lung morphogenesis239.2×0.032SOX9, CTNNB1
glial cell fate determination1391.9×0.037CTNNB1
chemorepulsion of branchiomotor axon1391.9×0.037PLXNA4
regulation of endodermal cell fate specification1391.9×0.037DKK1
extracellular structure organization1391.9×0.037TGFBR1

Therapeutics

Drugs indicated for this disease

0 approved, 19 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
BupivacainePhase 3 (in late-stage trials)
CalciumPhase 3 (in late-stage trials)
CholecalciferolPhase 3 (in late-stage trials)
DenosumabPhase 3 (in late-stage trials)
DexmedetomidinePhase 3 (in late-stage trials)
EpinephrinePhase 3 (in late-stage trials)
IbuprofenPhase 3 (in late-stage trials)
KetaminePhase 3 (in late-stage trials)
Lactose, AnhydrousPhase 3 (in late-stage trials)
LidocainePhase 3 (in late-stage trials)
MidazolamPhase 3 (in late-stage trials)
OxygenPhase 3 (in late-stage trials)
PregabalinPhase 3 (in late-stage trials)
RopivacainePhase 3 (in late-stage trials)
Sodium ChloridePhase 3 (in late-stage trials)
TeriparatidePhase 3 (in late-stage trials)
TobramycinPhase 3 (in late-stage trials)
ToremifenePhase 3 (in late-stage trials)
Tranexamic AcidPhase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Abaloparatide, Acetaminophen, Cannabidiol, Cefazolin, Dextrose, Dibotermin Alfa, Fentanyl, Insulin Pork, Lithium Carbonate, Romosozumab, Somatropin, Vancomycin.

Drug target analysis

Approved (phase 4): 6 · Phase ≥3: 6 · Phased (≥1): 11 · Undrugged: 40

Druggability breadth: 27 of 51 evidence-associated genes (53%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

SymbolExample approved molecule
RPS6KA5FEDRATINIB
SEM1BORTEZOMIB
TGFBR1MOMELOTINIB
SOSTCIANIDANOL
CTNNB1DITHIAZANINE IODIDE
ESR1CANDESARTAN CILEXETIL

Top cohort targets by molecule count

SymbolMoleculesMax phase
ESR11624
TGFBR1284
RPS6KA5254
CTNNB144
RNMT22
SEM124
SOST24
SLC40A111
SPTBN112
PPP6R312

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
FEDRATINIB4RPS6KA5
RUXOLITINIB4RPS6KA5
NINTEDANIB4RPS6KA5, TGFBR1
SUNITINIB4RPS6KA5
MIDOSTAURIN4RPS6KA5
BORTEZOMIB4SEM1
CARFILZOMIB4SEM1
MOMELOTINIB4TGFBR1
DABRAFENIB4TGFBR1
DASATINIB4TGFBR1
CRIZOTINIB4TGFBR1
CIANIDANOL4SOST
COUMARIN4SOST
DITHIAZANINE IODIDE4CTNNB1
CANDESARTAN CILEXETIL4ESR1
DIENESTROL4ESR1
BEXAROTENE4ESR1
VARENICLINE4ESR1
ACETOPHENAZINE4ESR1
ARIPIPRAZOLE4ESR1
RALOXIFENE HYDROCHLORIDE4ESR1
NORETHINDRONE4ESR1
TRIMETREXATE4ESR1
ESTRADIOL ACETATE4ESR1
ETHYLESTRENOL4ESR1
ETHYNODIOL DIACETATE4ESR1
CHLOROTRIANISENE4ESR1
ESTRADIOL CYPIONATE4ESR1
MESTRANOL4ESR1
QUINESTROL4ESR1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 7.

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

SymbolAssaysType breakdown
ESR12,435Binding:2037, Functional:363, ADMET:35
RPS6KA5659Binding:656, ADMET:2, Functional:1
TGFBR1541Binding:516, Functional:13, ADMET:12
CTNNB1361Binding:358, Functional:3
DUSP3101Binding:95, Functional:5, ADMET:1
VRK174Binding:74
SEM126Binding:26
RNMT18Binding:13, ADMET:5
SLC40A114Binding:14
MOGAT211Binding:11
SLC8A19Binding:8, Functional:1
SOST9Binding:9
GRB109Binding:9
AQP18Binding:8
SPTBN17Binding:7
PPP6R37Binding:7
DKK15Binding:5
SOX93Binding:3
MBL23Binding:3
SETMAR1Binding:1
TRIB11Binding:1
NSMCE21Binding:1
FUBP31Binding:1
LRP51Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
RNMT2.1.1.56mRNA (guanine-N7)-methyltransferase
SETMAR2.1.1.357, 2.7.7.B22[histone H3]-lysine36 N-dimethyltransferase,
TGFBR12.7.10.2, 2.7.11.30non-specific protein-tyrosine kinase, receptor protein serine/threonine kinase
NPL4.1.3.3N-acetylneuraminate lyase
SUMF11.8.3.7formylglycine-generating enzyme
MOGAT22.3.1.222-acylglycerol O-acyltransferase
DUSP33.1.3.16, 3.1.3.48protein-serine/threonine phosphatase, protein-tyrosine-phosphatase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

SymbolChEMBL assays
RPS6KA5659
TGFBR1541
CTNNB1361
DUSP3101
ESR12,435

Pharmacogenomics

Cohort genes with a PharmGKB record: 48; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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)
FEDRATINIB4RPS6KA5
RUXOLITINIB4RPS6KA5
NINTEDANIB4RPS6KA5, TGFBR1
SUNITINIB4RPS6KA5
MIDOSTAURIN4RPS6KA5
BORTEZOMIB4SEM1
CARFILZOMIB4SEM1
MOMELOTINIB4TGFBR1
DABRAFENIB4TGFBR1
DASATINIB4TGFBR1
CRIZOTINIB4TGFBR1
CIANIDANOL4SOST
COUMARIN4SOST
DITHIAZANINE IODIDE4CTNNB1
CANDESARTAN CILEXETIL4ESR1
DIENESTROL4ESR1
BEXAROTENE4ESR1
VARENICLINE4ESR1
ACETOPHENAZINE4ESR1
ARIPIPRAZOLE4ESR1
RALOXIFENE HYDROCHLORIDE4ESR1
NORETHINDRONE4ESR1
TRIMETREXATE4ESR1
ESTRADIOL ACETATE4ESR1
ETHYLESTRENOL4ESR1
ETHYNODIOL DIACETATE4ESR1
CHLOROTRIANISENE4ESR1
ESTRADIOL CYPIONATE4ESR1
MESTRANOL4ESR1
QUINESTROL4ESR1

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)6RPS6KA5, SEM1, TGFBR1, SOST, CTNNB1, ESR1
BPhased (≥1) drug, not yet approved5RNMT, SLC40A1, SPTBN1, PPP6R3, MOGAT2
CDruggable family + PDB, no drug7SETMAR, VRK1, NPL, TRIB1, SUMF1, DUSP3, PLXNA4
DDruggable family + AlphaFold only, no drug3LRRN1, COL7A1, FGFRL1
EDifficult family or no structure, no drug30SLC8A1, SOX9, SVIL, HAGHL, WNT16, STARD3NL, RSPO3, CCDC170, COL15A1, COBL (+20 more)

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
SOX93CTNNB1
WNT160CTNNB1
CCDC1700ESR1
LRP51SOST
MEOX10SOST
DUSP3101—
SETMAR1—
SLC8A19—
SVIL0—
VRK174—
HAGHL0—
NPL0—
TRIB11—
STARD3NL0—
SUMF10—
RSPO30—
LRRN10—
COL15A10—
COL7A10—
COBL0—
LUZP20—
PROSER20—
CPED10—
TMEM1350—
NSMCE21—
PROSER2-AS10—
DOK60—
MIMS10—
DKK15—
ETS20—

Clinical trials & evidence

Clinical trials

Clinical trials: 258.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified200
PHASE422
PHASE213
PHASE310
PHASE2/PHASE36
PHASE1/PHASE25
PHASE12

Top trials by phase / activity

NCTPhaseStatusTitle
NCT05292001PHASE4RECRUITINGSingle-dose Intravenous Iron Therapy for Anemia After Orthopaedic Trauma
NCT07221019PHASE4RECRUITINGSingle Shot Exparel vs Catheters in Lower Extremity Trauma
NCT00114556PHASE4COMPLETEDThe Effect of Zoledronic Acid on Bone Density in Liver Transplant Patients
NCT00254631PHASE4COMPLETEDPreemptive Analgesia With OxyContin Versus Placebo Before Surgery for Long Bone Fractures
NCT00490997PHASE4COMPLETEDKetamine/Propofol vs Ketamine Alone for Pediatric Fracture Reduction
NCT00560443PHASE4COMPLETEDRCT on Ketorolac and Tramadol in Bone Fractures Pain of Child
NCT00592917PHASE4COMPLETEDOSTPRE-Fracture Prevention Study
NCT00766532PHASE4COMPLETEDDo Aromatase Inhibitors (AIs) Decrease Intestinal Calcium Absorption?
NCT00869622PHASE4COMPLETEDAntiepileptic Drugs and Osteoporotic Prevention Trial
NCT00892606PHASE4COMPLETEDMethadone Versus Morphine for Orthopedic Surgery Patients
NCT00969839PHASE4UNKNOWNNovaLign Intramedullary Fixation System (IFS) for the Treatment of Humeral Fractures
NCT01173081PHASE4UNKNOWNThe Use of Teriparatide as an Adjunctive Therapy for the Treatment of Jones Fractures
NCT01544725PHASE4COMPLETEDKetamine-propofol Versus Ketamine Alone for Procedural Sedation in Adults
NCT01574833PHASE4COMPLETEDEarly Application of Pulsed Electromagnetic Field in the Treatment of Postoperative Delayed Union
NCT02013986PHASE4UNKNOWNEffects of Etomidate on Postoperative Circadian Rhythm Changes of Salivary Cortisol in Children
NCT02035774PHASE4COMPLETEDA Novel Selective Block of the Suprascapular Nerve
NCT02076321PHASE4COMPLETEDThe Effect of NSAID Use in the Acute Phase of Skeletally Immature Bone Healing: A Prospective Study
NCT02280291PHASE4COMPLETEDSingle Shot Versus OnQ Pump in Extremity Fractures
NCT02609074PHASE4COMPLETEDPilot Clinical Trial of CPC/rhBMP-2 Microffolds as Bone Substitute for Bone Regeneration
NCT02698228PHASE4WITHDRAWNRegional Anaesthesia for Painful Injuries After Disasters
NCT03845153PHASE4COMPLETEDMetformin Effect on Fracture Healing in Post-Menopausal Women
NCT06060236PHASE4UNKNOWNDexketoprofen and Ibuprofen in Long Bone Fractures
NCT04195256PHASE2/PHASE3RECRUITINGIntranasal Dexmedetomidine Plus Ketamine for Procedural Sedation
NCT05699174PHASE3RECRUITINGPO vs IV Antibiotics for the Treatment of Infected Nonunion of Fractures After Fixation
NCT00129142PHASE3COMPLETEDToremifene Citrate for Prevention of Bone Fractures in Men With Prostate Cancer on Androgen Deprivation Therapy
NCT00133640PHASE3UNKNOWNEarly Rehabilitation After Hip Fracture
NCT00387686PHASE2/PHASE3TERMINATEDA Phase 2/3 Multicenter, Controlled Trial Of rhBMP-2/CPM In Tibial Fractures
NCT00416039PHASE3COMPLETEDEfficacy of Sublingual Midazolam in Association With Oral Morphine in Children Analgesia After Bone Fracture
NCT00697463PHASE2/PHASE3COMPLETEDForteo for the Treatment of Unexplained Osteoporosis in Premenopausal Women
NCT00973167PHASE2/PHASE3COMPLETEDLow-magnitude High-frequency Vibration Study on Fracture Rate in Community Elderly
NCT01199653PHASE2/PHASE3COMPLETEDStudy Comparing Plate Stabilization to Conservative Treatment in Midshaft Clavicle Fractures
NCT01452243PHASE3UNKNOWNPrevention of Falls and Fractures in Old People by Administration of Calcium and Vitamin D. Randomized Clinical Trial
NCT01646437PHASE3COMPLETEDThe International Polycap Study 3 (TIPS-3)
NCT02062879PHASE3TERMINATEDKetamine Patient-Controlled Analgesia for Acute Pain
NCT02346786PHASE3UNKNOWNEpidemiology of Incidents and Accidents in Sport. Influence of Moisture.
NCT02402868PHASE3COMPLETEDIntranasal Versus Intravenous Ketamine for Procedural Sedation in Children
NCT02448849PHASE2/PHASE3UNKNOWNAutologous BM-MSC Transplantation in Combination With Platelet Lysate (PL) for Nonunion Treatment
NCT02828566PHASE3UNKNOWNIntranasal Ketamine for Procedural Sedation
NCT03024008PHASE1/PHASE2RECRUITINGEnhancement of Bone Regeneration and Healing in the Extremities by the Use of Autologous BonoFill-II
NCT06448923PHASE2RECRUITINGCannabidiol After Multi-Trauma for Pain and Opioid Therapy

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
DIBOTERMIN ALFA43
KETOROLAC43
TOREMIFENE43
ZOLEDRONIC ACID ANHYDROUS43
CHOLECALCIFEROL42
CALCITRIOL41
CALCIUM CARBONATE41
CODEINE41
DEXKETOPROFEN41
ERGOCALCIFEROL41
ETOMIDATE41
HYDROMORPHONE41
IBUPROFEN41
KETAMINE41
KETOPROFEN41
LITHIUM CARBONATE41
METHADONE41
MIDAZOLAM41
MORPHINE41
OXYCODONE HYDROCHLORIDE41
POTASSIUM BICARBONATE41
RISEDRONIC ACID41
TERIPARATIDE41
TRAMADOL41
COCOA31
LACTOSE, ANHYDROUS31
CHEMBL405972201
CHEMBL458922601
CHEMBL507282601
CHEMBL236971701

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 68

This page pulls from 68 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityfantom5_genefantom5_promotergenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromeshmimmondomondochildmondoparentncitorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureuniprot