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Atlas / Disease / Autoimmune disease

Autoimmune disease

disease
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Also known as autoimmune disease or disorderautoimmune disorderdisease, autoimmune

Summary

Autoimmune disease (MONDO:0007179) is a disease (an umbrella term covering 47 Mondo subtypes) with 75 cohort genes (182 GWAS associations across 10 studies) and 349 clinical trials. The dominant Reactome pathway is Interleukin-23 signaling (5 cohort genes). Top therapeutic interventions include doxycycline anhydrous, cephalexin anhydrous, and deucravacitinib.

At a glance

  • Umbrella term: 47 Mondo subtypes
  • Cohort genes: 75
  • GWAS associations: 182
  • Clinical trials: 349

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameautoimmune disease
Mondo IDMONDO:0007179
EFOEFO:0005809
MeSHD001327
OMIM109100
DOIDDOID:417
NCITC2889
SNOMED CT85828009
UMLSC0004364
MedGen2135
Is cancer (heuristic)no

Also known as: autoimmune disease · autoimmune disease or disorder · autoimmune disorder · disease, autoimmune

Data availability: 182 GWAS associations (10 studies) · 7 GenCC gene-disease records.

Disease family

An umbrella term covering 47 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › immune system disorder › autoimmune disease

Related subtypes (46): hypersensitivity reaction disease, immune system cancer, immune system organ benign neoplasm, bone marrow disorder, thymus gland disorder, inborn error of immunity, leukocyte disorder, psoriasis, spondyloarthropathy, aggressive insulitis, benign insulitis, inflammatory bowel disease, TNF receptor 1-associated periodic fever syndrome, epidermodysplasia verruciformis, Vici syndrome, proteosome-associated autoinflammatory syndrome, hyperimmunoglobulinemia D with periodic fever, transcobalamin II deficiency, pyogenic arthritis-pyoderma gangrenosum-acne syndrome, granulomatosis with polyangiitis, autosomal recessive osteopetrosis 7, graft versus host disease, congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome, Roifman syndrome, cryopyrin-associated periodic syndrome, anti-HLA hyperimmunization, acquired immunodeficiency, erythroderma desquamativum, autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis, familial Mediterranean fever, 22q11.2 deletion syndrome, T-cell large granular lymphocyte leukemia, twin to twin transfusion syndrome, immunodeficiency disease, immunoproliferative disorder, cytokine receptor deficiency, immunodeficiency-related disorder, phagocytic cell dysfunction, thrombocytopenic purpura, lymphoid system disorder, immune reconstitution inflammatory syndrome, growth hormone insensitivity with immune dysregulation 1, autosomal recessive, cytokine release syndrome, early-onset autoimmunity-autoinflammation-immunodeficiency syndrome, CADINS disease, autoinflammation, panniculitis, and dermatosis syndrome

Subtypes (47): autoimmune disease, multisystem, infantile-onset, autoimmune disorder of endocrine system, autoimmune disorder of exocrine system, autoimmune disease of ear, nose and throat, autoimmune disorder of gastrointestinal tract, autoimmune disorder of musculoskeletal system, autoimmune disorder of blood, autoimmune disorder of cardiovascular system, phacolytic glaucoma, Jaccoud syndrome, autoimmune disorder of the nervous system, lupus erythematosus, anti-neutrophil antibody associated vasculitis, cryoglobulinemia, CNS demyelinating autoimmune disease, type III hypersensitivity disease, vitiligo, anti-glomerular basement membrane disease, autoimmune pulmonary alveolar proteinosis, Reynolds syndrome, overlapping connective tissue disease, tempi syndrome, immunoglobulin G4-related sclerosing disease, rheumatic fever, autoerythrocyte sensitization syndrome, autoimmune lymphoproliferative syndrome, secondary neonatal autoimmune disease, euthyroid Graves orbitopathy, Kimura disease, autoimmune thrombocytopenia, autoimmune bullous skin disease, scleroderma, Susac syndrome, undifferentiated connective tissue syndrome, type II hypersensitivity reaction disease, autoimmune urticaria, autoimmune glomerulonephritis, multisystem autoimmune disease due to IKAROS gain of function, autoimmune pulmonary disease due to PD-1 deficiency, non-specific autoimmune supratentorial encephalitis with characteristic antibodies, non-specific autoimmune supratentorial encephalitis without characteristic antibodies, non-specific autoimmune brainstem encephalitis with characteristic antibodies, non-specific autoimmune brainstem encephalitis without characteristic antibodies, non-specific autoimmune cerebellar ataxia with characteristic antibodies, non-specific autoimmune cerebellar ataxia without characteristic antibodies, autoimmune disease with susceptibility to mycobacterium tuberculosis, antiphospholipid syndrome

Genetics & variants

GWAS landscape

182 GWAS associations across 10 studies. Top hits map to 41 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs24766016e-119AP4B1-AS1, PTPN22A
rs73106152e-76SH2B3?
rs30872437e-49CTLA4 - ICOS?
rs14434381e-39PTCSC2?
rs10641733e-36HLA-DQB1A1.8
rs20305192e-30LPP?
rs177536412e-29IL12A-AS1G
rs345364434e-28TYK2?
rs75682752e-24STAT4?
rs715089035e-24ARID5B?
rs93565512e-23RNASET2 - MIR3939?
rs729280385e-23BACH2?
rs44097854e-21LNCRNA-IUR - FAM76B?
rs111717392e-20ERBB3C
rs764281063e-20FLT3?
rs31043943e-20HLA-DQB1 - MTCO3P1G0.57
rs126195311e-18LINC01934G
rs104940793e-18VAV3?
rs7067784e-18IL2RA?
rs749566152e-17RAVER1A
rs38073077e-17IRF5?
rs18932178e-17PTPN2?
rs568176152e-16LINC02498?
rs2295413e-16C1QTNF6?
rs25421485e-16LINC01882 - PTPN2C
rs95072877e-16SPATA13?
rs31329401e-15GPSM3T0.62
rs70058342e-15CCN4?
rs1158846582e-15EHMT2A1.83
rs76559154e-15ATP5MGP4 - RNU7-197P?

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90454272Zeng Y202348,730328,141Genetic Associations Between Stress-Related Disorders and Autoimmune Disease.
GCST009873Marquez A201811,48922,308Meta-analysis of Immunochip data of four autoimmune diseases reveals novel single-disease and cross-phenotype associations.
GCST011008Liu X20201,38362,656Genetic factors underlying the bidirectional relationship between autoimmune and mental disorders - findings from a Danish population-based study.
GCST011009Liu X20201,03619,790Genetic factors underlying the bidirectional relationship between autoimmune and mental disorders - findings from a Danish population-based study.
GCST011005Liu X202034762,656Genetic factors underlying the bidirectional relationship between autoimmune and mental disorders - findings from a Danish population-based study.
GCST003097Li YR20159710,718Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases.
GCST90012738Dennis JK202100Clinical laboratory test-wide association scan of polygenic scores identifies biomarkers of complex disease.
GCST007071Kichaev G201800Leveraging Polygenic Functional Enrichment to Improve GWAS Power.
GCST90029015Loh PR201800Mixed-model association for biobank-scale datasets.
GCST90029016Loh PR201800Mixed-model association for biobank-scale datasets.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding5
Tier 2: splice/UTR4
Tier 3: regulatory0
Tier 4: intronic/intergenic41

MAF distribution

BucketVariants
common (>=0.05)47
low_freq (0.01-0.05)1
rare (<0.01)0
unknown2

Functional consequences

ConsequenceCount
intron_variant30
intergenic_variant10
missense_variant5
3_prime_UTR_variant2
non_coding_transcript_exon_variant1
5_prime_UTR_variant1
splice_donor_region_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs24766011113834946A>G,T0.05missense_variantAP4B1-AS1, PTPN226e-119Tier 1: coding
rs731061512111427245C>A,G,T0.05intron_variantSH2B32e-76Tier 4: intronic/intergenic
rs30872432203874196G>A,T0.05intergenic_variantCTLA4 - ICOS7e-49Tier 4: intronic/intergenic
rs1443438997787746T>A,C,G0.05non_coding_transcript_exon_variantPTCSC21e-39Tier 4: intronic/intergenic
rs1064173632659703G>A,T0.253_prime_UTR_variantHLA-DQB13e-36Tier 2: splice/UTR
rs20305193188402113G>A0.05intron_variantLPP2e-30Tier 4: intronic/intergenic
rs177536413159929885A>G0.05intron_variantIL12A-AS12e-29Tier 4: intronic/intergenic
rs345364431910352442G>C,T0.05missense_variantTYK24e-28Tier 1: coding
rs75682752191101726G>C,T0.05intron_variantSTAT42e-24Tier 4: intronic/intergenic
rs715089031062020112C>T0.05intron_variantARID5B5e-24Tier 4: intronic/intergenic
rs93565516166986857T>A,C0.05intron_variantRNASET2 - MIR39392e-23Tier 4: intronic/intergenic
rs72928038690267049G>A0.05intron_variantBACH25e-23Tier 4: intronic/intergenic
rs44097851195578258T>C0.05intron_variantLNCRNA-IUR - FAM76B4e-21Tier 4: intronic/intergenic
rs111717391256076841C>G,T0.05intergenic_variantERBB32e-20Tier 4: intronic/intergenic
rs764281061328029870T>C,Gintron_variantFLT33e-20Tier 4: intronic/intergenic
rs3104394632699743G>A,C,T0.16intergenic_variantHLA-DQB1 - MTCO3P13e-20Tier 4: intronic/intergenic
rs126195312181192913T>G0.05intron_variantLINC019341e-18Tier 4: intronic/intergenic
rs104940791107832253G>A,C0.05intron_variantVAV33e-18Tier 4: intronic/intergenic
rs706778106056986C>G,T0.05intron_variantIL2RA4e-18Tier 4: intronic/intergenic
rs749566151910317045T>A,C0.053_prime_UTR_variantRAVER12e-17Tier 2: splice/UTR
rs38073077128939148T>C0.05intron_variantIRF57e-17Tier 4: intronic/intergenic
rs18932171812809341A>C,G,T0.05intron_variantPTPN28e-17Tier 4: intronic/intergenic
rs56817615410717222A>G0.05intron_variantLINC024982e-16Tier 4: intronic/intergenic
rs2295412237195278G>A,C,T0.05intergenic_variantC1QTNF63e-16Tier 4: intronic/intergenic
rs25421481812777574C>G,T0.05intergenic_variantLINC01882 - PTPN25e-16Tier 4: intronic/intergenic
rs95072871324212439T>C0.05intron_variantSPATA137e-16Tier 4: intronic/intergenic
rs3132940632193619T>A,G0.15intron_variantGPSM31e-15Tier 4: intronic/intergenic
rs70058348133201961C>A,T0.05intron_variantCCN42e-15Tier 4: intronic/intergenic
rs115884658631896761G>A0.047missense_variantEHMT22e-15Tier 1: coding
rs76559154148712316C>G,T0.05intron_variantATP5MGP4 - RNU7-197P4e-15Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 24 · Orphanet: 94 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 3

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

GeneHGNCEvidence routes
PTPN22PTPN22GWAS, GenCC, Orphanet
FASLGFASLGGWAS, Orphanet
CTLA4CTLA4GWAS, Orphanet

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

GeneClassificationInheritanceDiseaseRecords
IKZF1ModerateAutosomal dominantautoimmune disease7
CCDC40LimitedAutosomal recessiveautoimmune disease7
PTPN22LimitedAutosomal dominantautoimmune disease4
SIRT1LimitedAutosomal dominantautoimmune disease
SOCS1LimitedAutosomal dominantautoimmune disease3
SOCS4LimitedAutosomal dominantautoimmune disease
SMG7No Known Disease RelationshipAutosomal dominantautoimmune disease

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
PTPN22Orphanet:3437Vogt-Koyanagi-Harada disease
PTPN22Orphanet:397Giant cell arteritis
PTPN22Orphanet:536Systemic lupus erythematosus
PTPN22Orphanet:85408Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
PTPN22Orphanet:85410Oligoarticular juvenile idiopathic arthritis
PTPN22Orphanet:900Granulomatosis with polyangiitis
IKZF1Orphanet:317473Common variable immunodeficiency phenotype due to IKAROS functional haploinsufficiency
IKZF1Orphanet:36426Stevens-Johnson syndrome
IKZF1Orphanet:585909B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
IKZF1Orphanet:695172Combined immunodeficiency due to dimerization defective IKAROS mutation
IKZF1Orphanet:697414Early-onset combined immunodeficiency with low Ig due to dominant negative IKAROS mutation
SOCS1Orphanet:619948Early-onset autoimmunity-autoinflammation-immunodeficiency syndrome due to SOCS1 haploinsufficiency
CCDC40Orphanet:244Primary ciliary dyskinesia
STAT4Orphanet:117Behçet disease
STAT4Orphanet:536Systemic lupus erythematosus
STAT4Orphanet:85408Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
STAT4Orphanet:85410Oligoarticular juvenile idiopathic arthritis
STAT4Orphanet:93552Pediatric systemic lupus erythematosus
SUOXOrphanet:99731Isolated sulfite oxidase deficiency
TNFAIP3Orphanet:536Systemic lupus erythematosus
TNFAIP3Orphanet:674762Early-onset autoinflammatory syndrome due to A20 haploinsufficiency
TNFSF15Orphanet:186Primary biliary cholangitis
CD40LGOrphanet:101088X-linked hyper-IgM syndrome
FASLGOrphanet:3261Autoimmune lymphoproliferative syndrome
TYK2Orphanet:300865Primary cutaneous anaplastic large cell lymphoma
TYK2Orphanet:331226Susceptibility to infection due to TYK2 deficiency
TYK2Orphanet:98842Lymphomatoid papulosis
IKZF3Orphanet:67038B-cell chronic lymphocytic leukemia
IKZF3Orphanet:699590Immune dysregulation with immunodeficiency due to AIOLOS haploinsufficiency
IKZF3Orphanet:699593Combined immunodeficiency-lymphopenia-cancer predisposing syndrome due to AIOLOS deficiency
BACH2Orphanet:714472Inflammatory bowel disease-autoimmunity-sinopulmonary infections-lymphadenopathy syndrome
MMEL1Orphanet:186Primary biliary cholangitis
CARD9Orphanet:457088Predisposition to invasive fungal disease due to CARD9 deficiency
ZMIZ1Orphanet:528084Non-specific syndromic intellectual disability
CD28Orphanet:2584Classic mycosis fungoides
CD28Orphanet:3162Sézary syndrome
TNIP1Orphanet:536Systemic lupus erythematosus
ZNF365Orphanet:2073Narcolepsy type 1
ZNF365Orphanet:83465Narcolepsy type 2
LRRK2Orphanet:2828Young-onset Parkinson disease
LRRK2Orphanet:411602Hereditary late-onset Parkinson disease
IL23ROrphanet:117Behçet disease
CRB1Orphanet:251295Pigmented paravenous retinochoroidal atrophy
CRB1Orphanet:35612Nanophthalmos
CRB1Orphanet:65Leber congenital amaurosis
CRB1Orphanet:791Retinitis pigmentosa
CTLA4Orphanet:2584Classic mycosis fungoides
CTLA4Orphanet:3162Sézary syndrome
CTLA4Orphanet:391490Adult-onset myasthenia gravis
CTLA4Orphanet:436159Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency

Cohort genes → proteins

75 cohort genes, 75 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only68
gwas_and_gencc1
multi_evidence6

