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Sclerosing cholangitis

disease
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Also known as sclerosing cholangitis (disease)

Summary

Sclerosing cholangitis (MONDO:0018646) is a disease (an umbrella term covering 5 Mondo subtypes) with 75 cohort genes (342 GWAS associations across 18 studies) and 5 clinical trials. The dominant Reactome pathway is Interleukin-23 signaling (5 cohort genes). Top therapeutic interventions include aldesleukin.

At a glance

  • Umbrella term: 5 Mondo subtypes
  • Cohort genes: 75
  • GWAS associations: 342
  • Clinical trials: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namesclerosing cholangitis
Mondo IDMONDO:0018646
EFOEFO:0004268
Orphanet447771
DOIDDOID:14268
SNOMED CT235917005
UMLSC0008313
MedGen3036
GARD0021868
Anatomy (UBERON)UBERON:0002294
Is cancer (heuristic)no

Also known as: sclerosing cholangitis · sclerosing cholangitis (disease)

Data availability: 342 GWAS associations (18 studies) · 1 HPO phenotype.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › hepatobiliary disorder › biliary tract disorder › bile duct disorder › non-neoplastic bile duct disorder › cholangitis › sclerosing cholangitis

Related subtypes (8): suppurative cholangitis, ascending cholangitis, acute cholangitis, pericholangitis, cholecystitis, chronic cholangitis, primary biliary cholangitis/primary sclerosing cholangitis and autoimmune hepatitis overlap syndrome, autoimmune cholangitis

Subtypes (5): neonatal ichthyosis-sclerosing cholangitis syndrome, primary sclerosing cholangitis, IgG4-related sclerosing cholangitis, secondary sclerosing cholangitis, isolated neonatal sclerosing cholangitis

Genetics & variants

GWAS landscape

342 GWAS associations across 18 studies. Top hits map to 30 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs57432931e-320NOD2, CYLD-AS1?
rs41433321e-250ZDHHC20P2?
rs25235938e-247HLA-BC0.51
HLA-B*08:014e-246?2.82
HLA-DQA1*05:016e-175?2.39
rs801746461e-143IL23R?
rs47135705e-112HLA-DQA1 - HLA-DQB1T0.27
HLA-DQA*01:031e-100?2.23
rs75178471e-98IL23R, C1orf141?
rs20668456e-94NOD2?
rs20726334e-89CFBG0.21
rs283833142e-75HLA-DRB1 - HLA-DQA1C0.2
rs19926611e-74RNU1-150P - TTC33?
rs353002425e-67ATG16L1?
rs64268337e-62RNF186-AS1 - OTUD3?
rs30942101e-61PSORS1C1, CDSNA0.18
rs176223782e-55IRF1, CARINH?
rs31979997e-55MST1?
rs99776725e-54LINC02940 - RPL23AP12?
rs4697586e-54ERAP1?
rs46725052e-52RN7SL51P - RN7SL18P?
rs107487816e-51LINC01475?
rs109952713e-48LINC02929 - ALDH7A1P4?
rs23576234e-48NKD1 - SNX20?
rs108700776e-45CARD9?
rs561673323e-43IL12B-AS1?
rs112367973e-43EMSY - LINC02757?
rs107586695e-43HNRNPA1P41 - JAK2?
rs117493912e-42IRGM?
rs121317965e-41INAVA?

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST005537Ellinghaus D20168,72634,213Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.
GCST005563Liu JZ20136,333106,357Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis.
GCST006670Liu JZ20133,78925,079Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis.
GCST90435163Khrom M20243,2558,572Comprehensive association analyses of extraintestinal manifestations in inflammatory bowel disease.
GCST90428828Yu X20242,87128,685Shared genetic architecture between autoimmune disorders and B-cell acute lymphoblastic leukemia: insights from large-scale genome-wide cross-trait analysis.
GCST90271580Han Y20232,87112,019Multitrait genome-wide analyses identify new susceptibility loci and candidate drugs to primary sclerosing cholangitis.
GCST004030Ji SG20162,87112,019Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease.
GCST90435162Khrom M20241,70410,190Comprehensive association analyses of extraintestinal manifestations in inflammatory bowel disease.
GCST005859Alberts R20178740Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis.
GCST000915Melum E20107152,962Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding3
Tier 2: splice/UTR1
Tier 3: regulatory2
Tier 4: intronic/intergenic44

MAF distribution

BucketVariants
common (>=0.05)46
low_freq (0.01-0.05)0
rare (<0.01)0
unknown4

Functional consequences

ConsequenceCount
intron_variant23
intergenic_variant15
non_coding_transcript_exon_variant3
unknown3
missense_variant2
frameshift_variant1
TF_binding_site_variant1
regulatory_region_variant1
splice_donor_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs57432931650729868frameshift_variantNOD2, CYLD-AS11e-320Tier 1: coding
rs4143332631380588G>A0.05non_coding_transcript_exon_variantZDHHC20P21e-250Tier 4: intronic/intergenic
rs2523593631358926T>C0.05intron_variantHLA-B8e-247Tier 4: intronic/intergenic
HLA-B*08:010.1234e-246Tier 4: intronic/intergenic
HLA-DQA1*05:010.166e-175Tier 4: intronic/intergenic
rs80174646167242472G>T0.05intron_variantIL23R1e-143Tier 4: intronic/intergenic
rs4713570632658263C>G,T0.05intergenic_variantHLA-DQA1 - HLA-DQB15e-112Tier 4: intronic/intergenic
HLA-DQA*01:030.0731e-100Tier 4: intronic/intergenic
rs7517847167215986T>A,C,G0.05intron_variantIL23R, C1orf1411e-98Tier 4: intronic/intergenic
rs20668451650722629G>C,Tmissense_variantNOD26e-94Tier 1: coding
rs2072633631951801A>C,G,T0.05intron_variantCFB4e-89Tier 4: intronic/intergenic
rs28383314632619436T>A,C0.05non_coding_transcript_exon_variantHLA-DRB1 - HLA-DQA12e-75Tier 4: intronic/intergenic
rs1992661540414887G>A0.05intron_variantRNU1-150P - TTC331e-74Tier 4: intronic/intergenic
rs353002422233260144G>A,C0.05intron_variantATG16L15e-67Tier 4: intronic/intergenic
rs6426833119845367G>A,C,T0.05TF_binding_site_variantRNF186-AS1 - OTUD37e-62Tier 3: regulatory
rs3094210631119821G>A0.05intron_variantPSORS1C1, CDSN1e-61Tier 4: intronic/intergenic
rs176223785132442760A>G0.05intron_variantIRF1, CARINH2e-55Tier 4: intronic/intergenic
rs3197999349684099G>A,C,T0.05missense_variantMST17e-55Tier 1: coding
rs99776722139091357G>A0.05intergenic_variantLINC02940 - RPL23AP125e-54Tier 4: intronic/intergenic
rs469758596786011C>T0.05intron_variantERAP16e-54Tier 4: intronic/intergenic
rs4672505262333197A>C,G,T0.05intron_variantRN7SL51P - RN7SL18P2e-52Tier 4: intronic/intergenic
rs107487811099523573C>A,G0.05non_coding_transcript_exon_variantLINC014756e-51Tier 4: intronic/intergenic
rs109952711062678726G>A,C0.05intergenic_variantLINC02929 - ALDH7A1P43e-48Tier 4: intronic/intergenic
rs23576231650660100A>G,T0.05intergenic_variantNKD1 - SNX204e-48Tier 4: intronic/intergenic
rs108700779136369439C>G,T0.05intron_variantCARD96e-45Tier 4: intronic/intergenic
rs561673325159400761C>A,T0.05intergenic_variantIL12B-AS13e-43Tier 4: intronic/intergenic
rs112367971176588605C>A0.05regulatory_region_variantEMSY - LINC027573e-43Tier 3: regulatory
rs1075866994981602C>A,G,T0.05intergenic_variantHNRNPA1P41 - JAK25e-43Tier 4: intronic/intergenic
rs117493915150849504T>C0.05intergenic_variantIRGM2e-42Tier 4: intronic/intergenic
rs121317961200909599G>A0.05intron_variantINAVA5e-41Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 55 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 3

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

GeneHGNCEvidence routes
TCF4TCF4GWAS, Orphanet
TNFSF15TNFSF15GWAS, Orphanet
MMEL1MMEL1GWAS, Orphanet

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
RORCOrphanet:477857Mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency
ATXN2Orphanet:803Amyotrophic lateral sclerosis
ATXN2Orphanet:98756Spinocerebellar ataxia type 2
STAT3Orphanet:2314Autosomal dominant hyper-IgE syndrome due to STAT3 deficiency
STAT3Orphanet:438159STAT3-related early-onset multisystem autoimmune disease
STAT3Orphanet:512017Chronic lymphoproliferative disorder of natural killer cells
STAT3Orphanet:520Acute promyelocytic leukemia
STAT3Orphanet:667662Breast implant-associated anaplastic large cell lymphoma
STAT3Orphanet:86872T-cell large granular lymphocyte leukemia
STAT3Orphanet:99885Isolated permanent neonatal diabetes mellitus
STK11Orphanet:2869Peutz-Jeghers syndrome
TCF4Orphanet:171Primary sclerosing cholangitis
TCF4Orphanet:178469Autosomal dominant non-syndromic intellectual disability
TCF4Orphanet:2896Pitt-Hopkins syndrome
TCF4Orphanet:98974Fuchs endothelial corneal dystrophy
MYRFOrphanet:647811Cardiac-urogenital syndrome
TLR4Orphanet:117Behçet disease
TNFAIP3Orphanet:536Systemic lupus erythematosus
TNFAIP3Orphanet:674762Early-onset autoinflammatory syndrome due to A20 haploinsufficiency
TNFRSF1AOrphanet:32960Tumor necrosis factor receptor 1 associated periodic syndrome
TNFRSF1AOrphanet:329967Intermittent hydrarthrosis
CD40Orphanet:101090Hyper-IgM syndrome type 3
TNFSF15Orphanet:186Primary biliary cholangitis
TYK2Orphanet:300865Primary cutaneous anaplastic large cell lymphoma
TYK2Orphanet:331226Susceptibility to infection due to TYK2 deficiency
TYK2Orphanet:98842Lymphomatoid papulosis
UBE2L3Orphanet:536Systemic lupus erythematosus
ACTA2Orphanet:2573Moyamoya disease
ACTA2Orphanet:404463Multisystemic smooth muscle dysfunction syndrome
ACTA2Orphanet:91387Familial thoracic aortic aneurysm and aortic dissection
BACH2Orphanet:714472Inflammatory bowel disease-autoimmunity-sinopulmonary infections-lymphadenopathy syndrome
MMEL1Orphanet:186Primary biliary cholangitis
PARK7Orphanet:2828Young-onset Parkinson disease
PARK7Orphanet:90020Parkinson-dementia complex of Guam
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
PPP2R3COrphanet:171709Male infertility due to globozoospermia
PPP2R3COrphanet:1770XY type gonadal dysgenesis-associated anomalies syndrome
ERAP1Orphanet:117Behçet disease
ZNF365Orphanet:2073Narcolepsy type 1
ZNF365Orphanet:83465Narcolepsy type 2
BANK1Orphanet:536Systemic lupus erythematosus
LRRK2Orphanet:2828Young-onset Parkinson disease
LRRK2Orphanet:411602Hereditary late-onset Parkinson disease
IFIH1Orphanet:51Aicardi-Goutières syndrome
IFIH1Orphanet:689231IFIH1-related hereditary spastic paraplegia
IFIH1Orphanet:85191Singleton-Merten dysplasia

Cohort genes → proteins

75 cohort genes, 75 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only75

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
RORCHGNC:10260ENSG00000143365P51449Nuclear receptor ROR-gammagwas
RPS6KB1HGNC:10436ENSG00000108443P23443Ribosomal protein S6 kinase beta-1gwas
ATXN2HGNC:10555ENSG00000204842Q99700Ataxin-2gwas
CCL21HGNC:10620ENSG00000137077O00585C-C motif chemokine 21gwas
SLCO3A1HGNC:10952ENSG00000176463Q9UIG8Solute carrier organic anion transporter family member 3A1gwas
BSNHGNC:1117ENSG00000164061Q9UPA5Protein bassoongwas
SP100HGNC:11206ENSG00000067066P23497Nuclear autoantigen Sp-100gwas
STAT3HGNC:11364ENSG00000168610P40763Signal transducer and activator of transcription 3gwas
STK11HGNC:11389ENSG00000118046Q15831Serine/threonine-protein kinase STK11gwas
TCF4HGNC:11634ENSG00000196628P15884Transcription factor 4gwas
MYRFHGNC:1181ENSG00000124920Q9Y2G1Myelin regulatory factorgwas
TLR4HGNC:11850ENSG00000136869O00206Toll-like receptor 4gwas
TNFAIP3HGNC:11896ENSG00000118503P21580Tumor necrosis factor alpha-induced protein 3gwas
TNFRSF14HGNC:11912ENSG00000157873Q92956Tumor necrosis factor receptor superfamily member 14gwas
TNFRSF1AHGNC:11916ENSG00000067182P19438Tumor necrosis factor receptor superfamily member 1Agwas
CD40HGNC:11919ENSG00000101017P25942Tumor necrosis factor receptor superfamily member 5gwas
TNFRSF6BHGNC:11921ENSG00000243509O95407Tumor necrosis factor receptor superfamily member 6Bgwas
TNFSF15HGNC:11931ENSG00000181634O95150Tumor necrosis factor ligand superfamily member 15gwas
TNFSF8HGNC:11938ENSG00000106952P32971Tumor necrosis factor ligand superfamily member 8gwas
TNP2HGNC:11952ENSG00000178279Q05952Nuclear transition protein 2gwas
TYK2HGNC:12440ENSG00000105397P29597Non-receptor tyrosine-protein kinase TYK2gwas
UBASH3AHGNC:12462ENSG00000160185P57075Ubiquitin-associated and SH3 domain-containing protein Agwas
UBE2L3HGNC:12488ENSG00000185651P68036Ubiquitin-conjugating enzyme E2 L3gwas
ACTA2HGNC:130ENSG00000107796P62736Actin, aortic smooth musclegwas
SIRAL2HGNC:1313ENSG00000100376Q9NWS6Protein FAM118Agwas
GLYATHGNC:13734ENSG00000149124Q6IB77Glycine N-acyltransferasegwas
CACNA2D2HGNC:1400ENSG00000007402Q9NY47Voltage-dependent calcium channel subunit alpha-2/delta-2gwas
HDAC7HGNC:14067ENSG00000061273Q8WUI4Histone deacetylase 7gwas
BACH2HGNC:14078ENSG00000112182Q9BYV9Transcription regulator protein BACH2gwas
SLC39A11HGNC:14463ENSG00000133195Q8N1S5Zinc transporter ZIP11gwas
MMEL1HGNC:14668ENSG00000142606Q495T6Membrane metallo-endopeptidase-like 1gwas
KCNIP1HGNC:15521ENSG00000182132Q9NZI2A-type potassium channel modulatory protein KCNIP1gwas
SKAP2HGNC:15687ENSG00000005020O75563Src kinase-associated phosphoprotein 2gwas
STRN4HGNC:15721ENSG00000090372Q9NRL3Striatin-4gwas
ZNF831HGNC:16167ENSG00000124203Q5JPB2Zinc finger protein 831gwas
PARK7HGNC:16369ENSG00000116288Q99497Parkinson disease protein 7gwas
CARD9HGNC:16391ENSG00000187796Q9H257Caspase recruitment domain-containing protein 9gwas
ZMIZ1HGNC:16493ENSG00000108175Q9ULJ6Zinc finger MIZ domain-containing protein 1gwas
CD28HGNC:1653ENSG00000178562P10747T-cell-specific surface glycoprotein CD28gwas
SV2BHGNC:16874ENSG00000185518Q7L1I2Synaptic vesicle glycoprotein 2Bgwas
TNIP1HGNC:16903ENSG00000145901Q15025TNFAIP3-interacting protein 1gwas
CD6HGNC:1691ENSG00000013725P30203T-cell differentiation antigen CD6gwas
MYDGFHGNC:16948ENSG00000074842Q969H8Myeloid-derived growth factorgwas
CD226HGNC:16961ENSG00000150637Q15762CD226 antigengwas
CEP43HGNC:17012ENSG00000213066O95684Centrosomal protein 43gwas
SP140HGNC:17133ENSG00000079263Q13342Nuclear body protein SP140gwas
PRKD2HGNC:17293ENSG00000105287Q9BZL6Serine/threonine-protein kinase D2gwas
ARID5BHGNC:17362ENSG00000150347Q14865AT-rich interactive domain-containing protein 5Bgwas
PPP2R3CHGNC:17485ENSG00000092020Q969Q6Serine/threonine-protein phosphatase 2A regulatory subunit B’’ subunit gammagwas
NDFIP1HGNC:17592ENSG00000131507Q9BT67NEDD4 family-interacting protein 1gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
RORCNuclear receptor ROR-gammaNuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5’-AGGTCA-3’ preceded by a short A-T-rich sequence.
RPS6KB1Ribosomal protein S6 kinase beta-1Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression.
ATXN2Ataxin-2Involved in EGFR trafficking, acting as negative regulator of endocytic EGFR internalization at the plasma membrane.
CCL21C-C motif chemokine 21Inhibits hemopoiesis and stimulates chemotaxis.
SLCO3A1Solute carrier organic anion transporter family member 3A1Putative organic anion antiporter with apparent broad substrate specificity.
BSNProtein bassoonScaffold protein of the presynaptic cytomatrix at the active zone (CAZ) which is the place in the synapse where neurotransmitter is released.
SP100Nuclear autoantigen Sp-100Together with PML, this tumor suppressor is a major constituent of the PML bodies, a subnuclear organelle involved in a large number of physiological processes including cell growth, differentiation and apoptosis.
STAT3Signal transducer and activator of transcription 3Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors.
STK11Serine/threonine-protein kinase STK11Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage…
TCF4Transcription factor 4Transcription factor that binds to the immunoglobulin enhancer Mu-E5/KE5-motif.
MYRFMyelin regulatory factorConstitutes a precursor of the transcription factor.
TLR4Toll-like receptor 4Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstream signaling pathways.
TNFAIP3Tumor necrosis factor alpha-induced protein 3Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities.
TNFRSF14Tumor necrosis factor receptor superfamily member 14Receptor for four distinct ligands: The TNF superfamily members TNFSF14/LIGHT and homotrimeric LTA/lymphotoxin-alpha and the immunoglobulin superfamily members BTLA and CD160, altogether defining a complex stimulatory and inhibitory signal…
TNFRSF1ATumor necrosis factor receptor superfamily member 1AReceptor for TNFSF2/TNF and homotrimeric TNFSF1/lymphotoxin-alpha.
CD40Tumor necrosis factor receptor superfamily member 5Receptor for TNFSF5/CD40LG.
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.
TNFSF8Tumor necrosis factor ligand superfamily member 8Cytokine that binds to TNFRSF8/CD30.
TNP2Nuclear transition protein 2Plays a key role in the replacement of histones to protamine in the elongating spermatids of mammals.
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.
UBE2L3Ubiquitin-conjugating enzyme E2 L3Ubiquitin-conjugating enzyme E2 that specifically acts with HECT-type and RBR family E3 ubiquitin-protein ligases.
ACTA2Actin, aortic smooth muscleActins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
GLYATGlycine N-acyltransferaseMitochondrial acyltransferase which transfers an acyl group to the N-terminus of glycine and glutamine, although much less efficiently.
CACNA2D2Voltage-dependent calcium channel subunit alpha-2/delta-2The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel.
HDAC7Histone deacetylase 7Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).
BACH2Transcription regulator protein BACH2Transcriptional regulator that acts as a repressor or activator.
SLC39A11Zinc transporter ZIP11Zinc importer that regulates cytosolic zinc concentrations either via zinc influx from the extracellular compartment or efflux from intracellular organelles such as Golgi apparatus.
MMEL1Membrane metallo-endopeptidase-like 1Metalloprotease involved in sperm function, possibly by modulating the processes of fertilization and early embryonic development.
KCNIP1A-type potassium channel modulatory protein KCNIP1Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly inactivating A-type potassium channels.
SKAP2Src kinase-associated phosphoprotein 2May be involved in B-cell and macrophage adhesion processes.
STRN4Striatin-4Calmodulin-binding scaffolding protein which is the center of the striatin-interacting phosphatase and kinase (STRIPAK) complexes.
PARK7Parkinson disease protein 7Multifunctional protein with controversial molecular function which plays an important role in cell protection against oxidative stress and cell death acting as oxidative stress sensor and redox-sensitive chaperone and protease.
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.
SV2BSynaptic vesicle glycoprotein 2BProbably plays a role in the control of regulated secretion in neural and endocrine cells.
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.
CD6T-cell differentiation antigen CD6Cell adhesion molecule that mediates cell-cell contacts and regulates T-cell responses via its interaction with ALCAM/CD166.
MYDGFMyeloid-derived growth factorBone marrow-derived monocyte and paracrine-acting protein that promotes cardiac myocyte survival and adaptive angiogenesis for cardiac protection and/or repair after myocardial infarction (MI).
CD226CD226 antigenCell surface receptor that plays an important role in the immune system, particularly in intercellular adhesion, lymphocyte signaling, cytotoxicity and lymphokine secretion mediated by cytotoxic T-cells and NK cells.
CEP43Centrosomal protein 43Required for anchoring microtubules to the centrosomes.
SP140Nuclear body protein SP140Component of the nuclear body, also known as nuclear domain 10, PML oncogenic domain, and KR body.
PRKD2Serine/threonine-protein kinase D2Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of cell proliferation via MAPK1/3 (ERK1/2) signaling, oxidative…
ARID5BAT-rich interactive domain-containing protein 5BTranscription coactivator that binds to the 5’-AATA[CT]-3’ core sequence and plays a key role in adipogenesis and liver development.
PPP2R3CSerine/threonine-protein phosphatase 2A regulatory subunit B’’ subunit gammaMay regulate MCM3AP phosphorylation through phosphatase recruitment.
NDFIP1NEDD4 family-interacting protein 1Activates HECT domain-containing E3 ubiquitin-protein ligases, including NEDD4 and ITCH, and consequently modulates the stability of their targets.
ERAP1Endoplasmic reticulum aminopeptidase 1Aminopeptidase that plays a central role in peptide trimming, a step required for the generation of most HLA class I-binding peptides.
ZNF365TalaninMay play a role in uric acid excretion.

Protein-family classification

Druggable: 24 · Difficult: 15 · Unknown: 36 · Druggable fraction: 0.32

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
Kinase72.6×0.202
Antibody/Immunoglobulin62.3×0.239
Nuclear receptor15.2×0.650
Transporter22.1×0.690
Scaffold/PPI51.1×0.805
Transcription factor101.1×0.805
Phosphatase11.1×0.841
Protease21.0×0.841
Other/Unknown360.9×0.960
Enzyme (other)40.6×0.960
GPCR10.3×0.960

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
RORCNuclear receptoryesNucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt
RPS6KB1Kinaseyes2.7.11.1Prot_kinase_dom, AGC-kinase_C, Ser/Thr_kinase_AS
ATXN2Other/UnknownnoLsmAD_domain, PAM2_motif, LSM_dom_sf
CCL21Other/UnknownnoChemokine_IL8-like_dom, Chemokine_CC_DCCL, Interleukin_8-like_sf
SLCO3A1TransporteryesKazal_dom, OATP, Kazal_dom_sf
BSNTranscription factornoZnf_piccolo, Znf_FYVE_PHD, Znf_RING/FYVE/PHD
SP100Other/UnknownnoSAND_dom, HSR_dom, HMG_box_dom
STAT3Transcription factornoSH2, STAT, p53-like_TF_DNA-bd_sf
STK11Kinaseyes2.7.11.1Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
TCF4Transcription factorno7.6.2.3bHLH_dom, HLH_DNA-bd_sf, NeuroDiff_E-box_TFs
MYRFTranscription factornop53-like_TF_DNA-bd_sf, NDT80_DNA-bd_dom, MYRF_C2
TLR4Other/UnknownnoTIR_dom, Cys-rich_flank_reg_C, Leu-rich_rpt
TNFAIP3Transcription factornoZnf_A20, OTU_dom, OTU_Deubiquitinase
TNFRSF14Other/UnknownnoTNFR/NGFR_Cys_rich_reg, TNFR_14, TNFRSF14/UL144_N
TNFRSF1AOther/UnknownnoDeath_dom, TNFR/NGFR_Cys_rich_reg, DEATH-like_dom_sf
CD40Other/UnknownnoTNFR/NGFR_Cys_rich_reg, TNFR_5, TNFRSF5_N
TNFRSF6BOther/UnknownnoTNFR/NGFR_Cys_rich_reg, TNFRSF6B_N, TNFRSF_decoy_receptor
TNFSF15Other/UnknownnoTNF_dom, TNF, Tumour_necrosis_fac-like_dom
TNFSF8Other/UnknownnoTNF_dom, Tumour_necrosis_fac-like_dom, TNF_CS
TNP2Other/UnknownnoTP2
TYK2Kinaseyes2.7.10.2FERM_domain, Prot_kinase_dom, SH2
UBASH3APhosphataseyesSH3_domain, UBA-like_sf, His_Pase_superF_clade-1
UBE2L3Enzyme (other)yes2.3.2.23UBC, UBQ-conjugating_enzyme/RWD, UBQ-conjugating_AS
ACTA2Other/UnknownnoActin, Actin_CS, Actin/actin-like_CS
SIRAL2Other/UnknownnoFAM118
GLYATEnzyme (other)yes2.3.1.13Glycine_N-acyltransferase, Glycine_N-acyltransferase_C, Glycine_N-acyltransferase_N
CACNA2D2Other/UnknownnoVWF_A, VWA_N, VDCC_a2/dsu
HDAC7Enzyme (other)yes3.5.1.98HDACs, Ureohydrolase_dom_sf, His_deacetylse_dom
BACH2Transcription factornoBTB/POZ_dom, bZIP_Maf, bZIP
SLC39A11Other/UnknownnoZIP
MMEL1Proteaseyes3.4.24.B14Peptidase_M13, Peptidase_M13_N, Peptidase_M13_C
KCNIP1Other/UnknownnoEF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS
SKAP2Scaffold/PPInoSH3_domain, PH_domain, PH-like_dom_sf
STRN4Scaffold/PPInoWD40_rpt, Striatin_N, WD40/YVTN_repeat-like_dom_sf
ZNF831Transcription factornoZnf_C2H2_type, Znf_C2H2_sf
PARK7Enzyme (other)yes3.5.1.124DJ-1/PfpI, DJ-1, Class_I_gatase-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
SV2BTransporteryesMFS_sugar_transport-like, Sugar_transporter_CS, MFS
TNIP1Other/Unknownno
CD6Other/UnknownnoSRCR, SRCR-like_dom_sf
MYDGFOther/UnknownnoMYDGF
CD226Antibody/ImmunoglobulinyesIg_sub2, Ig_sub, Ig-like_dom
CEP43Other/UnknownnoLisH, FOP_dimerisation-dom_N
SP140Transcription factornoSAND_dom, Bromodomain, Znf_PHD
PRKD2Kinaseyes2.7.11.13Prot_kinase_dom, PH_domain, PKC_DAG/PE
ARID5BOther/UnknownnoARID_dom, ARID5B_ARID/BRIGHT_DNA-bd, ARID_dom_sf
PPP2R3COther/UnknownnoEF-hand-dom_pair, EF_Hand_1_Ca_BS, PPP2R3C
NDFIP1Other/UnknownnoNEDD4/Bsd2

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)1
moderate (6-20)1
broad (>20)73
unknown0

Top tissues across cohort

TissueCohort genes
lymph node9
left testis9
granulocyte9
right testis6
monocyte6
pericardium5
leukocyte5
spleen5
secondary oocyte5
hindlimb stylopod muscle4
male germ line stem cell (sensu Vertebrata) in testis4
Brodmann (1909) area 234
calcaneal tendon4
endothelial cell4
buccal mucosa cell4
vermiform appendix4
mononuclear cell4
jejunal mucosa4
sperm4
blood4

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
RORC209broadmarkergastrocnemius, male germ line stem cell (sensu Vertebrata) in testis, hindlimb stylopod muscle
RPS6KB1275ubiquitousmarkerendothelial cell, Brodmann (1909) area 23, calcaneal tendon
ATXN2286ubiquitousmarkerbuccal mucosa cell, colonic epithelium, olfactory bulb
CCL21206tissue_specificmarkerlymph node, right lobe of thyroid gland, vermiform appendix
SLCO3A1279ubiquitousmarkerbuccal mucosa cell, endothelial cell, C1 segment of cervical spinal cord
BSN156broadmarkerfrontal pole, paraflocculus, middle temporal gyrus
SP100286ubiquitousmarkercalcaneal tendon, lymph node, right lung
STAT3301ubiquitousmarkertype B pancreatic cell, pericardium, lower lobe of lung
STK11238ubiquitousmarkerleft testis, right testis, hindlimb stylopod muscle
TCF4292ubiquitousmarkerendothelial cell, skin of hip, pericardium
MYRF223ubiquitousmarkermiddle frontal gyrus, C1 segment of cervical spinal cord, inferior vagus X ganglion
TLR4233ubiquitousmarkermonocyte, mononuclear cell, leukocyte
TNFAIP3274ubiquitousmarkervena cava, mucosa of paranasal sinus, vermiform appendix
TNFRSF14134ubiquitousmarkergranulocyte, spleen, right uterine tube
TNFRSF1A292ubiquitousmarkertendon of biceps brachii, gall bladder, left uterine tube
CD40242ubiquitousmarkerlymph node, right lung, spleen
TNFRSF6B127broadyesolfactory segment of nasal mucosa, spleen, subcutaneous adipose tissue
TNFSF15149broadmarkercartilage tissue, jejunal mucosa, duodenum
TNFSF8179broadmarkermonocyte, leukocyte, mononuclear cell
TNP232tissue_specificyessperm, male germ cell, left testis
TYK2288ubiquitousmarkergranulocyte, right hemisphere of cerebellum, adenohypophysis
UBASH3A133broadmarkergranulocyte, blood, lymph node
UBE2L3287ubiquitousmarkeroocyte, secondary oocyte, mucosa of transverse colon
ACTA2289ubiquitousmarkercauda epididymis, blood vessel layer, saphenous vein
SIRAL2239ubiquitousmarkerright testis, left testis, gall bladder
GLYAT142tissue_specificmarkerright lobe of liver, nephron tubule, adult mammalian kidney
CACNA2D2218broadmarkerlower lobe of lung, cerebellar vermis, superior vestibular nucleus
HDAC7282ubiquitousmarkersural nerve, mucosa of stomach, metanephros cortex
BACH2237ubiquitousmarkercortical plate, sural nerve, epithelium of nasopharynx
SLC39A11239ubiquitousmarkerbone marrow cell, ileal mucosa, pancreatic ductal cell

Protein interactions among cohort

Intra-cohort edges: 48.

Hub genes (top 10 by interactor count)

SymbolInteractor count
STAT310,108
LRRK27,628
TLR46,974
PARK75,722
RPS6KB15,474
STK115,146
KEAP15,022
TNFRSF1A4,523
TYK23,932
ATG16L13,843

Intra-cohort edges

ABSources
ANTXR2ATG16L1intact
ANTXR2ERAP1string_interaction
ANTXR2IL23Rstring_interaction
ATG16L1TNFSF15string_interaction
ATXN2CPEB4biogrid_interaction
BACH2UBASH3Astring_interaction
BANK1TNFAIP3string_interaction
CACNA2D2TNIP1intact
CARD9IFIH1string_interaction
CD226THADAintact
CD28CD40string_interaction
CD40SLC39A11intact
CD40THADAintact
CD40TNFSF8string_interaction
CD6UBASH3Astring_interaction
CDKAL1SV2Bbiogrid_interaction
CDKAL1THADAstring_interaction
CEP43PPP2R3Cbiogrid_interaction
CISHSTAT3string_interaction
CISHTYK2string_interaction
ERAP1IL23Rstring_interaction
ERAP1TNFRSF1Astring_interaction
ERAP1TNIP1string_interaction
HDAC7PRKD2intact
IFNLR1TYK2string_interaction
IL23RRORCstring_interaction
IL23RTNIP1string_interaction
IL23RTYK2string_interaction
KEAP1PARK7string_interaction
KEAP1TNFRSF6Bbiogrid_interaction
LRRK2MYDGFintact
LRRK2PARK7string_interaction
NDFIP1UBE2L3biogrid_interaction
OR5B21TNP2string_interaction
PPP2R3CSTRN4string_interaction
SIRAL2SPMIP7string_interaction
STAT3TYK2string_interaction
TNFAIP3TNFRSF1Abiogrid_interaction
TNFAIP3TNIP1biogrid_interaction, intact, string_interaction
TNFRSF14TNFRSF6Bstring_interaction
TNFRSF14TNFSF15string_interaction
TNFRSF14TNFSF8string_interaction
TNFRSF1ATNFRSF6Bstring_interaction
TNFRSF1ATNFSF15string_interaction
TNFRSF1ATNFSF8string_interaction
TNFRSF6BTNFSF15biogrid_interaction, intact, string_interaction
TNFRSF6BTNFSF8string_interaction
TNFSF15TNFSF8string_interaction

Structural data

PDB: 50 · AlphaFold-only: 25 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
RORCP51449161
SP100P23497122
KEAP1Q14145122
PARK7Q9949788
TYK2P2959752
LRRK2Q5S00744
ERAP1Q9NZ0823
RPS6KB1P2344322
UBE2L3P6803621
TNFAIP3P2158017
ATG16L1Q676U516
TLR4O0020615
CD40P2594214
ANTXR2P5833514
TNFRSF1AP1943813
KCNIP1Q9NZI210
CD28P1074710
IFIH1Q9BYX49
CENPWQ5EE019
TNFRSF14Q929568
TNFRSF6BO954078
CARD9Q9H2578
TNIP1Q150258
IFNLR1Q8IU578
TNFSF15O951507
STAT3P407636
HDAC7Q8WUI46
SV2BQ7L1I26
FNDC3AQ9Y2H66
CCL21O005855

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
GLYATQ6IB7795.71
ACTA2P6273695.43
MMEL1Q495T690.34
PPP2R3CQ969Q690.08
OR5B21A6NL2688.83
ZPBP2Q6X78486.81
SIRAL2Q9NWS683.77
CDKAL1Q5VV4282.72
CACNA2D2Q9NY4781.48
TNFSF8P3297180.07
RSPO3Q9BXY478.27
SLC39A11Q8N1S576.64
SLC9A8Q9Y2E876.02
SLCO3A1Q9UIG875.19
CISHQ9NSE273.91
UBAC2Q8NBM472.34
STRN4Q9NRL368.59
NDFIP1Q9BT6763.27
BANK1Q8NDB261.25
TNP2Q0595259.17
SIK2Q9H0K158.68
SPMIP7A4D26355.76
HIPK1Q86Z0252.62
ZNF365Q70YC430.21
BSNQ9UPA5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 590. Enrichment computed across 193 evidence-associated genes (122 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 122 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Interleukin-23 signaling552.0×9e-06STAT3, TYK2, IL23R, IL12B, JAK2
Interleukin-10 signaling713.4×2e-04STAT3, TNFRSF1A, TYK2, IL10, IL12B, IL1R1, IL1R2
Interleukin-4 and Interleukin-13 signaling97.6×5e-04RORC, STAT3, TYK2, IL23R, FOS, IL10, IL12B, IL6R (+1 more)
Interleukin-6 signaling431.2×8e-04STAT3, TYK2, IL6R, JAK2
TNFs bind their physiological receptors516.1×0.001TNFRSF14, TNFRSF1A, TNFRSF6B, TNFSF15, TNFSF8
Interferon gamma signaling77.2×0.005SP100, HLA-B, HLA-DQA1, HLA-DRB1, IFNGR2, IRF5, JAK2
Interleukin-37 signaling417.0×0.007STAT3, IL18R1, SMAD3, PTPN2
Activation of STAT3 by cadherin engagement68.0×0.007STAT3, TYK2, ACTA2, IL6R, JAK2, NFKB1
MAPK1 (ERK2) activation328.1×0.008TYK2, IL6R, JAK2
MAPK3 (ERK1) activation325.5×0.008TYK2, IL6R, JAK2
Interleukin-27 signaling325.5×0.008STAT3, TYK2, JAK2
Interleukin-20 family signaling413.9×0.008STAT3, TYK2, IFNLR1, JAK2
Immune System222.3×0.008RORC, SP100, STAT3, CARD9, CD28, CD226, ITLN1, IFNLR1 (+14 more)
Cytokine Signaling in Immune system113.7×0.008RORC, SP100, STAT3, IFNLR1, SH2B3, IFNGR2, IRF5, JAK2 (+3 more)
Interleukin-35 Signalling323.4×0.010STAT3, TYK2, JAK2
Regulation of IFNG signaling320.1×0.015IFNGR2, JAK2, PTPN2
Potential therapeutics for SARS65.6×0.024TYK2, KEAP1, IFNGR2, IL1R1, IL6R, JAK2
Translocation of ZAP-70 to Immunological synapse315.6×0.027HLA-DQA1, HLA-DRB1, PTPN22
IL-6-type cytokine receptor ligand interactions315.6×0.027TYK2, JAK2, OSMR
Ovarian tumor domain proteases49.1×0.027TNFAIP3, TNIP1, IFIH1, NOD2
RUNX3 regulates BCL2L11 (BIM) transcription237.4×0.030SMAD3, BCL2L11
NOTCH4 Intracellular Domain Regulates Transcription314.0×0.030ACTA2, SMAD3, NOTCH1
Signaling by CSF3 (G-CSF)314.0×0.030STAT3, TYK2, JAK2
Phosphorylation of CD3 and TCR zeta chains313.4×0.033HLA-DQA1, HLA-DRB1, PTPN22
Diseases of signal transduction by growth factor receptors and second messengers83.7×0.033STAT3, CD28, CEP43, JAK2, KSR1, SMAD3, BCL2A1, BCL2L11
RUNX3 Regulates Immune Response and Cell Migration231.2×0.037RORC, ITGAL
Growth hormone receptor signaling311.7×0.045STAT3, CISH, JAK2
IkBA variant leads to EDA-ID226.7×0.047NFKB1, NFKBIA
TRAF6 mediated NF-kB activation311.2×0.047IFIH1, NFKB1, NFKBIA
Inactivation of CSF3 (G-CSF) signaling310.8×0.050STAT3, TYK2, JAK2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 165 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
positive regulation of interleukin-17 production932.8×5e-09TYK2, CARD9, IL23R, NOD2, IL12B, IL2, IL21, JAK2 (+1 more)
immune response226.3×5e-09CCL21, TLR4, TNFRSF14, TNFSF15, TNFSF8, TYK2, ETS1, HLA-B (+14 more)
positive regulation of type II interferon production1115.0×9e-08TLR4, TYK2, CD226, IL23R, IL12B, IL18R1, IL1R1, IL2 (+3 more)
nucleotide-binding oligomerization domain containing 2 signaling pathway655.7×1e-07TLR4, INAVA, IRGM, NOD2, IRF5, NFKBIA
response to muramyl dipeptide651.1×2e-07TNFAIP3, CARD9, INAVA, NOD2, NFKBIA, NOTCH1
positive regulation of T-helper 17 type immune response651.1×2e-07TYK2, CARD9, IL23R, IL12B, JAK2, PRKCQ
negative regulation of inflammatory response1210.0×7e-07TNFAIP3, TNFRSF1A, NDFIP1, IRGM, IL10, IL2, IL2RA, SMAD3 (+4 more)
cellular response to virus1012.2×2e-06TYK2, IFNLR1, IFIH1, IRGM, IFNGR2, IL21, IRF5, JAK2 (+2 more)
positive regulation of canonical NF-kappaB signal transduction156.6×2e-06CCL21, SLCO3A1, STAT3, TLR4, TNFRSF1A, CD40, TNFSF15, CARD9 (+7 more)
positive regulation of T cell proliferation914.1×2e-06TYK2, CD28, CD6, IL23R, CCDC88B, IL12B, IL21, JAK2 (+1 more)
cytokine-mediated signaling pathway118.7×8e-06STAT3, TNFRSF1A, TYK2, IFNLR1, IL23R, CISH, IFNGR2, IL6R (+3 more)
adaptive immune response136.6×1e-05TNFRSF14, CD6, PRKD2, ERAP1, ERAP2, HLA-B, HLA-DQA1, NOD2 (+5 more)
inflammatory response194.3×1e-05CCL21, STAT3, TLR4, TNFAIP3, TNFRSF1A, CD40, PARK7, TNIP1 (+11 more)
interleukin-23-mediated signaling pathway468.1×2e-05STAT3, TYK2, IL23R, JAK2
positive regulation of interleukin-10 production717.0×2e-05STAT3, TLR4, CD28, INAVA, NOD2, IL12B, IL21
positive regulation of transcription by RNA polymerase II312.8×2e-05SP100, STAT3, TCF4, TLR4, TNFRSF1A, CD40, TNFSF8, PARK7 (+23 more)
positive regulation of tumor necrosis factor production98.4×1e-04STAT3, TLR4, CARD9, LRRK2, IFIH1, FCGR2A, NOD2, IL12B (+1 more)
cell surface receptor signaling pathway via JAK-STAT712.3×1e-04STAT3, TNFRSF1A, CD40, TYK2, IL23R, IL12B, JAK2
positive regulation of inflammatory response97.9×2e-04STAT3, TLR4, TNFRSF1A, TNIP1, ETS1, IL12B, IL2, IL21 (+1 more)
positive regulation of natural killer cell proliferation434.0×3e-04TYK2, IL23R, IL12B, JAK2
response to lipopolysaccharide96.8×6e-04TLR4, CD6, IL23R, FOS, FOSL2, FOXP1, MAPKAPK3, NOTCH1 (+1 more)
cellular response to lipopolysaccharide105.9×6e-04TLR4, TNFAIP3, CD40, TNIP1, SBNO2, IRGM, NOD2, IL10 (+2 more)
type II interferon-mediated signaling pathway429.2×6e-04SP100, TYK2, IFNGR2, JAK2
positive regulation of cytokine production involved in inflammatory response516.5×8e-04STAT3, TLR4, CARD9, CD6, NOD2
lipopolysaccharide-mediated signaling pathway516.0×9e-04TLR4, CD6, JAK2, NFKBIA, PTPN22
T cell receptor signaling pathway87.4×9e-04STK11, CD28, PRKD2, DENND1B, FOSL2, HLA-DRB1, LCP2, PTPN22
positive regulation of tissue remodeling351.1×0.001IL12B, IL2, IL21
positive regulation of NK T cell proliferation351.1×0.001TYK2, IL12B, JAK2
positive regulation of cytokine production involved in immune response424.0×0.001TNFRSF14, INAVA, NOD2, IRF5
inflammatory response to antigenic stimulus422.7×0.001FOSL2, HLA-DRB1, IL2RA, NOTCH1

Therapeutics

Drugs indicated or in trials for this disease

No drug has an approved disease-direct ChEMBL indication for this disease.

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

DrugHighest phase
BezafibratePhase 3
CilofexorPhase 3
Norucholic AcidPhase 3
SimvastatinPhase 3
VancomycinPhase 3
CenicrivirocPhase 2
CladribinePhase 2
ElafibranorPhase 2
MitomycinPhase 2
Obeticholic AcidPhase 2
SeladelparPhase 2
Sodium ChloridePhase 2
SulfasalazinePhase 2
ThalidomidePhase 2
TretinoinPhase 2
UrsodiolPhase 2
VidofludimusPhase 2

Drug target analysis

Approved (phase 4): 13 · Phase ≥3: 13 · Phased (≥1): 17 · Undrugged: 58

Druggability breadth: 101 of 193 evidence-associated genes (52%) 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
RORCDIGOXIN
RPS6KB1FEDRATINIB
STAT3MOMELOTINIB
STK11FEDRATINIB
TLR4METHOTREXATE
TYK2FEDRATINIB
CACNA2D2NIMODIPINE
HDAC7CELECOXIB
PRKD2MOMELOTINIB
LRRK2PONATINIB
HIPK1FEDRATINIB
SIK2MOMELOTINIB
KEAP1DUTASTERIDE

Top cohort targets by molecule count

SymbolMoleculesMax phase
TYK2724
PRKD2634
SIK2494
LRRK2424
RPS6KB1394
HDAC7284
HIPK1214
STAT3184
STK11174
RORC94

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
DIGOXIN4RORC, STAT3
TRETINOIN4RORC
ALITRETINOIN4RORC
FEDRATINIB4HIPK1, LRRK2, RPS6KB1, SIK2, STK11, TYK2
SORAFENIB4HIPK1, RPS6KB1
VANDETANIB4LRRK2, RPS6KB1, SIK2
BOSUTINIB4HIPK1, LRRK2, RPS6KB1, SIK2, TYK2
NINTEDANIB4HIPK1, LRRK2, PRKD2, RPS6KB1, SIK2, STK11
SUNITINIB4HIPK1, LRRK2, PRKD2, RPS6KB1, SIK2, STK11
CRIZOTINIB4PRKD2, RPS6KB1, SIK2, TYK2
MIDOSTAURIN4LRRK2, PRKD2, RPS6KB1, SIK2, STK11, TYK2
MOMELOTINIB4PRKD2, SIK2, STAT3, TYK2
NITAZOXANIDE4STAT3
NICLOSAMIDE4STAT3
BARICITINIB4STAT3, TYK2
DIGITOXIN4STAT3
DEUCRAVACITINIB4STAT3, TYK2
PACRITINIB4STK11, TYK2
METHOTREXATE4TLR4
POLYMYXIN B4TLR4
CARVEDILOL4TLR4
RUXOLITINIB4HIPK1, LRRK2, TYK2
TOFACITINIB4LRRK2, TYK2
UPADACITINIB4TYK2
FILGOTINIB4TYK2
ABROCITINIB4TYK2
AXITINIB4LRRK2, TYK2
RUXOLITINIB PHOSPHATE4TYK2
INFIGRATINIB PHOSPHATE4TYK2
INFIGRATINIB4TYK2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 11.

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

SymbolAssaysType breakdown
HDAC71,710Binding:1695, ADMET:10, Functional:4, Toxicity:1
STAT31,319Binding:1304, Functional:12, Unclassified:2, ADMET:1
TYK21,083Binding:1043, Functional:39, ADMET:1
LRRK2809Binding:799, ADMET:7, Functional:3
RORC758Binding:707, Functional:50, Unclassified:1
RPS6KB1585Binding:582, Functional:2, ADMET:1
KEAP1537Binding:535, Functional:1, ADMET:1
PRKD2360Binding:359, Functional:1
HIPK1285Binding:285
TLR4267Binding:254, Functional:10, ADMET:3
SIK2259Binding:258, Functional:1
STK11244Binding:244
ERAP188Binding:85, Functional:2, ADMET:1
PARK762Binding:62
TCF431Binding:31
TNFRSF1A24Binding:23, Functional:1
CACNA2D217Binding:17
IL23R13Binding:13
CD4010Binding:10
SLCO3A19Functional:9
SP1408Binding:8
ATXN25Binding:3, Functional:2
BACH23Binding:3
ANTXR23Binding:3
SP1002Binding:2
UBE2L32Binding:2
MMEL12Binding:2
CEP432Binding:2
TNFAIP31Binding:1
UBASH3A1Binding:1
SLC39A111Binding:1
CD281Functional:1
IFIH11Binding:1
CDKAL11Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
RPS6KB12.7.11.1non-specific serine/threonine protein kinase
STK112.7.11.1non-specific serine/threonine protein kinase
TCF47.6.2.3ABC-type glutathione-S-conjugate transporter
TYK22.7.10.2non-specific protein-tyrosine kinase
UBE2L32.3.2.23, 2.3.2.24E2 ubiquitin-conjugating enzyme, (E3-independent) E2 ubiquitin-conjugating enzyme
GLYAT2.3.1.13, 2.3.1.71glycine N-acyltransferase, glycine N-benzoyltransferase
HDAC73.5.1.98histone deacetylase
MMEL13.4.24.B14
PARK73.5.1.124, 4.2.1.130protein deglycase, D-lactate dehydratase
PRKD22.7.11.13protein kinase C
ERAP13.4.11.1, 3.4.11.22leucyl aminopeptidase, aminopeptidase I

Cohort genes with high screening signal

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

SymbolChEMBL assays
RORC758
RPS6KB1585
STAT31,319
STK11244
TLR4267
TYK21,083
HDAC71,710
PRKD2360
LRRK2809
HIPK1285
SIK2259
KEAP1537

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

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)
DIGOXIN4RORC, STAT3
TRETINOIN4RORC
ALITRETINOIN4RORC
FEDRATINIB4HIPK1, LRRK2, RPS6KB1, SIK2, STK11, TYK2
SORAFENIB4HIPK1, RPS6KB1
VANDETANIB4LRRK2, RPS6KB1, SIK2
BOSUTINIB4HIPK1, LRRK2, RPS6KB1, SIK2, TYK2
NINTEDANIB4HIPK1, LRRK2, PRKD2, RPS6KB1, SIK2, STK11
SUNITINIB4HIPK1, LRRK2, PRKD2, RPS6KB1, SIK2, STK11
CRIZOTINIB4PRKD2, RPS6KB1, SIK2, TYK2
MIDOSTAURIN4LRRK2, PRKD2, RPS6KB1, SIK2, STK11, TYK2
MOMELOTINIB4PRKD2, SIK2, STAT3, TYK2
NITAZOXANIDE4STAT3
NICLOSAMIDE4STAT3
BARICITINIB4STAT3, TYK2
DIGITOXIN4STAT3
DEUCRAVACITINIB4STAT3, TYK2
PACRITINIB4STK11, TYK2
METHOTREXATE4TLR4
POLYMYXIN B4TLR4
CARVEDILOL4TLR4
RUXOLITINIB4HIPK1, LRRK2, TYK2
TOFACITINIB4LRRK2, TYK2
UPADACITINIB4TYK2
FILGOTINIB4TYK2
ABROCITINIB4TYK2
AXITINIB4LRRK2, TYK2
RUXOLITINIB PHOSPHATE4TYK2
INFIGRATINIB PHOSPHATE4TYK2
INFIGRATINIB4TYK2

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)13RORC, RPS6KB1, STAT3, STK11, TLR4, TYK2, CACNA2D2, HDAC7, PRKD2, LRRK2 (+3 more)
BPhased (≥1) drug, not yet approved4TCF4, TNFRSF1A, PARK7, ERAP1
CDruggable family + PDB, no drug8UBASH3A, UBE2L3, CD28, SV2B, CD226, IFNLR1, IL23R, FNDC3A
DDruggable family + AlphaFold only, no drug5SLCO3A1, GLYAT, MMEL1, OR5B21, ZPBP2
EDifficult family or no structure, no drug45ATXN2, CCL21, BSN, SP100, MYRF, TNFAIP3, TNFRSF14, CD40, TNFRSF6B, TNFSF15 (+35 more)

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
TNFRSF6B0TNFRSF1A
ANTXR23ERAP1
ATXN25—
CCL210—
SLCO3A19—
BSN0—
SP1002—
MYRF0—
TNFAIP31—
TNFRSF140—
CD4010—
TNFSF150—
TNFSF80—
TNP20—
UBASH3A1—
UBE2L32—
ACTA20—
SIRAL20—
GLYAT0—
BACH23—
SLC39A111—
MMEL12—
KCNIP10—
SKAP20—
STRN40—
ZNF8310—
CARD90—
ZMIZ10—
CD281—
SV2B0—

Clinical trials & evidence

Clinical trials

Clinical trials: 5.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified3
PHASE21
PHASE1/PHASE21

Top trials by phase / activity

NCTPhaseStatusTitle
NCT01988506PHASE2COMPLETEDInduction of Regulatory t Cells by Low Dose il2 in Autoimmune and Inflammatory Diseases
NCT02424175PHASE1/PHASE2COMPLETEDFecal Microbiota Transplantation for the Treatment of Primary Sclerosing Cholangitis.
NCT05187312Not specifiedRECRUITINGRegistry for Advanced Endoscopy
NCT06670547Not specifiedNOT_YET_RECRUITINGSpanish Registry of Quality Indicators and Adverse Events of Endoscopic Retrograde Cholangiopancreatography
NCT01556555Not specifiedCOMPLETEDClinical Utility of the Spyglass System in Primary Sclerosing Cholangitis (PSC)

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
ALDESLEUKIN41

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 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_promotergardgenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptuberonufeatureumlsuniprot