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Immune system disorder

disease
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Also known as disease of immune systemdisease or disorder of immune systemdisorder of immune systemimmune diseaseimmune disorderimmune dysfunctionimmune system disease or disorder

Summary

Immune system disorder (MONDO:0005046) is a disease (an umbrella term covering 47 Mondo subtypes) caused by IL10 (GenCC Strong), with 18 cohort genes (33 GWAS associations across 16 studies) and 50 clinical trials. Top therapeutic interventions include belumosudil, mycophenolate mofetil, and denileukin diftitox.

At a glance

  • Causal gene: IL10 (GenCC Strong)
  • Umbrella term: 47 Mondo subtypes
  • Cohort genes: 18
  • GWAS associations: 33
  • Clinical trials: 50

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameimmune system disorder
Mondo IDMONDO:0005046
EFOEFO:0000540
MeSHD007154
DOIDDOID:2914
NCITC3507
SNOMED CT414029004
UMLSC0021053
MedGen5759
Anatomy (UBERON)UBERON:0002405
Is cancer (heuristic)no

Also known as: disease of immune system · disease or disorder of immune system · disorder of immune system · immune disease · immune disorder · immune dysfunction · immune system disease or disorder · immune system disorder

Data availability: 33 GWAS associations (16 studies) · 2 GenCC gene-disease records · 16 cell lines.

Disease family

An umbrella term covering 47 Mondo subtypes.

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

Related subtypes (18): disorder of orbital region, integumentary system disorder, musculoskeletal system disorder, urinary system disorder, syndromic disease, auditory system disorder, breast disorder, connective tissue disorder, digestive system disorder, cardiovascular disorder, reproductive system disorder, nervous system disorder, respiratory system disorder, endocrine system disorder, hematologic disorder, mouth disorder, disorder of visual system, otorhinolaryngologic disease

Subtypes (47): 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, autoimmune 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

Genetics & variants

GWAS landscape

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

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs31305442e-90RNU6-1133P - C6orf15A5.64
rs6531783e-19ATXN2C
rs5603350841e-13RFC3P1 - STACA3.35
rs1426142041e-13OSTN-AS1, OSTNG3.13
rs108922791e-12RNU6-376P - DDX6?
rs5464832182e-12TEKT1 - ALOX12P2G2.93
rs18932175e-12PTPN2G
rs1475856691e-11VTI1AA2.98
rs8645372e-11CD247?
rs1910911302e-11FAM167A-AS1A3
rs1813130853e-11TLE1T3.75
rs1393517833e-11ANO2T4.1
rs5388362673e-11RN7SL714P - LINC02914G2.56
rs19531264e-11PHF19T
rs8887994394e-11SLCO3A1T2.46
rs22984283e-10YDJCT
rs49588813e-10TNIP1G1.73
rs75748654e-10STAT4T
rs24766018e-10AP4B1-AS1, PTPN22A1.71
rs288770645e-09CHSY1 - SELENOS?
rs112032031e-08UBASH3AA
rs75799441e-08H3P5 - LBH?
rs9757302e-08RN7SKP226 - LINC00824?
rs18765182e-08SPRED2?
rs1891786844e-08MTND4P3 - RNA5SP231?
rs119840755e-08ELMO1G
rs792573368e-08LINC00578 - LINC02015?
rs10203883e-07RNA5SP185 - PSMC1P4?
rs17724088e-07IFI16?
rs71695232e-06TRPM1 - LINC03034G1.4

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90038603Donertas HM202141,530443,068Common genetic associations between age-related diseases.
GCST000987Zhernakova A20114,53327,981Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci.
GCST90473145UK Biobank Whole-Genome Sequencing Consortium20253,187455,253Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90651641Liu TY20251,986233,841Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90477440Verma A20241,767447,680Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90651803Liu TY2025934233,841Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90481644Verma A2024832450,109Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90473149UK Biobank Whole-Genome Sequencing Consortium2025751457,689Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90651395Liu TY2025491233,841Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90435789Zhou W2018489408,472Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding2
Tier 2: splice/UTR0
Tier 3: regulatory1
Tier 4: intronic/intergenic29

MAF distribution

BucketVariants
common (>=0.05)21
low_freq (0.01-0.05)0
rare (<0.01)9
unknown2

Functional consequences

ConsequenceCount
intron_variant17
intergenic_variant12
missense_variant2
regulatory_region_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs3130544631090563C>A0.13intergenic_variantRNU6-1133P - C6orf152e-90Tier 4: intronic/intergenic
rs65317812111569952C>A,G,T0.05intron_variantATXN23e-19Tier 4: intronic/intergenic
rs560335084336217745A>G0intergenic_variantRFC3P1 - STAC1e-13Tier 4: intronic/intergenic
rs1426142043191217482G>A,C0.001intron_variantOSTN-AS1, OSTN1e-13Tier 4: intronic/intergenic
rs1089227911118741072G>A,T0.05intron_variantRNU6-376P - DDX61e-12Tier 4: intronic/intergenic
rs546483218176852118G>A0intergenic_variantTEKT1 - ALOX12P22e-12Tier 4: intronic/intergenic
rs18932171812809341A>C,G,T0.05intron_variantPTPN25e-12Tier 4: intronic/intergenic
rs14758566910112775363A>G0intron_variantVTI1A1e-11Tier 4: intronic/intergenic
rs8645371167442147A>C,G,T0.05intron_variantCD2472e-11Tier 4: intronic/intergenic
rs191091130811399919A>G0intron_variantFAM167A-AS12e-11Tier 4: intronic/intergenic
rs181313085981669309T>C,G0intron_variantTLE13e-11Tier 4: intronic/intergenic
rs139351783125928427T>C0.001intron_variantANO23e-11Tier 4: intronic/intergenic
rs5388362671498368141G>A0intergenic_variantRN7SL714P - LINC029143e-11Tier 4: intronic/intergenic
rs19531269120878222T>C0.05intergenic_variantPHF194e-11Tier 4: intronic/intergenic
rs8887994391592136668T>G0intron_variantSLCO3A14e-11Tier 4: intronic/intergenic
rs22984282221628603C>A,T0.05missense_variantYDJC3e-10Tier 1: coding
rs49588815151070675T>C0.09intron_variantTNIP13e-10Tier 4: intronic/intergenic
rs75748652191099907T>A,G0.05intron_variantSTAT44e-10Tier 4: intronic/intergenic
rs24766011113834946A>G,T0.11missense_variantAP4B1-AS1, PTPN228e-10Tier 1: coding
rs2887706415101260135G>A0.05intergenic_variantCHSY1 - SELENOS5e-09Tier 4: intronic/intergenic
rs112032032142416077G>A0.05intron_variantUBASH3A1e-08Tier 4: intronic/intergenic
rs7579944230222160T>C,G0.05intergenic_variantH3P5 - LBH1e-08Tier 4: intronic/intergenic
rs9757308128303768G>A,C,T0.05intergenic_variantRN7SKP226 - LINC008242e-08Tier 4: intronic/intergenic
rs1876518265381775C>A,G,T0.05intron_variantSPRED22e-08Tier 4: intronic/intergenic
rs189178684768584704C>A,Tintergenic_variantMTND4P3 - RNA5SP2314e-08Tier 4: intronic/intergenic
rs11984075737397251A>G0.05intron_variantELMO15e-08Tier 4: intronic/intergenic
rs792573363177802470C>Tregulatory_region_variantLINC00578 - LINC020158e-08Tier 3: regulatory
rs1020388556264200T>A,C,G0.05intergenic_variantRNA5SP185 - PSMC1P43e-07Tier 4: intronic/intergenic
rs17724081159035859A>C,G,T0.05intron_variantIFI168e-07Tier 4: intronic/intergenic
rs71695231531171175G>A,T0.22intergenic_variantTRPM1 - LINC030342e-06Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 30 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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
IL10StrongAutosomal recessiveimmune system disorder5
TOM1LimitedAutosomal dominantimmune system disorder3

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
IL10Orphanet:117Behçet disease
IL10Orphanet:238569Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections syndrome
IL10Orphanet:536Systemic lupus erythematosus
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
UBE2L3Orphanet:536Systemic lupus erythematosus
CD247Orphanet:169160T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta
CD247Orphanet:85408Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
CD247Orphanet:85410Oligoarticular juvenile idiopathic arthritis
TNIP1Orphanet:536Systemic lupus erythematosus
SPRED2Orphanet:648Noonan syndrome
CDK4Orphanet:618Familial melanoma
CDK4Orphanet:99970Dedifferentiated liposarcoma
CDK4Orphanet:99971Well-differentiated liposarcoma
ANKRD55Orphanet:85408Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
ANKRD55Orphanet:85410Oligoarticular juvenile idiopathic arthritis
DDX6Orphanet:528084Non-specific syndromic intellectual disability
SH2B3Orphanet:3318Essential thrombocythemia
SH2B3Orphanet:391366Growth retardation-mild developmental delay-chronic hepatitis syndrome
PTPN2Orphanet:85408Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
PTPN2Orphanet:85410Oligoarticular juvenile idiopathic arthritis
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

Cohort genes → proteins

18 cohort genes, 18 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only16
multi_evidence2

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
TOM1HGNC:11982ENSG00000100284O60784Target of Myb1 membrane trafficking proteingencc
IL10HGNC:5962ENSG00000136634P22301Interleukin-10gencc
STAT4HGNC:11365ENSG00000138378Q14765Signal transducer and activator of transcription 4gwas
TRAF1HGNC:12031ENSG00000056558Q13077TNF receptor-associated factor 1gwas
UBASH3AHGNC:12462ENSG00000160185P57075Ubiquitin-associated and SH3 domain-containing protein Agwas
UBE2L3HGNC:12488ENSG00000185651P68036Ubiquitin-conjugating enzyme E2 L3gwas
SMIM29HGNC:1340ENSG00000186577Q86T20Small integral membrane protein 29gwas
ELMO1HGNC:16286ENSG00000155849Q92556Engulfment and cell motility protein 1gwas
CD247HGNC:1677ENSG00000198821P20963T-cell surface glycoprotein CD3 zeta chaingwas
TNIP1HGNC:16903ENSG00000145901Q15025TNFAIP3-interacting protein 1gwas
SPRED2HGNC:17722ENSG00000198369Q7Z698Sprouty-related, EVH1 domain-containing protein 2gwas
CDK4HGNC:1773ENSG00000135446P11802Cyclin-dependent kinase 4gwas
ANKRD55HGNC:25681ENSG00000164512Q3KP44Ankyrin repeat domain-containing protein 55gwas
DDX6HGNC:2747ENSG00000110367P26196Probable ATP-dependent RNA helicase DDX6gwas
SH2B3HGNC:29605ENSG00000111252Q9UQQ2SH2B adapter protein 3gwas
IFI16HGNC:5395ENSG00000163565Q16666Gamma-interferon-inducible protein 16gwas
PTPN2HGNC:9650ENSG00000175354P17706Tyrosine-protein phosphatase non-receptor type 2gwas
PTPN22HGNC:9652ENSG00000134242Q9Y2R2Tyrosine-protein phosphatase non-receptor type 22gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
TOM1Target of Myb1 membrane trafficking proteinAdapter protein that plays a role in the intracellular membrane trafficking of ubiquitinated proteins, thereby participating in autophagy, ubiquitination-dependent signaling and receptor recycling pathways.
IL10Interleukin-10Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation.
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.
TRAF1TNF receptor-associated factor 1Adapter molecule that regulates the activation of NF-kappa-B and JNK.
UBASH3AUbiquitin-associated and SH3 domain-containing protein AInterferes with CBL-mediated down-regulation and degradation of receptor-type tyrosine kinases.
UBE2L3Ubiquitin-conjugating enzyme E2 L3Ubiquitin-conjugating enzyme E2 that specifically acts with HECT-type and RBR family E3 ubiquitin-protein ligases.
ELMO1Engulfment and cell motility protein 1Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility.
CD247T-cell surface glycoprotein CD3 zeta chainPart of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response.
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.
SPRED2Sprouty-related, EVH1 domain-containing protein 2Negatively regulates Ras signaling pathways and downstream activation of MAP kinases.
CDK4Cyclin-dependent kinase 4Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition.
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.
SH2B3SH2B adapter protein 3Links T-cell receptor activation signal to phospholipase C-gamma-1, GRB2 and phosphatidylinositol 3-kinase.
IFI16Gamma-interferon-inducible protein 16Binds double-stranded DNA.
PTPN2Tyrosine-protein phosphatase non-receptor type 2Non-receptor type tyrosine-specific phosphatase that dephosphorylates receptor protein tyrosine kinases including INSR, EGFR, CSF1R, PDGFR.
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.

Protein-family classification

Druggable: 6 · Difficult: 4 · Unknown: 8 · Druggable fraction: 0.33

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
Phosphatase314.0×0.007
Scaffold/PPI32.9×0.247
Kinase11.5×0.726
Enzyme (other)21.3×0.726
Other/Unknown80.8×0.902
Transcription factor10.5×0.902

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
TOM1Other/UnknownnoVHS_dom, GAT_dom, ENTH_VHS
IL10Other/UnknownnoIL-10, 4_helix_cytokine-like_core, IL-10_CS
STAT4Transcription factornoSH2, STAT, p53-like_TF_DNA-bd_sf
TRAF1Other/UnknownnoMATH/TRAF_dom, TRAF-like, TNF_rcpt-assoc_TRAF_met
UBASH3APhosphataseyesSH3_domain, UBA-like_sf, His_Pase_superF_clade-1
UBE2L3Enzyme (other)yes2.3.2.23UBC, UBQ-conjugating_enzyme/RWD, UBQ-conjugating_AS
SMIM29Other/UnknownnoSMIM29
ELMO1Scaffold/PPInoPH_domain, ELMO_dom, ARM-like
CD247Other/UnknownnoPhos_immunorcpt_sig_ITAM, CD3_zeta/IgE_Fc_rcpt_gamma, T-cell_CD3_zeta
TNIP1Other/Unknownno
SPRED2Other/UnknownnoWH1/EVH1_dom, Sprouty, PH-like_dom_sf
CDK4Kinaseyes2.7.11.22Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
ANKRD55Scaffold/PPInoAnkyrin_rpt, Ankyrin_rpt-contain_sf
DDX6Enzyme (other)yes3.6.4.13RNA-helicase_DEAD-box_CS, Helicase_C-like, DEAD/DEAH_box_helicase_dom
SH2B3Scaffold/PPInoSH2, PH_domain, PH-like_dom_sf
IFI16Other/UnknownnoDAPIN, HIN200/IF120x, DEATH-like_dom_sf
PTPN2Phosphataseyes3.1.3.48PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat
PTPN22Phosphataseyes3.1.3.48PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat

Expression context

Cohort genes with no expression data: 0.

18 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)18
unknown0

Top tissues across cohort

TissueCohort genes
granulocyte5
blood3
ventricular zone3
monocyte3
lower esophagus mucosa2
sperm2
ganglionic eminence2
gastrocnemius1
muscle of leg1
cartilage tissue1
gall bladder1
vermiform appendix1
middle temporal gyrus1
descending thoracic aorta1
right coronary artery1
lymph node1
mucosa of transverse colon1
oocyte1
secondary oocyte1
amygdala1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
TOM1207ubiquitousmarkerlower esophagus mucosa, gastrocnemius, muscle of leg
IL10158broadmarkervermiform appendix, gall bladder, cartilage tissue
STAT4201broadmarkergranulocyte, sperm, middle temporal gyrus
TRAF1178ubiquitousmarkergranulocyte, right coronary artery, descending thoracic aorta
UBASH3A133broadmarkergranulocyte, blood, lymph node
UBE2L3287ubiquitousmarkeroocyte, secondary oocyte, mucosa of transverse colon
SMIM29225ubiquitousmarkeranterior cingulate cortex, amygdala, hypothalamus
ELMO1248ubiquitousmarkerprefrontal cortex, C1 segment of cervical spinal cord, corpus callosum
CD247179broadmarkergranulocyte, thymus, blood
TNIP1298ubiquitousmarkerlower esophagus mucosa, blood, hindlimb stylopod muscle
SPRED2270ubiquitousmarkersural nerve, mucosa of sigmoid colon, ventricular zone
CDK4138ubiquitousmarkerembryo, ganglionic eminence, ventricular zone
ANKRD55169broadmarkermale germ line stem cell (sensu Vertebrata) in testis, sperm, primordial germ cell in gonad
DDX6271ubiquitousmarkerganglionic eminence, calcaneal tendon, ventricular zone
SH2B3260ubiquitousmarkermonocyte, mononuclear cell, leukocyte
IFI16296ubiquitousmarkergerminal epithelium of ovary, pericardium, palpebral conjunctiva
PTPN2296ubiquitousmarkertendon of biceps brachii, granulocyte, monocyte
PTPN22190broadmarkerbone marrow cell, bone marrow, monocyte

Protein interactions among cohort

Intra-cohort edges: 8.

Hub genes (top 10 by interactor count)

SymbolInteractor count
CDK48,412
IL106,185
DDX65,922
IFI163,614
TRAF13,557
TNIP13,304
PTPN22,705
PTPN222,480
CD2472,417
STAT42,370

Intra-cohort edges

ABSources
ANKRD55PTPN22string_interaction
CD247PTPN22intact
CD247UBASH3Abiogrid_interaction
PTPN2SH2B3string_interaction
PTPN2STAT4string_interaction
PTPN22STAT4string_interaction
PTPN22UBASH3Astring_interaction
SH2B3UBASH3Astring_interaction

Structural data

PDB: 14 · AlphaFold-only: 4 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
CD247P2096338
UBE2L3P6803621
ELMO1Q9255618
CDK4P1180215
PTPN2P1770614
PTPN22Q9Y2R214
IL10P223019
DDX6P261969
TNIP1Q150258
IFI16Q166668
TOM1O607846
TRAF1Q130773
UBASH3AP570752
SPRED2Q7Z6982

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
STAT4Q1476586.87
SMIM29Q86T2071.70
SH2B3Q9UQQ263.45
ANKRD55Q3KP4463.43

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 114. Enrichment computed across 18 evidence-associated genes (15 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 15 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Nef and signal transduction2169.2×0.007ELMO1, CD247
Translocation of ZAP-70 to Immunological synapse284.6×0.013CD247, PTPN22
Phosphorylation of CD3 and TCR zeta chains272.5×0.013CD247, PTPN22
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation240.1×0.026STAT4, IL10
FCGR3A-mediated IL10 synthesis239.0×0.026CD247, IL10
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK41380.7×0.028CDK4
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK41380.7×0.028CDK4
Diseases of Cellular Senescence1253.8×0.028CDK4
Evasion of Oncogene Induced Senescence Due to p16INK4A Defects1253.8×0.028CDK4
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK61253.8×0.028CDK4
Evasion of Oxidative Stress Induced Senescence Due to p16INK4A Defects1253.8×0.028CDK4
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK61253.8×0.028CDK4
Diseases of cellular response to stress1253.8×0.028CDK4
Regulation of TNFR1 signaling229.9×0.028TRAF1, UBE2L3
FCGR3A-mediated phagocytosis225.0×0.028ELMO1, CD247
Regulation of actin dynamics for phagocytic cup formation224.6×0.028ELMO1, CD247
Drug-mediated inhibition of CDK4/CDK6 activity1152.3×0.044CDK4
PTK6 Regulates Cell Cycle1126.9×0.050CDK4
RAS signaling downstream of NF1 loss-of-function variants1108.8×0.055SPRED2
Interleukin-23 signaling184.6×0.065STAT4
Interleukin-21 signaling176.1×0.065STAT4
CD163 mediating an anti-inflammatory response176.1×0.065IL10
STING mediated induction of host immune responses169.2×0.065IFI16
Interleukin-35 Signalling163.4×0.065STAT4
FCGR activation158.6×0.065CD247
FGFRL1 modulation of FGFR1 signaling158.6×0.065SPRED2
Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects158.6×0.065CDK4
Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells)158.6×0.065STAT4
IRF3-mediated induction of type I IFN154.4×0.065IFI16
Signaling by FGFR1154.4×0.065SPRED2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 16 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
negative regulation of T cell receptor signaling pathway368.7×0.003UBASH3A, PTPN2, PTPN22
negative regulation of ERK1 and ERK2 cascade340.5×0.006TNIP1, SPRED2, PTPN2
negative regulation of interleukin-8 production2123.9×0.009IL10, PTPN22
negative regulation of receptor signaling pathway via JAK-STAT2110.9×0.009SH2B3, PTPN2
negative regulation of chronic inflammatory response to antigenic stimulus11053.2×0.016IL10
phosphoanandamide dephosphorylation11053.2×0.016PTPN22
negative regulation of cytokine activity11053.2×0.016IL10
negative regulation of interleukin-2-mediated signaling pathway11053.2×0.016PTPN2
negative regulation of positive thymic T cell selection11053.2×0.016PTPN2
regulation of response to wounding11053.2×0.016IL10
chronic inflammatory response to antigenic stimulus1526.6×0.016IL10
viral RNA genome packaging1526.6×0.016DDX6
negative regulation of interleukin-18 production1526.6×0.016IL10
regulation of natural killer cell proliferation1526.6×0.016PTPN22
regulation of type II interferon-mediated signaling pathway1526.6×0.016PTPN2
negative regulation of interleukin-6-mediated signaling pathway1526.6×0.016PTPN2
negative regulation of Kit signaling pathway1526.6×0.016SH2B3
regulation of hepatocyte growth factor receptor signaling pathway1526.6×0.016PTPN2
negative regulation of interleukin-4-mediated signaling pathway1526.6×0.016PTPN2
regulation of endosome organization1526.6×0.016TOM1
T cell differentiation247.9×0.016PTPN2, PTPN22
negative regulation of viral genome replication246.8×0.016TNIP1, IFI16
negative regulation of interleukin-6 production243.9×0.016IL10, PTPN22
negative regulation of MAPK cascade237.6×0.016SPRED2, SH2B3
positive regulation of cytokine production234.0×0.016IFI16, IL10
negative regulation of autophagy232.4×0.016IL10, PTPN22
negative regulation of tumor necrosis factor production231.4×0.016IL10, PTPN22
cellular response to lipopolysaccharide318.4×0.016TNIP1, CDK4, IL10
response to inactivity1351.1×0.018IL10
response to carbon monoxide1351.1×0.018IL10

Therapeutics

Drugs indicated for this disease

45 approved, 9 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
AbataceptApproved (phase 4)
AdalimumabApproved (phase 4)
AlefaceptApproved (phase 4)
AnakinraApproved (phase 4)
ApremilastApproved (phase 4)
AzathioprineApproved (phase 4)
BasiliximabApproved (phase 4)
BelataceptApproved (phase 4)
BelumosudilApproved (phase 4)
BimekizumabApproved (phase 4)
BrodalumabApproved (phase 4)
CanakinumabApproved (phase 4)
Certolizumab PegolApproved (phase 4)
CladribineApproved (phase 4)
CyclosporineApproved (phase 4)
DaclizumabApproved (phase 4)
DarvadstrocelApproved (phase 4)
Dimethyl FumarateApproved (phase 4)
Diroximel FumarateApproved (phase 4)
Efgartigimod AlfaApproved (phase 4)
EtanerceptApproved (phase 4)
GolimumabApproved (phase 4)
GuselkumabApproved (phase 4)
Idecabtagene VicleucelApproved (phase 4)
ImlifidaseApproved (phase 4)
InfliximabApproved (phase 4)
IxekizumabApproved (phase 4)
LenalidomideApproved (phase 4)
MethotrexateApproved (phase 4)
MirikizumabApproved (phase 4)
Mycophenolic AcidApproved (phase 4)
PirfenidoneApproved (phase 4)
PomalidomideApproved (phase 4)
RilonaceptApproved (phase 4)
RisankizumabApproved (phase 4)
SarilumabApproved (phase 4)
SatralizumabApproved (phase 4)
SecukinumabApproved (phase 4)
SiltuximabApproved (phase 4)
SpesolimabApproved (phase 4)
ThalidomideApproved (phase 4)
TildrakizumabApproved (phase 4)
TocilizumabApproved (phase 4)
UstekinumabApproved (phase 4)
VoclosporinApproved (phase 4)
BriakinumabPhase 3 (in late-stage trials)
GoflikiceptPhase 3 (in late-stage trials)
GusperimusPhase 3 (in late-stage trials)
Human Immunoglobulin GPhase 3 (in late-stage trials)
LevilimabPhase 3 (in late-stage trials)
OlokizumabPhase 3 (in late-stage trials)
RemibrutinibPhase 3 (in late-stage trials)
RituximabPhase 3 (in late-stage trials)
SirukumabPhase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Alemtuzumab, Bortezomib, Busulfan, Dexamethasone, Emapalumab, Omalizumab.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 4 · Undrugged: 14

Druggability breadth: 9 of 18 evidence-associated genes (50%) 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
CDK4PALBOCICLIB

Top cohort targets by molecule count

SymbolMoleculesMax phase
CDK4564
PTPN242
ELMO112
DDX612
TOM100
IL1000
STAT400
TRAF100
UBASH3A00
UBE2L300

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
PALBOCICLIB4CDK4
ABEMACICLIB4CDK4
RIBOCICLIB4CDK4
TRILACICLIB4CDK4
FEDRATINIB4CDK4
DABRAFENIB4CDK4
CERITINIB4CDK4
ENCORAFENIB4CDK4
GILTERITINIB4CDK4
NINTEDANIB4CDK4
SUNITINIB4CDK4
DINACICLIB3CDK4
LEROCICLIB3CDK4
ALVOCIDIB3CDK4
QUERCETIN3CDK4
DALPICICLIB3CDK4
DOVITINIB3CDK4
LESTAURTINIB3CDK4
RUBOXISTAURIN3CDK4
MOLIBRESIB2ELMO1
INDIRUBIN2CDK4
SELICICLIB2CDK4
REBASTINIB2CDK4
NARAZACICLIB2CDK4
RIVICICLIB2CDK4
RG-5472CDK4
VORUCICLIB2CDK4
ULECACICLIB2CDK4
CROZBACICLIB2CDK4
RONICICLIB2CDK4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 5.

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

SymbolAssaysType breakdown
CDK41,142Binding:1086, Functional:53, ADMET:2, Toxicity:1
PTPN2250Binding:246, ADMET:4
PTPN22137Binding:122, Functional:10, ADMET:5
STAT420Binding:20
ELMO16Binding:6
DDX64Binding:4
UBE2L32Binding:2
UBASH3A1Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
UBE2L32.3.2.23, 2.3.2.24E2 ubiquitin-conjugating enzyme, (E3-independent) E2 ubiquitin-conjugating enzyme
CDK42.7.11.22cyclin-dependent kinase
DDX63.6.4.13RNA helicase
PTPN23.1.3.48protein-tyrosine-phosphatase
PTPN223.1.3.48protein-tyrosine-phosphatase

Cohort genes with high screening signal

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

SymbolChEMBL assays
CDK41,142
PTPN2250
PTPN22137

Pharmacogenomics

Cohort genes with a PharmGKB record: 18; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

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

CompoundMax phaseCohort target (bioactivity)
PALBOCICLIB4CDK4
ABEMACICLIB4CDK4
RIBOCICLIB4CDK4
TRILACICLIB4CDK4
FEDRATINIB4CDK4
DABRAFENIB4CDK4
CERITINIB4CDK4
ENCORAFENIB4CDK4
GILTERITINIB4CDK4
NINTEDANIB4CDK4
SUNITINIB4CDK4
DINACICLIB3CDK4
LEROCICLIB3CDK4
ALVOCIDIB3CDK4
QUERCETIN3CDK4
DALPICICLIB3CDK4
DOVITINIB3CDK4
LESTAURTINIB3CDK4
RUBOXISTAURIN3CDK4
MOLIBRESIB2ELMO1
INDIRUBIN2CDK4
SELICICLIB2CDK4
REBASTINIB2CDK4
NARAZACICLIB2CDK4
RIVICICLIB2CDK4
RG-5472CDK4
VORUCICLIB2CDK4
ULECACICLIB2CDK4
CROZBACICLIB2CDK4
RONICICLIB2CDK4

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1CDK4
BPhased (≥1) drug, not yet approved3ELMO1, DDX6, PTPN2
CDruggable family + PDB, no drug3UBASH3A, UBE2L3, PTPN22
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug11TOM1, IL10, STAT4, TRAF1, SMIM29, CD247, TNIP1, SPRED2, ANKRD55, SH2B3 (+1 more)

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
PTPN22137—
TOM10—
IL100—
STAT420—
TRAF10—
UBASH3A1—
UBE2L32—
SMIM290—
CD2470—
TNIP10—
SPRED20—
ANKRD550—
SH2B30—
IFI160—

Clinical trials & evidence

Clinical trials

Clinical trials: 50.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified35
PHASE17
PHASE24
PHASE1/PHASE22
PHASE41
PHASE31

Top trials by phase / activity

NCTPhaseStatusTitle
NCT02053740PHASE4COMPLETEDUse of Traditional Chinese Medicine (Ren Shen Yang Rong Tang) Against Microinflammation in Hemodialysis Patients: A Quasi-randomized Controlled Trial
NCT01002742PHASE3COMPLETEDAcute Graft-versus-Host Disease Treatment (BMT CTN 0802)
NCT05507242PHASE2RECRUITINGEffects of Blocking TSLP on Airway Inflammation and the Epithelial Immune-response to Exacerbation Triggers in Patients With COPD
NCT00224874PHASE2COMPLETEDTreatment for Acute Graft-Versus-Host Disease (BMT CTN 0302)
NCT02519816PHASE2UNKNOWNContinuous Alloreactive T Cell Depletion and Regulatory T Cell Expansion for the Treatment of Steroid-refractory or Dependent Chronic GVHD
NCT03744676PHASE2COMPLETEDA Safety Trial of Lisocabtagene Maraleucel (JCAR017) for Relapsed and Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL) in the Outpatient Setting (TRANSCEND-OUTREACH-007)
NCT04294459PHASE1/PHASE2TERMINATEDSafety, Pharmacokinetics, and Preliminary Efficacy of Isatuximab in Patients Awaiting Kidney Transplantation
NCT04928963PHASE1/PHASE2UNKNOWNFighting Immunosenescence and Promoting Immunity by a Fasting-mimicking Diet Elderly.
NCT00008450PHASE1COMPLETEDTotal-Body Irradiation Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Severe Combined Immunodeficiency Undergoing Donor Bone Marrow Transplant
NCT03351543PHASE1COMPLETEDEffect of Microbial Exposure on Health, Particularly Immune System
NCT03357939PHASE1COMPLETEDPhase I Study of HLX3 vs Adalimumab in Chinese Healthy Subjects
NCT05806567PHASE1COMPLETEDA Study to Assess the Effect of Oral Belumosudil on Inhibition of Various Proteins in the Fed State in Healthy Male Subjects
NCT05918588PHASE1COMPLETEDA Study to Determine the Effect of Multiple Oral Doses and Regimens of KD025 in Healthy Male and Post-menopausal Female Subjects
NCT05918614PHASE1COMPLETEDA Study to Determine the Effect of 500 mg Oral Dose of KD025 in Healthy Male and Post-menopausal Female Subjects
NCT05918627PHASE1COMPLETEDA Study to Determine the Effect of Multiple Oral Doses of SLx-2119 in Healthy Male Subjects
NCT03207854Not specifiedRECRUITINGCollection of Immunology Specimens From Patients With Cancer or Blood Disorders, and Healthy Volunteers
NCT03908736Not specifiedRECRUITINGThinking Zinc: a Study of Zinc Supplements on the Navajo Nation
NCT04430972Not specifiedNOT_YET_RECRUITINGImmune Responsiveness and Outcome After Aortic Valve Surgery (Measure)
NCT05002023Not specifiedRECRUITINGPRINCE Study - Cohort Study of Healthy Pregnant Women Followed by the Assessment of Children´s Health and Immunity
NCT05139706Not specifiedRECRUITINGMontreal Immune-Related Adverse Events (MIRAE) Study
NCT05266664Not specifiedRECRUITINGPreterm Immune System Development and Response to Immunization
NCT05318196Not specifiedRECRUITINGMolecular Prediction of Development, Progression or Complications of Kidney, Immune or Transplantation-related Diseases
NCT06235580Not specifiedRECRUITINGGenotype-phenotype Characterization Study on Genetic Diseases With Immune and Neurological Dysfunctions
NCT06540027Not specifiedENROLLING_BY_INVITATIONThe Effect of Minimally Invasive Surgery on Systemic Inflammatory Response in Rectal Cancer
NCT07040774Not specifiedRECRUITINGNatural History of Type 1 Interferonopathies: Insights From a European Cohort
NCT07562243Not specifiedNOT_YET_RECRUITINGProject PHOENIX: Molecular Signatures of Burn Pit Exposure
NCT01367821Not specifiedUNKNOWNImmune Function in Patients With Obstructive Jaundice
NCT01821820Not specifiedCOMPLETEDPistachios, Performance, Metabolomics
NCT02417766Not specifiedCOMPLETEDNIAID Clinical Center Genomics Opportunity Protocol
NCT02824237Not specifiedUNKNOWNGEOHealth Hub: Household Air Pollution and Cardio-pulmonary and Immune Function Outcomes
NCT02981992Not specifiedCOMPLETEDT Regulatory Cells in Hemodialysis Patients: Observational Study
NCT03364699Not specifiedCOMPLETEDFish Oils and Soybean Lecithin Supplementation Modulate Immune Function in Runners
NCT03370627Not specifiedCOMPLETEDEffect of Anti-CD303 Antibodies in Autoimmune Diseases
NCT03385850Not specifiedCOMPLETEDThe Th17/Treg Cells and IL-23/IL-17 Axis and Early Enteral Nutrition in Sepsis
NCT03994302Not specifiedCOMPLETEDMonitoring the Antiphospholipid Syndrome:TOXicity of Drugs (APSTOX)
NCT04386395Not specifiedCOMPLETEDImmune Changes in Severe COVID-19 Pulmonary Infections
NCT04444609Not specifiedUNKNOWNPROSAIC-19 - Prospective Longitudinal Assessment in a COVID-19 Infected Cohort
NCT04445402Not specifiedCOMPLETEDPediatrics HOT COVID-19 Database in NY Tristate
NCT04458246Not specifiedUNKNOWNHome-based Aerobic Training Among Adolescents With Chronic Diseases During COVID-19 Pandemic
NCT04802044Not specifiedUNKNOWNCOVID-19, Aging, and Cardiometabolic Risk Factors Study

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
BELUMOSUDIL47
MYCOPHENOLATE MOFETIL43
DENILEUKIN DIFTITOX41
ISATUXIMAB41
PENTOSTATIN41
TEZEPELUMAB41
LISOCABTAGENE MARALEUCEL31
CHEMBL541522901
PEANUT OIL-11

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
v1.1.2
BioBTree
v2.0.2

Sources 72

This page pulls from 72 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_interactiontranscriptuberonufeatureumlsuniprot