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
PTPN22HGNC:9652ENSG00000134242Q9Y2R2Tyrosine-protein phosphatase non-receptor type 22gwas,gencc
IKZF1HGNC:13176ENSG00000185811Q13422DNA-binding protein Ikarosgencc
SIRT1HGNC:14929ENSG00000096717Q96EB6NAD-dependent protein deacetylase sirtuin-1gencc
SMG7HGNC:16792ENSG00000116698Q92540Nonsense-mediated mRNA decay factor SMG7gencc
SOCS1HGNC:19383ENSG00000185338O15524Suppressor of cytokine signaling 1gencc
SOCS4HGNC:19392ENSG00000180008Q8WXH5Suppressor of cytokine signaling 4gencc
CCDC40HGNC:26090ENSG00000141519Q4G0X9Coiled-coil domain-containing protein 40gencc
CCL21HGNC:10620ENSG00000137077O00585C-C motif chemokine 21gwas
STAT4HGNC:11365ENSG00000138378Q14765Signal transducer and activator of transcription 4gwas
SUOXHGNC:11460ENSG00000139531P51687Sulfite oxidase, mitochondrialgwas
TNFAIP3HGNC:11896ENSG00000118503P21580Tumor necrosis factor alpha-induced protein 3gwas
TNFRSF6BHGNC:11921ENSG00000243509O95407Tumor necrosis factor receptor superfamily member 6Bgwas
TNFSF15HGNC:11931ENSG00000181634O95150Tumor necrosis factor ligand superfamily member 15gwas
TNFSF18HGNC:11932ENSG00000120337Q9UNG2Tumor necrosis factor ligand superfamily member 18gwas
CD40LGHGNC:11935ENSG00000102245P29965CD40 ligandgwas
FASLGHGNC:11936ENSG00000117560P48023Tumor necrosis factor ligand superfamily member 6gwas
EIPR1HGNC:12383ENSG00000032389Q53HC9EARP and GARP complex-interacting protein 1gwas
TYK2HGNC:12440ENSG00000105397P29597Non-receptor tyrosine-protein kinase TYK2gwas
UBASH3AHGNC:12462ENSG00000160185P57075Ubiquitin-associated and SH3 domain-containing protein Agwas
IKZF3HGNC:13178ENSG00000161405Q9UKT9Zinc finger protein Aiolosgwas
IKZF4HGNC:13179ENSG00000123411Q9H2S9Zinc finger protein Eosgwas
BACH2HGNC:14078ENSG00000112182Q9BYV9Transcription regulator protein BACH2gwas
MMEL1HGNC:14668ENSG00000142606Q495T6Membrane metallo-endopeptidase-like 1gwas
TAGAPHGNC:15669ENSG00000164691Q8N103T-cell activation Rho GTPase-activating proteingwas
ORMDL3HGNC:16038ENSG00000172057Q8N138ORM1-like protein 3gwas
ELMO1HGNC:16286ENSG00000155849Q92556Engulfment and cell motility protein 1gwas
CARD9HGNC:16391ENSG00000187796Q9H257Caspase recruitment domain-containing protein 9gwas
ZMIZ1HGNC:16493ENSG00000108175Q9ULJ6Zinc finger MIZ domain-containing protein 1gwas
CD28HGNC:1653ENSG00000178562P10747T-cell-specific surface glycoprotein CD28gwas
TNIP1HGNC:16903ENSG00000145901Q15025TNFAIP3-interacting protein 1gwas
FNBP1HGNC:17069ENSG00000187239Q96RU3Formin-binding protein 1gwas
ANKRD30AHGNC:17234ENSG00000148513Q9BXX3Ankyrin repeat domain-containing protein 30Agwas
SBK1HGNC:17699ENSG00000188322Q52WX2Serine/threonine-protein kinase SBK1gwas
ZNF365HGNC:18194ENSG00000138311Q70YC4Talaningwas
PADI4HGNC:18368ENSG00000159339Q9UM07Protein-arginine deiminase type-4gwas
ADGRL2HGNC:18582ENSG00000117114O95490Adhesion G protein-coupled receptor L2gwas
LRRK2HGNC:18618ENSG00000188906Q5S007Leucine-rich repeat serine/threonine-protein kinase 2gwas
IL23RHGNC:19100ENSG00000162594Q5VWK5Interleukin-23 receptorgwas
ATG16L1HGNC:21498ENSG00000085978Q676U5Autophagy-related protein 16-1gwas
COBLHGNC:22199ENSG00000106078O75128Protein cordon-bleugwas
CRB1HGNC:2343ENSG00000134376P82279Protein crumbs homolog 1gwas
ADCY7HGNC:238ENSG00000121281P51828Adenylate cyclase type 7gwas
CYTL1HGNC:24435ENSG00000170891Q9NRR1Cytokine-like protein 1gwas
CTLA4HGNC:2505ENSG00000163599P16410Cytotoxic T-lymphocyte protein 4gwas
CTSHHGNC:2535ENSG00000103811P09668Pro-cathepsin Hgwas
ANKRD55HGNC:25681ENSG00000164512Q3KP44Ankyrin repeat domain-containing protein 55gwas
DAG1HGNC:2666ENSG00000173402Q14118Dystroglycan 1gwas
YDJCHGNC:27158ENSG00000161179A8MPS7Carbohydrate deacetylasegwas
DDX6HGNC:2747ENSG00000110367P26196Probable ATP-dependent RNA helicase DDX6gwas
ERAP2HGNC:29499ENSG00000164308Q6P179Endoplasmic reticulum aminopeptidase 2gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
PTPN22Tyrosine-protein phosphatase non-receptor type 22Acts 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.
IKZF1DNA-binding protein IkarosTranscription regulator of hematopoietic cell differentiation.
SIRT1NAD-dependent protein deacetylase sirtuin-1NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics and participates in the coordination of several separated cellular functions such as cell cycle, response to DNA damage, metabolis…
SMG7Nonsense-mediated mRNA decay factor SMG7Plays a role in nonsense-mediated mRNA decay.
SOCS1Suppressor of cytokine signaling 1Essential negative regulator of type I and type II interferon (IFN) signaling, as well as that of other cytokines, including IL2, IL4, IL6 and leukemia inhibitory factor (LIF).
SOCS4Suppressor of cytokine signaling 4SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction.
CCDC40Coiled-coil domain-containing protein 40Required for assembly of dynein regulatory complex (DRC) and inner dynein arm (IDA) complexes, which are responsible for ciliary beat regulation, thereby playing a central role in motility in cilia and flagella.
CCL21C-C motif chemokine 21Inhibits hemopoiesis and stimulates chemotaxis.
STAT4Signal transducer and activator of transcription 4Transcriptional regulator mainly expressed in hematopoietic cells that plays a critical role in cellular growth, differentiation and immune response.
SUOXSulfite oxidase, mitochondrialCatalyzes the oxidation of sulfite to sulfate, the terminal reaction in the oxidative degradation of sulfur-containing amino acids.
TNFAIP3Tumor necrosis factor alpha-induced protein 3Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities.
TNFRSF6BTumor necrosis factor receptor superfamily member 6BDecoy receptor that can neutralize the cytotoxic ligands TNFS14/LIGHT, TNFSF15 and TNFSF6/FASL.
TNFSF15Tumor necrosis factor ligand superfamily member 15Receptor for TNFRSF25 and TNFRSF6B.
TNFSF18Tumor necrosis factor ligand superfamily member 18Cytokine that binds to TNFRSF18/AITR/GITR.
CD40LGCD40 ligandCytokine that acts as a ligand to CD40/TNFRSF5.
FASLGTumor necrosis factor ligand superfamily member 6Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells.
EIPR1EARP and GARP complex-interacting protein 1Acts as a component of endosomal retrieval machinery that is involved in protein transport from early endosomes to either recycling endosomes or the trans-Golgi network.
TYK2Non-receptor tyrosine-protein kinase TYK2Tyrosine kinase of the non-receptor type involved in numerous cytokines and interferons signaling, which regulates cell growth, development, cell migration, innate and adaptive immunity.
UBASH3AUbiquitin-associated and SH3 domain-containing protein AInterferes with CBL-mediated down-regulation and degradation of receptor-type tyrosine kinases.
IKZF3Zinc finger protein AiolosTranscription factor that plays an important role in the regulation of lymphocyte differentiation.
IKZF4Zinc finger protein EosDNA-binding protein that binds to the 5’GGGAATRCC-3’ Ikaros-binding sequence.
BACH2Transcription regulator protein BACH2Transcriptional regulator that acts as a repressor or activator.
MMEL1Membrane metallo-endopeptidase-like 1Metalloprotease involved in sperm function, possibly by modulating the processes of fertilization and early embryonic development.
TAGAPT-cell activation Rho GTPase-activating proteinMay function as a GTPase-activating protein and may play important roles during T-cell activation.
ORMDL3ORM1-like protein 3Plays an essential role in the homeostatic regulation of sphingolipid de novo biosynthesis by modulating the activity of the serine palmitoyltransferase (SPT) in response to ceramide levels.
ELMO1Engulfment and cell motility protein 1Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility.
CARD9Caspase recruitment domain-containing protein 9Adapter protein that plays a key role in innate immune response against fungi by forming signaling complexes downstream of C-type lectin receptors.
ZMIZ1Zinc finger MIZ domain-containing protein 1Acts as a transcriptional coactivator.
CD28T-cell-specific surface glycoprotein CD28Receptor that plays a role in T-cell activation, proliferation, survival and the maintenance of immune homeostasis.
TNIP1TNFAIP3-interacting protein 1Inhibits 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.
FNBP1Formin-binding protein 1May act as a link between RND2 signaling and regulation of the actin cytoskeleton.
SBK1Serine/threonine-protein kinase SBK1May be involved in signal-transduction pathways related to the control of brain development.
ZNF365TalaninMay play a role in uric acid excretion.
PADI4Protein-arginine deiminase type-4Catalyzes the citrullination/deimination of arginine residues of proteins such as histones, thereby playing a key role in histone code and regulation of stem cell maintenance.
ADGRL2Adhesion G protein-coupled receptor L2Orphan adhesion G-protein coupled receptor (aGPCR), which mediates synapse specificity.
LRRK2Leucine-rich repeat serine/threonine-protein kinase 2Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking.
IL23RInterleukin-23 receptorAssociates with IL12RB1 to form the interleukin-23 receptor.
ATG16L1Autophagy-related protein 16-1Plays an essential role in both canonical and non-canonical autophagy: interacts with ATG12-ATG5 to mediate the lipidation to ATG8 family proteins (MAP1LC3A, MAP1LC3B, MAP1LC3C, GABARAPL1, GABARAPL2 and GABARAP).
COBLProtein cordon-bleuPlays an important role in the reorganization of the actin cytoskeleton.
CRB1Protein crumbs homolog 1Plays a role in photoreceptor morphogenesis in the retina.
ADCY7Adenylate cyclase type 7Adenylate cyclase that mediates formation of both cyclic AMP (cAMP) and cyclic di-AMP (c-di-AMP).
CTLA4Cytotoxic T-lymphocyte protein 4Inhibitory receptor acting as a major negative regulator of T-cell responses.
CTSHPro-cathepsin HImportant for the overall degradation of proteins in lysosomes.
DAG1Dystroglycan 1The dystroglycan complex is involved in a number of signaling events and processes including laminin deposition and extracellular matrix assembly, acetylcholine receptor clustering, sarcolemmal stability, cell survival, peripheral nerve my…
YDJCCarbohydrate deacetylaseProbably catalyzes the deacetylation of acetylated carbohydrates an important step in the degradation of oligosaccharides.
DDX6Probable ATP-dependent RNA helicase DDX6Essential for the formation of P-bodies, cytosolic membrane-less ribonucleoprotein granules involved in RNA metabolism through the coordinated storage of mRNAs encoding regulatory functions.
ERAP2Endoplasmic reticulum aminopeptidase 2Aminopeptidase that plays a central role in peptide trimming, a step required for the generation of most HLA class I-binding peptides.
DNASE1L3Deoxyribonuclease gammaHas DNA hydrolytic activity.
PSMG1Proteasome assembly chaperone 1Chaperone protein which promotes assembly of the 20S proteasome as part of a heterodimer with PSMG2.
ATXN2LAtaxin-2-like proteinInvolved in the regulation of stress granule and P-body formation.

Protein-family classification

Druggable: 27 · Difficult: 19 · Unknown: 29 · Druggable fraction: 0.36

Family distribution

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

FamilyGenesFoldFDR
Antibody/Immunoglobulin72.7×0.142
Phosphatase33.4×0.225
Scaffold/PPI81.8×0.225
Complement13.6×0.481
Kinase41.5×0.481
Protease31.5×0.481
Transcription factor111.2×0.481
Enzyme (other)71.1×0.545
GPCR20.6×0.918
Other/Unknown290.7×0.999

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
PTPN22Phosphataseyes3.1.3.48PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat
IKZF1Transcription factornoZnf_C2H2_type, Znf_C2H2_sf, Ikaros_C2H2-ZF
SIRT1Enzyme (other)yes2.3.1.286Sirtuin, Ssirtuin_cat_dom, Sirtuin_cat_small_dom_sf
SMG7Other/UnknownnoTPR-like_helical_dom_sf, DNA/RNA-bd_Est1-type, Est1-like_N
SOCS1Scaffold/PPInoSH2, SOCS_box, SOCS1_SH2
SOCS4Scaffold/PPInoSH2, SOCS_box, SOCS4/SOCS5_dom
CCDC40Other/UnknownnoCCDC40
CCL21Other/UnknownnoChemokine_IL8-like_dom, Chemokine_CC_DCCL, Interleukin_8-like_sf
STAT4Transcription factornoSH2, STAT, p53-like_TF_DNA-bd_sf
SUOXEnzyme (other)yes1.8.3.1OxRdtase_Mopterin-bd_dom, Cyt_B5-like_heme/steroid-bd, MoCF_OxRdtse_dimer
TNFAIP3Transcription factornoZnf_A20, OTU_dom, OTU_Deubiquitinase
TNFRSF6BOther/UnknownnoTNFR/NGFR_Cys_rich_reg, TNFRSF6B_N, TNFRSF_decoy_receptor
TNFSF15Other/UnknownnoTNF_dom, TNF, Tumour_necrosis_fac-like_dom
TNFSF18Other/UnknownnoTNF_dom, Tumour_necrosis_fac-like_dom, TNFSF18
CD40LGOther/UnknownnoCD40L, TNF_dom, Tumour_necrosis_fac-like_dom
FASLGOther/UnknownnoTNF_dom, TNF, Tumour_necrosis_fac-like_dom
EIPR1Scaffold/PPInoWD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS
TYK2Kinaseyes2.7.10.2FERM_domain, Prot_kinase_dom, SH2
UBASH3APhosphataseyesSH3_domain, UBA-like_sf, His_Pase_superF_clade-1
IKZF3Transcription factornoZnf_C2H2_type, Znf_C2H2_sf, Ikaros_C2H2-ZF
IKZF4Transcription factornoZnf_C2H2_type, Znf_C2H2_sf, Ikaros_C2H2-ZF
BACH2Transcription factornoBTB/POZ_dom, bZIP_Maf, bZIP
MMEL1Proteaseyes3.4.24.B14Peptidase_M13, Peptidase_M13_N, Peptidase_M13_C
TAGAPOther/UnknownnoRhoGAP_dom, Rho_GTPase_activation_prot, ARHGAP20-like_RhoGAP
ORMDL3Other/UnknownnoORMDL
ELMO1Scaffold/PPInoPH_domain, ELMO_dom, ARM-like
CARD9Other/UnknownnoCARD, DEATH-like_dom_sf, CARD_CARD9
ZMIZ1Transcription factornoZnf_MIZ, Znf_RING/FYVE/PHD, ZMIZ1_N
CD28Antibody/ImmunoglobulinyesCD28, Ig_V-set, Ig-like_fold
TNIP1Other/Unknownno
FNBP1Scaffold/PPInoFCH_dom, SH3_domain, HR1_rho-bd
ANKRD30AScaffold/PPInoAnkyrin_rpt, Ankyrin_rpt-contain_sf, CC144C-like_CC_dom
SBK1KinaseyesProt_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
ZNF365Transcription factornoGenomicStab_NeuMorph_Reg, FBX41/ZN365_Znf-C2H2
PADI4Enzyme (other)yes3.5.3.15PAD, Cupredoxin, PAD_C
ADGRL2GPCRyesGPS, GPCR_2_secretin-like, Lectin_gal-bd_dom
LRRK2KinaseyesProt_kinase_dom, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp
IL23RAntibody/ImmunoglobulinyesFN3_dom, Ig-like_fold, FN3_sf
ATG16L1Scaffold/PPInoWD40_rpt, Autophagy-rel_prot_16_dom, WD40/YVTN_repeat-like_dom_sf
COBLOther/UnknownnoWH2_dom, Cordon-bleu_ubiquitin_domain, COBL-like
CRB1Other/UnknownnoEGF-type_Asp/Asn_hydroxyl_site, EGF, Laminin_G
ADCY7Enzyme (other)yes4.6.1.1A/G_cyclase, Adcy_conserved_dom, A/G_cyclase_CS
CYTL1Other/UnknownnoCYTL1
CTLA4Antibody/ImmunoglobulinyesIg_sub, CTLA4, Ig_V-set
CTSHProteaseyes3.4.22.16Pept_cys_AS, Peptidase_C1A_C, Peptidase_C1A
ANKRD55Scaffold/PPInoAnkyrin_rpt, Ankyrin_rpt-contain_sf
DAG1Antibody/ImmunoglobulinyesCadg, DAG1_C, Ig-like_fold
YDJCEnzyme (other)yes3.5.1.105YdjC-like, Glyco_hydro/deAcase_b/a-brl
DDX6Enzyme (other)yes3.6.4.13RNA-helicase_DEAD-box_CS, Helicase_C-like, DEAD/DEAH_box_helicase_dom
ERAP2Proteaseyes3.4.11.1Peptidase_M1, Peptidase_M1_dom, ERAP1-like_C_dom

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)75
unknown0

Top tissues across cohort

TissueCohort genes
granulocyte11
monocyte9
lymph node9
ganglionic eminence7
blood7
mononuclear cell6
vermiform appendix6
male germ line stem cell (sensu Vertebrata) in testis6
leukocyte5
calcaneal tendon5
bone marrow cell4
ventricular zone4
buccal mucosa cell4
left testis4
primordial germ cell in gonad4
bone marrow3
sperm3
type B pancreatic cell3
tibia3
spleen3

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
PTPN22190broadmarkerbone marrow cell, bone marrow, monocyte
IKZF1225broadmarkerleukocyte, monocyte, mononuclear cell
SIRT1280ubiquitousmarkercalcaneal tendon, ganglionic eminence, ventricular zone
SMG7284ubiquitousmarkermedial globus pallidus, tendon of biceps brachii, right uterine tube
SOCS1211ubiquitousmarkertype B pancreatic cell, sperm, endocervix
SOCS4253broadyesepithelial cell of pancreas, tibia, visceral pleura
CCDC40184ubiquitousmarkerright uterine tube, bronchial epithelial cell, sural nerve
CCL21206tissue_specificmarkerlymph node, right lobe of thyroid gland, vermiform appendix
STAT4201broadmarkergranulocyte, sperm, middle temporal gyrus
SUOX267ubiquitousmarkerright lobe of liver, right adrenal gland, right adrenal gland cortex
TNFAIP3274ubiquitousmarkervena cava, mucosa of paranasal sinus, vermiform appendix
TNFRSF6B127broadyesolfactory segment of nasal mucosa, spleen, subcutaneous adipose tissue
TNFSF15149broadmarkercartilage tissue, jejunal mucosa, duodenum
TNFSF1898broadyesmale germ line stem cell (sensu Vertebrata) in testis, gall bladder, stromal cell of endometrium
CD40LG124tissue_specificmarkergranulocyte, lymph node, blood
FASLG118tissue_specificmarkergranulocyte, blood, lymph node
EIPR1249ubiquitousmarkerprefrontal cortex, adenohypophysis, nucleus accumbens
TYK2288ubiquitousmarkergranulocyte, right hemisphere of cerebellum, adenohypophysis
UBASH3A133broadmarkergranulocyte, blood, lymph node
IKZF3155broadmarkergranulocyte, lymph node, epithelium of nasopharynx
IKZF4242ubiquitousmarkerbuccal mucosa cell, left adrenal gland, adrenal cortex
BACH2237ubiquitousmarkercortical plate, sural nerve, epithelium of nasopharynx
MMEL1131broadyesmale germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, left testis
TAGAP210broadmarkerbone marrow cell, blood, bone marrow
ORMDL3256ubiquitousmarkerright lobe of liver, bone marrow cell, granulocyte
ELMO1248ubiquitousmarkerprefrontal cortex, C1 segment of cervical spinal cord, corpus callosum
CARD9172broadmarkermonocyte, mononuclear cell, leukocyte
ZMIZ1295ubiquitousmarkerdorsal motor nucleus of vagus nerve, tibia, seminal vesicle
CD28154broadmarkerlymph node, vermiform appendix, blood
TNIP1298ubiquitousmarkerlower esophagus mucosa, blood, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 83.

Hub genes (top 10 by interactor count)

SymbolInteractor count
INS11,670
SIRT18,285
LRRK27,628
SMAD36,440
JAK26,197
IL106,185
GATA35,990
DDX65,922
FASLG4,373
IKZF14,096

Intra-cohort edges

ABSources
ADGRL2ATG16L1intact
ADGRL2LURAP1Lstring_interaction
AFF3ANKRD55string_interaction
AFF3PTPN22string_interaction
ANKRD55BACH2intact
ANKRD55PTPN22string_interaction
ATG16L1NKX2-3string_interaction
ATG16L1NOD2biogrid_interaction, string_interaction
ATG16L1SMG7intact
ATG16L1TNFSF15string_interaction
ATXN2LDDX6intact, string_interaction
BACH2CTSHstring_interaction
BACH2TAGAPstring_interaction
BACH2UBASH3Astring_interaction
CARD9NKX2-3string_interaction
CARD9NOD2string_interaction
CD28CD40LGstring_interaction
CD28CTLA4intact, string_interaction
CD28ITGA4string_interaction
CD28TNFSF18string_interaction
CD40LGIL21string_interaction
CTLA4IKZF4string_interaction
CTLA4PTPN22string_interaction
CTLA4TNFSF18string_interaction
CTSHTAGAPstring_interaction
DDX6IKZF1biogrid_interaction
DNASE1L3IRF5string_interaction
EFNB2TYK2biogrid_interaction
FASLGFNBP1biogrid_interaction, intact
FASLGTNFRSF6Bbiogrid_interaction, intact, string_interaction
GATA3IKZF4string_interaction
GATA3IL5string_interaction
GATA3STAT4string_interaction
IKZF1IKZF4biogrid_interaction, intact
IKZF3IKZF4intact
IKZF3ORMDL3string_interaction
IKZF4IL2RAstring_interaction
IKZF4SUOXstring_interaction
IL10IL12Astring_interaction
IL10IL12Bstring_interaction
IL10IL23Rstring_interaction
IL10IL2RAstring_interaction
IL10IL5string_interaction
IL10IRF5string_interaction
IL12AIL12Bbiogrid_interaction, intact, string_interaction
IL12BIL23Rstring_interaction
IL12BTYK2string_interaction
IL18R1NKX2-3string_interaction
IL18R1TAGAPstring_interaction
IL23RJAK2string_interaction

Structural data

PDB: 57 · AlphaFold-only: 18 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
INSP01308382
JAK2O60674164
TYK2P2959752
LRRK2Q5S00744
PADI4Q9UM0728
CTLA4P1641022
IL12BP2946020
ELMO1Q9255618
TNFAIP3P2158017
ATG16L1Q676U516
PTPN22Q9Y2R214
ERAP2Q6P17914
ORMDL3Q8N13813
PSMG1O9545613
SMAD3P8402212
IKZF1Q1342210
CD28P1074710
EFNB2P5279910
IL2RAP0158910
SIRT1Q96EB69
DDX6P261969
IL10P223019
TNFRSF6BO954078
CD40LGP299658
CARD9Q9H2578
TNIP1Q150258
DAG1Q141188
TNFSF15O951507
TNFSF18Q9UNG27
ITGA4P136127

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
YDJCA8MPS791.77
FUT2Q1098190.65
MMEL1Q495T690.34
EIPR1Q53HC989.26
STAT4Q1476586.87
CYTL1Q9NRR185.86
NOD2Q9HC2984.76
SOCS1O1552484.20
SBK1Q52WX277.87
ADCY7P5182877.32
LURAP1LQ8IV0366.08
ANKRD55Q3KP4463.43
NKX2-3Q8TAU060.75
TAGAPQ8N10357.36
AFF3P5182652.20
ATXN2LQ8WWM749.52
IKZF3Q9UKT948.06
ZNF365Q70YC430.21

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 392. Enrichment computed across 80 evidence-associated genes (60 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 60 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Interleukin-23 signaling5105.7×2e-07STAT4, TYK2, IL23R, IL12B, JAK2
Interleukin-4 and Interleukin-13 signaling915.4×1e-06FASLG, TYK2, IL23R, SOCS1, GATA3, IL10, IL12A, IL12B (+1 more)
Interleukin-35 Signalling463.4×3e-05STAT4, TYK2, IL12A, JAK2
Interleukin-12 signaling534.0×3e-05STAT4, TYK2, IL12A, IL12B, JAK2
TNFs bind their physiological receptors426.2×0.001TNFRSF6B, TNFSF15, TNFSF18, FASLG
Regulation of IFNG signaling340.8×0.003SOCS1, JAK2, PTPN2
Interleukin-10 signaling415.5×0.007TYK2, IL10, IL12A, IL12B
Signaling by CSF3 (G-CSF)328.6×0.007TYK2, SOCS1, JAK2
Interleukin-37 signaling325.9×0.009IL18R1, SMAD3, PTPN2
Inactivation of CSF3 (G-CSF) signaling322.0×0.013TYK2, SOCS1, JAK2
Interleukin-20 family signaling321.1×0.013STAT4, TYK2, JAK2
Interleukin receptor SHC signaling320.4×0.013IL2RA, IL5, JAK2
Cytokine Signaling in Immune system74.8×0.019STAT4, CD40LG, FASLG, SOCS1, IRF5, JAK2, SMAD3
FOXO-mediated transcription316.8×0.021SIRT1, INS, SMAD3
NOD1/2 Signaling Pathway315.9×0.023TNFAIP3, CARD9, NOD2
MAPK1 (ERK2) activation238.1×0.026TYK2, JAK2
RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)238.1×0.026CTLA4, IL2RA
Interleukin-21 signaling238.1×0.026STAT4, IL21
MAPK3 (ERK1) activation234.6×0.026TYK2, JAK2
Interleukin-27 signaling234.6×0.026TYK2, JAK2
Ovarian tumor domain proteases313.9×0.026TNFAIP3, TNIP1, NOD2
Transcriptional regulation by RUNX3313.6×0.026RBPJ, ITGA4, SMAD3
Interleukin-6 signaling231.7×0.030TYK2, JAK2
Immune System122.6×0.030STAT4, CD40LG, FASLG, CARD9, CD28, SOCS1, CTSH, IRF5 (+4 more)
RAF/MAP kinase cascade55.1×0.046IL2RA, IL5, JAK2, PRKCQ, RASGRP1
Regulation of beta-cell development223.8×0.047RBPJ, INS
Interleukin-2 family signaling221.1×0.055STAT4, JAK2
IL-6-type cytokine receptor ligand interactions221.1×0.055TYK2, JAK2
NOTCH4 Intracellular Domain Regulates Transcription219.0×0.066RBPJ, SMAD3
Signaling by NOTCH4216.6×0.084RBPJ, SMAD3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 77 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
positive regulation of interleukin-17 production862.5×4e-10TYK2, CARD9, IL23R, NOD2, IL12B, IL21, JAK2, PRKCQ
positive regulation of T-helper 17 type immune response6109.4×4e-09TYK2, CARD9, IL23R, IL12B, JAK2, PRKCQ
interleukin-12-mediated signaling pathway5121.6×8e-08STAT4, TYK2, IL12A, IL12B, JAK2
positive regulation of type II interferon production823.3×5e-07PTPN22, TYK2, IL23R, IL12A, IL12B, IL18R1, IL21, JAK2
immune response138.0×2e-06CCL21, TNFSF15, TYK2, CTLA4, CTSH, IL10, IL12A, IL18R1 (+5 more)
positive regulation of T cell proliferation723.6×3e-06CD40LG, TYK2, CD28, IL23R, IL12B, IL21, JAK2
positive regulation of natural killer cell proliferation473.0×3e-05TYK2, IL23R, IL12B, JAK2
cell surface receptor signaling pathway via JAK-STAT622.6×4e-05STAT4, TYK2, IL23R, SOCS1, IL12B, JAK2
positive regulation of cytokine production621.2×5e-05CARD9, CD28, IL10, IL21, INS, PTGER4
inflammatory response125.9×9e-05CCL21, TNFAIP3, CD40LG, TNIP1, IL23R, GATA3, IL18R1, IL2RA (+4 more)
positive regulation of NK T cell activation3131.3×9e-05IL23R, IL12A, IL12B
positive regulation of interleukin-10 production526.1×1e-04CD40LG, CD28, NOD2, IL12B, IL21
B cell differentiation617.1×1e-04CD40LG, IKZF3, RBPJ, IL10, ITGA4, PTPN2
negative regulation of inflammatory response712.5×1e-04TNFAIP3, GATA3, IL10, IL2RA, SMAD3, PTGER4, PTPN2
interleukin-23-mediated signaling pathway3109.4×1e-04TYK2, IL23R, JAK2
positive regulation of NK T cell proliferation3109.4×1e-04TYK2, IL12B, JAK2
obsolete positive regulation of NF-kappaB transcription factor activity616.0×1e-04TNFSF18, CD40LG, CARD9, NOD2, IL18R1, PRKCQ
cytokine-mediated signaling pathway711.9×1e-04STAT4, TYK2, IL23R, SOCS1, SOCS4, IRF5, JAK2
cellular response to virus615.6×1e-04TYK2, IL12A, IL21, IRF5, JAK2, SMAD3
positive regulation of tyrosine phosphorylation of STAT protein438.1×2e-04TNFSF18, IL12A, IL21, JAK2
cellular response to muramyl dipeptide365.7×5e-04PTPN22, NOD2, IRF5
positive regulation of interleukin-4 production429.2×5e-04CD40LG, CD28, GATA3, PRKCQ
positive regulation of canonical NF-kappaB signal transduction87.5×5e-04CCL21, TNFSF15, CD40LG, FASLG, CARD9, LURAP1L, NOD2, INS
positive regulation of transcription by RNA polymerase II173.3×5e-04STAT4, IKZF4, SIRT1, ZMIZ1, CD28, TNIP1, CYTL1, GATA3 (+9 more)
response to muramyl dipeptide354.7×9e-04TNFAIP3, CARD9, NOD2
macrophage differentiation424.3×9e-04SIRT1, SOCS1, GATA3, NKX2-3
positive regulation of receptor signaling pathway via JAK-STAT422.4×0.001TYK2, IL10, IL5, JAK2
positive regulation of MHC class II biosynthetic process346.9×0.001SIRT1, IL10, JAK2
adaptive immune response77.7×0.001TNFSF18, CTLA4, CTSH, ERAP2, NOD2, IL18R1, JAK2
positive regulation of interleukin-12 production420.4×0.002CD40LG, IL23R, IL12B, IRF5

Therapeutics

Drugs indicated or in trials for this disease

4 approved drugs — disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugStatus
EfavirenzApproved (phase 4)
FamciclovirApproved (phase 4)
LamivudineApproved (phase 4)
ZidovudineApproved (phase 4)

6 drugs in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

DrugHighest phase
DazdotuftidePhase 2
LitifilimabPhase 2
Mycophenolate MofetilPhase 2
PrednisonePhase 2
RiliprubartPhase 2
SemzuvolimabPhase 2

Drug target analysis

Approved (phase 4): 12 · Phase ≥3: 12 · Phased (≥1): 16 · Undrugged: 59

Druggability breadth: 50 of 80 evidence-associated genes (62%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

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

SymbolExample approved molecule
IKZF1POMALIDOMIDE
SIRT1NIACINAMIDE
TYK2FEDRATINIB
IKZF3POMALIDOMIDE
SBK1AFATINIB
PADI4CHLORTETRACYCLINE
LRRK2PONATINIB
GPR35AMLEXANOX
NOD2PACLITAXEL
IL5BUDESONIDE
JAK2FEDRATINIB
SMAD3FLUORESCEIN

Top cohort targets by molecule count

SymbolMoleculesMax phase
JAK21004
TYK2724
LRRK2424
GPR35304
SBK1144
SIRT164
NOD264
IKZF354
IKZF134
PADI434

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
POMALIDOMIDE4IKZF1, IKZF3
LENALIDOMIDE4IKZF1, IKZF3
NIACINAMIDE4SIRT1
FEDRATINIB4JAK2, LRRK2, SBK1, TYK2
RUXOLITINIB4JAK2, LRRK2, SBK1, TYK2
TOFACITINIB4JAK2, LRRK2, TYK2
UPADACITINIB4JAK2, TYK2
BARICITINIB4JAK2, TYK2
FILGOTINIB4JAK2, TYK2
ABROCITINIB4JAK2, TYK2
DEUCRAVACITINIB4JAK2, TYK2
MOMELOTINIB4JAK2, TYK2
AXITINIB4JAK2, LRRK2, TYK2
RUXOLITINIB PHOSPHATE4JAK2, TYK2
INFIGRATINIB PHOSPHATE4JAK2, TYK2
INFIGRATINIB4JAK2, TYK2
PACRITINIB4JAK2, TYK2
TOFACITINIB CITRATE4JAK2, LRRK2, TYK2
BOSUTINIB4JAK2, LRRK2, TYK2
PEFICITINIB4JAK2, TYK2
CRAVACITINIB4JAK2, TYK2
PAZOPANIB4JAK2, TYK2
NINTEDANIB4JAK2, LRRK2, SBK1, TYK2
SUNITINIB4JAK2, LRRK2, SBK1, TYK2
DASATINIB4JAK2, SBK1, TYK2
ERLOTINIB4JAK2, LRRK2, SBK1, TYK2
CRIZOTINIB4JAK2, SBK1, TYK2
MIDOSTAURIN4JAK2, LRRK2, TYK2
IMATINIB4TYK2
THALIDOMIDE4IKZF3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 13.

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

SymbolAssaysType breakdown
JAK22,018Binding:1911, Functional:51, ADMET:48, Unclassified:4, Toxicity:4
TYK21,083Binding:1043, Functional:39, ADMET:1
LRRK2809Binding:799, ADMET:7, Functional:3
SIRT1645Binding:642, ADMET:3
ITGA4299Binding:282, Functional:17
GPR35162Binding:84, Functional:78
PTPN22137Binding:122, Functional:10, ADMET:5
NOD2126Binding:121, Functional:5
IKZF1106Binding:105, Functional:1
IKZF3101Binding:100, Functional:1
SBK197Binding:97
PADI486Binding:84, Functional:2
CTSH58Binding:58
ERAP246Binding:40, ADMET:4, Functional:2
SMAD324Binding:18, Functional:6
STAT420Binding:20
ADCY716Binding:14, Functional:2
IL23R13Binding:13
CD40LG8Binding:8
RBPJ8Binding:8
INS8Binding:7, ADMET:1
ELMO16Binding:6
DNASE1L35Binding:5
PSMG15Binding:5
DAG14Binding:4
DDX64Binding:4
IL54Binding:4
BACH23Binding:3
FASLG2Binding:2
MMEL12Binding:2
FUT22Binding:2
IL2RA2Binding:2
SMG71Binding:1
TNFAIP31Binding:1
UBASH3A1Binding:1
ORMDL31Binding:1
CD281Functional:1
CTLA41Binding:1
ATXN2L1Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
PTPN223.1.3.48protein-tyrosine-phosphatase
SIRT12.3.1.286protein acetyllysine N-acetyltransferase
SUOX1.8.3.1sulfite oxidase
TYK22.7.10.2non-specific protein-tyrosine kinase
MMEL13.4.24.B14
PADI43.5.3.15protein-arginine deiminase
ADCY74.6.1.1adenylate cyclase
CTSH3.4.22.16cathepsin H
YDJC3.5.1.105chitin disaccharide deacetylase
DDX63.6.4.13RNA helicase
ERAP23.4.11.1, 3.4.11.6leucyl aminopeptidase, aminopeptidase B
FUT22.4.1.344, 2.4.1.69type 2 galactoside alpha-(1,2)-fucosyltransferase, type 1 galactoside alpha-(1,2)-fucosyltransferase
JAK22.7.10.2non-specific protein-tyrosine kinase

Cohort genes with high screening signal

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

SymbolChEMBL assays
PTPN22137
IKZF1106
SIRT1645
TYK21,083
IKZF3101
LRRK2809
GPR35162
NOD2126
ITGA4299
JAK22,018

Pharmacogenomics

Cohort genes with a PharmGKB record: 75; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

29 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

CompoundMax phaseCohort target (bioactivity)
POMALIDOMIDE4IKZF1, IKZF3
LENALIDOMIDE4IKZF1, IKZF3
NIACINAMIDE4SIRT1
FEDRATINIB4JAK2, LRRK2, SBK1, TYK2
RUXOLITINIB4JAK2, LRRK2, SBK1, TYK2
TOFACITINIB4JAK2, LRRK2, TYK2
UPADACITINIB4JAK2, TYK2
BARICITINIB4JAK2, TYK2
FILGOTINIB4JAK2, TYK2
ABROCITINIB4JAK2, TYK2
MOMELOTINIB4JAK2, TYK2
AXITINIB4JAK2, LRRK2, TYK2
RUXOLITINIB PHOSPHATE4JAK2, TYK2
INFIGRATINIB PHOSPHATE4JAK2, TYK2
INFIGRATINIB4JAK2, TYK2
PACRITINIB4JAK2, TYK2
TOFACITINIB CITRATE4JAK2, LRRK2, TYK2
BOSUTINIB4JAK2, LRRK2, TYK2
PEFICITINIB4JAK2, TYK2
CRAVACITINIB4JAK2, TYK2
PAZOPANIB4JAK2, TYK2
NINTEDANIB4JAK2, LRRK2, SBK1, TYK2
SUNITINIB4JAK2, LRRK2, SBK1, TYK2
DASATINIB4JAK2, SBK1, TYK2
ERLOTINIB4JAK2, LRRK2, SBK1, TYK2
CRIZOTINIB4JAK2, SBK1, TYK2
MIDOSTAURIN4JAK2, LRRK2, TYK2
IMATINIB4TYK2
THALIDOMIDE4IKZF3

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)12IKZF1, SIRT1, TYK2, IKZF3, SBK1, PADI4, LRRK2, GPR35, NOD2, IL5 (+2 more)
BPhased (≥1) drug, not yet approved4ELMO1, CTSH, DDX6, ERAP2
CDruggable family + PDB, no drug13PTPN22, SUOX, UBASH3A, CD28, ADGRL2, IL23R, CTLA4, DAG1, DNASE1L3, IL12B (+3 more)
DDruggable family + AlphaFold only, no drug4MMEL1, ADCY7, YDJC, FUT2
EDifficult family or no structure, no drug42SMG7, SOCS1, SOCS4, CCDC40, CCL21, STAT4, TNFAIP3, TNFRSF6B, TNFSF15, TNFSF18 (+32 more)

