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Atlas / Disease / Autoimmune thyroid disease

Autoimmune thyroid disease

disease
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Also known as autoimmune thyroid gland inflammationautoimmune thyroiditidesautoimmune thyroiditislymphocytic thyroiditideslymphocytic thyroiditislymphomatous thyroiditideslymphomatous thyroiditisthyroiditides, autoimmunethyroiditides, lymphocyticthyroiditides, lymphomatousthyroiditis, lymphocyticthyroiditis, lymphomatous

Summary

Autoimmune thyroid disease (MONDO:0005623) is a disease (an umbrella term covering 5 Mondo subtypes) with 75 cohort genes (636 GWAS associations across 9 studies) and 22 clinical trials. The dominant Reactome pathway is Interleukin-23 signaling (6 cohort genes). Top therapeutic interventions include levothyroxine and thyroxine.

At a glance

  • Umbrella term: 5 Mondo subtypes
  • Cohort genes: 75
  • GWAS associations: 636
  • Clinical trials: 22

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameautoimmune thyroid disease
Mondo IDMONDO:0005623
EFOEFO:0006812
MeSHD013967
UMLSC0920350
MedGen183088
Is cancer (heuristic)no

Also known as: autoimmune thyroid gland inflammation · autoimmune thyroiditides · autoimmune thyroiditis · lymphocytic thyroiditides · lymphocytic thyroiditis · lymphomatous thyroiditides · lymphomatous thyroiditis · thyroiditides, autoimmune · thyroiditides, lymphocytic · thyroiditides, lymphomatous · thyroiditis, lymphocytic · thyroiditis, lymphomatous

Data availability: 636 GWAS associations (9 studies).

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › endocrine system disorder › autoimmune disorder of endocrine system › autoimmune thyroid disease

Related subtypes (12): type 1 diabetes mellitus, immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome, autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome, autoimmune pancreatitis, autoimmune hepatitis, autoimmune polyendocrinopathy, autoimmune hypoparathyroidism, insulin autoimmune syndrome, IgG4-related sclerosing cholangitis, lymphocytic hypophysitis, autoimmune oophoritis, autoimmune primary ovarian failure

Subtypes (5): Graves disease, atrophic thyroiditis, Hashimoto thyroiditis, IgG4-related thyroid disease, postpartum thyroiditis

Genetics & variants

GWAS landscape

636 GWAS associations across 9 studies. Top hits map to 38 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs24766015e-324AP4B1-AS1, PTPN22?0.29
rs132902585e-324PTCSC2?0.23
rs31845045e-324ATXN2, SH2B3?0.16
rs115712973e-251CTLA4 - ICOS?0.13
rs116753421e-236TPO?0.13
rs20460457e-197PDE8B?0.12
rs92724261e-196HLA-DQA1G1.31
rs12039233e-146LNCNEF?0.12
rs787659713e-143VAV3?0.23
rs113352333e-139LPP?0.1
rs343340841e-117ATP5MGP4 - RNU7-197P?0.12
rs8818581e-115VEGFA - LINC02537?0.1
rs9254899e-110PTCSC2T1.25
rs120910478e-104CAPZB?0.09
rs77542519e-100BACH2?0.08
rs75826945e-93STAT4?0.09
rs109174691e-92MICOS10?0.12
rs10794181e-89PDE10A?0.09
rs67243634e-89TESHL?0.08
rs94979652e-84SAMD5 - SASH1?0.08
rs355664813e-79ITPK1?0.09
rs29210532e-77LINC02950 - RN7SL178P?0.07
rs93660787e-75RNASET2 - MIR3939?0.07
rs2317752e-74CTLA4G1.18
rs108447372e-74CD69 - GCNAP1?0.08
rs48044335e-72INSR?0.08
rs58453233e-71C1QTNF6?0.07
rs44097858e-69LNCRNA-IUR - FAM76B?0.09
rs8975861e-68CASC19, PCAT1?0.07
rs101165208e-68NEK6?0.07

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90837324Reeve MP202681,718732,951Genome-wide association analyses of autoimmune hypothyroidism reveal autoimmune and thyroid-specific contributions and an inverse relationship with cancer risk.
GCST010571Saevarsdottir S202030,234724,172FLT3 stop mutation increases FLT3 ligand level and risk of autoimmune thyroid disease.
GCST90454273Zeng Y202322,224354,647Genetic Associations Between Stress-Related Disorders and Autoimmune Disease.
GCST005524Cooper JD20122,2820Seven newly identified loci for autoimmune thyroid disease.
GCST90014440Glanville KP2021859324,074Investigating Pleiotropy Between Depression and Autoimmune Diseases Using the UK Biobank.
GCST90014441Glanville KP2021607324,074Investigating Pleiotropy Between Depression and Autoimmune Diseases Using the UK Biobank.
GCST002876Tomer Y20153460Genome wide identification of new genes and pathways in patients with both autoimmune thyroiditis and type 1 diabetes.
GCST002705Oryoji D20142630Identification of a Hashimoto thyroiditis susceptibility locus via a genome-wide comparison with Graves’ disease.
GCST003097Li YR20159710,718Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding3
Tier 2: splice/UTR2
Tier 3: regulatory1
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_variant35
intergenic_variant6
missense_variant3
non_coding_transcript_exon_variant3
5_prime_UTR_variant1
TF_binding_site_variant1
3_prime_UTR_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs24766011113834946A>G,T0.05missense_variantAP4B1-AS1, PTPN225e-324Tier 1: coding
rs13290258997796811C>A,G,T0.05intron_variantPTCSC25e-324Tier 4: intronic/intergenic
rs318450412111446804T>A,C,G0.05missense_variantATXN2, SH2B35e-324Tier 1: coding
rs115712972203880280T>C0.05intergenic_variantCTLA4 - ICOS3e-251Tier 4: intronic/intergenic
rs1167534221403856C>T0.05intron_variantTPO1e-236Tier 4: intronic/intergenic
rs2046045577239986T>A,C,G0.05intron_variantPDE8B7e-197Tier 4: intronic/intergenic
rs9272426632637412A>C,G,T0.4485_prime_UTR_variantHLA-DQA11e-196Tier 2: splice/UTR
rs12039232022605190T>A,C,G0.05intron_variantLNCNEF3e-146Tier 4: intronic/intergenic
rs787659711107819548GAC>G,GACAC0.05intron_variantVAV33e-143Tier 4: intronic/intergenic
rs113352333188407205AC>A,ACC0.05intron_variantLPP3e-139Tier 4: intronic/intergenic
rs343340844148737418ATT>A,AT,ATTT0.05intron_variantATP5MGP4 - RNU7-197P1e-117Tier 4: intronic/intergenic
rs881858643838872G>A,C0.05intron_variantVEGFA - LINC025371e-115Tier 4: intronic/intergenic
rs925489997784318C>A,G,T0.326intron_variantPTCSC29e-110Tier 4: intronic/intergenic
rs12091047119445431C>T0.05intron_variantCAPZB8e-104Tier 4: intronic/intergenic
rs7754251690279406G>A,C,T0.05intron_variantBACH29e-100Tier 4: intronic/intergenic
rs75826942191105394C>G0.05intron_variantSTAT45e-93Tier 4: intronic/intergenic
rs10917469119517082A>G,T0.05intron_variantMICOS101e-92Tier 4: intronic/intergenic
rs10794186165633546A>G0.05intron_variantPDE10A1e-89Tier 4: intronic/intergenic
rs67243632216761868G>A,C,T0.05intron_variantTESHL4e-89Tier 4: intronic/intergenic
rs94979656148200156C>T0.05intergenic_variantSAMD5 - SASH12e-84Tier 4: intronic/intergenic
rs355664811493097223GC>CAintron_variantITPK13e-79Tier 4: intronic/intergenic
rs292105388462453G>A,C,T0.05non_coding_transcript_exon_variantLINC02950 - RN7SL178P2e-77Tier 4: intronic/intergenic
rs93660786166986024A>G0.05intron_variantRNASET2 - MIR39397e-75Tier 4: intronic/intergenic
rs2317752203867991A>G,T0.385missense_variantCTLA42e-74Tier 1: coding
rs10844737129770056A>C,T0.05intergenic_variantCD69 - GCNAP12e-74Tier 4: intronic/intergenic
rs4804433197240765G>T0.05intron_variantINSR5e-72Tier 4: intronic/intergenic
rs58453232237187693G>GC0.05intron_variantC1QTNF63e-71Tier 4: intronic/intergenic
rs44097851195578258T>C0.05intron_variantLNCRNA-IUR - FAM76B8e-69Tier 4: intronic/intergenic
rs8975868127181049G>A,C,T0.05intron_variantCASC19, PCAT11e-68Tier 4: intronic/intergenic
rs101165209124267351A>G0.05intron_variantNEK68e-68Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 68 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 4

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

GeneHGNCEvidence routes
STAT3STAT3GWAS, Orphanet
TGTGGWAS, Orphanet
TPOTPOGWAS, Orphanet
CTLA4CTLA4GWAS, Orphanet

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
CFBOrphanet:544472Atypical hemolytic uremic syndrome with complement gene abnormality
SLC1A2Orphanet:442835Non-specific early-onset epileptic encephalopathy
SS18Orphanet:3273Synovial sarcoma
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
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
BTNL2Orphanet:797Sarcoidosis
SUOXOrphanet:99731Isolated sulfite oxidase deficiency
TGOrphanet:95716Familial thyroid dyshormonogenesis
TLR3Orphanet:1930Herpes simplex virus encephalitis
TNFSF15Orphanet:186Primary biliary cholangitis
CD40LGOrphanet:101088X-linked hyper-IgM syndrome
TNXBOrphanet:230839Classical-like Ehlers-Danlos syndrome type 1
TNXBOrphanet:289365Familial vesicoureteral reflux
TPOOrphanet:95716Familial thyroid dyshormonogenesis
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
TIMMDC1Orphanet:2609Isolated complex I deficiency
BACH2Orphanet:714472Inflammatory bowel disease-autoimmunity-sinopulmonary infections-lymphadenopathy syndrome
EDARADDOrphanet:1810Autosomal dominant hypohidrotic ectodermal dysplasia
EDARADDOrphanet:248Autosomal recessive hypohidrotic ectodermal dysplasia
EDARADDOrphanet:99798Oligodontia
MMEL1Orphanet:186Primary biliary cholangitis
CCR6Orphanet:220393Diffuse cutaneous systemic sclerosis
CCR6Orphanet:220402Limited cutaneous systemic sclerosis
CARD9Orphanet:457088Predisposition to invasive fungal disease due to CARD9 deficiency
ZMIZ1Orphanet:528084Non-specific syndromic intellectual disability
CD247Orphanet:169160T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta
CD247Orphanet:85408Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
CD247Orphanet:85410Oligoarticular juvenile idiopathic arthritis
PRICKLE1Orphanet:308Progressive myoclonic epilepsy type 1
ZNF365Orphanet:2073Narcolepsy type 1
ZNF365Orphanet:83465Narcolepsy type 2
LRRK2Orphanet:2828Young-onset Parkinson disease
LRRK2Orphanet:411602Hereditary late-onset Parkinson disease
IFIH1Orphanet:51Aicardi-Goutières syndrome
IFIH1Orphanet:689231IFIH1-related hereditary spastic paraplegia

Cohort genes → proteins

75 cohort genes, 74 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only75

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
CFBHGNC:1037ENSG00000243649P00751Complement factor Bgwas
SH2D2AHGNC:10821ENSG00000027869Q9NP31SH2 domain-containing protein 2Agwas
SLC1A2HGNC:10940ENSG00000110436P43004Excitatory amino acid transporter 2gwas
SS18HGNC:11340ENSG00000141380Q15532Protein SSXTgwas
STAT3HGNC:11364ENSG00000168610P40763Signal transducer and activator of transcription 3gwas
STAT4HGNC:11365ENSG00000138378Q14765Signal transducer and activator of transcription 4gwas
BTNL2HGNC:1142ENSG00000204290Q9UIR0Butyrophilin-like protein 2gwas
SUOXHGNC:11460ENSG00000139531P51687Sulfite oxidase, mitochondrialgwas
TBX21HGNC:11599ENSG00000073861Q9UL17T-box transcription factor TBX21gwas
TCF7HGNC:11639ENSG00000081059P36402Transcription factor 7gwas
TGHGNC:11764ENSG00000042832P01266Thyroglobulingwas
TLR3HGNC:11849ENSG00000164342O15455Toll-like receptor 3gwas
TNFRSF14HGNC:11912ENSG00000157873Q92956Tumor necrosis factor receptor superfamily member 14gwas
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
TNXBHGNC:11976ENSG00000168477P22105Tenascin-Xgwas
TPOHGNC:12015ENSG00000115705P07202Thyroid peroxidasegwas
EIPR1HGNC:12383ENSG00000032389Q53HC9EARP and GARP complex-interacting protein 1gwas
TYK2HGNC:12440ENSG00000105397P29597Non-receptor tyrosine-protein kinase TYK2gwas
VAV3HGNC:12659ENSG00000134215Q9UKW4Guanine nucleotide exchange factor VAV3gwas
IKZF3HGNC:13178ENSG00000161405Q9UKT9Zinc finger protein Aiolosgwas
TIMMDC1HGNC:1321ENSG00000113845Q9NPL8Complex I assembly factor TIMMDC1, mitochondrialgwas
PRRC2AHGNC:13918ENSG00000204469P48634Protein PRRC2Agwas
BACH2HGNC:14078ENSG00000112182Q9BYV9Transcription regulator protein BACH2gwas
PLEKHA1HGNC:14335ENSG00000107679Q9HB21Pleckstrin homology domain-containing family A member 1gwas
EDARADDHGNC:14341ENSG00000186197Q8WWZ3Ectodysplasin-A receptor-associated adapter proteingwas
C1QTNF6HGNC:14343ENSG00000133466Q9BXI9Complement C1q tumor necrosis factor-related protein 6gwas
CLEC2DHGNC:14351ENSG00000069493Q9UHP7C-type lectin domain family 2 member Dgwas
CAMK4HGNC:1464ENSG00000152495Q16566Calcium/calmodulin-dependent protein kinase type IVgwas
MMEL1HGNC:14668ENSG00000142606Q495T6Membrane metallo-endopeptidase-like 1gwas
QRFPRHGNC:15565ENSG00000186867Q96P65Pyroglutamylated RF-amide peptide receptorgwas
CCR6HGNC:1607ENSG00000112486P51684C-C chemokine receptor type 6gwas
ELMO1HGNC:16286ENSG00000155849Q92556Engulfment and cell motility protein 1gwas
TRIM31HGNC:16289ENSG00000204616Q9BZY9E3 ubiquitin-protein ligase TRIM31gwas
CARD9HGNC:16391ENSG00000187796Q9H257Caspase recruitment domain-containing protein 9gwas
ACAP1HGNC:16467ENSG00000072818Q15027Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 1gwas
ZMIZ1HGNC:16493ENSG00000108175Q9ULJ6Zinc finger MIZ domain-containing protein 1gwas
CD247HGNC:1677ENSG00000198821P20963T-cell surface glycoprotein CD3 zeta chaingwas
CD226HGNC:16961ENSG00000150637Q15762CD226 antigengwas
CD80HGNC:1700ENSG00000121594P33681T-lymphocyte activation antigen CD80gwas
CEP43HGNC:17012ENSG00000213066O95684Centrosomal protein 43gwas
PRICKLE1HGNC:17019ENSG00000139174Q96MT3Prickle-like protein 1gwas
CD86HGNC:1705ENSG00000114013P42081T-lymphocyte activation antigen CD86gwas
FNBP1HGNC:17069ENSG00000187239Q96RU3Formin-binding protein 1gwas
PSORS1C1HGNC:17202ENSG00000204540Q9UIG5Psoriasis susceptibility 1 candidate gene 1 proteingwas
ANKRD30AHGNC:17234ENSG00000148513Q9BXX3Ankyrin repeat domain-containing protein 30Agwas
ARID5BHGNC:17362ENSG00000150347Q14865AT-rich interactive domain-containing protein 5Bgwas
SBK1HGNC:17699ENSG00000188322Q52WX2Serine/threonine-protein kinase SBK1gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
CFBComplement factor BPrecursor of the catalytic component of the C3 and C5 convertase complexes of the alternative pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the…
SH2D2ASH2 domain-containing protein 2ACould be a T-cell-specific adapter protein involved in the control of T-cell activation.
SLC1A2Excitatory amino acid transporter 2Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate.
SS18Protein SSXTAppears to function synergistically with RBM14 as a transcriptional coactivator.
STAT3Signal transducer and activator of transcription 3Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors.
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.
BTNL2Butyrophilin-like protein 2Negative regulator of T-cell proliferation.
SUOXSulfite oxidase, mitochondrialCatalyzes the oxidation of sulfite to sulfate, the terminal reaction in the oxidative degradation of sulfur-containing amino acids.
