Osteoarthritis, knee

disease

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Summary

Osteoarthritis, knee (MONDO:0005416) is a disease with 31 cohort genes (760 GWAS associations across 60 studies) and 987 clinical trials. Top therapeutic interventions include celecoxib, hyaluronic acid, and ketorolac.

At a glance

Cohort genes: 31
GWAS associations: 760
Clinical trials: 987

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	osteoarthritis, knee
Mondo ID	MONDO:0005416
EFO	EFO:0004616
MeSH	D020370
UMLS	C0409959
MedGen	98371
Is cancer (heuristic)	no

Data availability: 760 GWAS associations (60 studies).

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone inflammation disease › arthritic joint disease › osteoarthritis › osteoarthritis, knee

Genetics & variants

GWAS landscape

760 GWAS associations across 60 studies. Top hits map to 26 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs13021737	1e-169	LINC01875 - TMEM18	A
rs62106258	2e-92	LINC01865	T
rs13107325	2e-48	SLC39A8	T
rs224333	6e-42	GDF5	A	0.94
rs3814883	1e-40	TAOK2	T
rs9930333	8e-38	FTO	T	0.95
rs889398	2e-35	CYB5B - NFAT5	T
rs11075989	1e-34	FTO	T	1.05
rs11731421	2e-32	TACC3 - FGFR3	A	1.05
rs2521349	2e-30	MAP2K6	A	1.07
rs4606747	3e-30	SRR	T	0.95
rs1851610	4e-28	TGFA	T	1.04
rs6060401	5e-28	UQCC1 - GDF5-AS1	T	1.05
chr20:35431781	6e-28		C	0.08
rs3755384	9e-27	TGFA	A	1.07
rs12310519	1e-25	SOX5	T	1.06
rs12509303	3e-25	TACC3 - FGFR3	T	1.06
rs687339	7e-25	RPL31P23 - PCCB	T
rs1421085	9e-25	FTO	T	0.94
rs429358	1e-24	APOE	T	1.06
rs2302417	4e-24	ITIH1	A	1.06
rs143384	1e-23	GDF5	A	1.07
rs28685250	2e-23	ECM1P2 - U6	T	1.06
rs11724531	3e-23	TACC3 - FGFR3	A	0.93
rs10131337	9e-23	PAX9	T	0.95
rs775208	2e-22	AARS1	T
rs7217226	2e-22	SMG6	T
rs6060355	2e-22	FAM83C - UQCC1	A	0.94
rs3755380	3e-22	TGFA	C	1.04
rs12195339	2e-21	SUPT3H	T	0.94

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90566799	Hatzikotoulas K	2025	201,533	901,637	Translational genomics of osteoarthritis in 1,962,069 individuals.
GCST90566800	Hatzikotoulas K	2025	161,228	965,985	Translational genomics of osteoarthritis in 1,962,069 individuals.
GCST90297779	Hollis B	2023	90,888	263,673	Lifetime risk and genetic predisposition to post-traumatic OA of the knee in the UK Biobank.
GCST90034521	Boer CG	2021	88,842	397,208	Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations.
GCST90566804	Hatzikotoulas K	2025	76,604	771,801	Translational genomics of osteoarthritis in 1,962,069 individuals.
GCST90271770	Zhang L	2023	62,497	333,557	A sex- and site-specific relationship between body mass index and osteoarthritis: evidence from observational and genetic analyses.
GCST90034523	Boer CG	2021	61,588	330,161	Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations.
GCST90474022	UK Biobank Whole-Genome Sequencing Consortium	2025	44,190	414,250	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90034526	Boer CG	2021	40,887	327,689	Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations.
GCST90061025	Boer CG	2021	40,887	327,689	Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	2
Tier 2: splice/UTR	3
Tier 3: regulatory	5
Tier 4: intronic/intergenic	40

MAF distribution

Bucket	Variants
common (>=0.05)	48
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	2

Functional consequences

Consequence	Count
intron_variant	30
intergenic_variant	7
regulatory_region_variant	4
missense_variant	2
unknown	2
3_prime_UTR_variant	2
synonymous_variant	1
TF_binding_site_variant	1
5_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs9922708	16	53797234	C>T	0.05	intron_variant	FTO		Tier 4: intronic/intergenic
rs13021737	2	632348	A>C,G,T	0.05	intergenic_variant	LINC01875 - TMEM18	1e-169	Tier 4: intronic/intergenic
rs62106258	2	417167	T>C	0.05	intron_variant	LINC01865	2e-92	Tier 4: intronic/intergenic
rs13107325	4	102267552	C>A,T	0.05	missense_variant	SLC39A8	2e-48	Tier 1: coding
rs224333	20	35436182	A>G	0.383	intron_variant	GDF5	6e-42	Tier 4: intronic/intergenic
rs3814883	16	29983601	C>T	0.05	synonymous_variant	TAOK2	1e-40	Tier 4: intronic/intergenic
rs9930333	16	53766065	T>C,G	0.432	intron_variant	FTO	8e-38	Tier 4: intronic/intergenic
rs889398	16	69522812	C>T	0.05	regulatory_region_variant	CYB5B - NFAT5	2e-35	Tier 3: regulatory
rs11075989	16	53785965	C>A,G,T	0.406	intron_variant	FTO	1e-34	Tier 4: intronic/intergenic
rs11731421	4	1747433	G>A,C	0.366	regulatory_region_variant	TACC3 - FGFR3	2e-32	Tier 3: regulatory
rs2521349	17	69507360	G>A,T	0.387	intron_variant	MAP2K6	2e-30	Tier 4: intronic/intergenic
rs4606747	17	2306577	C>G,T	0.379	intron_variant	SRR	3e-30	Tier 4: intronic/intergenic
rs1851610	2	70472027	T>A,C,G	0.489	intron_variant	TGFA	4e-28	Tier 4: intronic/intergenic
rs6060401	20	35417411	C>A,G,T	0.386	intergenic_variant	UQCC1 - GDF5-AS1	5e-28	Tier 4: intronic/intergenic
chr20:35431781							6e-28	Tier 4: intronic/intergenic
rs3755384	2	70477379	A>C,G	0.479	intron_variant	TGFA	9e-27	Tier 4: intronic/intergenic
rs12310519	12	23822285	C>T	0.157	intron_variant	SOX5	1e-25	Tier 4: intronic/intergenic
rs12509303	4	1763447	T>C	0.154	regulatory_region_variant	TACC3 - FGFR3	3e-25	Tier 3: regulatory
rs687339	3	136213517	C>T	0.05	TF_binding_site_variant	RPL31P23 - PCCB	7e-25	Tier 3: regulatory
rs1421085	16	53767042	T>C	0.411	intron_variant	FTO	9e-25	Tier 4: intronic/intergenic
rs429358	19	44908684	T>C	0.156	missense_variant	APOE	1e-24	Tier 1: coding
rs2302417	3	52780240	T>A,G	0.489	intron_variant	ITIH1	4e-24	Tier 4: intronic/intergenic
rs143384	20	35437976	G>A,C,T	0.409	5_prime_UTR_variant	GDF5	1e-23	Tier 2: splice/UTR
rs28685250	4	13004948	T>C	0.381	intergenic_variant	ECM1P2 - U6	2e-23	Tier 4: intronic/intergenic
rs11724531	4	1751697	A>G	0.206	regulatory_region_variant	TACC3 - FGFR3	3e-23	Tier 3: regulatory
rs10131337	14	36675311	C>A,T	0.252	intron_variant	PAX9	9e-23	Tier 4: intronic/intergenic
rs775208	16	70282008	T>C	0.05	intron_variant	AARS1	2e-22	Tier 4: intronic/intergenic
rs7217226	17	2232771	T>G	0.05	intron_variant	SMG6	2e-22	Tier 4: intronic/intergenic
rs6060355	20	35302258	G>A	0.381	intergenic_variant	FAM83C - UQCC1	2e-22	Tier 4: intronic/intergenic
rs3755380	2	70491888	C>A,G,T	0.45	intron_variant	TGFA	3e-22	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 31 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 1

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

Gene	HGNC	Evidence routes
SMAD3	SMAD3	GWAS, Orphanet

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BTNL2	Orphanet:797	Sarcoidosis
GLT8D1	Orphanet:803	Amyotrophic lateral sclerosis
FRMD4A	Orphanet:466688	Severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome
GLIS3	Orphanet:79118	Neonatal diabetes-congenital hypothyroidism-congenital glaucoma-hepatic fibrosis-polycystic kidneys syndrome
CRBN	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability
GDF5	Orphanet:2098	Acromesomelic dysplasia, Grebe type
GDF5	Orphanet:2639	Fibular aplasia-complex brachydactyly syndrome
GDF5	Orphanet:3237	Multiple synostoses syndrome
GDF5	Orphanet:3250	Proximal symphalangism
GDF5	Orphanet:63442	Angel-shaped phalango-epiphyseal dysplasia
GDF5	Orphanet:93384	Brachydactyly type C
GDF5	Orphanet:93388	Brachydactyly type A1
GDF5	Orphanet:93396	Brachydactyly type A2
GDF5	Orphanet:968	Acromesomelic dysplasia, Hunter-Thompson type
HLA-DQB1	Orphanet:2073	Narcolepsy type 1
HLA-DQB1	Orphanet:477738	Pediatric multiple sclerosis
HLA-DQB1	Orphanet:703	Bullous pemphigoid
HLA-DQB1	Orphanet:83465	Narcolepsy type 2
HLA-DQB1	Orphanet:930	Idiopathic achalasia
LTBP1	Orphanet:90349	Autosomal recessive cutis laxa type 1
SMAD3	Orphanet:284984	Aneurysm-osteoarthritis syndrome
SMAD3	Orphanet:60030	Loeys-Dietz syndrome
SMAD3	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
PAX7	Orphanet:99756	Alveolar rhabdomyosarcoma
PLA2G4A	Orphanet:468635	Cryptogenic multifocal ulcerous stenosing enteritis
PLA2G4A	Orphanet:477787	Cytosolic phospholipase-A2 alpha deficiency associated bleeding disorder
PLEC	Orphanet:1114	Aplasia cutis congenita
PLEC	Orphanet:158684	Epidermolysis bullosa simplex with pyloric atresia
PLEC	Orphanet:254361	Plectin-related limb-girdle muscular dystrophy R17
PLEC	Orphanet:257	Epidermolysis bullosa simplex with muscular dystrophy
PLEC	Orphanet:79401	PLEC-related intermediate epidermolysis bullosa simplex without extracutaneous involvement

Cohort genes → proteins

31 cohort genes, 30 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	31

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BTNL2	HGNC:1142	ENSG00000204290	Q9UIR0	Butyrophilin-like protein 2	gwas
SUPT3H	HGNC:11466	ENSG00000196284	O75486	Transcription initiation protein SPT3 homolog	gwas
PARD3B	HGNC:14446	ENSG00000116117	Q8TEW8	Partitioning defective 3 homolog B	gwas
TAS1R2	HGNC:14905	ENSG00000179002	Q8TE23	Taste receptor type 1 member 2	gwas
EPPK1	HGNC:15577	ENSG00000261150	P58107	Epiplakin	gwas
NOD1	HGNC:16390	ENSG00000106100	Q9Y239	Nucleotide-binding oligomerization domain-containing protein 1	gwas
WWP2	HGNC:16804	ENSG00000198373	O00308	NEDD4-like E3 ubiquitin-protein ligase WWP2	gwas
ANKRD6	HGNC:17280	ENSG00000135299	Q9Y2G4	Ankyrin repeat domain-containing protein 6	gwas
LRRN1	HGNC:20980	ENSG00000175928	Q6UXK5	Leucine-rich repeat neuronal protein 1	gwas
SBNO1	HGNC:22973	ENSG00000139697	A3KN83	Protein strawberry notch homolog 1	gwas
CNKSR3	HGNC:23034	ENSG00000153721	Q6P9H4	Connector enhancer of kinase suppressor of ras 3	gwas
GLT8D1	HGNC:24870	ENSG00000016864	Q68CQ7	Glycosyltransferase 8 domain-containing protein 1	gwas
FRMD4A	HGNC:25491	ENSG00000151474	Q9P2Q2	FERM domain-containing protein 4A	gwas
DDX10	HGNC:2735	ENSG00000178105	Q13206	Probable ATP-dependent RNA helicase DDX10	gwas
GLIS3	HGNC:28510	ENSG00000107249	Q8NEA6	Zinc finger protein GLIS3	gwas
DYNC1I1	HGNC:2963	ENSG00000158560	O14576	Cytoplasmic dynein 1 intermediate chain 1	gwas
CRBN	HGNC:30185	ENSG00000113851	Q96SW2	Protein cereblon	gwas
GALNT18	HGNC:30488	ENSG00000110328	Q6P9A2	Polypeptide N-acetylgalactosaminyltransferase 18	gwas
ZBED5	HGNC:30803	ENSG00000236287	Q49AG3	Zinc finger BED domain-containing protein 5	gwas
C11orf87	HGNC:33788	ENSG00000185742	Q6NUJ2	Uncharacterized protein C11orf87	gwas
LSP1P3	HGNC:39718	ENSG00000162685		LSP1 pseudogene 3	gwas
GDF5	HGNC:4220	ENSG00000125965	P43026	Growth/differentiation factor 5	gwas
RNF32-DT	HGNC:48971	ENSG00000182648	Q8NI28	Putative transmembrane protein RNF32-DT	gwas
HLA-DQA2	HGNC:4943	ENSG00000237541	P01906	HLA class II histocompatibility antigen, DQ alpha 2 chain	gwas
HLA-DQB1	HGNC:4944	ENSG00000179344	P01920	HLA class II histocompatibility antigen, DQ beta 1 chain	gwas
LTBP1	HGNC:6714	ENSG00000049323	Q14766	Latent-transforming growth factor beta-binding protein 1	gwas
SMAD3	HGNC:6769	ENSG00000166949	P84022	SMAD family member 3	gwas
PAX7	HGNC:8621	ENSG00000009709	P23759	Paired box protein Pax-7	gwas
PLA2G4A	HGNC:9035	ENSG00000116711	P47712	Cytosolic phospholipase A2	gwas
PLEC	HGNC:9069	ENSG00000178209	Q15149	Plectin	gwas
PTGS2	HGNC:9605	ENSG00000073756	P35354	Prostaglandin G/H synthase 2	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BTNL2	Butyrophilin-like protein 2	Negative regulator of T-cell proliferation.
SUPT3H	Transcription initiation protein SPT3 homolog	Probable transcriptional activator.
PARD3B	Partitioning defective 3 homolog B	Putative adapter protein involved in asymmetrical cell division and cell polarization processes.
TAS1R2	Taste receptor type 1 member 2	Putative taste receptor.
EPPK1	Epiplakin	Cytoskeletal linker protein that connects to intermediate filaments and controls their reorganization in response to stress.
NOD1	Nucleotide-binding oligomerization domain-containing protein 1	Pattern recognition receptor (PRR) that detects bacterial peptidoglycan fragments and other danger signals and thus participates in both innate and adaptive immune responses.
WWP2	NEDD4-like E3 ubiquitin-protein ligase WWP2	E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates.
ANKRD6	Ankyrin repeat domain-containing protein 6	Recruits CKI-epsilon to the beta-catenin degradation complex that consists of AXN1 or AXN2 and GSK3-beta and allows efficient phosphorylation of beta-catenin, thereby inhibiting beta-catenin/Tcf signals.
SBNO1	Protein strawberry notch homolog 1	Plays a crucial role in the regulation of neural stem cells (NSCs) proliferation.
CNKSR3	Connector enhancer of kinase suppressor of ras 3	Involved in transepithelial sodium transport.
GLT8D1	Glycosyltransferase 8 domain-containing protein 1	In vitro, catalyzes the transfer of a galactose residue from UDP-galactose onto GalNAc and GlcNAc structures.
FRMD4A	FERM domain-containing protein 4A	Scaffolding protein that regulates epithelial cell polarity by connecting ARF6 activation with the PAR3 complex.
DDX10	Probable ATP-dependent RNA helicase DDX10	Putative ATP-dependent RNA helicase that plays various role in innate immunity or inflammation.
GLIS3	Zinc finger protein GLIS3	Acts both as a repressor and an activator of transcription.
DYNC1I1	Cytoplasmic dynein 1 intermediate chain 1	Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function.
CRBN	Protein cereblon	Substrate recognition component of a DCX (DDB1-CUL4-X-box) E3 protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as MEIS2, ILF2 or GLUL.
GALNT18	Polypeptide N-acetylgalactosaminyltransferase 18	Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine (GalNAc) residue from UDP-GalNAc to a serine or threonine residue on the protein receptor.
GDF5	Growth/differentiation factor 5	Growth factor involved in bone and cartilage formation.
HLA-DQA2	HLA class II histocompatibility antigen, DQ alpha 2 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
HLA-DQB1	HLA class II histocompatibility antigen, DQ beta 1 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
LTBP1	Latent-transforming growth factor beta-binding protein 1	Key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space.
SMAD3	SMAD family member 3	Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases.
PAX7	Paired box protein Pax-7	Transcription factor that is involved in the regulation of muscle stem cells proliferation, playing a role in myogenesis and muscle regeneration.
PLA2G4A	Cytosolic phospholipase A2	Has primarily calcium-dependent phospholipase and lysophospholipase activities, with a major role in membrane lipid remodeling and biosynthesis of lipid mediators of the inflammatory response.
PLEC	Plectin	Interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes.
PTGS2	Prostaglandin G/H synthase 2	Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory respon…

Protein-family classification

Druggable: 8 · Difficult: 9 · Unknown: 14 · Druggable fraction: 0.26

Family distribution

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

Family	Genes	Fold	FDR
Scaffold/PPI	6	3.4×	0.047
Antibody/Immunoglobulin	4	3.8×	0.062
Enzyme (other)	3	1.2×	0.891
Transcription factor	3	0.8×	0.891
GPCR	1	0.8×	0.891
Other/Unknown	14	0.8×	0.915