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
PTPN22137PADI4
SOCS10JAK2, TYK2
STAT420TYK2
CARD90NOD2
IL23R13JAK2
ATG16L10NOD2
IRF50TYK2
NKX2-30NOD2
ITGA4299—
SMG71—
SOCS40—
CCDC400—
CCL210—
SUOX0—
TNFAIP31—
TNFRSF6B0—
TNFSF150—
TNFSF180—
CD40LG8—
FASLG2—
EIPR10—
UBASH3A1—
IKZF40—
BACH23—
MMEL12—
TAGAP0—
ORMDL31—
ZMIZ10—
CD281—
TNIP10—

Clinical trials & evidence

Clinical trials

Clinical trials: 349.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified187
PHASE160
EARLY_PHASE132
PHASE223
PHASE1/PHASE221
PHASE314
PHASE410
PHASE2/PHASE32

Top trials by phase / activity

NCTPhaseStatusTitle
NCT04297592PHASE4ENROLLING_BY_INVITATIONAntibiotic Prophylaxis in High-Risk Arthroplasty Patients
NCT06499233PHASE4RECRUITINGEfficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT06723548PHASE4NOT_YET_RECRUITINGTelitacicept and Low-dose Steroids in Refractory Myasthenia Gravis
NCT06964269PHASE4RECRUITINGUse of Acthar Gel Single-Dose Pre-Filled SelfJectTM Injector in Patients With Moderate-Severe Keratitis and Autoimmune Disease
NCT00001658PHASE4COMPLETEDAmoxicillin for the Treatment of Pediatric Autoimmune Disorders Associated With Streptococcal Infections
NCT00820469PHASE4COMPLETEDStudy of the Influence of Plasma Exchange on the Pharmacokinetics of Rituximab
NCT00862693PHASE4UNKNOWNCalcitriol in the Treatment of Immunoglobulin A Nephropathy
NCT01065285PHASE4COMPLETEDVaccination Against Influenza in Autoimmune Diseases
NCT04015596PHASE4TERMINATEDTrial of Naproxen Sodium for the Treatment of OCD in Children With PANDAS
NCT04127747PHASE4UNKNOWNEfficacy of Individualized Rituximab in Maintaining Remission of Moderate and Severe Systemic Lupus Erythematosus
NCT00001768PHASE3COMPLETEDTreatment of Childhood Onset Psychiatric Disorders With Intravenous Immunoglobulin (IVIg)
NCT00035308PHASE3COMPLETEDSafety and Efficacy Study of LJP 394 (Abetimus Sodium) to Treat Lupus Kidney Disease
NCT00114530PHASE2/PHASE3COMPLETEDScleroderma: Cyclophosphamide or Transplantation
NCT00351377PHASE3COMPLETEDGastrointestinal and Health-related Quality of Life Outcomes in Patients With Autoimmune Diseases Treated With Mycophenolate
NCT00419419PHASE3COMPLETEDPhase III Study of a Topical Gel Formulation for Treatment and Prevention of Raynaud’s Phenomenon
NCT01004432PHASE3COMPLETEDGolimumab in Rheumatoid Arthritis Participants With an Inadequate Response to Etanercept (ENBREL) or Adalimumab (HUMIRA)
NCT01196091PHASE3COMPLETEDA Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01205438PHASE3COMPLETEDA Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01210716PHASE3COMPLETEDEvaluation of Therapeutic Plasma Exchange (TPE) Procedure Using the AMICUS Device
NCT01281969PHASE3COMPLETEDIntravenous Immunoglobulin for PANDAS
NCT01488708PHASE3TERMINATEDOn Open-Label Study in Participants With Systemic Lupus Erythematosus
NCT01601028PHASE3COMPLETEDHydroxychloroquine Treatment of Dry Eyes in Patients With Primary Sjögren’s Syndrome
NCT02263703PHASE3COMPLETEDImmunogenicity of HPV Vaccine in Immunosuppressed Children
NCT03790293PHASE3COMPLETEDClinical and Immunological Long-term Follow-up of Patients With Pemphigus Included in the RITUXIMAB 3 Trial
NCT04274257PHASE2/PHASE3COMPLETEDA Study of the Efficacy and Safety of Rituximab in Participants With Systemic Sclerosis
NCT05069714PHASE3COMPLETEDOne or Two Week Methotrexate Discontinuation on Efficacy of Influenza Vaccination in Rheumatoid Arthritis.
NCT00716066PHASE2ACTIVE_NOT_RECRUITINGAutologous Stem Cell Transplant for Neurologic Autoimmune Diseases
NCT00977977PHASE2RECRUITINGRituximab Plus Cyclosporine in Idiopathic Membranous Nephropathy
NCT02682511PHASE2ACTIVE_NOT_RECRUITINGOral Ifetroban to Treat Diffuse Cutaneous Systemic Sclerosis (SSc) or SSc-associated Pulmonary Arterial Hypertension
NCT04663204PHASE2ACTIVE_NOT_RECRUITINGA Study of the Safety and Activity of Sparsentan for the Treatment of Incident Patients With Immunoglobulin A Nephropathy
NCT04684602PHASE1/PHASE2RECRUITINGMesenchymal Stem Cells for the Treatment of Various Chronic and Acute Conditions
NCT05459870PHASE1/PHASE2RECRUITINGCAR-T Cells Targeting Autoimmune Diseases
NCT05671757PHASE1/PHASE2RECRUITINGDaratumumab in Primary Antiphospholipid Syndrome
NCT05683990PHASE2ACTIVE_NOT_RECRUITINGStudy to Evaluate the Safety and Feasibility of Diamyd® in Individuals at Risk for Type 1 Diabetes
NCT06350110PHASE1/PHASE2RECRUITINGFourth-gen CAR T Cells Targeting BCMA/CD19 for Refractory Systemic Lupus Erythematosus (SLE)
NCT06428188PHASE1/PHASE2RECRUITINGSequential CAR-T Cells Targeting BCMA/CD19 in Patients With Relapsed/ Refractory Autoimmune Diseases
NCT06434363PHASE1/PHASE2RECRUITINGPhase I/II Study of AD-PluReceptor Plus Tafasitamab-cxix and Lymphodepleting Chemotherapy in Patients With Autoimmune Disorders
NCT06435897PHASE1/PHASE2RECRUITINGAutoimmune Disease Treatment With Mesenchymal Stem Cells (MSCs) and CAR-T Cells
NCT06575426PHASE1/PHASE2RECRUITINGA Study to Investigate Safety and Effectiveness of Porcine Pancreatic Cells (OPF-310) in Patients With Type 1 Diabetes Mellitus
NCT06688799PHASE1/PHASE2RECRUITINGAnti-CD19 Chimeric Antigen Receptor T Cells for Refractory Autoimmune Diseases

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
DOXYCYCLINE ANHYDROUS45
CEPHALEXIN ANHYDROUS43
DEUCRAVACITINIB42
LEFLUNOMIDE42
OCRELIZUMAB42
AMOXICILLIN41
ANAKINRA41
BELUMOSUDIL41
CALCITRIOL41
CEFADROXIL41
CORTICOTROPIN41
ECULIZUMAB41
EFALIZUMAB41
EFGARTIGIMOD ALFA41
FISH OIL41
GLATIRAMER ACETATE41
GOLIMUMAB41
HUMAN IMMUNOGLOBULIN G41
HYDROXYCHLOROQUINE41
INEBILIZUMAB41
KETOCONAZOLE41
LEVAMISOLE41
LEVOKETOCONAZOLE41
NAPROXEN SODIUM41
PYRIMETHAMINE41
RABEPRAZOLE41
REMDESIVIR41
RIBOFLAVIN41
RITUXIMAB41
SPARSENTAN41

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 71

This page pulls from 71 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentncitorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot