Osteoarthritis

Summary

Osteoarthritis (MONDO:0005178) is a disease (an umbrella term covering 5 Mondo subtypes) with 31 cohort genes (822 GWAS associations across 168 studies) and 1,574 clinical trials. The dominant Reactome pathway is MAPK family signaling cascades (3 cohort genes). Top therapeutic interventions include celecoxib, hyaluronic acid, and diclofenac.

At a glance

• Umbrella term: 5 Mondo subtypes
• Cohort genes: 31
• GWAS associations: 822
• ClinVar variants: 4
• Clinical trials: 1,574

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	osteoarthritis
Mondo ID	MONDO:0005178
MeSH	D010003
DOID	DOID:8398
ICD-10-CM	M15-M19, M19
ICD-11	558562409
NCIT	C3293
SNOMED CT	396275006
UMLS	C0029408
MedGen	45244
Is cancer (heuristic)	no

Also known as: degenerative joint disease

Data availability: 4 ClinVar variants · 822 GWAS associations (168 studies) · 1 HPO phenotype · 10 cell lines.

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 inflammation disease › arthritic joint disease › osteoarthritis

Related subtypes (12): chondrocalcinosis, transient arthritis, synovitis, periarthritis, rheumatoid arthritis, juvenile idiopathic arthritis, reactive arthritis, adult-onset Still disease, polyarticular arthritis, infective arthritis, negative rheumatoid factor polyarthritis, hemophilic arthropathy

Subtypes (5): osteoarthritis, knee, osteoarthritis, hip, osteoarthritis, spine, osteoarthritis, toe, osteoarthritis, hand

Genetics & variants

GWAS landscape

822 GWAS associations across 168 studies. Top hits map to 31 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs62106258	3e-98	LINC01865	T
rs6743060	1e-94	LINC01875 - TMEM18	A
rs2681781	7e-52	CAMKV	A
rs13107325	2e-51	SLC39A8	T
rs34811474	3e-39	ANAPC4	A
rs3755380	1e-37	TGFA	C	1.04
rs71325101	1e-34	FYCO1	C	0.03
rs12446632	6e-33	GPRC5B - GPR139	A
rs34460587	5e-31	XCR1 - CCR3	T	0.02
rs10843013	3e-30	RN7SKP15 - PTHLH	A	0.86
rs12209223	2e-29	FILIP1	A	1.22
rs4240673	5e-29	XKR6	T
rs6855246	5e-29	BANK1 - SLC39A8	A	0.09
rs12509303	4e-28	TACC3 - FGFR3	T	1.05
rs6446187	1e-27	CAMKV	A
rs3910146	2e-27	ECM1P2 - U6	T	0.96
rs11731421	5e-27	TACC3 - FGFR3	A	1.03
rs35225200	1e-26	BANK1 - SLC39A8	A	0.1
rs13079478	1e-25	FYCO1	T	0.03
rs981819	6e-25	UQCC1	T	0.97
rs9930333	2e-24	FTO	T	0.97
rs429358	2e-22	APOE	T	1.04
rs71327024	1e-21	XCR1 - CCR3	T	0.03
rs28579874	2e-21	SLC25A13	A	0.97
chr12:123732769	3e-21		A	0.96
rs10416125	6e-21	SLC44A2 - ILF3-DT	A	0.97
rs11719514	1e-20	PBRM1	T	0.97
rs2109069	6e-20	DPP9	A	0.02
rs4252548	2e-19	IL11	T	1.39
rs1321917	1e-18	ASTN2, ASTN2-AS1	C	1.1

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90034520	Boer CG	2021	175,803	644,862	Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations.
GCST007093	Tachmazidou I	2019	77,052	378,169	Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK Biobank data.
GCST90038686	Donertas HM	2021	39,515	445,083	Common genetic associations between age-related diseases.
GCST90077875	Backman JD	2021	39,005	292,749	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90081861	Backman JD	2021	39,005	292,749	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90077876	Backman JD	2021	33,708	295,344	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90081862	Backman JD	2021	33,708	295,344	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90080427	Backman JD	2021	29,459	339,413	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST010771	Bi W	2020	29,071	253,800	A Fast and Accurate Method for Genome-Wide Time-to-Event Data Analysis and Its Application to UK Biobank.
GCST90080426	Backman JD	2021	23,959	354,957	Exome sequencing and analysis of 454,787 UK Biobank participants.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	6
Tier 2: splice/UTR	0
Tier 3: regulatory	3
Tier 4: intronic/intergenic	41

MAF distribution

Bucket	Variants
common (>=0.05)	45
low_freq (0.01-0.05)	3
rare (<0.01)	0
unknown	2

Functional consequences

Consequence	Count
intron_variant	28
intergenic_variant	8
missense_variant	5
regulatory_region_variant	3
unknown	3
synonymous_variant	1
non_coding_transcript_exon_variant	1
frameshift_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs55872725	16	53775211	C>G,T	0.05	intron_variant	FTO		Tier 4: intronic/intergenic
rs62106258	2	417167	T>C	0.05	intron_variant	LINC01865	3e-98	Tier 4: intronic/intergenic
rs6743060	2	629510	C>A	0.05	intergenic_variant	LINC01875 - TMEM18	1e-94	Tier 4: intronic/intergenic
rs2681781	3	49860840	A>G	0.05	synonymous_variant	CAMKV	7e-52	Tier 4: intronic/intergenic
rs13107325	4	102267552	C>A,T	0.05	missense_variant	SLC39A8	2e-51	Tier 1: coding
rs34811474	4	25407216	G>A,C,T	0.05	missense_variant	ANAPC4	3e-39	Tier 1: coding
rs3755380	2	70491888	C>A,G,T	0.453	intron_variant	TGFA	1e-37	Tier 4: intronic/intergenic
rs71325101	3	45974077	T>C	0.05	intron_variant	FYCO1	1e-34	Tier 4: intronic/intergenic
rs12446632	16	19924067	G>A	0.05	intron_variant	GPRC5B - GPR139	6e-33	Tier 4: intronic/intergenic
rs34460587	3	46100972	C>T	0.05	non_coding_transcript_exon_variant	XCR1 - CCR3	5e-31	Tier 4: intronic/intergenic
rs10843013	12	27872263	A>C,T	0.216	intron_variant	RN7SKP15 - PTHLH	3e-30	Tier 4: intronic/intergenic
rs12209223	6	75454873	C>A	0.111	intron_variant	FILIP1	2e-29	Tier 4: intronic/intergenic
rs4240673	8	10930102	T>C,G	0.05	intron_variant	XKR6	5e-29	Tier 4: intronic/intergenic
rs6855246	4	102191313	A>C,G	0.097	intergenic_variant	BANK1 - SLC39A8	5e-29	Tier 4: intronic/intergenic
rs12509303	4	1763447	T>C	0.156	regulatory_region_variant	TACC3 - FGFR3	4e-28	Tier 3: regulatory
rs6446187	3	49869678	C>A	0.05	intron_variant	CAMKV	1e-27	Tier 4: intronic/intergenic
rs3910146	4	13041970	G>A,T	0.373	intergenic_variant	ECM1P2 - U6	2e-27	Tier 4: intronic/intergenic
rs11731421	4	1747433	G>A,C	0.357	regulatory_region_variant	TACC3 - FGFR3	5e-27	Tier 3: regulatory
rs35225200	4	102225731	A>C	0.086	intron_variant	BANK1 - SLC39A8	1e-26	Tier 4: intronic/intergenic
rs13079478	3	45966331	G>T	0.05	missense_variant	FYCO1	1e-25	Tier 1: coding
rs981819	20	35336309	C>T	0.398	intron_variant	UQCC1	6e-25	Tier 4: intronic/intergenic
rs9930333	16	53766065	T>C,G	0.429	intron_variant	FTO	2e-24	Tier 4: intronic/intergenic
rs429358	19	44908684	T>C	0.158	missense_variant	APOE	2e-22	Tier 1: coding
rs71327024	3	46098581	G>T	0.05	intron_variant	XCR1 - CCR3	1e-21	Tier 4: intronic/intergenic
rs28579874	7	96207766	A>C,G,T	0.382	intron_variant	SLC25A13	2e-21	Tier 4: intronic/intergenic
chr12:123732769				0.203			3e-21	Tier 4: intronic/intergenic
rs10416125	19	10649331	G>A,C,T	0.36	intergenic_variant	SLC44A2 - ILF3-DT	6e-21	Tier 4: intronic/intergenic
rs11719514	3	52638515	T>A,C	0.396	intron_variant	PBRM1	1e-20	Tier 4: intronic/intergenic
rs2109069	19	4719431	G>A	0.05	intron_variant	DPP9	6e-20	Tier 4: intronic/intergenic
rs4252548	19	55368304	C>T	0.024	missense_variant	IL11	2e-19	Tier 1: coding

ClinVar germline variants

4 retrieved; paginated sample, class counts are floors:

2 association, 1 conflicting classifications of pathogenicity, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1679885	NM_001844.5(COL2A1):c.3397C>T (p.Arg1133Cys)	COL2A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
522886	NM_001463.4(FRZB):c.282del (p.Ile95fs)	FRZB	Uncertain significance	criteria provided, single submitter
590975	NC_000023.11:g.12906527G>C	TLR8	association	no assertion criteria provided
590976	NC_000023.11:g.12906538T>A	TLR8	association	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 42 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TGFA	Orphanet:99798	Oligodontia
CAMK2B	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
COG5	Orphanet:263487	COG5-CDG
TLR8	Orphanet:675628	TLR8-related inflammation-severe neutropenia-bone marrow failure-lymphoproliferation syndrome
RP1L1	Orphanet:247834	Occult macular dystrophy
RP1L1	Orphanet:791	Retinitis pigmentosa
COL2A1	Orphanet:137678	Spondyloepiphyseal dysplasia with metatarsal shortening
COL2A1	Orphanet:166100	Autosomal dominant otospondylomegaepiphyseal dysplasia
COL2A1	Orphanet:1856	Spondyloperipheral dysplasia-short ulna syndrome
COL2A1	Orphanet:209867	Autosomal dominant rhegmatogenous retinal detachment
COL2A1	Orphanet:2380	Legg-Calvé-Perthes disease
COL2A1	Orphanet:459051	Spondyloepiphyseal dysplasia, Stanescu type
COL2A1	Orphanet:485	Kniest dysplasia
COL2A1	Orphanet:85166	Platyspondylic dysplasia, Torrance type
COL2A1	Orphanet:85198	Dysspondyloenchondromatosis
COL2A1	Orphanet:86820	Familial avascular necrosis of femoral head
COL2A1	Orphanet:90653	Stickler syndrome type 1
COL2A1	Orphanet:93279	Mild spondyloepiphyseal dysplasia due to COL2A1 mutation with early-onset osteoarthritis
COL2A1	Orphanet:93296	Achondrogenesis type 2
COL2A1	Orphanet:93297	Hypochondrogenesis
COL2A1	Orphanet:93315	Spondylometaphyseal dysplasia, ‘corner fracture’ type
COL2A1	Orphanet:93316	Spondylometaphyseal dysplasia, Schmidt type
COL2A1	Orphanet:93346	Spondyloepimetaphyseal dysplasia congenita, Strudwick type
COL2A1	Orphanet:94068	Spondyloepiphyseal dysplasia congenita
COMP	Orphanet:750	Pseudoachondroplasia
COMP	Orphanet:93308	Multiple epiphyseal dysplasia type 1
KANSL1	Orphanet:363958	17q21.31 microdeletion syndrome
KANSL1	Orphanet:363965	Koolen-De Vries syndrome due to a point mutation
FTO	Orphanet:210144	Lethal polymalformative syndrome, Boissel type
GLT8D1	Orphanet:803	Amyotrophic lateral sclerosis
SLC30A10	Orphanet:309854	Cirrhosis-dystonia-polycythemia-hypermanganesemia syndrome
DNAH10	Orphanet:137893	Male infertility due to large-headed multiflagellar polyploid spermatozoa
DNAH10	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
IFRD1	Orphanet:98771	Spinocerebellar ataxia type 18
MAPT	Orphanet:100069	Semantic dementia
MAPT	Orphanet:100070	Progressive non-fluent aphasia
MAPT	Orphanet:240071	Classic progressive supranuclear palsy syndrome
MAPT	Orphanet:240085	Progressive supranuclear palsy-predominant parkinsonism syndrome
MAPT	Orphanet:240094	Progressive supranuclear palsy-pure akinesia with gait freezing syndrome
MAPT	Orphanet:240103	Progressive supranuclear palsy-corticobasal syndrome
MAPT	Orphanet:240112	Progressive supranuclear palsy-progressive non-fluent aphasia syndrome
MAPT	Orphanet:275864	Behavioral variant of frontotemporal dementia

Cohort genes → proteins

31 cohort genes, 28 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	28
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SUPT3H	HGNC:11466	ENSG00000196284	O75486	Transcription initiation protein SPT3 homolog	gwas
TGFA	HGNC:11765	ENSG00000163235	P01135	Protransforming growth factor alpha	gwas
MCF2L	HGNC:14576	ENSG00000126217	O15068	Guanine nucleotide exchange factor DBS	gwas
CAMK2B	HGNC:1461	ENSG00000058404	Q13554	Calcium/calmodulin-dependent protein kinase type II subunit beta	gwas
COG5	HGNC:14857	ENSG00000164597	Q9UP83	Conserved oligomeric Golgi complex subunit 5	gwas
ALDH1A2	HGNC:15472	ENSG00000128918	O94788	Retinal dehydrogenase 2	gwas
TLR8	HGNC:15632	ENSG00000101916	Q9NR97	Toll-like receptor 8	clinvar
RP1L1	HGNC:15946	ENSG00000183638	Q8IWN7	Retinitis pigmentosa 1-like 1 protein	gwas
CDC5L	HGNC:1743	ENSG00000096401	Q99459	Cell division cycle 5-like protein	gwas
LYPLAL1	HGNC:20440	ENSG00000143353	Q5VWZ2	Lysophospholipase-like protein 1	gwas
DUS4L	HGNC:21517	ENSG00000105865	O95620	tRNA-dihydrouridine(20a/20b) synthase [NAD(P)+]-like	gwas
COL2A1	HGNC:2200	ENSG00000139219	P02458	Collagen alpha-1(II) chain	clinvar
COMP	HGNC:2227	ENSG00000105664	P49747	Cartilage oligomeric matrix protein	gwas
NACA2	HGNC:23290	ENSG00000253506	Q9H009	Nascent polypeptide-associated complex subunit alpha-2	gwas
KANSL1	HGNC:24565	ENSG00000120071	Q7Z3B3	KAT8 regulatory NSL complex subunit 1	gwas
FTO	HGNC:24678	ENSG00000140718	Q9C0B1	Alpha-ketoglutarate-dependent dioxygenase FTO	gwas
GLT8D1	HGNC:24870	ENSG00000016864	Q68CQ7	Glycosyltransferase 8 domain-containing protein 1	gwas
DOT1L	HGNC:24948	ENSG00000104885	Q8TEK3	Histone-lysine N-methyltransferase, H3 lysine-79 specific	gwas
CHADL	HGNC:25165	ENSG00000100399	Q6NUI6	Chondroadherin-like protein	gwas
SLC30A10	HGNC:25355	ENSG00000196660	Q6XR72	Calcium/manganese antiporter SLC30A10	gwas
LRRC37A4P	HGNC:25479	ENSG00000214425		leucine rich repeat containing 37 member A4, pseudogene	gwas
RFLNA	HGNC:27051	ENSG00000178882	Q6ZTI6	Refilin-A	gwas
LRRC37A	HGNC:29069	ENSG00000176681	A6NMS7	Leucine-rich repeat-containing protein 37A	gwas
DNAH10	HGNC:2941	ENSG00000197653	Q8IVF4	Dynein axonemal heavy chain 10	gwas
GNL3	HGNC:29931	ENSG00000163938	Q9BVP2	Guanine nucleotide-binding protein-like 3	gwas
MIR4286	HGNC:38186	ENSG00000263762		microRNA 4286	gwas
FRZB	HGNC:3959	ENSG00000162998	Q92765	Secreted frizzled-related protein 3	clinvar
MAPK8IP1P2	HGNC:52402	ENSG00000263503		mitogen-activated protein kinase 8 interacting protein 1 pseudogene 2	gwas
IFRD1	HGNC:5456	ENSG00000006652	O00458	Interferon-related developmental regulator 1	gwas
MAPT	HGNC:6893	ENSG00000186868	P10636	Microtubule-associated protein tau	gwas
NCOA3	HGNC:7670	ENSG00000124151	Q9Y6Q9	Nuclear receptor coactivator 3	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SUPT3H	Transcription initiation protein SPT3 homolog	Probable transcriptional activator.
TGFA	Protransforming growth factor alpha	TGF alpha is a mitogenic polypeptide that is able to bind to the EGF receptor/EGFR and to act synergistically with TGF beta to promote anchorage-independent cell proliferation in soft agar.
MCF2L	Guanine nucleotide exchange factor DBS	Guanine nucleotide exchange factor that catalyzes guanine nucleotide exchange on RHOA and CDC42, and thereby contributes to the regulation of RHOA and CDC42 signaling pathways.
CAMK2B	Calcium/calmodulin-dependent protein kinase type II subunit beta	Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in dendritic spine and synapse formation, neuronal plasticity and regulation of sarcoplasmic r…
COG5	Conserved oligomeric Golgi complex subunit 5	Required for normal Golgi function.
ALDH1A2	Retinal dehydrogenase 2	Catalyzes the NAD-dependent oxidation of aldehyde substrates, such as all-trans-retinal and all-trans-13,14-dihydroretinal, to their corresponding carboxylic acids, all-trans-retinoate and all-trans-13,14-dihydroretinoate, respectively.
TLR8	Toll-like receptor 8	Endosomal receptor that plays a key role in innate and adaptive immunity.
RP1L1	Retinitis pigmentosa 1-like 1 protein	Required for the differentiation of photoreceptor cells.
CDC5L	Cell division cycle 5-like protein	DNA-binding protein involved in cell cycle control.
LYPLAL1	Lysophospholipase-like protein 1	Palmitoyl thioesterase that catalyzes depalmitoylation of CGAS and KCNMA1.
DUS4L	tRNA-dihydrouridine(20a/20b) synthase [NAD(P)+]-like	Catalyzes the synthesis of dihydrouridine, a modified base found in the D-loop of most tRNAs.
COL2A1	Collagen alpha-1(II) chain	Type II collagen is specific for cartilaginous tissues.
COMP	Cartilage oligomeric matrix protein	Plays a role in the structural integrity of cartilage via its interaction with other extracellular matrix proteins such as the collagens and fibronectin.
NACA2	Nascent polypeptide-associated complex subunit alpha-2	Prevents inappropriate targeting of non-secretory polypeptides to the endoplasmic reticulum (ER).
KANSL1	KAT8 regulatory NSL complex subunit 1	Non-catalytic component of the NSL histone acetyltransferase complex, a multiprotein complex that mediates histone H4 acetylation at ‘Lys-5’- and ‘Lys-8’ (H4K5ac and H4K8ac) at transcription start sites and promotes transcription initiatio…
FTO	Alpha-ketoglutarate-dependent dioxygenase FTO	RNA demethylase that mediates oxidative demethylation of different RNA species, such as mRNAs, tRNAs and snRNAs, and acts as a regulator of fat mass, adipogenesis and energy homeostasis.
GLT8D1	Glycosyltransferase 8 domain-containing protein 1	In vitro, catalyzes the transfer of a galactose residue from UDP-galactose onto GalNAc and GlcNAc structures.
DOT1L	Histone-lysine N-methyltransferase, H3 lysine-79 specific	Histone methyltransferase that methylates ‘Lys-79’ of histone H3.
CHADL	Chondroadherin-like protein	Potential negative modulator of chondrocyte differentiation.
SLC30A10	Calcium/manganese antiporter SLC30A10	Calcium:manganese antiporter of the plasma membrane mediating the efflux of intracellular manganese coupled to an active extracellular calcium exchange.
RFLNA	Refilin-A	Involved in the regulation of the perinuclear actin network and nuclear shape through interaction with filamins.
DNAH10	Dynein axonemal heavy chain 10	Force generating protein of respiratory cilia.
GNL3	Guanine nucleotide-binding protein-like 3	May be required to maintain the proliferative capacity of stem cells.
FRZB	Secreted frizzled-related protein 3	Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts.
IFRD1	Interferon-related developmental regulator 1	Could play a role in regulating gene activity in the proliferative and/or differentiative pathways induced by NGF.
MAPT	Microtubule-associated protein tau	Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity.
NCOA3	Nuclear receptor coactivator 3	Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion.

Protein-family classification

Druggable: 4 · Difficult: 3 · Unknown: 24 · Druggable fraction: 0.13

Family distribution

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

Family	Genes	Fold	FDR
Other/Unknown	24	1.4×	0.053
Enzyme (other)	3	1.2×	0.904
Kinase	1	0.9×	0.904
Scaffold/PPI	1	0.6×	0.904
Transcription factor	2	0.5×	0.904

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SUPT3H	Other/Unknown	no		TFIID_TAF13, Histone-fold
TGFA	Other/Unknown	no		EGF
MCF2L	Scaffold/PPI	no		DH_dom, CRAL-TRIO_dom, GDS_CDC24_CS
CAMK2B	Kinase	yes	2.7.11.17	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
COG5	Other/Unknown	no		Cog5, COG5_helical, COG5_N
ALDH1A2	Enzyme (other)	yes	1.2.1.36	Aldehyde_DH_dom, Ald_DH_CS_CYS, Ald_DH/histidinol_DH
TLR8	Other/Unknown	no		TIR_dom, Cys-rich_flank_reg_C, Leu-rich_rpt
RP1L1	Other/Unknown	no		Doublecortin_dom, Doublecortin_dom_sf
CDC5L	Transcription factor	no		SANT/Myb, Homeodomain-like_sf, Myb_dom
LYPLAL1	Other/Unknown	no		PLipase/COase/thioEstase, AB_hydrolase_fold, LYPA1-2/EST-like
DUS4L	Other/Unknown	no		DUS_fam, Aldolase_TIM, tRNA_hU_synthase_CS
COL2A1	Other/Unknown	no		Fib_collagen_C, VWF_dom, Collagen
COMP	Other/Unknown	no		EGF, EGF-like_Ca-bd_dom, Thrombospondin_3-like_rpt
NACA2	Other/Unknown	no		Nas_poly-pep-assoc_cplx_dom, EGD2/NACA0like, NAC_A/B_dom_sf
KANSL1	Other/Unknown	no		NSL1, PEHE_dom
FTO	Enzyme (other)	yes	1.14.11.53	FTO_C, FTO_cat_dom, FTO
GLT8D1	Other/Unknown	no		Glyco_trans_8, Nucleotide-diphossugar_trans, Glycosyltrans_8_dom-fam
DOT1L	Enzyme (other)	yes	2.1.1.355	DOT1L/grappa, DOT1_dom, SAM-dependent_MTases_sf
CHADL	Other/Unknown	no		LRRNT, Cys-rich_flank_reg_C, Leu-rich_rpt
SLC30A10	Other/Unknown	no		Cation_efflux, Cation_efflux_TMD_sf, Cation_efflux_CTD
LRRC37A4P	Other/Unknown	no
RFLNA	Other/Unknown	no		Refilin
LRRC37A	Other/Unknown	no		Leu-rich_rpt, Leu-rich_rpt_typical-subtyp, LRRC37
DNAH10	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
GNL3	Other/Unknown	no		GTP-bd, Gnl3_N_dom, P-loop_NTPase
MIR4286	Other/Unknown	no
FRZB	Other/Unknown	no		Netrin_domain, TIMP-like_OB-fold, Frizzled/SFRP
MAPK8IP1P2	Other/Unknown	no
IFRD1	Other/Unknown	no		Interferon-rel_develop_reg_C, Interferon-rel_develop_reg_N, ARM-like
MAPT	Other/Unknown	no		MAP_tubulin-bd_rpt, Tau, MAP2/MAP4/Tau
NCOA3	Transcription factor	no	2.3.1.48	PAS, Nuc_rcpt_coact, NCO_DUF1518

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	31
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	4
bone marrow cell	4
cortical plate	4
male germ line stem cell (sensu Vertebrata) in testis	3
primordial germ cell in gonad	3
sperm	3
tibia	3
right testis	3
right uterine tube	3
cerebellar cortex	2
cerebellar hemisphere	2
right hemisphere of cerebellum	2
buccal mucosa cell	2
cartilage tissue	2
left testis	2
bronchial epithelial cell	2
ileal mucosa	2
jejunal mucosa	2
body of pancreas	2
epithelium of esophagus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SUPT3H	206	ubiquitous	yes	primordial germ cell in gonad, sperm, male germ line stem cell (sensu Vertebrata) in testis
TGFA	252	broad	yes	esophagus squamous epithelium, epithelium of esophagus, squamous epithelium
MCF2L	253	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
CAMK2B	233	broad	marker	cerebellar cortex, cerebellar hemisphere, right hemisphere of cerebellum
COG5	142	ubiquitous	marker	corpus callosum, calcaneal tendon, tonsil
ALDH1A2	226	broad	marker	germinal epithelium of ovary, decidua, sperm
TLR8	174	broad	marker	monocyte, mononuclear cell, leukocyte
RP1L1	30	tissue_specific	yes	primordial germ cell in gonad, buccal mucosa cell, bone marrow cell
CDC5L	290	ubiquitous	marker	buccal mucosa cell, sperm, male germ cell
LYPLAL1	255	ubiquitous	marker	kidney epithelium, left ventricle myocardium, calcaneal tendon
DUS4L	140	broad	yes	endometrium, cortical plate, male germ line stem cell (sensu Vertebrata) in testis
COL2A1	145	broad	marker	tibia, cartilage tissue, corpus epididymis
COMP	195	broad	marker	tibia, cartilage tissue, calcaneal tendon
NACA2	129	ubiquitous	marker	left testis, right testis, testis
KANSL1	250	ubiquitous	marker	bone marrow cell, colonic epithelium, thymus
FTO	294	ubiquitous	marker	cortical plate, bronchial epithelial cell, Brodmann (1909) area 10
GLT8D1	296	ubiquitous	marker	pituitary gland, bronchial epithelial cell, adenohypophysis
DOT1L	194	ubiquitous	marker	right testis, left testis, ileal mucosa
CHADL	179	tissue_specific	yes	C1 segment of cervical spinal cord, spinal cord, tibia
SLC30A10	111	broad	marker	jejunal mucosa, right lobe of liver, mucosa of transverse colon
LRRC37A4P	134		marker	bone marrow cell, ventricular zone, right uterine tube
RFLNA	168	broad	marker	ileal mucosa, body of stomach, stomach
LRRC37A	134		yes	bone marrow cell, right uterine tube, male germ line stem cell (sensu Vertebrata) in testis
DNAH10	134	tissue_specific	marker	right uterine tube, cortical plate, olfactory segment of nasal mucosa
GNL3	286	ubiquitous	marker	calcaneal tendon, body of pancreas, lower esophagus mucosa
MIR4286	60		yes	primordial germ cell in gonad, tibial artery, adrenal tissue
FRZB	269	broad	marker	pigmented layer of retina, retina, right coronary artery
MAPK8IP1P2	118	tissue_specific	yes	right testis, granulocyte, apex of heart
IFRD1	299	ubiquitous	marker	body of pancreas, jejunal mucosa, skeletal muscle tissue of rectus abdominis
MAPT	141	broad	marker	cortical plate, superior frontal gyrus, prefrontal cortex

Protein interactions among cohort

Intra-cohort edges: 10.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MAPT	7,289
CDC5L	5,930
ALDH1A2	4,289
GNL3	4,283
TLR8	3,532
DOT1L	3,218
TGFA	2,986
NCOA3	2,889
CAMK2B	2,679
FTO	2,496

Intra-cohort edges

A	B	Sources
CAMK2B	DUS4L	biogrid_interaction, intact
COG5	DUS4L	string_interaction
COL2A1	COMP	string_interaction
DUS4L	MCF2L	string_interaction
GLT8D1	GNL3	string_interaction
GLT8D1	MCF2L	string_interaction
GLT8D1	SUPT3H	string_interaction
KANSL1	LRRC37A	string_interaction
KANSL1	MAPT	string_interaction
LRRC37A	MAPT	string_interaction

Structural data

PDB: 16 · AlphaFold-only: 12 · No structure: 3

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MAPT	P10636	293
DOT1L	Q8TEK3	48
TLR8	Q9NR97	39
CDC5L	Q99459	37
FTO	Q9C0B1	28
GNL3	Q9BVP2	21
TGFA	P01135	11
COL2A1	P02458	11
ALDH1A2	O94788	7
NCOA3	Q9Y6Q9	6
SUPT3H	O75486	4
CAMK2B	Q13554	4
SLC30A10	Q6XR72	3
LYPLAL1	Q5VWZ2	2
KANSL1	Q7Z3B3	2
COMP	P49747	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DUS4L	O95620	94.36
GLT8D1	Q68CQ7	85.35
CHADL	Q6NUI6	84.58
IFRD1	O00458	84.46
COG5	Q9UP83	84.37
FRZB	Q92765	81.00
MCF2L	O15068	77.32
NACA2	Q9H009	72.87
RFLNA	Q6ZTI6	59.78
LRRC37A	A6NMS7	42.27
RP1L1	Q8IWN7	38.97
DNAH10	Q8IVF4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 165. 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
MAPK family signaling cascades	3	18.2×	0.047	TGFA, CAMK2B, NCOA3
Signaling by Nuclear Receptors	3	18.0×	0.047	TGFA, ALDH1A2, NCOA3
Signaling by Overexpressed Wild-Type EGFR in Cancer	1	167.9×	0.129	TGFA
Reversal of alkylation damage by DNA dioxygenases	1	96.0×	0.129	FTO
CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde	1	84.0×	0.129	CAMK2B
Inhibition of Signaling by Overexpressed EGFR	1	74.6×	0.129	TGFA
CaMK IV-mediated phosphorylation of CREB	1	67.2×	0.129	CAMK2B
Signaling by EGFR in Cancer	1	67.2×	0.129	TGFA
EGFR interacts with phospholipase C-gamma	1	67.2×	0.129	TGFA
Caspase-mediated cleavage of cytoskeletal proteins	1	56.0×	0.129	MAPT
CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling	1	51.7×	0.129	CAMK2B
Trafficking and processing of endosomal TLR	1	48.0×	0.129	TLR8
GRB2 events in EGFR signaling	1	44.8×	0.129	TGFA
Glutamate binding, activation of AMPA receptors and synaptic plasticity	1	44.8×	0.129	CAMK2B
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	1	44.8×	0.129	TGFA
SHC1 events in EGFR signaling	1	42.0×	0.129	TGFA
GAB1 signalosome	1	37.3×	0.129	TGFA
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1	37.3×	0.129	TGFA
Metal ion SLC transporters	1	35.4×	0.129	SLC30A10
Fibronectin matrix formation	1	33.6×	0.129	COL2A1
Ras activation upon Ca2+ influx through NMDA receptor	1	33.6×	0.129	CAMK2B
Trafficking of AMPA receptors	1	32.0×	0.129	CAMK2B
Unblocking of NMDA receptors, glutamate binding and activation	1	32.0×	0.129	CAMK2B
Negative regulation of NMDA receptor-mediated neuronal transmission	1	32.0×	0.129	CAMK2B
Developmental Lineage of Mammary Gland Myoepithelial Cells	1	32.0×	0.129	TGFA
Apoptotic cleavage of cellular proteins	1	28.0×	0.129	MAPT
RA biosynthesis pathway	1	28.0×	0.129	ALDH1A2
Apoptotic execution phase	1	28.0×	0.129	MAPT
Long-term potentiation	1	28.0×	0.129	CAMK2B
Developmental Lineage of Mammary Gland Luminal Epithelial Cells	1	26.9×	0.129	TGFA

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
determination of bilateral symmetry	1	648.1×	0.041	ALDH1A2
regulation of white fat cell proliferation	1	648.1×	0.041	FTO
negative regulation of hepatocyte differentiation	1	648.1×	0.041	FRZB
plus-end-directed organelle transport along microtubule	1	648.1×	0.041	MAPT
manganese ion export across plasma membrane	1	648.1×	0.041	SLC30A10
negative regulation of hemostasis	1	648.1×	0.041	COMP
myoblast fate determination	1	324.1×	0.041	IFRD1
detoxification of zinc ion	1	324.1×	0.041	SLC30A10
negative regulation of cell development	1	324.1×	0.041	FRZB
regulation of skeletal muscle adaptation	1	324.1×	0.041	CAMK2B
inter-Golgi cisterna vesicle-mediated transport	1	324.1×	0.041	COG5
convergent extension involved in organogenesis	1	324.1×	0.041	FRZB
neurofibrillary tangle assembly	1	324.1×	0.041	MAPT
negative regulation of protein localization to mitochondrion	1	324.1×	0.041	MAPT
negative regulation of collagen fibril organization	1	324.1×	0.041	CHADL
toll-like receptor 8 signaling pathway	1	216.1×	0.041	TLR8
RNA repair	1	216.1×	0.041	FTO
regulation of respiratory system process	1	216.1×	0.041	FTO
negative regulation of chondrocyte development	1	216.1×	0.041	RFLNA
actin filament bundle organization	1	216.1×	0.041	RFLNA
positive regulation of protein localization to chromosome, telomeric region	1	216.1×	0.041	GNL3
regulation of vascular endothelial cell proliferation	1	216.1×	0.041	ALDH1A2
retinoic acid biosynthetic process	1	162.0×	0.041	ALDH1A2
tRNA dihydrouridine synthesis	1	162.0×	0.041	DUS4L
striated muscle tissue development	1	162.0×	0.041	IFRD1
rRNA metabolic process	1	162.0×	0.041	MAPT
ureter maturation	1	162.0×	0.041	ALDH1A2
tendon development	1	162.0×	0.041	COMP
photoreceptor cell development	1	162.0×	0.041	RP1L1
9-cis-retinoic acid biosynthetic process	1	162.0×	0.041	ALDH1A2

Therapeutics

Drugs indicated for this disease

29 approved, 41 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Capsaicin	Approved (phase 4)
Celecoxib	Approved (phase 4)
Cortisone Acetate	Approved (phase 4)
Dexamethasone	Approved (phase 4)
Diclofenac	Approved (phase 4)
Diflunisal	Approved (phase 4)
Etodolac	Approved (phase 4)
Famotidine	Approved (phase 4)
Hydrocortisone	Approved (phase 4)
Ibuprofen	Approved (phase 4)
Indomethacin	Approved (phase 4)
Ketoprofen	Approved (phase 4)
Lidocaine	Approved (phase 4)
Meloxicam	Approved (phase 4)
Menthol	Approved (phase 4)
Methylprednisolone	Approved (phase 4)
Methylprednisolone Acetate	Approved (phase 4)
Misoprostol	Approved (phase 4)
Nabumetone	Approved (phase 4)
Naproxen	Approved (phase 4)
Oxaprozin	Approved (phase 4)
Piroxicam	Approved (phase 4)
Prasterone	Approved (phase 4)
Prednisolone	Approved (phase 4)
Prednisone	Approved (phase 4)
Sulindac	Approved (phase 4)
Triamcinolone Acetonide	Approved (phase 4)
Triamcinolone Hexacetonide	Approved (phase 4)
Valdecoxib	Approved (phase 4)
Acetaminophen	Phase 3 (in late-stage trials)
Adalimumab	Phase 3 (in late-stage trials)
Aspirin	Phase 3 (in late-stage trials)
Betamethasone Acetate	Phase 3 (in late-stage trials)
Bupivacaine	Phase 3 (in late-stage trials)
Buprenorphine	Phase 3 (in late-stage trials)
Chondroitin Sulfate	Phase 3 (in late-stage trials)
Chondroitin Sulfate Sodium	Phase 3 (in late-stage trials)
Diacerein	Phase 3 (in late-stage trials)
Duloxetine	Phase 3 (in late-stage trials)
Esomeprazole	Phase 3 (in late-stage trials)
Etoricoxib	Phase 3 (in late-stage trials)
Fentanyl	Phase 3 (in late-stage trials)
Fulranumab	Phase 3 (in late-stage trials)
Glucosamine	Phase 3 (in late-stage trials)
Golimumab	Phase 3 (in late-stage trials)
Hyaluronic Acid	Phase 3 (in late-stage trials)
Hydrocodone	Phase 3 (in late-stage trials)
Hydroxychloroquine	Phase 3 (in late-stage trials)
Ibuprofen Trelamine	Phase 3 (in late-stage trials)
Ketorolac	Phase 3 (in late-stage trials)
Lansoprazole	Phase 3 (in late-stage trials)
Lumiracoxib	Phase 3 (in late-stage trials)
Metformin	Phase 3 (in late-stage trials)
Methotrexate	Phase 3 (in late-stage trials)
Naloxone	Phase 3 (in late-stage trials)
Naproxcinod	Phase 3 (in late-stage trials)
Omeprazole	Phase 3 (in late-stage trials)
Oxycodone	Phase 3 (in late-stage trials)
Polmacoxib	Phase 3 (in late-stage trials)
Powdered Cellulose	Phase 3 (in late-stage trials)
Pregabalin	Phase 3 (in late-stage trials)
Rebamipide	Phase 3 (in late-stage trials)
Rofecoxib	Phase 3 (in late-stage trials)
SMC021	Phase 3 (in late-stage trials)
Secukinumab	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)
Tranexamic Acid	Phase 3 (in late-stage trials)
Triamcinolone	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Alendronic Acid, Anakinra, Canakinumab, Cannabidiol, Codeine, Difelikefalin, Fasinumab, Gevokizumab, Hyaluronic Acid (Non-Animal Stabilized), Infliximab, Lacosamide, Lorecivivint, Odanacatib, Onabotulinumtoxina, Otilimab, Oxytocin, Ropivacaine, Tramadol.

Drug target analysis

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

Druggability breadth: 13 of 31 evidence-associated genes (42%) 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
CAMK2B	FEDRATINIB
FTO	FLUORESCEIN
DOT1L	ADENOSINE
MAPT	BEPRIDIL
NCOA3	METHOTREXATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MAPT	449	4
CAMK2B	25	4
FTO	18	4
TLR8	8	2
NCOA3	4	4
DOT1L	3	4
SUPT3H	0	0
TGFA	0	0
MCF2L	0	0
COG5	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	CAMK2B
SORAFENIB	4	CAMK2B
RUXOLITINIB	4	CAMK2B
PALBOCICLIB	4	CAMK2B
ABEMACICLIB	4	CAMK2B
SUNITINIB	4	CAMK2B
MIDOSTAURIN	4	CAMK2B
FLUORESCEIN	4	FTO, MAPT
DEMECLOCYCLINE	4	FTO
ROXADUSTAT	4	FTO
MECLOFENAMIC ACID	4	FTO
AMILORIDE	4	FTO
TACRINE	4	FTO
ENTACAPONE	4	FTO
ADENOSINE	4	DOT1L
BEPRIDIL	4	MAPT
PHENYLBUTAZONE	4	MAPT
CEFOTAXIME SODIUM	4	MAPT
DIENESTROL	4	MAPT
PROGESTERONE	4	MAPT
CLOTRIMAZOLE	4	MAPT
CHOLECALCIFEROL	4	MAPT
LATANOPROST	4	MAPT
CHLORTHALIDONE	4	MAPT
OXCARBAZEPINE	4	MAPT
NABUMETONE	4	MAPT
GLIPIZIDE	4	MAPT
AMIODARONE HYDROCHLORIDE	4	MAPT
TRICLABENDAZOLE	4	MAPT
MESORIDAZINE	4	MAPT

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 5.

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

Symbol	Assays	Type breakdown
TLR8	395	Binding:378, Functional:16, ADMET:1
CAMK2B	314	Binding:313, Functional:1
DOT1L	236	Binding:235, ADMET:1
MAPT	184	Binding:180, Functional:4
FTO	153	Binding:153
NCOA3	42	Binding:39, Functional:3
ALDH1A2	32	Binding:32
TGFA	3	Binding:3
MCF2L	2	Binding:2
LYPLAL1	2	Binding:2
COL2A1	2	Binding:2
COG5	1	Binding:1
CDC5L	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CAMK2B	2.7.11.17	Ca2+/calmodulin-dependent protein kinase
ALDH1A2	1.2.1.36	retinal dehydrogenase
FTO	1.14.11.53	mRNA N6-methyladenine demethylase
DOT1L	2.1.1.355, 2.1.1.360	[histone H3]-lysine9 N-trimethyltransferase, [histone H3]-lysine79 N-trimethyltransferase
NCOA3	2.3.1.48	histone acetyltransferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CAMK2B	314
TLR8	395
FTO	153
DOT1L	236
MAPT	184

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

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.

Compound	Max phase	Cohort target (bioactivity)
FEDRATINIB	4	CAMK2B
SORAFENIB	4	CAMK2B
RUXOLITINIB	4	CAMK2B
PALBOCICLIB	4	CAMK2B
ABEMACICLIB	4	CAMK2B
SUNITINIB	4	CAMK2B
MIDOSTAURIN	4	CAMK2B
FLUORESCEIN	4	FTO, MAPT
DEMECLOCYCLINE	4	FTO
ROXADUSTAT	4	FTO
MECLOFENAMIC ACID	4	FTO
AMILORIDE	4	FTO
TACRINE	4	FTO
ENTACAPONE	4	FTO
ADENOSINE	4	DOT1L
BEPRIDIL	4	MAPT
PHENYLBUTAZONE	4	MAPT
CEFOTAXIME SODIUM	4	MAPT
DIENESTROL	4	MAPT
PROGESTERONE	4	MAPT
CLOTRIMAZOLE	4	MAPT
CHOLECALCIFEROL	4	MAPT
LATANOPROST	4	MAPT
CHLORTHALIDONE	4	MAPT
OXCARBAZEPINE	4	MAPT
NABUMETONE	4	MAPT
GLIPIZIDE	4	MAPT
AMIODARONE HYDROCHLORIDE	4	MAPT
TRICLABENDAZOLE	4	MAPT
MESORIDAZINE	4	MAPT

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	5	CAMK2B, FTO, DOT1L, MAPT, NCOA3
B	Phased (≥1) drug, not yet approved	1	TLR8
C	Druggable family + PDB, no drug	1	ALDH1A2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	24	SUPT3H, TGFA, MCF2L, COG5, RP1L1, CDC5L, LYPLAL1, DUS4L, COL2A1, COMP (+14 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)
SUPT3H	0	—
TGFA	3	—
MCF2L	2	—
COG5	1	—
ALDH1A2	32	—
RP1L1	0	—
CDC5L	1	—
LYPLAL1	2	—
DUS4L	0	—
COL2A1	2	—
COMP	0	—
NACA2	0	—
KANSL1	0	—
GLT8D1	0	—
CHADL	0	—
SLC30A10	0	—
LRRC37A4P	0	—
RFLNA	0	—
LRRC37A	0	—
DNAH10	0	—
GNL3	0	—
MIR4286	0	—
FRZB	0	—
MAPK8IP1P2	0	—
IFRD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,574.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	529
PHASE4	176
PHASE3	157
PHASE2	110
PHASE1	65
PHASE1/PHASE2	33
PHASE2/PHASE3	21
EARLY_PHASE1	9

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05292339	PHASE4	RECRUITING	Ketorolac in Upper Extremity Tendinopathy and Arthropathy
NCT05660824	PHASE4	NOT_YET_RECRUITING	Effectiveness of Stromal Vascular Fraction (SVF) and Platelet -Rich Plasma (PRP) in Patients With Knee Osteoarthritis: Study Protocol for a Phase III, Prospective, Randomized, Controlled Multi-center Study.
NCT06603662	PHASE4	RECRUITING	Systemic Oral Glucocorticoids for the Treatment of Acute Osteoarthritis Pain in the Emergency Department
NCT06787417	PHASE4	RECRUITING	Kinematic and Mechanical Alignment Randomized Trial
NCT07006714	PHASE4	ACTIVE_NOT_RECRUITING	Preoperative Correction of Vitamin D Deficiency in Total Joint Arthroplasty (TJA)
NCT07203547	PHASE4	NOT_YET_RECRUITING	Phase 4 Study of Laybon Tab. in Knee Osteoarthritis
NCT07430085	PHASE4	NOT_YET_RECRUITING	Post-Operative Pain Relief: Zynrelef or Periarticular Injections in RATKA
NCT07489521	PHASE4	RECRUITING	Arthrosamid vs. Steroid for the Management of Knee Osteoarthritis
NCT07614087	PHASE4	NOT_YET_RECRUITING	Plasma Concentrations of Intraosseous Versus Intravenous Tranexamic Acid in Joint Arthroplasty
NCT00130468	PHASE4	COMPLETED	TREAD-20: Trial of Hyalgan Three Injection-Regimen for the Treatment of Knee Pain Due to Osteoarthritis
NCT00138892	PHASE4	UNKNOWN	A Randomized Controlled Trial of Long Versus Short Wait For Primary Total Hip and Knee Arthroplasty
NCT00140972	PHASE4	COMPLETED	A Study to Assess Etoricoxib Versus Diclofenac in Chinese Patients With Osteoarthritis of the Knee or Hip (0663-080)(COMPLETED)
NCT00141102	PHASE4	COMPLETED	Study Of Celecoxib Or Diclofenac And Omeprazole For Gastrointestinal (GI) Safety In High GI Risk Patients With Arthritis
NCT00208364	PHASE4	TERMINATED	A Two Centre Study to Assess the Long-term Performance of the Pinnacle™ Cup With a Metal-on-Metal Bearing in Primary Total Hip Replacement
NCT00208377	PHASE4	TERMINATED	A Multi-centre Study to Assess the Long-term Performance of the DePuy ASR™ System in Primary Hip Resurfacing Surgery
NCT00208390	PHASE4	TERMINATED	A Multi-centre Study to Assess the Long-term Performance of the Summit™ Hip in Primary Total Hip Replacement
NCT00208403	PHASE4	TERMINATED	A Randomised Single Centre Study to Compare the Long-term Performance of Acryloc™ and Palacos® R Bone Cements in Primary Total Hip Replacement
NCT00208416	PHASE4	TERMINATED	A Randomised Multi-centre Study to Compare the Short-term Outcomes of Minimally Invasive and Conventional Surgery in Primary Total Hip Replacement
NCT00208429	PHASE4	WITHDRAWN	A Multi-centre Study to Assess the Long-term Performance of the Pinnacle™ Cup With a Polyethylene-on-metal Bearing in Primary Total Hip Replacement
NCT00208442	PHASE4	COMPLETED	A Randomised Single Centre Study to Compare the Long-term Wear Characteristics of Marathon™ and Enduron™ Polyethylene Cup Liners in Primary Total Hip Replacement
NCT00208455	PHASE4	TERMINATED	A Multi-centre Study to Assess the Long-term Performance of the DePuy PROXIMA™ Hip in Primary Total Hip Replacement
NCT00236366	PHASE4	COMPLETED	A Study of the Effect on Pain Control of Treatment With Fentanyl, Administered Through the Skin, Compared With Placebo in Patients With Osteoarthritis
NCT00251069	PHASE4	COMPLETED	Glucosamine Sulphate and Increased Level of Blood Cholesterol
NCT00253851	PHASE4	COMPLETED	Does Thinning the Blood During Surgery Prevent Blood Clots Following Total Knee Replacement Surgery
NCT00267176	PHASE4	COMPLETED	Safety and Efficacy of Lumiracoxib in Patients With Osteoarthritis and With Controlled Hypertension
NCT00270322	PHASE4	TERMINATED	Pain Treatment After Total Knee Replacement - Continuous Epidural Versus Intravenous Patient Controlled Analgesia With Morphine
NCT00279838	PHASE4	COMPLETED	Computer Assisted Total Knee Replacement
NCT00294801	PHASE4	UNKNOWN	Effect of Flex-a-New on Osteoarthritis of the Knee
NCT00324038	PHASE4	COMPLETED	Buprenorphine in the Treatment of Osteoarthritis (OA) in the Elderly
NCT00346788	PHASE4	COMPLETED	The Subvastus Approach in Total Knee Arthroplasty
NCT00359151	PHASE4	TERMINATED	Celebrex Total Knee Arthroplasty Study
NCT00373685	PHASE4	COMPLETED	GI-Reasons- A Trial Of GI Safety Of Celecoxib Compared With Non-Selective Nonsteroidal Antiinflammatory Drugs (NSAIDS)
NCT00393393	PHASE4	UNKNOWN	Effectiveness Study of Hylan G-F 20 to Preserve Cartilage in Osteoarthritis of the Knee
NCT00399178	PHASE4	COMPLETED	A Randomised Open Controlled Parallel Group Study Comparing Norspan and Tramadol
NCT00426647	PHASE4	COMPLETED	Norspan® Patches Versus Tramadol in Subjects With Chronic, Moderate to Severe Osteoarthritis Pain in the Hip Knee and/or Lumbar Spine
NCT00431509	PHASE4	UNKNOWN	Trial Comparing Navigated and Conventional Implantation Techniques in Knee Replacement Surgery
NCT00440661	PHASE4	COMPLETED	Exploration of the Synovial Fluid Inflammation Mediators Under Diacerhein in Knee Osteoarthritis
NCT00443092	PHASE4	COMPLETED	Efficacy of Proprietary Cherry Juice Blend in Osteoarthritis of the Knee
NCT00447759	PHASE4	COMPLETED	The Standard Care Versus Celecoxib Outcome Trial
NCT00484718	PHASE4	TERMINATED	Measuring Gait And Self-Reported Pain In Patients With Osteoarthritis Of The Knee Using Placebo/Oxycodone/Celecoxib.

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CELECOXIB	4	23
HYALURONIC ACID	4	13
DICLOFENAC	4	12
BUPRENORPHINE	4	11
NAPROXEN	4	10
MELOXICAM	4	9
ETORICOXIB	4	8
LUMIRACOXIB	4	7
GLUCOSAMINE	4	6
METHYLPREDNISOLONE	4	5
TRAMADOL	4	5
ACETAMINOPHEN	4	4
CALCITONIN SALMON	4	4
CODEINE	4	3
DULOXETINE	4	3
FENTANYL	4	3
MORPHINE SULFATE	4	3
ROFECOXIB	4	3
ROPIVACAINE	4	3
EPINEPHRINE	4	2
ESOMEPRAZOLE	4	2
KETOROLAC TROMETHAMINE	4	2
LACOSAMIDE	4	2
MILNACIPRAN	4	2
NALTREXONE HYDROCHLORIDE	4	2
ONABOTULINUMTOXINA	4	2
OXYCODONE	4	2
TAPENTADOL	4	2
TRANEXAMIC ACID	4	2
TRIAMCINOLONE	4	2