Myositis disease

disease

On this page

Also known as inflammation of muscle tissueinflammatory disorder of muscle (disorder)muscle tissue inflammation

Summary

Myositis disease (MONDO:0021167) is a disease (an umbrella term covering 11 Mondo subtypes) with 34 cohort genes (72 GWAS associations across 16 studies). The dominant Reactome pathway is Interferon gamma signaling (10 cohort genes).

At a glance

Umbrella term: 11 Mondo subtypes
Cohort genes: 34
GWAS associations: 72

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myositis disease
Mondo ID	MONDO:0021167
EFO	EFO:0000783
MeSH	D009220
DOID	DOID:633
NCIT	C27578
SNOMED CT	128496001
UMLS	C0027121
MedGen	44564
Anatomy (UBERON)	UBERON:0000383
Is cancer (heuristic)	no

Also known as: inflammation of muscle tissue · inflammatory disorder of muscle (disorder) · muscle tissue inflammation

Data availability: 72 GWAS associations (16 studies).

Disease family

An umbrella term covering 11 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › myositis disease

Subtypes (11): idiopathic granulomatous myositis, myositis ossificans, tendinitis, myositis fibrosa, inclusion body myositis, viral myositis, bacterial myositis, fungal myositis, infectious myositis, orbital myositis, idiopathic inflammatory myopathy

Genetics & variants

GWAS landscape

72 GWAS associations across 16 studies. Top hits map to 21 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs3129843	9e-133	TSBP1-AS1 - HLA-DRA	G	2.74
rs9268813	7e-120	HLA-DRA - HLA-DRB9	?	2.49
rs114771815	1e-49	MICB-DT, HCP5	C	2.31
rs114050967	3e-49	DDX39B, ATP6V1G2-DDX39B	G	2.32
rs116662199	5e-49	MICB-DT, HCP5	A	2.3
rs9267488	6e-49	ATP6V1G2-DDX39B, ATP6V1G2	G	2.32
rs3130614	4e-48	MICB	A	2.31
DRB1*03	1e-46		?	2.25
DRB1*03:01	8e-46		?	2.23
rs114012716	2e-45	HCP5	A	2.24
rs115902351	2e-45	HCP5	G	2.25
rs115146037	3e-45	HCP5	T	2.24
DQB1*02:01	8e-45		?	2.18
B*08:01	8e-44		?	2.21
B*08	2e-43		?	2.2
rs116088953	3e-43	HCP5	A	2.11
rs10174238	3e-42	STAT4	?	1.37
rs13238352	1e-38	TNPO3	T	1.44
rs6679677	2e-28	PHTF1 - RSBN1	A	1.34
rs2476601	2e-28	AP4B1-AS1, PTPN22	?	1.33
C*07:01	9e-28		?	1.77
rs58721818	5e-23	TNFAIP3 - LINC02865	T	1.64
rs2736337	5e-22	FAM167A - BLK	C	1.23
DPB1*01:01	4e-21		?	2.07
rs13389408	3e-17	STAT4	C	1.27
rs10954214	7e-17	IRF5	T	1.18
DQA1*05:01	1e-15		?	1.45
rs17849502	4e-15	NCF2, SMG7	T	1.36
rs5754467	1e-13	YDJC - CCDC116	G	1.2
DPA1*01:03	9e-13		?	1.44

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90479115	Verma A	2024	26,813	398,649	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90479114	Verma A	2024	8,441	103,976	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481141	Verma A	2024	8,441	103,976	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90652100	Liu TY	2025	5,536	223,283	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST007278	Acosta-Herrera M	2018	4,595	19,704	Genome-wide meta-analysis reveals shared new loci in systemic seropositive rheumatic diseases.
GCST90479113	Verma A	2024	4,069	52,009	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90270216	Rothwell S	2022	2,565	10,260	Genome-wide imputation identifies novel associations and localises signals in idiopathic inflammatory myopathies.
GCST006051	Rothwell S	2015	2,556	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.
GCST003092	Miller FW	2015	1,710	4,724	Genome-wide association study identifies HLA 8.1 ancestral haplotype alleles as major genetic risk factors for myositis phenotypes.
GCST90474092	UK Biobank Whole-Genome Sequencing Consortium	2025	743	457,697	Whole-genome sequencing of 490,640 UK Biobank participants.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	3
Tier 2: splice/UTR	2
Tier 3: regulatory	0
Tier 4: intronic/intergenic	45

MAF distribution

Bucket	Variants
common (>=0.05)	38
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	12

Functional consequences

Consequence	Count
intron_variant	20
unknown	12
intergenic_variant	12
missense_variant	3
non_coding_transcript_exon_variant	1
splice_region_variant	1
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs3129843	6	32427949	A>G	0.11	intron_variant	TSBP1-AS1 - HLA-DRA	9e-133	Tier 4: intronic/intergenic
rs9268813	6	32456817	T>C	0.05	intron_variant	HLA-DRA - HLA-DRB9	7e-120	Tier 4: intronic/intergenic
rs114771815	6	31484059			intron_variant	MICB-DT, HCP5	1e-49	Tier 4: intronic/intergenic
rs114050967	6	31537703			intron_variant	DDX39B, ATP6V1G2-DDX39B	3e-49	Tier 4: intronic/intergenic
rs116662199	6	31481199			non_coding_transcript_exon_variant	MICB-DT, HCP5	5e-49	Tier 4: intronic/intergenic
rs9267488	6	31546470	A>C,G	0.05	splice_region_variant	ATP6V1G2-DDX39B, ATP6V1G2	6e-49	Tier 2: splice/UTR
rs3130614	6	31508681	T>A	0.05	intron_variant	MICB	4e-48	Tier 4: intronic/intergenic
DRB1*03				0.142			1e-46	Tier 4: intronic/intergenic
DRB1*03:01				0.142			8e-46	Tier 4: intronic/intergenic
rs114012716	6	31466589			intron_variant	HCP5	2e-45	Tier 4: intronic/intergenic
rs115902351	6	31466844			intron_variant	HCP5	2e-45	Tier 4: intronic/intergenic
rs115146037	6	31466554			intron_variant	HCP5	3e-45	Tier 4: intronic/intergenic
DQB1*02:01				0.146			8e-45	Tier 4: intronic/intergenic
B*08:01				0.141			8e-44	Tier 4: intronic/intergenic
B*08				0.14			2e-43	Tier 4: intronic/intergenic
rs116088953	6	31475005			intron_variant	HCP5	3e-43	Tier 4: intronic/intergenic
rs10174238	2	191108308	G>A,T	0.05	intron_variant	STAT4	3e-42	Tier 4: intronic/intergenic
rs13238352	7	129007888	C>A,T	0.05	intron_variant	TNPO3	1e-38	Tier 4: intronic/intergenic
rs6679677	1	113761186	C>A,T	0.05	intergenic_variant	PHTF1 - RSBN1	2e-28	Tier 4: intronic/intergenic
rs2476601	1	113834946	A>G,T	0.05	missense_variant	AP4B1-AS1, PTPN22	2e-28	Tier 1: coding
C*07:01				0.174			9e-28	Tier 4: intronic/intergenic
rs58721818	6	137922602	C>G,T	0.05	intergenic_variant	TNFAIP3 - LINC02865	5e-23	Tier 4: intronic/intergenic
rs2736337	8	11484371	T>A,C,G	0.05	intergenic_variant	FAM167A - BLK	5e-22	Tier 4: intronic/intergenic
DPB1*01:01				0.058			4e-21	Tier 4: intronic/intergenic
rs13389408	2	191068557	T>C	0.05	intron_variant	STAT4	3e-17	Tier 4: intronic/intergenic
rs10954214	7	128949579	C>T	0.05	3_prime_UTR_variant	IRF5	7e-17	Tier 2: splice/UTR
DQA1*05:01				0.246			1e-15	Tier 4: intronic/intergenic
rs17849502	1	183563445	G>A,C,T	0.05	missense_variant	NCF2, SMG7	4e-15	Tier 1: coding
rs5754467	22	21630805	A>G,T	0.05	intergenic_variant	YDJC - CCDC116	1e-13	Tier 4: intronic/intergenic
DPA1*01:03				0.183			9e-13	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 66 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
STAT4	Orphanet:117	Behçet disease
STAT4	Orphanet:536	Systemic lupus erythematosus
STAT4	Orphanet:85408	Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
STAT4	Orphanet:85410	Oligoarticular juvenile idiopathic arthritis
STAT4	Orphanet:93552	Pediatric systemic lupus erythematosus
TNFAIP3	Orphanet:536	Systemic lupus erythematosus
TNFAIP3	Orphanet:674762	Early-onset autoinflammatory syndrome due to A20 haploinsufficiency
TRAF6	Orphanet:1810	Autosomal dominant hypohidrotic ectodermal dysplasia
TYK2	Orphanet:300865	Primary cutaneous anaplastic large cell lymphoma
TYK2	Orphanet:331226	Susceptibility to infection due to TYK2 deficiency
TYK2	Orphanet:98842	Lymphomatoid papulosis
TNIP1	Orphanet:536	Systemic lupus erythematosus
TNPO3	Orphanet:186	Primary biliary cholangitis
TNPO3	Orphanet:55595	TNP03-related limb-girdle muscular dystrophy D2
PRR12	Orphanet:659904	Multiple congenital anomalies-neurodevelopmental delay-ocular abnormalities syndrome
DNASE1L3	Orphanet:300345	Autosomal systemic lupus erythematosus
DNASE1L3	Orphanet:36412	Hypocomplementemic urticarial vasculitis
HLA-B	Orphanet:117	Behçet disease
HLA-B	Orphanet:275798	Pulmonary arterial hypertension associated with connective tissue disease
HLA-B	Orphanet:29207	Reactive arthritis
HLA-B	Orphanet:3287	Takayasu arteritis
HLA-B	Orphanet:36426	Stevens-Johnson syndrome
HLA-B	Orphanet:397	Giant cell arteritis
HLA-C	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
HLA-DPA1	Orphanet:900	Granulomatosis with polyangiitis
HLA-DPB1	Orphanet:133	Chronic beryllium disease
HLA-DPB1	Orphanet:900	Granulomatosis with polyangiitis
HLA-DQA1	Orphanet:391490	Adult-onset myasthenia gravis
HLA-DQA1	Orphanet:930	Idiopathic achalasia
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
HLA-DRB1	Orphanet:2073	Narcolepsy type 1
HLA-DRB1	Orphanet:220393	Diffuse cutaneous systemic sclerosis
HLA-DRB1	Orphanet:220402	Limited cutaneous systemic sclerosis
HLA-DRB1	Orphanet:220407	Limited systemic sclerosis
HLA-DRB1	Orphanet:3437	Vogt-Koyanagi-Harada disease
HLA-DRB1	Orphanet:397	Giant cell arteritis
HLA-DRB1	Orphanet:477738	Pediatric multiple sclerosis
HLA-DRB1	Orphanet:536	Systemic lupus erythematosus
HLA-DRB1	Orphanet:545	Follicular lymphoma
HLA-DRB1	Orphanet:703	Bullous pemphigoid
HLA-DRB1	Orphanet:747	Autoimmune pulmonary alveolar proteinosis
HLA-DRB1	Orphanet:797	Sarcoidosis
HLA-DRB1	Orphanet:83465	Narcolepsy type 2
HLA-DRB1	Orphanet:85414	Systemic-onset juvenile idiopathic arthritis
IRF8	Orphanet:319600	Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency
AP4B1	Orphanet:280763	Severe intellectual disability and progressive spastic paraplegia

Cohort genes → proteins

34 cohort genes, 32 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	34

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
STAT4	HGNC:11365	ENSG00000138378	Q14765	Signal transducer and activator of transcription 4	gwas
TNFAIP3	HGNC:11896	ENSG00000118503	P21580	Tumor necrosis factor alpha-induced protein 3	gwas
TRAF6	HGNC:12036	ENSG00000175104	Q9Y4K3	TNF receptor-associated factor 6	gwas
TYK2	HGNC:12440	ENSG00000105397	P29597	Non-receptor tyrosine-protein kinase TYK2	gwas
DDX39B	HGNC:13917	ENSG00000198563	Q13838	Spliceosome RNA helicase DDX39B	gwas
TNIP1	HGNC:16903	ENSG00000145901	Q15025	TNFAIP3-interacting protein 1	gwas
TNPO3	HGNC:17103	ENSG00000064419	Q9Y5L0	Transportin-3	gwas
CYCSP5	HGNC:24416	ENSG00000227735		CYCS pseudogene 5	gwas
PRR5L	HGNC:25878	ENSG00000135362	Q6MZQ0	Proline-rich protein 5-like	gwas
YDJC	HGNC:27158	ENSG00000161179	A8MPS7	Carbohydrate deacetylase	gwas
DGKQ	HGNC:2856	ENSG00000145214	P52824	Diacylglycerol kinase theta	gwas
PRR12	HGNC:29217	ENSG00000126464	Q9ULL5	Proline-rich protein 12	gwas
DNASE1L3	HGNC:2959	ENSG00000163687	Q13609	Deoxyribonuclease gamma	gwas
HCG26	HGNC:29671			HLA complex group 26	gwas
HLA-B	HGNC:4932	ENSG00000234745	P01889	HLA class I histocompatibility antigen, B alpha chain	gwas
HLA-C	HGNC:4933	ENSG00000204525	P10321	HLA class I histocompatibility antigen, C alpha chain	gwas
HLA-DPA1	HGNC:4938	ENSG00000231389	P20036	HLA class II histocompatibility antigen, DP alpha 1 chain	gwas
HLA-DPB1	HGNC:4940	ENSG00000223865	P04440	HLA class II histocompatibility antigen, DP beta 1 chain	gwas
HLA-DQA1	HGNC:4942	ENSG00000196735	P01909	HLA class II histocompatibility antigen, DQ alpha 1 chain	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
HLA-DRB1	HGNC:4948	ENSG00000196126	P01911	HLA class II histocompatibility antigen, DRB1 beta chain	gwas
IRF8	HGNC:5358	ENSG00000140968	Q02556	Interferon regulatory factor 8	gwas
AP4B1	HGNC:572	ENSG00000134262	Q9Y6B7	AP-4 complex subunit beta-1	gwas
IL12RB2	HGNC:5972	ENSG00000081985	Q99665	Interleukin-12 receptor subunit beta-2	gwas
IRF5	HGNC:6120	ENSG00000128604	Q13568	Interferon regulatory factor 5	gwas
LIMK1	HGNC:6613	ENSG00000106683	P53667	LIM domain kinase 1	gwas
MGAT4A	HGNC:7047	ENSG00000071073	Q9UM21	Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase A	gwas
MICB	HGNC:7091	ENSG00000204516	Q29980	MHC class I polypeptide-related sequence B	gwas
NAB1	HGNC:7626	ENSG00000138386	Q13506	NGFI-A-binding protein 1	gwas
NCF2	HGNC:7661	ENSG00000116701	P19878	Neutrophil cytosol factor 2	gwas
ATP6V1G2	HGNC:862	ENSG00000213760	O95670	V-type proton ATPase subunit G 2	gwas
PTPN11	HGNC:9644	ENSG00000179295	Q06124	Tyrosine-protein phosphatase non-receptor type 11	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)
STAT4	Signal transducer and activator of transcription 4	Transcriptional regulator mainly expressed in hematopoietic cells that plays a critical role in cellular growth, differentiation and immune response.
TNFAIP3	Tumor necrosis factor alpha-induced protein 3	Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities.
TRAF6	TNF receptor-associated factor 6	E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of ‘Lys-63’-linked-polyubiquitin chains conjugated to proteins, such as ECSIT, IKBKG, IRAK1, AKT1 and AKT2.
TYK2	Non-receptor tyrosine-protein kinase TYK2	Tyrosine kinase of the non-receptor type involved in numerous cytokines and interferons signaling, which regulates cell growth, development, cell migration, innate and adaptive immunity.
DDX39B	Spliceosome RNA helicase DDX39B	Involved in nuclear export of spliced and unspliced mRNA.
TNIP1	TNFAIP3-interacting protein 1	Inhibits NF-kappa-B activation and TNF-induced NF-kappa-B-dependent gene expression by regulating TAX1BP1 and A20/TNFAIP3-mediated deubiquitination of IKBKG; proposed to link A20/TNFAIP3 to ubiquitinated IKBKG.
TNPO3	Transportin-3	Importin, which transports target proteins into the nucleus.
PRR5L	Proline-rich protein 5-like	Associates with the mTORC2 complex that regulates cellular processes including survival and organization of the cytoskeleton.
YDJC	Carbohydrate deacetylase	Probably catalyzes the deacetylation of acetylated carbohydrates an important step in the degradation of oligosaccharides.
DGKQ	Diacylglycerol kinase theta	Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids.
PRR12	Proline-rich protein 12	May play a role in the regulation of cohesin complex loading onto chromatin, probably acting in coordination with NIPBL and MAU2.
DNASE1L3	Deoxyribonuclease gamma	Has DNA hydrolytic activity.
HLA-B	HLA class I histocompatibility antigen, B alpha chain	Antigen-presenting major histocompatibility complex class I (MHCI) molecule.
HLA-C	HLA class I histocompatibility antigen, C alpha chain	Antigen-presenting major histocompatibility complex class I (MHCI) molecule with an important role in reproduction and antiviral immunity.
HLA-DPA1	HLA class II histocompatibility antigen, DP alpha 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.
HLA-DPB1	HLA class II histocompatibility antigen, DP 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.
HLA-DQA1	HLA class II histocompatibility antigen, DQ alpha 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.
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.
HLA-DRB1	HLA class II histocompatibility antigen, DRB1 beta chain	A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule.
IRF8	Interferon regulatory factor 8	Transcription factor that specifically binds to the upstream regulatory region of type I interferon (IFN) and IFN-inducible MHC class I genes (the interferon consensus sequence (ICS)).
AP4B1	AP-4 complex subunit beta-1	Component of the adaptor protein complex 4 (AP-4).
IL12RB2	Interleukin-12 receptor subunit beta-2	Receptor for interleukin-12.
IRF5	Interferon regulatory factor 5	Transcription factor that plays a critical role in innate immunity by activating expression of type I interferon (IFN) IFNA and INFB and inflammatory cytokines downstream of endolysosomal toll-like receptors TLR7, TLR8 and TLR9.
LIMK1	LIM domain kinase 1	Serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics.
MGAT4A	Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase A	Glycosyltransferase that catalyze the transfer of GlcNAc from UDP-GlcNAc to the GlcNAcbeta1-2Manalpha1-3 arm of the core structure of N-linked glycans through a beta1-4 linkage and participates in the production of tri- and tetra-antennary…
MICB	MHC class I polypeptide-related sequence B	Widely expressed membrane-bound protein which acts as a ligand to stimulate an activating receptor KLRK1/NKG2D, expressed on the surface of essentially all human natural killer (NK), gammadelta T and CD8+ alphabeta T-cells.
NAB1	NGFI-A-binding protein 1	Acts as a transcriptional repressor for zinc finger transcription factors EGR1 and EGR2.
NCF2	Neutrophil cytosol factor 2	Subunit of the phagocyte NADPH oxidase complex that mediates the transfer of electrons from cytosolic NADPH to O2 to produce the superoxide anion (O2(-)).
ATP6V1G2	V-type proton ATPase subunit G 2	Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons.
PTPN11	Tyrosine-protein phosphatase non-receptor type 11	Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus.
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: 18 · Difficult: 4 · Unknown: 12 · Druggable fraction: 0.53

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
Antibody/Immunoglobulin	10	8.6×	9e-07
Phosphatase	3	7.4×	0.027
Kinase	3	2.5×	0.287
Transcription factor	3	0.7×	0.995
Enzyme (other)	2	0.7×	0.995
Other/Unknown	12	0.6×	0.995
Scaffold/PPI	1	0.5×	0.995

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
STAT4	Transcription factor	no		SH2, STAT, p53-like_TF_DNA-bd_sf
TNFAIP3	Transcription factor	no		Znf_A20, OTU_dom, OTU_Deubiquitinase
TRAF6	Transcription factor	no		Znf_TRAF, Znf_RING, MATH/TRAF_dom
TYK2	Kinase	yes	2.7.10.2	FERM_domain, Prot_kinase_dom, SH2
DDX39B	Other/Unknown	no		Helicase_C-like, DEAD/DEAH_box_helicase_dom, Helicase_ATP-bd
TNIP1	Other/Unknown	no
TNPO3	Other/Unknown	no		ARM-like, Exportin-1/Importin-b-like, ARM-type_fold
CYCSP5	Other/Unknown	no
PRR5L	Other/Unknown	no		Bit61/PRR5
YDJC	Enzyme (other)	yes	3.5.1.105	YdjC-like, Glyco_hydro/deAcase_b/a-brl
DGKQ	Kinase	yes	2.7.1.107	RA_dom, Diacylglycerol_kin_accessory, Diacylglycerol_kinase_cat_dom
PRR12	Other/Unknown	no		DUF4211, DNA_MethProtect_Complex
DNASE1L3	Phosphatase	yes		Endo/exonuclease/phosphatase, DNase_I, Deoxyribonuclease-1_AS
HCG26	Other/Unknown	no
HLA-B	Antibody/Immunoglobulin	yes		MHC_I_a_a1/a2, Ig/MHC_CS, Ig_C1-set
HLA-C	Antibody/Immunoglobulin	yes		MHC_I_a_a1/a2, Ig_C1-set, Ig-like_dom
HLA-DPA1	Antibody/Immunoglobulin	yes		MHC_II_a_N, Ig/MHC_CS, Ig_C1-set
HLA-DPB1	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
HLA-DQA1	Antibody/Immunoglobulin	yes		MHC_II_a_N, Ig/MHC_CS, Ig_C1-set
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
HLA-DRB1	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
IRF8	Other/Unknown	no		Interferon_reg_fact_DNA-bd_dom, SMAD_FHA_dom_sf, SMAD-like_dom_sf
AP4B1	Other/Unknown	no		Clathrin/coatomer_adapt-like_N, ARM-like, TBP_dom_sf
IL12RB2	Antibody/Immunoglobulin	yes		Hematopoietin_rcpt_Gp130_CS, FN3_dom, IgC2-like_lig-bd
IRF5	Other/Unknown	no		Interferon_reg_fact_DNA-bd_dom, SMAD_FHA_dom_sf, SMAD-like_dom_sf
LIMK1	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PDZ
MGAT4A	Enzyme (other)	yes	2.4.1.145	Glyco_transf_54, MGAT4_A/B/C_C, MGAT4
MICB	Antibody/Immunoglobulin	yes		Ig_C1-set, Ig-like_dom, MHC_I-like_Ag-recog
NAB1	Other/Unknown	no		Nab1_C, Nab_N, NAB_co-repressor_dom
NCF2	Scaffold/PPI	no		PB1_dom, SH3_domain, TPR-like_helical_dom_sf
ATP6V1G2	Other/Unknown	no		V-ATPase_G
PTPN11	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, SH2
PTPN22	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat

Expression context

Cohort genes with no expression data: 1.

28 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)	33
unknown	1

Top tissues across cohort

Tissue	Cohort genes
granulocyte	14
monocyte	7
vermiform appendix	4
spleen	4
leukocyte	4
blood	3
right lung	3
mononuclear cell	3
primordial germ cell in gonad	2
secondary oocyte	2
adenohypophysis	2
right hemisphere of cerebellum	2
hindlimb stylopod muscle	2
medial globus pallidus	2
male germ line stem cell (sensu Vertebrata) in testis	2
mucosa of transverse colon	2
rectum	2
kidney epithelium	2
cerebellar hemisphere	2
middle temporal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
STAT4	201	broad	marker	granulocyte, sperm, middle temporal gyrus
TNFAIP3	274	ubiquitous	marker	vena cava, mucosa of paranasal sinus, vermiform appendix
TRAF6	235	ubiquitous	marker	secondary oocyte, endothelial cell, primordial germ cell in gonad
TYK2	288	ubiquitous	marker	granulocyte, right hemisphere of cerebellum, adenohypophysis
DDX39B	263	ubiquitous	marker	granulocyte, adenohypophysis, ventricular zone
TNIP1	298	ubiquitous	marker	lower esophagus mucosa, blood, hindlimb stylopod muscle
TNPO3	299	ubiquitous	marker	secondary oocyte, tendon of biceps brachii, medial globus pallidus
CYCSP5	97		yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, corpus callosum
PRR5L	203	ubiquitous	marker	mucosa of transverse colon, granulocyte, rectum
YDJC	177	ubiquitous	marker	kidney epithelium, granulocyte, mucosa of transverse colon
DGKQ	235	ubiquitous	yes	ileal mucosa, pancreatic ductal cell, granulocyte
PRR12	210	ubiquitous	yes	kidney epithelium, cardia of stomach, nipple
DNASE1L3	228	broad	marker	periodontal ligament, spleen, gingival epithelium
HCG26
HLA-B	134	ubiquitous	marker	blood, spleen, granulocyte
HLA-C	134	ubiquitous	marker	blood, right lung, spleen
HLA-DPA1	133	ubiquitous	marker	monocyte, leukocyte, granulocyte
HLA-DPB1	135	ubiquitous	marker	granulocyte, lymph node, vermiform appendix
HLA-DQA1	244	broad	marker	gall bladder, rectum, monocyte
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
HLA-DRB1	131	tissue_specific	marker	vermiform appendix, granulocyte, right lung
IRF8	265	broad	marker	monocyte, mononuclear cell, leukocyte
AP4B1	258	ubiquitous	marker	granulocyte, cerebellar hemisphere, right hemisphere of cerebellum
IL12RB2	170	broad	marker	hindlimb stylopod muscle, gastrocnemius, muscle of leg
IRF5	214	broad	marker	monocyte, mononuclear cell, granulocyte
LIMK1	184	ubiquitous	yes	stromal cell of endometrium, right frontal lobe, cingulate cortex
MGAT4A	266	ubiquitous	marker	jejunal mucosa, colonic mucosa, renal medulla
MICB	133	ubiquitous	yes	granulocyte, leukocyte, monocyte
NAB1	290	ubiquitous	marker	ganglionic eminence, skin of hip, upper leg skin

Protein interactions among cohort

Intra-cohort edges: 29.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TRAF6	6,163
PTPN11	6,009
DDX39B	5,600
TYK2	3,932
TNFAIP3	3,716
IRF8	3,554
HLA-DRB1	3,448
TNIP1	3,304
HLA-B	3,209
LIMK1	3,112

Intra-cohort edges

A	B	Sources
DNASE1L3	IRF5	string_interaction
HLA-B	HLA-C	biogrid_interaction, intact
HLA-B	HLA-DQA2	string_interaction
HLA-C	HLA-DQB1	intact
HLA-DPA1	HLA-DPB1	intact
HLA-DPA1	HLA-DQB1	intact
HLA-DQA1	HLA-DQA2	intact
HLA-DQA1	HLA-DQB1	biogrid_interaction, intact
HLA-DQA2	HLA-DRB1	string_interaction
HLA-DRB1	IRF5	string_interaction
HLA-DRB1	PTPN22	string_interaction
IL12RB2	STAT4	biogrid_interaction, intact, string_interaction
IL12RB2	TYK2	string_interaction
IRF5	IRF8	string_interaction
IRF5	PTPN22	string_interaction
IRF5	STAT4	string_interaction
IRF5	TNFAIP3	string_interaction
IRF5	TNIP1	string_interaction
IRF5	TNPO3	string_interaction
IRF5	TRAF6	biogrid_interaction, string_interaction
IRF5	TYK2	string_interaction
IRF8	TRAF6	string_interaction
NAB1	STAT4	string_interaction
PTPN22	STAT4	string_interaction
PTPN22	TNFAIP3	string_interaction
STAT4	TYK2	string_interaction
TNFAIP3	TNIP1	biogrid_interaction, intact, string_interaction
TNFAIP3	TRAF6	biogrid_interaction, string_interaction
TNIP1	TRAF6	string_interaction

Structural data

PDB: 24 · AlphaFold-only: 8 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HLA-B	P01889	237
PTPN11	Q06124	115
HLA-DRB1	P01911	108
TYK2	P29597	52
HLA-DQA1	P01909	28
TNFAIP3	P21580	17
DDX39B	Q13838	17
PTPN22	Q9Y2R2	14
TRAF6	Q9Y4K3	13
HLA-C	P10321	13
HLA-DPA1	P20036	10
HLA-DPB1	P04440	10
HLA-DQB1	P01920	10
LIMK1	P53667	10
TNIP1	Q15025	8
NCF2	P19878	7
TNPO3	Q9Y5L0	6
AP4B1	Q9Y6B7	5
IL12RB2	Q99665	2
MICB	Q29980	2
DNASE1L3	Q13609	1
IRF5	Q13568	1
MGAT4A	Q9UM21	1
NAB1	Q13506	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ATP6V1G2	O95670	94.14
YDJC	A8MPS7	91.77
HLA-DQA2	P01906	89.29
STAT4	Q14765	86.87
DGKQ	P52824	82.56
IRF8	Q02556	75.54
PRR5L	Q6MZQ0	68.40
PRR12	Q9ULL5	43.84

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 195. Enrichment computed across 34 evidence-associated genes (27 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 27 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interferon gamma signaling	10	46.5×	9e-13	HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRB1 (+2 more)
Translocation of ZAP-70 to Immunological synapse	6	141.0×	2e-10	HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DRB1, PTPN22
Phosphorylation of CD3 and TCR zeta chains	6	120.8×	3e-10	HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DRB1, PTPN22
Co-inhibition by PD-1	6	115.3×	3e-10	HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DRB1, PTPN11
Generation of second messenger molecules	5	64.1×	4e-07	HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DRB1
Interferon alpha/beta signaling	6	33.8×	6e-07	TYK2, HLA-B, HLA-C, IRF8, IRF5, PTPN11
Downstream TCR signaling	6	28.5×	1e-06	TRAF6, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DRB1
Interleukin-35 Signalling	3	105.7×	6e-05	STAT4, TYK2, IL12RB2
MHC class II antigen presentation	5	16.5×	2e-04	HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DRB1
SARS-CoV-2 activates/modulates innate and adaptive immune responses	5	16.5×	2e-04	TRAF6, TYK2, HLA-B, HLA-C, PTPN11
Interleukin-20 family signaling	3	47.0×	6e-04	STAT4, TYK2, PTPN11
Interleukin-12 signaling	3	45.3×	6e-04	STAT4, TYK2, IL12RB2
Ovarian tumor domain proteases	3	30.9×	0.002	TNFAIP3, TRAF6, TNIP1
Interleukin-23 signaling	2	94.0×	0.003	STAT4, TYK2
MAPK1 (ERK2) activation	2	84.6×	0.003	TYK2, PTPN11
MAPK3 (ERK1) activation	2	76.9×	0.003	TYK2, PTPN11
Endosomal/Vacuolar pathway	2	76.9×	0.003	HLA-B, HLA-C
Interleukin-6 signaling	2	70.5×	0.004	TYK2, PTPN11
Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells)	2	65.1×	0.004	STAT4, IL12RB2
Signaling by CSF3 (G-CSF)	2	42.3×	0.010	TYK2, PTPN11
DAP12 interactions	2	35.2×	0.013	HLA-B, HLA-C
Regulation of IFNA/IFNB signaling	2	32.5×	0.015	TYK2, PTPN11
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	2	29.2×	0.018	HLA-B, HLA-C
ROS and RNS production in phagocytes	2	24.9×	0.023	NCF2, ATP6V1G2
NOD1/2 Signaling Pathway	2	23.5×	0.025	TNFAIP3, TRAF6
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	3	9.7×	0.026	HLA-B, HLA-C, MICB
MET activates PTPN11	1	84.6×	0.082	PTPN11
Co-inhibition by BTLA	1	84.6×	0.082	PTPN11
SLC15A4:TASL-dependent IRF5 activation	1	70.5×	0.095	IRF5
Immune System	6	2.9×	0.098	STAT4, IRF8, IRF5, LIMK1, MICB, NCF2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 32 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
antigen processing and presentation of exogenous peptide antigen via MHC class II	7	118.9×	4e-11	TRAF6, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRB1
peptide antigen assembly with MHC class II protein complex	6	197.5×	4e-11	HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRB1
positive regulation of immune response	6	90.3×	5e-09	HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRB1
positive regulation of T cell activation	6	83.2×	6e-09	HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRB1
immune response	10	14.7×	5e-08	TYK2, HLA-B, HLA-C, HLA-DPA1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRB1 (+2 more)
adaptive immune response	8	21.1×	2e-07	HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, MICB
positive regulation of type II interferon production	6	42.1×	3e-07	TYK2, HLA-DPA1, HLA-DPB1, IRF8, IL12RB2, PTPN22
interleukin-12-mediated signaling pathway	3	175.5×	2e-05	STAT4, TYK2, IL12RB2
T cell receptor signaling pathway	5	23.7×	8e-05	TRAF6, HLA-DPB1, HLA-DQB1, HLA-DRB1, PTPN22
cytokine-mediated signaling pathway	5	20.4×	1e-04	STAT4, TYK2, IL12RB2, IRF5, PTPN11
positive regulation of T cell proliferation	4	32.4×	2e-04	TRAF6, TYK2, HLA-DPA1, HLA-DPB1
negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway	2	263.3×	6e-04	TNFAIP3, PTPN22
positive regulation of T cell mediated cytotoxicity	3	47.9×	9e-04	HLA-B, HLA-C, HLA-DRB1
positive regulation of type I interferon production	3	39.5×	0.001	TRAF6, IRF5, PTPN22
positive regulation of interleukin-12 production	3	36.7×	0.002	TRAF6, IRF8, IRF5
T-helper 1 type immune response	2	117.0×	0.003	TRAF6, HLA-DRB1
cellular response to muramyl dipeptide	2	105.3×	0.003	IRF5, PTPN22
positive regulation of lipopolysaccharide-mediated signaling pathway	2	95.8×	0.004	TRAF6, PTPN11
detection of bacterium	2	87.8×	0.004	HLA-B, HLA-DRB1
antigen processing and presentation of endogenous peptide antigen via MHC class Ib	2	81.0×	0.004	HLA-B, HLA-C
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent	2	81.0×	0.004	HLA-B, HLA-C
cellular response to lipopolysaccharide	4	12.2×	0.005	TNFAIP3, TRAF6, TNIP1, IRF8
defense response	3	20.2×	0.006	STAT4, TNIP1, HLA-B
MyD88-dependent toll-like receptor signaling pathway	2	58.5×	0.007	TRAF6, TNIP1
regulation of interleukin-4 production	1	526.6×	0.019	HLA-DRB1
negative regulation of toll-like receptor 5 signaling pathway	1	526.6×	0.019	TNFAIP3
phosphoanandamide dephosphorylation	1	526.6×	0.019	PTPN22
negative regulation of cortisol secretion	1	526.6×	0.019	PTPN11
negative regulation of growth hormone secretion	1	526.6×	0.019	PTPN11
regulation of vascular wound healing	1	526.6×	0.019	TNFAIP3

Therapeutics

Drugs indicated for this disease

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

Drug	Development status
Dazukibart	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Aldesleukin, Baricitinib, Belimumab, Cyclosporine, Infliximab, Nipocalimab, OMEGA-3-ACID ETHYL ESTERS, Tofacitinib.

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 4 · Undrugged: 30

Druggability breadth: 15 of 34 evidence-associated genes (44%) 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
TYK2	FEDRATINIB
LIMK1	FEDRATINIB
PTPN11	ESTRAMUSTINE PHOSPHATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TYK2	72	4
LIMK1	38	4
PTPN11	8	4
PRR12	1	2
STAT4	0	0
TNFAIP3	0	0
TRAF6	0	0
DDX39B	0	0
TNIP1	0	0
TNPO3	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	LIMK1, TYK2
RUXOLITINIB	4	TYK2
TOFACITINIB	4	TYK2
UPADACITINIB	4	TYK2
BARICITINIB	4	TYK2
FILGOTINIB	4	TYK2
ABROCITINIB	4	TYK2
DEUCRAVACITINIB	4	TYK2
MOMELOTINIB	4	TYK2
AXITINIB	4	TYK2
RUXOLITINIB PHOSPHATE	4	TYK2
INFIGRATINIB PHOSPHATE	4	TYK2
INFIGRATINIB	4	TYK2
PACRITINIB	4	TYK2
TOFACITINIB CITRATE	4	TYK2
BOSUTINIB	4	TYK2
PEFICITINIB	4	TYK2
CRAVACITINIB	4	TYK2
PAZOPANIB	4	LIMK1, TYK2
NINTEDANIB	4	TYK2
SUNITINIB	4	TYK2
DASATINIB	4	LIMK1, TYK2
ERLOTINIB	4	TYK2
CRIZOTINIB	4	LIMK1, TYK2
MIDOSTAURIN	4	TYK2
IMATINIB	4	TYK2
SORAFENIB	4	LIMK1
IBRUTINIB	4	LIMK1
REGORAFENIB	4	LIMK1
DABRAFENIB	4	LIMK1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 7.

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

Symbol	Assays	Type breakdown
TYK2	1,083	Binding:1043, Functional:39, ADMET:1
PTPN11	588	Binding:585, Functional:2, ADMET:1
LIMK1	307	Binding:306, Functional:1
PTPN22	137	Binding:122, Functional:10, ADMET:5
STAT4	20	Binding:20
HLA-DRB1	17	Binding:17
TRAF6	6	Binding:6
PRR12	6	Binding:6
DNASE1L3	5	Binding:5
HLA-DQA1	2	Binding:2
TNFAIP3	1	Binding:1
DDX39B	1	Binding:1
TNPO3	1	Binding:1
HLA-B	1	Binding:1
HLA-C	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TYK2	2.7.10.2	non-specific protein-tyrosine kinase
YDJC	3.5.1.105	chitin disaccharide deacetylase
DGKQ	2.7.1.107	diacylglycerol kinase (ATP)
LIMK1	2.7.11.1	non-specific serine/threonine protein kinase
MGAT4A	2.4.1.145	alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase
PTPN11	3.1.3.48	protein-tyrosine-phosphatase
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
TYK2	1,083
LIMK1	307
PTPN11	588
PTPN22	137

Pharmacogenomics

Cohort genes with a PharmGKB record: 34; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
HLA-B	1

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	LIMK1, TYK2
RUXOLITINIB	4	TYK2
TOFACITINIB	4	TYK2
UPADACITINIB	4	TYK2
BARICITINIB	4	TYK2
FILGOTINIB	4	TYK2
ABROCITINIB	4	TYK2
DEUCRAVACITINIB	4	TYK2
MOMELOTINIB	4	TYK2
AXITINIB	4	TYK2
RUXOLITINIB PHOSPHATE	4	TYK2
INFIGRATINIB PHOSPHATE	4	TYK2
INFIGRATINIB	4	TYK2
PACRITINIB	4	TYK2
TOFACITINIB CITRATE	4	TYK2
BOSUTINIB	4	TYK2
PEFICITINIB	4	TYK2
CRAVACITINIB	4	TYK2
PAZOPANIB	4	LIMK1, TYK2
NINTEDANIB	4	TYK2
SUNITINIB	4	TYK2
DASATINIB	4	LIMK1, TYK2
ERLOTINIB	4	TYK2
CRIZOTINIB	4	LIMK1, TYK2
MIDOSTAURIN	4	TYK2
IMATINIB	4	TYK2
SORAFENIB	4	LIMK1
IBRUTINIB	4	LIMK1
REGORAFENIB	4	LIMK1
DABRAFENIB	4	LIMK1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	TYK2, LIMK1, PTPN11
B	Phased (≥1) drug, not yet approved	1	PRR12
C	Druggable family + PDB, no drug	12	DNASE1L3, HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRB1, IL12RB2, MGAT4A (+2 more)
D	Druggable family + AlphaFold only, no drug	3	YDJC, DGKQ, HLA-DQA2
E	Difficult family or no structure, no drug	15	STAT4, TNFAIP3, TRAF6, DDX39B, TNIP1, TNPO3, CYCSP5, PRR5L, HCG26, IRF8 (+5 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
STAT4	20	TYK2
IL12RB2	0	TYK2
IRF5	0	TYK2
PTPN22	137	—
TNFAIP3	1	—
TRAF6	6	—
DDX39B	1	—
TNIP1	0	—
TNPO3	1	—
CYCSP5	0	—
PRR5L	0	—
YDJC	0	—
DGKQ	0	—
DNASE1L3	5	—
HCG26	0	—
HLA-B	1	—
HLA-C	1	—
HLA-DPA1	0	—
HLA-DPB1	0	—
HLA-DQA1	2	—
HLA-DQA2	0	—
HLA-DQB1	0	—
HLA-DRB1	17	—
IRF8	0	—
AP4B1	0	—
MGAT4A	0	—
MICB	0	—
NAB1	0	—
NCF2	0	—
ATP6V1G2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: STAT4, TNFAIP3, TRAF6, TYK2, DDX39B, TNIP1, TNPO3, PRR5L, YDJC, DGKQ, PRR12, DNASE1L3, HCG26, HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRB1, IRF8, AP4B1, IL12RB2, IRF5, LIMK1, MGAT4A, MICB, NAB1, NCF2, ATP6V1G2, PTPN11, PTPN22