Polymyositis

Summary

Polymyositis (MONDO:0019127) is a disease with 10 cohort genes (17 GWAS associations across 5 studies) and 54 clinical trials. Top therapeutic interventions include siponimod, abatacept, and anakinra.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Cohort genes: 10
• GWAS associations: 17
• Phenotypes (HPO): 60
• Clinical trials: 54

Clinical features

Epidemiology

Prevalence records

8 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 1 000 000	0.585	Europe	Validated
Point prevalence	1-9 / 100 000	7.1	Europe	Validated
Annual incidence	1-9 / 1 000 000	0.75	Argentina	Validated
Annual incidence	1-9 / 1 000 000	0.41	Australia	Validated
Annual incidence	1-9 / 1 000 000	0.39	Spain	Validated
Annual incidence	1-9 / 1 000 000	0.76	Sweden	Validated
Point prevalence	1-9 / 100 000	7.2	Argentina	Validated
Point prevalence	1-9 / 100 000	7.2	Australia	Validated

Signs & symptoms

Clinical features (HPO)

60 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0001252	Hypotonia	Very frequent (80-99%)
HP:0002829	Arthralgia	Very frequent (80-99%)
HP:0002960	Autoimmunity	Very frequent (80-99%)
HP:0003236	Elevated circulating creatine kinase concentration	Very frequent (80-99%)
HP:0003457	EMG abnormality	Very frequent (80-99%)
HP:0003701	Proximal muscle weakness	Very frequent (80-99%)
HP:0004303	Abnormal muscle fiber morphology	Very frequent (80-99%)
HP:0012544	Elevated circulating aldolase concentration	Very frequent (80-99%)
HP:0012735	Cough	Very frequent (80-99%)
HP:0001369	Arthritis	Frequent (30-79%)
HP:0001824	Weight loss	Frequent (30-79%)
HP:0001945	Fever	Frequent (30-79%)
HP:0002019	Constipation	Frequent (30-79%)
HP:0002039	Anorexia	Frequent (30-79%)
HP:0002093	Respiratory insufficiency	Frequent (30-79%)
HP:0002875	Exertional dyspnea	Frequent (30-79%)
HP:0003326	Myalgia	Frequent (30-79%)
HP:0003493	Antinuclear antibody positivity	Frequent (30-79%)
HP:0006530	Abnormal pulmonary interstitial morphology	Frequent (30-79%)
HP:0012378	Fatigue	Frequent (30-79%)
HP:0033713	Anti-signal recognition particle antibody positivity	Frequent (30-79%)
HP:0034143	Anti-threonyl-tRNA synthetase antibody positivity	Frequent (30-79%)
HP:0034145	Anti-alanyl-tRNA synthetase antibody positivity	Frequent (30-79%)
HP:0034146	Anti-glycyl tRNA-synthetase antibody positivity	Frequent (30-79%)
HP:0034147	Anti-aminoacyl-tRNA synthetase antibody positivity	Frequent (30-79%)
HP:0034148	Anti-isoleucyl tRNA-synthetase antibody positivity	Frequent (30-79%)
HP:0034149	Anti-phenylalanyl tRNA synthetase antibody positivity	Frequent (30-79%)
HP:0034150	Anti-tyrosyl-tRNA synthetase antibody positivity	Frequent (30-79%)
HP:0034151	Anti-asparaginyl-tRNA synthetase antibody positivity	Frequent (30-79%)
HP:0034152	Anti-histidyl tRNA synthetase antibody positivity	Frequent (30-79%)
HP:0000091	Abnormal renal tubule morphology	Occasional (5-29%)
HP:0000934	Chondrocalcinosis	Occasional (5-29%)
HP:0000988	Skin rash	Occasional (5-29%)
HP:0001288	Gait disturbance	Occasional (5-29%)
HP:0001315	Reduced tendon reflexes	Occasional (5-29%)
HP:0001608	Abnormality of the voice	Occasional (5-29%)
HP:0001611	Hypernasal speech	Occasional (5-29%)
HP:0001618	Dysphonia	Occasional (5-29%)
HP:0001633	Abnormal mitral valve morphology	Occasional (5-29%)
HP:0001635	Congestive heart failure	Occasional (5-29%)
HP:0001639	Hypertrophic cardiomyopathy	Occasional (5-29%)
HP:0001644	Dilated cardiomyopathy	Occasional (5-29%)
HP:0001658	Myocardial infarction	Occasional (5-29%)
HP:0001701	Pericarditis	Occasional (5-29%)
HP:0001894	Thrombocytosis	Occasional (5-29%)
HP:0002020	Gastroesophageal reflux	Occasional (5-29%)
HP:0002027	Abdominal pain	Occasional (5-29%)
HP:0002068	Neuromuscular dysphagia	Occasional (5-29%)
HP:0002206	Pulmonary fibrosis	Occasional (5-29%)
HP:0002239	Gastrointestinal hemorrhage	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	polymyositis
Mondo ID	MONDO:0019127
EFO	EFO:0003063
MeSH	D017285
Orphanet	732
DOID	DOID:0080745
ICD-10-CM	M33.2
ICD-11	1157134196
NCIT	C26925
SNOMED CT	31384009
UMLS	C0085655
MedGen	39086
GARD	0007425
MedDRA	10036102
Is cancer (heuristic)	no

Also known as: PM · polymyositis

Data availability: 17 GWAS associations (5 studies).

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › acquired skeletal muscle disease › acquired idiopathic inflammatory myopathy › polymyositis

Related subtypes (8): eosinophilic fasciitis, immune-mediated necrotizing myopathy, overlap myositis, inflammatory myopathy with abundant macrophages, idiopathic eosinophilic myositis, juvenile idiopathic inflammatory myopathy, focal myositis, antisynthetase syndrome

Subtypes (2): dermatomyositis, juvenile polymyositis

Genetics & variants

GWAS landscape

17 GWAS associations across 5 studies. Top hits map to 10 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs3094013	6e-76	HCP5	T	2.97
rs3129716	2e-54	HLA-DQB1 - MTCO3P1	?	2.65
rs2476601	8e-11	AP4B1-AS1, PTPN22	A	1.58
rs577482058	6e-09	LRP5	T	68.96
rs6733720	2e-08	NAB1	?	1.41
rs9905921	2e-06	SDK2	C	1.26
rs1369496	2e-06	THSD7A - TMEM106B	?	0.78
rs17799348	2e-06	FAM167A - BLK	?	0.77
rs2241208	2e-06	UBE3B	?	0.78
rs7956536	4e-06	UBE3B - MMAB	?	1.25
rs2286896	4e-06	NAB1	G	1.35
rs7211759	5e-06	SDK2	?	1.25
rs1420095	6e-06	IL18R1	?	1.59
rs4690220	8e-06	SLC26A1, DGKQ	G	1.25

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST006052	Rothwell S	2015	931	15,651	Dense genotyping of immune-related loci in idiopathic inflammatory myopathies confirms HLA alleles as the strongest genetic risk factor and suggests different genetic background for major clinical subgroups.
GCST90270217	Rothwell S	2022	903	10,260	Genome-wide imputation identifies novel associations and localises signals in idiopathic inflammatory myopathies.
GCST005340	Kochi Y	2018	236	6,270	Splicing variant of WDFY4 augments MDA5 signalling and the risk of clinically amyopathic dermatomyositis.
GCST90018671	Sakaue S	2021	58	175,599	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90018891	Sakaue S	2021	44	350,228	A cross-population atlas of genetic associations for 220 human phenotypes.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	1
Tier 3: regulatory	1
Tier 4: intronic/intergenic	11

MAF distribution

Bucket	Variants
common (>=0.05)	13
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	1

Functional consequences

Consequence	Count
intron_variant	8
intergenic_variant	2
non_coding_transcript_exon_variant	1
missense_variant	1
regulatory_region_variant	1
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs3094013	6	31466589	G>A,C,T	0.12	intron_variant	HCP5	6e-76	Tier 4: intronic/intergenic
rs3129716	6	32689659	T>C	0.05	non_coding_transcript_exon_variant	HLA-DQB1 - MTCO3P1	2e-54	Tier 4: intronic/intergenic
rs2476601	1	113834946	A>G,T	0.09	missense_variant	AP4B1-AS1, PTPN22	8e-11	Tier 1: coding
rs577482058	11	68429137	C>T		intron_variant	LRP5	6e-09	Tier 4: intronic/intergenic
rs6733720	2	190651294	G>C	0.05	intron_variant	NAB1	2e-08	Tier 4: intronic/intergenic
rs9905921	17	73531104	T>C	0.43	intron_variant	SDK2	2e-06	Tier 4: intronic/intergenic
rs1369496	7	12133547	C>A,G	0.05	intergenic_variant	THSD7A - TMEM106B	2e-06	Tier 4: intronic/intergenic
rs17799348	8	11476012	T>A,C,G	0.05	regulatory_region_variant	FAM167A - BLK	2e-06	Tier 3: regulatory
rs2241208	12	109524990	G>C	0.05	intron_variant	UBE3B	2e-06	Tier 4: intronic/intergenic
rs7956536	12	109542711	C>G,T	0.47	intergenic_variant	UBE3B - MMAB	4e-06	Tier 4: intronic/intergenic
rs2286896	2	190670850	T>C	0.13	intron_variant	NAB1	4e-06	Tier 4: intronic/intergenic
rs7211759	17	73533037	G>A	0.05	intron_variant	SDK2	5e-06	Tier 4: intronic/intergenic
rs1420095	2	102396442	A>G	0.09	intron_variant	IL18R1	6e-06	Tier 4: intronic/intergenic
rs4690220	4	986676	A>G	0.45	3_prime_UTR_variant	SLC26A1, DGKQ	8e-06	Tier 2: splice/UTR

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BLK	Orphanet:536	Systemic lupus erythematosus
BLK	Orphanet:552	MODY
UBE3B	Orphanet:2707	Oculocerebrofacial syndrome, Kaufman type
MMAB	Orphanet:79311	Vitamin B12-responsive methylmalonic acidemia type cblB
IDUA	Orphanet:93473	Hurler syndrome
IDUA	Orphanet:93474	Scheie syndrome
IDUA	Orphanet:93476	Hurler-Scheie syndrome
PTPN22	Orphanet:3437	Vogt-Koyanagi-Harada disease
PTPN22	Orphanet:397	Giant cell arteritis
PTPN22	Orphanet:536	Systemic lupus erythematosus
PTPN22	Orphanet:85408	Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
PTPN22	Orphanet:85410	Oligoarticular juvenile idiopathic arthritis
PTPN22	Orphanet:900	Granulomatosis with polyangiitis

Cohort genes → proteins

10 cohort genes, 10 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	10

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RPL38	HGNC:10349	ENSG00000172809	P63173	Large ribosomal subunit protein eL38	gwas
BLK	HGNC:1057	ENSG00000136573	P51451	Tyrosine-protein kinase Blk	gwas
SLC26A1	HGNC:10993	ENSG00000145217	Q9H2B4	Sulfate anion transporter 1	gwas
UBE3B	HGNC:13478	ENSG00000151148	Q7Z3V4	Ubiquitin-protein ligase E3B	gwas
FAM167A	HGNC:15549	ENSG00000154319	Q96KS9	Protein FAM167A	gwas
MMAB	HGNC:19331	ENSG00000139428	Q96EY8	Corrinoid adenosyltransferase MMAB	gwas
IDUA	HGNC:5391	ENSG00000127415	P35475	Alpha-L-iduronidase	gwas
IL18R1	HGNC:5988	ENSG00000115604	Q13478	Interleukin-18 receptor 1	gwas
NAB1	HGNC:7626	ENSG00000138386	Q13506	NGFI-A-binding protein 1	gwas
PTPN22	HGNC:9652	ENSG00000134242	Q9Y2R2	Tyrosine-protein phosphatase non-receptor type 22	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPL38	Large ribosomal subunit protein eL38	Component of the large ribosomal subunit.
BLK	Tyrosine-protein kinase Blk	Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling.
SLC26A1	Sulfate anion transporter 1	Sodium-independent sulfate anion transporter.
UBE3B	Ubiquitin-protein ligase E3B	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.
MMAB	Corrinoid adenosyltransferase MMAB	Converts cob(I)alamin to adenosylcobalamin (adenosylcob(III)alamin), a coenzyme for methylmalonyl-CoA mutase, therefore participates in the final step of the vitamin B12 conversion.
IL18R1	Interleukin-18 receptor 1	Within the IL18 receptor complex, responsible for the binding of the pro-inflammatory cytokine IL18, but not IL1A nor IL1B.
NAB1	NGFI-A-binding protein 1	Acts as a transcriptional repressor for zinc finger transcription factors EGR1 and EGR2.
PTPN22	Tyrosine-protein phosphatase non-receptor type 22	Acts as a negative regulator of T-cell receptor (TCR) signaling by direct dephosphorylation of the Src family kinases LCK and FYN, ITAMs of the TCRz/CD3 complex, as well as ZAP70, VAV, VCP and other key signaling molecules.

Protein-family classification

Druggable: 7 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.7

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
Phosphatase	1	8.4×	0.243
Transporter	1	7.8×	0.243
Antibody/Immunoglobulin	2	5.8×	0.243
Enzyme (other)	2	2.4×	0.301
Kinase	1	2.8×	0.369
Other/Unknown	3	0.5×	0.976

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPL38	Other/Unknown	no		Ribosomal_eL38, Ribosomal_eL38_sf
BLK	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
SLC26A1	Transporter	yes		SLC26A/SulP_fam, STAS_dom, SLC26A/SulP_dom
UBE3B	Enzyme (other)	yes	2.3.2.26	IQ_motif_EF-hand-BS, HECT_dom, Hect_E3_ubiquitin_ligase
FAM167A	Other/Unknown	no		FAM167, FAM167_domain
MMAB	Enzyme (other)	yes	2.5.1.17	CblAdoTrfase-like, PduO-typ, CblAdoTrfase-like_sf
IDUA	Antibody/Immunoglobulin	yes	3.2.1.76	Glyco_hydro_39, Ig-like_fold, GH_hydrolase_sf
IL18R1	Antibody/Immunoglobulin	yes		TIR_dom, Ig_sub, IL-1_rcpt_I/II-typ
NAB1	Other/Unknown	no		Nab1_C, Nab_N, NAB_co-repressor_dom
PTPN22	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat

Expression context

Cohort genes with no expression data: 0.

9 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)	10
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right adrenal gland cortex	2
right lobe of liver	2
secondary oocyte	2
calcaneal tendon	1
cortical plate	1
olfactory bulb	1
lymph node	1
male germ line stem cell (sensu Vertebrata) in testis	1
spleen	1
left adrenal gland cortex	1
frontal pole	1
oocyte	1
islet of Langerhans	1
stromal cell of endometrium	1
right adrenal gland	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
right lung	1
upper lobe of left lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPL38	295	ubiquitous	marker	calcaneal tendon, cortical plate, olfactory bulb
BLK	145	tissue_specific	marker	spleen, male germ line stem cell (sensu Vertebrata) in testis, lymph node
SLC26A1	156	tissue_specific	yes	right adrenal gland cortex, left adrenal gland cortex, right lobe of liver
UBE3B	289	ubiquitous	marker	oocyte, secondary oocyte, frontal pole
FAM167A	207	broad	marker	stromal cell of endometrium, islet of Langerhans, secondary oocyte
MMAB	235	ubiquitous	marker	right lobe of liver, right adrenal gland cortex, right adrenal gland
IDUA	209	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
IL18R1	191	broad	marker	right lung, upper lobe of left lung, upper lobe of lung
NAB1	290	ubiquitous	marker	ganglionic eminence, skin of hip, upper leg skin
PTPN22	190	broad	marker	bone marrow cell, bone marrow, monocyte

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BLK	2,967
PTPN22	2,480
IDUA	1,927
IL18R1	1,767
SLC26A1	1,454
UBE3B	1,121
MMAB	1,121
FAM167A	796
NAB1	683
RPL38	677

Intra-cohort edges

A	B	Sources
BLK	FAM167A	string_interaction
FAM167A	PTPN22	string_interaction

Structural data

PDB: 6 · AlphaFold-only: 4 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPL38	P63173	188
PTPN22	Q9Y2R2	14
IDUA	P35475	11
MMAB	Q96EY8	6
IL18R1	Q13478	3
NAB1	Q13506	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
UBE3B	Q7Z3V4	85.14
SLC26A1	Q9H2B4	83.13
BLK	P51451	81.89
FAM167A	Q96KS9	71.98

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 63. Enrichment computed across 10 evidence-associated genes (9 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 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
MPS I - Hurler syndrome (HS-GAG degradation)	1	1268.9×	0.025	IDUA
MPS I - Hurler syndrome (CS/DS degradation)	1	1268.9×	0.025	IDUA
Defective MMAB causes MMA, cblB type	1	634.4×	0.033	MMAB
RUNX1 regulates transcription of genes involved in BCR signaling	1	211.5×	0.056	BLK
Transport and metabolism of PAPS	1	181.3×	0.056	SLC26A1
Interleukin-18 signaling	1	158.6×	0.056	IL18R1
Inorganic anion exchange by SLC26 transporters	1	141.0×	0.056	SLC26A1
Cobalamin (Cbl) metabolism	1	141.0×	0.056	MMAB
Defects in cobalamin (B12) metabolism	1	90.6×	0.067	MMAB
Cobalamin (Cbl, vitamin B12) transport and metabolism	1	70.5×	0.067	MMAB
Translocation of ZAP-70 to Immunological synapse	1	70.5×	0.067	PTPN22
Defects in vitamin and cofactor metabolism	1	66.8×	0.067	MMAB
CS/DS degradation	1	60.4×	0.067	IDUA
Phosphorylation of CD3 and TCR zeta chains	1	60.4×	0.067	PTPN22
Cytosolic sulfonation of small molecules	1	57.7×	0.067	SLC26A1
Interleukin-37 signaling	1	57.7×	0.067	IL18R1
HS-GAG degradation	1	55.2×	0.067	IDUA
EGR2 and SOX10-mediated initiation of Schwann cell myelination	1	40.9×	0.077	NAB1
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	1	39.6×	0.077	BLK
Nuclear Events (kinase and transcription factor activation)	1	38.5×	0.077	NAB1
Signaling by the B Cell Receptor (BCR)	1	38.5×	0.077	BLK
NGF-stimulated transcription	1	31.7×	0.087	NAB1
Phase II - Conjugation of compounds	1	30.9×	0.087	SLC26A1
Glycosaminoglycan metabolism	1	24.4×	0.106	SLC26A1
Signaling by NTRK1 (TRKA)	1	21.9×	0.113	NAB1
Signaling by NTRKs	1	20.1×	0.113	NAB1
Metabolism of water-soluble vitamins and cofactors	1	20.1×	0.113	MMAB
Transcriptional regulation by RUNX1	1	16.3×	0.120	BLK
Biological oxidations	1	14.4×	0.120	SLC26A1
R-HSA-425393	1	14.4×	0.120	SLC26A1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
disaccharide metabolic process	1	1872.4×	0.010	IDUA
heparin proteoglycan catabolic process	1	1872.4×	0.010	IDUA
90S preribosome assembly	1	1872.4×	0.010	RPL38
phosphoanandamide dephosphorylation	1	1872.4×	0.010	PTPN22
positive regulation of type II interferon production	2	49.9×	0.010	IL18R1, PTPN22
protein-RNA complex assembly	1	936.2×	0.012	RPL38
regulation of natural killer cell proliferation	1	936.2×	0.012	PTPN22
dermatan sulfate proteoglycan catabolic process	1	468.1×	0.015	IDUA
negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway	1	468.1×	0.015	PTPN22
regulation of epidermis development	1	374.5×	0.015	NAB1
axial mesoderm development	1	374.5×	0.015	RPL38
interleukin-18-mediated signaling pathway	1	312.1×	0.015	IL18R1
regulation of B cell receptor signaling pathway	1	312.1×	0.015	PTPN22
glycosaminoglycan catabolic process	1	267.5×	0.015	IDUA
Schwann cell differentiation	1	267.5×	0.015	NAB1
oxalate transport	1	267.5×	0.015	SLC26A1
positive regulation of toll-like receptor 3 signaling pathway	1	267.5×	0.015	PTPN22
negative regulation of JUN kinase activity	1	267.5×	0.015	PTPN22
positive regulation of protein K63-linked ubiquitination	1	234.1×	0.015	PTPN22
negative regulation of p38MAPK cascade	1	234.1×	0.015	PTPN22
positive regulation of T-helper 1 cell cytokine production	1	234.1×	0.015	IL18R1
heparan sulfate proteoglycan catabolic process	1	208.1×	0.017	IDUA
cellular response to muramyl dipeptide	1	187.2×	0.017	PTPN22
cobalamin metabolic process	1	170.2×	0.017	MMAB
T-helper 1 cell differentiation	1	170.2×	0.017	IL18R1
regulation of non-canonical NF-kappaB signal transduction	1	170.2×	0.017	PTPN22
sulfate transmembrane transport	1	133.8×	0.021	SLC26A1
negative regulation of interleukin-8 production	1	110.1×	0.024	PTPN22
positive regulation of toll-like receptor 4 signaling pathway	1	110.1×	0.024	PTPN22
middle ear morphogenesis	1	78.0×	0.032	RPL38

Therapeutics

Drugs indicated for this disease

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

Drug	Development status
Cortisone Acetate	Approved (phase 4)
Prednisone	Approved (phase 4)
Ustekinumab	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Abatacept, Infliximab, Methimazole, Siponimod, Tocilizumab.

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 8

Druggability breadth: 6 of 10 evidence-associated genes (60%) 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
RPL38	GENTAMICIN SULFATE
BLK	AFATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BLK	62	4
RPL38	1	4
SLC26A1	0	0
UBE3B	0	0
FAM167A	0	0
MMAB	0	0
IDUA	0	0
IL18R1	0	0
NAB1	0	0
PTPN22	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GENTAMICIN SULFATE	4	RPL38
AFATINIB	4	BLK
FEDRATINIB	4	BLK
AXITINIB	4	BLK
SORAFENIB	4	BLK
NERATINIB	4	BLK
IBRUTINIB	4	BLK
ENTRECTINIB	4	BLK
BELUMOSUDIL	4	BLK
AFATINIB DIMALEATE	4	BLK
VANDETANIB	4	BLK
NILOTINIB	4	BLK
BOSUTINIB	4	BLK
BRIGATINIB	4	BLK
ACALABRUTINIB	4	BLK
ZANUBRUTINIB	4	BLK
TIRABRUTINIB	4	BLK
RITLECITINIB	4	BLK
PAZOPANIB	4	BLK
NINTEDANIB	4	BLK
SUNITINIB	4	BLK
DASATINIB	4	BLK
ERLOTINIB	4	BLK
QUIZARTINIB	4	BLK
CRIZOTINIB	4	BLK
MIDOSTAURIN	4	BLK
GEFITINIB	4	BLK
IMATINIB	4	BLK
MASITINIB	3	BLK
LINIFANIB	3	BLK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 5.

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

Symbol	Assays	Type breakdown
BLK	483	Binding:477, ADMET:4, Functional:2
PTPN22	137	Binding:122, Functional:10, ADMET:5
RPL38	90	Binding:90
IDUA	15	Binding:15
MMAB	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BLK	2.7.10.2	non-specific protein-tyrosine kinase
UBE3B	2.3.2.26, 2.3.2.B11	HECT-type E3 ubiquitin transferase,
MMAB	2.5.1.17	corrinoid adenosyltransferase
IDUA	3.2.1.76	L-iduronidase
PTPN22	3.1.3.48	protein-tyrosine-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BLK	483
PTPN22	137

Pharmacogenomics

Cohort genes with a PharmGKB record: 10; 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)
GENTAMICIN SULFATE	4	RPL38
AFATINIB	4	BLK
FEDRATINIB	4	BLK
AXITINIB	4	BLK
SORAFENIB	4	BLK
NERATINIB	4	BLK
IBRUTINIB	4	BLK
ENTRECTINIB	4	BLK
BELUMOSUDIL	4	BLK
AFATINIB DIMALEATE	4	BLK
VANDETANIB	4	BLK
NILOTINIB	4	BLK
BOSUTINIB	4	BLK
BRIGATINIB	4	BLK
ACALABRUTINIB	4	BLK
ZANUBRUTINIB	4	BLK
TIRABRUTINIB	4	BLK
RITLECITINIB	4	BLK
PAZOPANIB	4	BLK
NINTEDANIB	4	BLK
SUNITINIB	4	BLK
DASATINIB	4	BLK
ERLOTINIB	4	BLK
QUIZARTINIB	4	BLK
CRIZOTINIB	4	BLK
MIDOSTAURIN	4	BLK
GEFITINIB	4	BLK
IMATINIB	4	BLK
MASITINIB	3	BLK
LINIFANIB	3	BLK

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	RPL38, BLK
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	4	MMAB, IDUA, IL18R1, PTPN22
D	Druggable family + AlphaFold only, no drug	2	SLC26A1, UBE3B
E	Difficult family or no structure, no drug	2	FAM167A, NAB1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
FAM167A	0	BLK
PTPN22	137	—
SLC26A1	0	—
UBE3B	0	—
MMAB	1	—
IDUA	15	—
IL18R1	0	—
NAB1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 54.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	22
PHASE2	15
PHASE3	7
PHASE2/PHASE3	4
PHASE1/PHASE2	4
PHASE1	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05523167	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Study to Investigate the Efficacy and Safety of Efgartigimod PH20 SC in Adult Participants With Active Idiopathic Inflammatory Myopathy.
NCT05832034	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Add-on Intravenous Immunoglobulins in Early Myositis
NCT05979441	PHASE3	ENROLLING_BY_INVITATION	A Study to Assess the Long-term Safety and Efficacy of a Subcutaneous Formulation of Efgartigimod in Adults With Active Idiopathic Inflammatory Myopathy
NCT06698796	PHASE3	RECRUITING	A Study to Understand How the Study Medicine Dazukibart Works in People With Idiopathic Inflammatory Myopathies
NCT00138983	PHASE3	COMPLETED	Prevention of Glucocorticoid-Induced Osteoporosis in Rheumatic Diseases: Alendronate Versus Alfacalcidol.
NCT00335985	PHASE3	COMPLETED	Efficacy and Safety Study of GB-0998 for Treatment of Steroid-resistant Polymyositis and Dermatomyositis (PM/DM)
NCT00504348	PHASE2/PHASE3	COMPLETED	Investigation in Myositis-associated Pneumonitis of Prednisolone And Concomitant Tacrolimus
NCT00651040	PHASE3	COMPLETED	Combined Treatment of Methotrexate + Glucocorticoids Versus Glucocorticoids Alone in Patients With PM and DM
NCT01165008	PHASE2/PHASE3	COMPLETED	Anakinra in Myositis
NCT02971683	PHASE3	COMPLETED	Trial to Evaluate the Efficacy and Safety of Abatacept in Combination With Standard Therapy Compared to Standard Therapy Alone in Improving Disease Activity in Adults With Active Idiopathic Inflammatory Myopathy
NCT03981744	PHASE3	TERMINATED	A Study of Ustekinumab in Participants With Active Polymyositis and Dermatomyositis Who Have Not Adequately Responded to One or More Standard-of-care Treatments
NCT06347718	PHASE1/PHASE2	RECRUITING	CAR-T Cells in Systemic B Cell Mediated Autoimmune Disease
NCT06685042	PHASE1/PHASE2	RECRUITING	Anti-CD19 CAR T-Cell Therapy in Refractory Systemic Autoimmune Diseases
NCT06888973	PHASE1/PHASE2	ENROLLING_BY_INVITATION	Mesenchymal Stem Cells Infusion in Patients With Autoimmune Diseases
NCT07122648	PHASE2	NOT_YET_RECRUITING	Phase 2 Trial to Evaluate the Efficacy, Safety of Allogeneic Mitochondria (PN-101) in Patients With Refractory Polymyositis or Dermatomyositis
NCT00001261	PHASE2	COMPLETED	Intravenousimmunoglobulin (IVIg) for the Treatment of Inflammatory Myopathies
NCT00001421	PHASE2	COMPLETED	Methimazole to Treat Polymyositis and Dermatomyositis
NCT00033891	PHASE2	COMPLETED	Infliximab (Remicade ) to Treat Dermatomyositis and Polymyositis
NCT00106184	PHASE2	COMPLETED	Rituximab for the Treatment of Refractory Adult and Juvenile Dermatomyositis (DM) and Adult Polymyositis (PM)
NCT01148810	PHASE2	TERMINATED	Efficacy and Tolerability of BAF312 in Patients With Polymyositis and Dermatomyositis
NCT01315938	PHASE2	COMPLETED	Abatacept Treatment in Polymyositis and Dermatomyositis
NCT01415219	PHASE2	COMPLETED	Efficacy of an Individual Rehabilitation Program in Polymyositis and Dermatomyositis
NCT01801917	PHASE2	TERMINATED	Efficacy and Tolerability of BAF312 in Patients With Polymyositis
NCT01906372	PHASE2	COMPLETED	Acthar in Treatment of Refractory Dermatomyositis and Polymyositis
NCT02043548	PHASE2	COMPLETED	Tocilizumab in the Treatment of Refractory Polymyositis and Dermatomyositis
NCT04033926	PHASE2	COMPLETED	A Phase 2 Study of KZR-616 to Evaluate Safety and Efficacy in Patients With Active Polymyositis or Dermatomyositis
NCT04628936	PHASE2	COMPLETED	Open-label Extension to the Phase 2 Crossover Study (PRESIDIO) Evaluating KZR-616 in Patients With PM and DM.
NCT04976140	PHASE1/PHASE2	COMPLETED	Allogeneic Mitochondria (PN-101) Transplantation for Refractory Polymyositis or Dermatomyositis
NCT05650567	PHASE2	TERMINATED	Study of M5049 in DM and PM Participants (NEPTUNIA)
NCT05833711	PHASE2	UNKNOWN	Study Evaluating Efficacy and Safety of Froniglutide (PF1801) in Patients With Idiopathic Inflammatory Myopathy
NCT03817424	PHASE1	COMPLETED	A Study to Evaluate VIB7734 in Participants With Systemic Lupus Erythematosus (SLE), Cutaneous Lupus Erythematosus (CLE), Sjogren’s Syndrome, Systemic Sclerosis, Polymyositis, and Dermatomyositis
NCT04723303	EARLY_PHASE1	COMPLETED	Phase 1 Study of ULSC in Patients With Polymyositis (PM) and Dermatomyositis (DM)
NCT00017914	Not specified	RECRUITING	Adult and Juvenile Myositis
NCT01276470	Not specified	RECRUITING	Environmental Risk Factors for the Anti-synthetase Syndrome
NCT04402086	Not specified	RECRUITING	Rheumatology Patient Registry and Biorepository
NCT07374107	Not specified	RECRUITING	MIHRA - Patient-Rooted Insights for Shaping Myositis Science (PRISMS)
NCT00001167	Not specified	COMPLETED	Ultrasound Evaluation of Tongue Movements in Speech and Swallowing
NCT00001265	Not specified	COMPLETED	Study and Treatment of Inflammatory Muscle Diseases
NCT00001331	Not specified	COMPLETED	Genetic and Family Studies of Inherited Muscle Diseases
NCT00213629	Not specified	COMPLETED	myoARRAY and TcLandscape Analysis for the Diagnosis of Inflammatory Myopathies

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SIPONIMOD	4	2
ABATACEPT	4	1
ANAKINRA	4	1
CORTICOTROPIN	4	1
EFGARTIGIMOD ALFA	4	1
HUMAN IMMUNOGLOBULIN G	4	1
METHIMAZOLE	4	1
TACROLIMUS ANHYDROUS	4	1
USTEKINUMAB	4	1
DAZUKIBART	3	1
ZETOMIPZOMIB	2	2
DAXDILIMAB	2	1
FRONIGLUTIDE	2	1
CHEMBL5220618	0	1