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BTNL2	Antibody/Immunoglobulin	yes		Ig_C1-set, Ig_sub, Ig-like_dom
SUPT3H	Other/Unknown	no		TFIID_TAF13, Histone-fold
PARD3B	Scaffold/PPI	no		PDZ, Par3/HAL_N, PDZ_sf
TAS1R2	GPCR	yes		GPCR_3_Ca_sens_rcpt-rel, GPCR_3, ANF_lig-bd_rcpt
EPPK1	Other/Unknown	no		Plectin_repeat, Plakin_repeat_sf, Plakin
NOD1	Other/Unknown	no		CARD, Leu-rich_rpt, NACHT_NTPase
WWP2	Scaffold/PPI	no	2.3.2.26	C2_dom, HECT_dom, WW_dom
ANKRD6	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf
LRRN1	Antibody/Immunoglobulin	yes		Cys-rich_flank_reg_C, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp
SBNO1	Other/Unknown	no		SNO, SBNO_Helicase_C_dom, P-loop_NTPase
CNKSR3	Scaffold/PPI	no		PDZ, SAM, CNK2/3_dom
GLT8D1	Other/Unknown	no		Glyco_trans_8, Nucleotide-diphossugar_trans, Glycosyltrans_8_dom-fam
FRMD4A	Other/Unknown	no		FERM_domain, PH-like_dom_sf, FERM/acyl-CoA-bd_prot_sf
DDX10	Other/Unknown	no		RNA-helicase_DEAD-box_CS, Helicase_C-like, DEAD/DEAH_box_helicase_dom
GLIS3	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, GLI-like
DYNC1I1	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, DYNC1I1/DYNC1I2
CRBN	Other/Unknown	no		Lon_prtase_N, Yippee/Mis18/Cereblon, PUA-like_sf
GALNT18	Enzyme (other)	yes	2.4.1.41	Ricin_B_lectin, Glyco_trans_2-like, Nucleotide-diphossugar_trans
ZBED5	Transcription factor	no		Znf_BED, RNaseH-like_sf
C11orf87	Other/Unknown	no		C11orf87
LSP1P3	Other/Unknown	no
GDF5	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGF-beta-like
RNF32-DT	Other/Unknown	no
HLA-DQA2	Antibody/Immunoglobulin	yes		MHC_II_a_N, Ig/MHC_CS, Ig_C1-set
HLA-DQB1	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
LTBP1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
SMAD3	Other/Unknown	no		SMAD_dom, MAD_homology1_Dwarfin-type, SMAD_FHA_dom_sf
PAX7	Transcription factor	no		HD, Paired_dom, OAR_dom
PLA2G4A	Enzyme (other)	yes	3.1.1.4	C2_dom, LysoPLipase_cat_dom, Acyl_Trfase/lysoPLipase
PLEC	Scaffold/PPI	no		Plectin_repeat, SH3_domain, Actinin_actin-bd_CS
PTGS2	Enzyme (other)	yes	1.14.99.1	EGF, Haem_peroxidase_sf, Haem_peroxidase_animal

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	1
moderate (6-20)	0
broad (>20)	30
unknown	0

Top tissues across cohort

Tissue	Cohort genes
sural nerve	7
ventricular zone	4
male germ line stem cell (sensu Vertebrata) in testis	4
cartilage tissue	4
ganglionic eminence	3
primordial germ cell in gonad	2
skin of hip	2
tendon of biceps brachii	2
tibia	2
blood vessel layer	2
right uterine tube	2
oocyte	2
calcaneal tendon	2
cortical plate	2
endothelial cell	2
Brodmann (1909) area 23	2
right lung	2
upper lobe of left lung	2
hindlimb stylopod muscle	2
seminal vesicle	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BTNL2	106		yes	sural nerve, ventricular zone, primordial germ cell in gonad
SUPT3H	206	ubiquitous	yes	primordial germ cell in gonad, sperm, male germ line stem cell (sensu Vertebrata) in testis
PARD3B	200	ubiquitous	marker	sural nerve, cardiac muscle of right atrium, ventricular zone
TAS1R2	5		yes	bone marrow cell, skin of leg, sural nerve
EPPK1	190	broad	marker	skin of hip, upper leg skin, gingival epithelium
NOD1	220	ubiquitous	marker	sural nerve, left ovary, right lobe of thyroid gland
WWP2	279	ubiquitous	marker	tibia, tendon of biceps brachii, ascending aorta
ANKRD6	272	ubiquitous	marker	blood vessel layer, right hemisphere of cerebellum, right uterine tube
LRRN1	209	broad	marker	ventricular zone, ganglionic eminence, dorsal root ganglion
SBNO1	275	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, postcentral gyrus, parietal lobe
CNKSR3	242	ubiquitous	marker	esophagus squamous epithelium, pigmented layer of retina, ileal mucosa
GLT8D1	296	ubiquitous	marker	pituitary gland, bronchial epithelial cell, adenohypophysis
FRMD4A	272	ubiquitous	marker	sural nerve, ganglionic eminence, oocyte
DDX10	261	ubiquitous	marker	sural nerve, male germ line stem cell (sensu Vertebrata) in testis, calcaneal tendon
GLIS3	213	ubiquitous	marker	buccal mucosa cell, epithelial cell of pancreas, pancreatic ductal cell
DYNC1I1	242	broad	marker	endothelial cell, pons, cortical plate
CRBN	288	ubiquitous	marker	calcaneal tendon, Brodmann (1909) area 23, skin of hip
GALNT18	222	ubiquitous	marker	right lung, upper lobe of left lung, upper lobe of lung
ZBED5	287	ubiquitous	marker	tibia, epithelium of nasopharynx, ganglionic eminence
C11orf87	93	broad	marker	endothelial cell, lateral nuclear group of thalamus, Brodmann (1909) area 23
LSP1P3	67	tissue_specific	yes	blood, colonic epithelium, ventricular zone
GDF5	116	broad	yes	parotid gland, pericardium, cartilage tissue
RNF32-DT	195	ubiquitous	marker	secondary oocyte, oocyte, cortical plate
HLA-DQA2	127	broad	marker	granulocyte, vermiform appendix, male germ line stem cell (sensu Vertebrata) in testis
HLA-DQB1	268	broad	marker	right lung, spleen, upper lobe of left lung
LTBP1	291	ubiquitous	marker	blood vessel layer, right coronary artery, descending thoracic aorta
SMAD3	288	ubiquitous	marker	tendon of biceps brachii, cartilage tissue, hindlimb stylopod muscle
PAX7	61	tissue_specific	marker	olfactory segment of nasal mucosa, nasal cavity epithelium, nasal cavity mucosa
PLA2G4A	248	ubiquitous	marker	seminal vesicle, cartilage tissue, right uterine tube
PLEC	283	ubiquitous	marker	sural nerve, hindlimb stylopod muscle, tibial nerve

Protein interactions among cohort

Intra-cohort edges: 6.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMAD3	6,440
PTGS2	5,663
WWP2	4,978
DDX10	4,282
PLEC	3,529
PAX7	2,847
PLA2G4A	2,535
CRBN	2,201
DYNC1I1	2,094
NOD1	2,067

Intra-cohort edges

A	B	Sources
BTNL2	HLA-DQA2	string_interaction
BTNL2	HLA-DQB1	intact
CRBN	LRRN1	string_interaction
GLT8D1	SUPT3H	string_interaction
PLA2G4A	PTGS2	string_interaction
SMAD3	WWP2	intact

Structural data

PDB: 13 · AlphaFold-only: 17 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CRBN	Q96SW2	90
TAS1R2	Q8TE23	25
GDF5	P43026	15
PLEC	Q15149	14
SMAD3	P84022	12
WWP2	O00308	11
HLA-DQB1	P01920	10
PTGS2	P35354	7
NOD1	Q9Y239	6
SUPT3H	O75486	4
PLA2G4A	P47712	3
DDX10	Q13206	1
LTBP1	Q14766	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HLA-DQA2	P01906	89.29
GALNT18	Q6P9A2	89.10
BTNL2	Q9UIR0	85.97
GLT8D1	Q68CQ7	85.35
LRRN1	Q6UXK5	82.05
ZBED5	Q49AG3	81.57
DYNC1I1	O14576	71.20
ANKRD6	Q9Y2G4	70.82
SBNO1	A3KN83	68.08
CNKSR3	Q6P9H4	64.67
PAX7	P23759	63.21
FRMD4A	Q9P2Q2	62.95
C11orf87	Q6NUJ2	58.55
PARD3B	Q8TEW8	55.56
GLIS3	Q8NEA6	49.95
RNF32-DT	Q8NI28	37.53
EPPK1	P58107

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 123. Enrichment computed across 31 evidence-associated genes (17 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 17 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
phospho-PLA2 pathway	1	335.9×	0.052	PLA2G4A
Biosynthesis of electrophilic ω-3 PUFA oxo-derivatives	1	335.9×	0.052	PTGS2
Loss of Function of SMAD4 in Cancer	1	223.9×	0.052	SMAD3
SMAD4 MH2 Domain Mutants in Cancer	1	223.9×	0.052	SMAD3
SMAD2/3 MH2 Domain Mutants in Cancer	1	223.9×	0.052	SMAD3
Biosynthesis of EPA-derived SPMs	1	167.9×	0.052	PTGS2
Biosynthesis of DPAn-3 SPMs	1	167.9×	0.052	PTGS2
Loss of Function of TGFBR1 in Cancer	1	134.3×	0.052	SMAD3
RUNX3 regulates BCL2L11 (BIM) transcription	1	134.3×	0.052	SMAD3
Acyl chain remodeling of CL	1	112.0×	0.052	PLA2G4A
Synthesis of 15-eicosatetraenoic acid derivatives	1	112.0×	0.052	PTGS2
Loss of Function of SMAD2/3 in Cancer	1	112.0×	0.052	SMAD3
Signaling by TGF-beta Receptor Complex in Cancer	1	112.0×	0.052	SMAD3
SMAD2/3 Phosphorylation Motif Mutants in Cancer	1	112.0×	0.052	SMAD3
TGFBR1 KD Mutants in Cancer	1	112.0×	0.052	SMAD3
Biosynthesis of DHA-derived SPMs	1	112.0×	0.052	PTGS2
TGF-beta receptor signaling activates SMADs	2	38.4×	0.052	LTBP1, SMAD3
Molecules associated with elastic fibres	2	36.3×	0.052	GDF5, LTBP1
COPI-independent Golgi-to-ER retrograde traffic	2	24.4×	0.052	DYNC1I1, PLA2G4A
Signaling by TGF-beta Receptor Complex	2	23.6×	0.052	LTBP1, SMAD3
Interferon gamma signaling	2	14.8×	0.052	HLA-DQA2, HLA-DQB1
Signaling by TGFB family members	2	13.6×	0.052	LTBP1, SMAD3
RUNX3 regulates CDKN1A transcription	1	96.0×	0.055	SMAD3
Hydrolysis of LPC	1	74.6×	0.068	PLA2G4A
MHC class II antigen presentation	2	10.5×	0.075	DYNC1I1, HLA-DQA2
Type I hemidesmosome assembly	1	61.1×	0.077	PLEC
Caspase-mediated cleavage of cytoskeletal proteins	1	56.0×	0.081	PLEC
Butyrophilin (BTN) family interactions	1	51.7×	0.081	BTNL2
Formation of axial mesoderm	1	48.0×	0.081	SMAD3
Signaling by Activin	1	44.8×	0.081	SMAD3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 26 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of wound healing	2	99.7×	0.016	EPPK1, SMAD3
cellular response to fluid shear stress	2	99.7×	0.016	PLEC, PTGS2
prostaglandin biosynthetic process	2	86.4×	0.016	PLA2G4A, PTGS2
peptide antigen assembly with MHC class II protein complex	2	81.0×	0.016	HLA-DQA2, HLA-DQB1
wound healing	3	26.3×	0.016	EPPK1, SMAD3, PLEC
positive regulation of chondrocyte differentiation	2	61.7×	0.020	GDF5, SMAD3
transcription by RNA polymerase II	4	10.8×	0.020	SUPT3H, WWP2, GLIS3, PAX7
skeletal muscle satellite cell commitment	1	648.1×	0.026	PAX7
protein-containing complex organization	1	648.1×	0.026	PLEC
negative regulation of lung blood pressure	1	648.1×	0.026	SMAD3
cellular response to non-ionic osmotic stress	1	648.1×	0.026	PTGS2
regulation of miRNA transcription	1	648.1×	0.026	SMAD3
regulation of epithelium regeneration	1	648.1×	0.026	EPPK1
actomyosin contractile ring assembly actin filament organization	1	648.1×	0.026	PLEC
antigen processing and presentation of exogenous peptide antigen via MHC class II	2	41.8×	0.026	HLA-DQA2, HLA-DQB1
positive regulation of immune response	2	37.0×	0.026	HLA-DQA2, HLA-DQB1
positive regulation of nitric oxide biosynthetic process	2	35.0×	0.026	SMAD3, PTGS2
positive regulation of T cell activation	2	34.1×	0.026	HLA-DQA2, HLA-DQB1
positive regulation of SMAD protein signal transduction	2	29.5×	0.033	GDF5, SMAD3
detection of chemical stimulus involved in sensory perception of sweet taste	1	324.1×	0.037	TAS1R2
skeletal myofibril assembly	1	324.1×	0.037	PLEC
positive regulation of transforming growth factor beta3 production	1	324.1×	0.037	SMAD3
phosphatidylglycerol catabolic process	1	324.1×	0.037	PLA2G4A
establishment of protein localization to extracellular region	1	324.1×	0.037	LTBP1
positive regulation of platelet-derived growth factor production	1	324.1×	0.037	PTGS2
leukocyte migration involved in immune response	1	216.1×	0.037	PLEC
extracellular transport	1	216.1×	0.037	WWP2
regulation of cell fate commitment	1	216.1×	0.037	PAX7
transport along microtubule	1	216.1×	0.037	DYNC1I1
negative regulation of monoatomic ion transmembrane transport	1	216.1×	0.037	CRBN

Therapeutics

Drugs indicated for this disease

0 approved, 42 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Acetaminophen	Phase 3 (in late-stage trials)
Aspartyl-Alanyl-Diketopiperazine	Phase 3 (in late-stage trials)
Bupivacaine	Phase 3 (in late-stage trials)
Cannabidiol	Phase 3 (in late-stage trials)
Capsaicin	Phase 3 (in late-stage trials)
Celecoxib	Phase 3 (in late-stage trials)
Chondroitin Sulfate Sodium	Phase 3 (in late-stage trials)
Crocin	Phase 3 (in late-stage trials)
Diacerein	Phase 3 (in late-stage trials)
Diclofenac	Phase 3 (in late-stage trials)
Diethylamine	Phase 3 (in late-stage trials)
Dronabinol	Phase 3 (in late-stage trials)
Duloxetine	Phase 3 (in late-stage trials)
Epinephrine	Phase 3 (in late-stage trials)
Ergocalciferol	Phase 3 (in late-stage trials)
Etoricoxib	Phase 3 (in late-stage trials)
Fasinumab	Phase 3 (in late-stage trials)
GW-406381	Phase 3 (in late-stage trials)
Glucosamine	Phase 3 (in late-stage trials)
HYLAN G-F 20	Phase 3 (in late-stage trials)
Histamine	Phase 3 (in late-stage trials)
Hyaluronic Acid	Phase 3 (in late-stage trials)
Hyaluronic Acid (Non-Animal Stabilized)	Phase 3 (in late-stage trials)
Hydromorphone	Phase 3 (in late-stage trials)
Ketoprofen	Phase 3 (in late-stage trials)
Lidocaine	Phase 3 (in late-stage trials)
Lorecivivint	Phase 3 (in late-stage trials)
Lumiracoxib	Phase 3 (in late-stage trials)
Naproxen	Phase 3 (in late-stage trials)
Oxycodone	Phase 3 (in late-stage trials)
Pentosan Polysulfate Sodium	Phase 3 (in late-stage trials)
Resveratrol	Phase 3 (in late-stage trials)
Rofecoxib	Phase 3 (in late-stage trials)
Ropivacaine	Phase 3 (in late-stage trials)
Sinomenine	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)
Tanezumab	Phase 3 (in late-stage trials)
Tapentadol	Phase 3 (in late-stage trials)
Tramadol	Phase 3 (in late-stage trials)
Triamcinolone Acetonide	Phase 3 (in late-stage trials)
Triamcinolone Hexacetonide	Phase 3 (in late-stage trials)
Zucapsaicin	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): ARRY-797, Adalimumab, Astaxanthin, Atorvastatin, Canakinumab, Cannabinol, Cebranopadol, Colchicine, Dextrose, Eptotermin Alfa, Galcanezumab, Gefapixant, Hydroxychloroquine, Ibuprofen Trelamine, Ketorolac, Lutikizumab, Mannitol, Meloxicam, Mepivacaine, Methylprednisolone, Microcrystalline Cellulose, Neridronic Acid, Olive Oil, Oxycodegol, Oxytocin, Piclidenoson, Piroxicam, Platelets, Polmacoxib, Prednisolone, Somatropin, Sorbitol, Teriparatide, Tranexamic Acid, Triamcinolone, Valdecoxib.

Drug target analysis

Approved (phase 4): 5 · Phase ≥3: 5 · Phased (≥1): 6 · Undrugged: 25

Druggability breadth: 8 of 31 evidence-associated genes (26%) 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.

Symbol	Example approved molecule
NOD1	GEFITINIB
CRBN	DASABUVIR
SMAD3	FLUORESCEIN
PLA2G4A	ZAFIRLUKAST
PTGS2	CELECOXIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PTGS2	192	4
CRBN	18	4
PLA2G4A	3	4
SMAD3	2	4
TAS1R2	1	1
NOD1	1	4
BTNL2	0	0
SUPT3H	0	0
PARD3B	0	0
EPPK1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GEFITINIB	4	NOD1
DASABUVIR	4	CRBN
POMALIDOMIDE	4	CRBN
THALIDOMIDE	4	CRBN
LENALIDOMIDE	4	CRBN
PONATINIB	4	CRBN
ASCIMINIB	4	CRBN
BRIGATINIB	4	CRBN
CRIZOTINIB	4	CRBN, PTGS2
FLUORESCEIN	4	SMAD3
ZAFIRLUKAST	4	PLA2G4A
CELECOXIB	4	PTGS2
ASPIRIN	4	PTGS2
INDOMETHACIN	4	PTGS2
ETODOLAC	4	PTGS2
BEPRIDIL	4	PTGS2
LEVODOPA	4	PTGS2
CANDESARTAN CILEXETIL	4	PTGS2
TOLMETIN	4	PTGS2
DICLOFENAC SODIUM	4	PTGS2
CLOTRIMAZOLE	4	PTGS2
SIMVASTATIN	4	PTGS2
OXAPROZIN	4	PTGS2
BROMFENAC	4	PTGS2
ACETOPHENAZINE	4	PTGS2
BIPERIDEN	4	PTGS2
RUCAPARIB	4	PTGS2
VILANTEROL	4	PTGS2
DESERPIDINE	4	PTGS2
OXYMETHOLONE	4	PTGS2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

Symbol	Assays	Type breakdown
CRBN	5,948	Binding:5779, Functional:154, ADMET:15
PTGS2	1,548	Binding:1478, Functional:35, ADMET:34, Toxicity:1
NOD1	111	Binding:100, Functional:11
PLA2G4A	95	Binding:91, Functional:4
TAS1R2	30	Functional:15, Binding:15
SMAD3	24	Binding:18, Functional:6
PLEC	12	Binding:12
DDX10	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
WWP2	2.3.2.26	HECT-type E3 ubiquitin transferase
GALNT18	2.4.1.41	polypeptide N-acetylgalactosaminyltransferase
PLA2G4A	3.1.1.4	phospholipase A2
PTGS2	1.14.99.1	prostaglandin-endoperoxide synthase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
NOD1	111
CRBN	5,948
PTGS2	1,548

Pharmacogenomics

Cohort genes with a PharmGKB record: 29; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

28 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.

Compound	Max phase	Cohort target (bioactivity)
GEFITINIB	4	NOD1
DASABUVIR	4	CRBN
POMALIDOMIDE	4	CRBN
THALIDOMIDE	4	CRBN
LENALIDOMIDE	4	CRBN
PONATINIB	4	CRBN
ASCIMINIB	4	CRBN
BRIGATINIB	4	CRBN
CRIZOTINIB	4	CRBN, PTGS2
FLUORESCEIN	4	SMAD3
ZAFIRLUKAST	4	PLA2G4A
ASPIRIN	4	PTGS2
INDOMETHACIN	4	PTGS2
ETODOLAC	4	PTGS2
BEPRIDIL	4	PTGS2
LEVODOPA	4	PTGS2
CANDESARTAN CILEXETIL	4	PTGS2
TOLMETIN	4	PTGS2
CLOTRIMAZOLE	4	PTGS2
SIMVASTATIN	4	PTGS2
OXAPROZIN	4	PTGS2
BROMFENAC	4	PTGS2
ACETOPHENAZINE	4	PTGS2
BIPERIDEN	4	PTGS2
RUCAPARIB	4	PTGS2
VILANTEROL	4	PTGS2
DESERPIDINE	4	PTGS2
OXYMETHOLONE	4	PTGS2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	5	NOD1, CRBN, SMAD3, PLA2G4A, PTGS2
B	Phased (≥1) drug, not yet approved	1	TAS1R2
C	Druggable family + PDB, no drug	1	HLA-DQB1
D	Druggable family + AlphaFold only, no drug	4	BTNL2, LRRN1, GALNT18, HLA-DQA2
E	Difficult family or no structure, no drug	20	SUPT3H, PARD3B, EPPK1, WWP2, ANKRD6, SBNO1, CNKSR3, GLT8D1, FRMD4A, DDX10 (+10 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
LRRN1	0	CRBN
BTNL2	0	—
SUPT3H	0	—
PARD3B	0	—
EPPK1	0	—
WWP2	0	—
ANKRD6	0	—
SBNO1	0	—
CNKSR3	0	—
GLT8D1	0	—
FRMD4A	0	—
DDX10	1	—
GLIS3	0	—
DYNC1I1	0	—
GALNT18	0	—
ZBED5	0	—
C11orf87	0	—
LSP1P3	0	—
GDF5	0	—
RNF32-DT	0	—
HLA-DQA2	0	—
HLA-DQB1	0	—
LTBP1	0	—
PAX7	0	—
PLEC	12	—

Clinical trials & evidence

Clinical trials

Clinical trials: 987.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	638
PHASE2	98
PHASE4	84
PHASE3	72
PHASE1	42
PHASE1/PHASE2	27
PHASE2/PHASE3	16
EARLY_PHASE1	10

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04082533	PHASE4	ACTIVE_NOT_RECRUITING	Intravenous (IV) Hydrocortisone for TKA (Total Knee Arthroplasty)
NCT04111718	PHASE4	ACTIVE_NOT_RECRUITING	The Impact of Procedural Awareness of Knee Injections for Osteoarthritis on Patient Perceptions of Effectiveness
NCT04641351	PHASE4	ACTIVE_NOT_RECRUITING	Corticosteroid Meniscectomy Randomized Trial
NCT05336968	PHASE4	RECRUITING	Triamcinolone Ketorolac (TriKe) Knee Trial
NCT05430230	PHASE4	ACTIVE_NOT_RECRUITING	Study of Nonsteroidal Anti-inflammatory Drugs in People With Painful Knee Osteoarthritis
NCT05761015	PHASE4	RECRUITING	Helping Osteoarthritis Patients to Walk With NSAID
NCT06083480	PHASE4	RECRUITING	Reducing Perioperative Oxidative Stress to Prevent Postoperative Chronic Pain Following Total Knee Arthroplasty
NCT06191848	PHASE4	RECRUITING	Subcutaneous Tirzepatide Once-weekly in Patients With Obesity and Knee Osteoarthritis (STOP KNEE-OA)
NCT06478186	PHASE4	RECRUITING	Knee Osteoarthritis Treatment With Zilretta vs. Kenalog in the Context of Type II Diabetes
NCT06557018	PHASE4	RECRUITING	Efficacy and Safety of Liposomal Bupivacaine Using Periarticular Injection in Total Knee Arthroplasty
NCT07203547	PHASE4	NOT_YET_RECRUITING	Phase 4 Study of Laybon Tab. in Knee Osteoarthritis
NCT00139776	PHASE4	COMPLETED	Study Of Continuous Use Of Celecoxib Vs. Usual or Intermittent Use
NCT00144820	PHASE4	UNKNOWN	Hyaluronan Versus NaCl 20 Ml Versus Placebo in Knee Osteoarthritis
NCT00208286	PHASE4	TERMINATED	P.F.C. Sigma Fixed Versus P.F.C. RP Mobile Bearing Total Knee Systems
NCT00208325	PHASE4	TERMINATED	PFC Sigma Fixed and Mobile Knee Study
NCT00294528	PHASE4	UNKNOWN	Comparing Clinical Outcome of 2 Different Total Knee Prostheses: Nexgen LPS-Flex Versus AGC
NCT00319280	PHASE4	COMPLETED	Proximal Tibial Open Wedge Osteotomy. A Clinical Prospective, Randomized RSA-trial.
NCT00375856	PHASE4	COMPLETED	Computer-Assisted Total Knee Replacement Kinematics: DePuy Sigma Posterior Cruciate Substituting Knee and the DePuy Sigma RP Rotating Platform Knee
NCT00426907	PHASE4	COMPLETED	Weightbearing After High Tibial Osteotomy
NCT00513422	PHASE4	UNKNOWN	The Long-term Evaluation of Glucosamine Sulphate Study
NCT00556608	PHASE4	COMPLETED	Efficacy Study of Intra-articular Hyaluronic Acid in the Knee Osteoarthritis
NCT00620867	PHASE4	COMPLETED	Efficacy and Safety of Celecoxib Versus Ibuprofen in the Treatment of Osteoarthritis of the Knee (United States)
NCT00630929	PHASE4	COMPLETED	Efficacy and Safety of Celecoxib Versus Ibuprofen in the Treatment of Osteoarthritis of the Knee (Europe)
NCT00638807	PHASE4	COMPLETED	Safety and Efficacy of Celecoxib Versus Placebo in the Treatment of Knee Osteoarthritis in Patients Who Were Unresponsive to Naproxen and Ibuprofen
NCT00640627	PHASE4	COMPLETED	Efficacy and Safety of Celecoxib Versus Placebo in the Treatment of Patients With Osteoarthritis of the Knee Who Were Unresponsive to Naproxen and Ibuprofen
NCT00643799	PHASE4	COMPLETED	Safety and Efficacy of Celecoxib Versus Naproxen in the 6-month Treatment of Knee Osteoarthritis
NCT00778076	PHASE4	UNKNOWN	The Impact of Hyaluronic Acid Injections on Osteoarthritic Knee Mechanics
NCT00894361	PHASE4	TERMINATED	Comparison of Mobile-Bearing and Fixed-Bearing All-Polyethylene Tibia Total Knee Designs
NCT00901628	PHASE4	COMPLETED	Periarticular Multimodal Drug Injections in Total Knee Arthroplasty
NCT00954954	PHASE4	COMPLETED	Outcomes After Standard and High-Flexion Posterior Stabilized Rotating-Platform Mobile-Bearing Total Knee Arthroplasty
NCT01102491	PHASE4	COMPLETED	Additional Anti-emetic Effect of Ramosetron Prophylaxis After Total Knee Arthroplasty
NCT01105936	PHASE4	COMPLETED	Assess the Blood-Oxygen-Level-Dependent (BOLD) Signal Changes in the Brain by Paracetamol as Measured by Functional Magnetic Resonance Imaging (fMRI) in Subjects With Osteoarthritis (OA)
NCT01120015	PHASE4	COMPLETED	Diacerein as Adjuvant to Diclofenac Sodium in Indian Patients of Osteoarthritis (OA) Knee
NCT01183624	PHASE4	COMPLETED	A Controlled Study of an Herbal Topical Patch in Treating Osteoarthritis (OA) of the Knee
NCT01475604	PHASE4	TERMINATED	Impact of Noninvasive Targeted Pulsed Electromagnetic Field (tPEMF) on Opioid Use, Pain, and Joint Function Following Total Knee Arthroplasty
NCT01538043	PHASE4	COMPLETED	Spa Therapy in Knee Osteoarthritis: Study on Cost/Effectiveness - Cost/Utility and Possible Mechanisms of Action
NCT01557868	PHASE4	COMPLETED	Prediction of Response to Intra-articular Injections of Hyaluronic Acid for Knee Osteoarthritis
NCT01612702	PHASE4	COMPLETED	Efficacy and Safety of Single, Low-dose Dexamethasone in Patients After Total Knee Arthroplasty
NCT01670578	PHASE4	COMPLETED	Platelet-rich Plasma vs Viscosupplementation in the Treatment of Knee Articular Degenerative Pathology
NCT01742897	PHASE4	COMPLETED	Efficacy and Safety Study of Transdermal Therapeutic System (TTS) Fentanyl in Participants With Osteoarthritis Knee Pain

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CELECOXIB	4	15
HYALURONIC ACID	4	14
KETOROLAC	4	9
GLUCOSAMINE	4	5
TRANEXAMIC ACID	4	5
NAPROXEN	4	4
RIVAROXABAN	4	4
EPINEPHRINE	4	3
TAPENTADOL	4	3
CAPSAICIN	4	2
CEFUROXIME	4	2
CLONIDINE	4	2
IBUPROFEN	4	2
KETOPROFEN	4	2
TRIAMCINOLONE	4	2
TRIAMCINOLONE ACETONIDE	4	2
ACETAMINOPHEN	4	1
ADALIMUMAB	4	1
ALFACALCIDOL	4	1
BETAMETHASONE	4	1
CHLORZOXAZONE	4	1
CORTISONE ACETATE	4	1
DENOSUMAB	4	1
DEXAMETHASONE	4	1
DEXTROSE	4	1
DICLOFENAC SODIUM	4	1
DRONABINOL	4	1
DULOXETINE	4	1
ENOXAPARIN SODIUM	4	1
FERRIC CARBOXYMALTOSE	4	1

Cohort genes: BTNL2, SUPT3H, PARD3B, TAS1R2, EPPK1, NOD1, WWP2, ANKRD6, LRRN1, SBNO1, CNKSR3, GLT8D1, FRMD4A, DDX10, GLIS3, DYNC1I1, CRBN, GALNT18, ZBED5, C11orf87, GDF5, RNF32-DT, HLA-DQA2, HLA-DQB1, LTBP1, SMAD3, PAX7, PLA2G4A, PLEC, PTGS2
Drugs: Celecoxib, Hyaluronic Acid, Ketorolac, Glucosamine, Tranexamic Acid, Naproxen, Rivaroxaban, Epinephrine, Tapentadol, Capsaicin, Cefuroxime, Clonidine, Ibuprofen, Ketoprofen, Triamcinolone, Triamcinolone Acetonide, Acetaminophen, Adalimumab, Alfacalcidol, Betamethasone, Chlorzoxazone, Cortisone Acetate, Denosumab, Dexamethasone, Dextrose, Diclofenac, Dronabinol, Duloxetine, Enoxaparin, Ferric Carboxymaltose