TBX21T-box transcription factor TBX21Lineage-defining transcription factor which initiates Th1 lineage development from naive Th precursor cells both by activating Th1 genetic programs and by repressing the opposing Th2 and Th17 genetic programs.
TCF7Transcription factor 7Transcriptional activator involved in T-cell lymphocyte differentiation.
TGThyroglobulinActs as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3).
TLR3Toll-like receptor 3Key component of innate and adaptive immunity.
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…
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.
TNXBTenascin-XAppears to mediate interactions between cells and the extracellular matrix.
TPOThyroid peroxidaseIodination and coupling of the hormonogenic tyrosines in thyroglobulin to yield the thyroid hormones T(3) and T(4).
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.
VAV3Guanine nucleotide exchange factor VAV3Exchange factor for GTP-binding proteins RhoA, RhoG and, to a lesser extent, Rac1.
IKZF3Zinc finger protein AiolosTranscription factor that plays an important role in the regulation of lymphocyte differentiation.
TIMMDC1Complex I assembly factor TIMMDC1, mitochondrialChaperone protein involved in the assembly of the mitochondrial NADH:ubiquinone oxidoreductase complex (complex I).
PRRC2AProtein PRRC2AMay play a role in the regulation of pre-mRNA splicing.
BACH2Transcription regulator protein BACH2Transcriptional regulator that acts as a repressor or activator.
PLEKHA1Pleckstrin homology domain-containing family A member 1Binds specifically to phosphatidylinositol 3,4-diphosphate (PtdIns3,4P2), but not to other phosphoinositides.
EDARADDEctodysplasin-A receptor-associated adapter proteinAdapter protein that interacts with EDAR DEATH domain and couples the receptor to EDA signaling pathway during morphogenesis of ectodermal organs.
CLEC2DC-type lectin domain family 2 member DReceptor for KLRB1 that protects target cells against natural killer cell-mediated lysis.
CAMK4Calcium/calmodulin-dependent protein kinase type IVCalcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK4 signaling cascade and regulates, mainly by phosphorylation, the activity of several transcription activators, such as CREB1, MEF2D, JUN and RORA…
MMEL1Membrane metallo-endopeptidase-like 1Metalloprotease involved in sperm function, possibly by modulating the processes of fertilization and early embryonic development.
QRFPRPyroglutamylated RF-amide peptide receptorReceptor for the orexigenic neuropeptide QRFP.
CCR6C-C chemokine receptor type 6Receptor for the C-C type chemokine CCL20.
ELMO1Engulfment and cell motility protein 1Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility.
TRIM31E3 ubiquitin-protein ligase TRIM31E3 ubiquitin-protein ligase that acts as a regulator of antiviral immune response and inflammation by mediating ubiquitination of substrates.
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.
ACAP1Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 1GTPase-activating protein (GAP) for ADP ribosylation factor 6 (ARF6) required for clathrin-dependent export of proteins from recycling endosomes to trans-Golgi network and cell surface.
ZMIZ1Zinc finger MIZ domain-containing protein 1Acts as a transcriptional coactivator.
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.
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.
CD80T-lymphocyte activation antigen CD80Costimulatory molecule that belongs to the immunoglobulin superfamily that plays an important role in T-lymphocyte activation.
CEP43Centrosomal protein 43Required for anchoring microtubules to the centrosomes.
PRICKLE1Prickle-like protein 1Involved in the planar cell polarity pathway that controls convergent extension during gastrulation and neural tube closure.
CD86T-lymphocyte activation antigen CD86Costimulatory molecule that belongs to the immunoglobulin superfamily that plays an important role in T-lymphocyte activation.
FNBP1Formin-binding protein 1May act as a link between RND2 signaling and regulation of the actin cytoskeleton.
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.
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.
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.

Protein-family classification

Druggable: 23 · Difficult: 22 · Unknown: 30 · Druggable fraction: 0.31

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
Scaffold/PPI133.0×0.003
Antibody/Immunoglobulin83.1×0.020
Complement13.6×0.714
Kinase41.5×0.714
GPCR41.3×0.766
Transporter11.0×0.777
Transcription factor91.0×0.777
Protease21.0×0.777
Other/Unknown300.7×0.998
Enzyme (other)30.5×0.998

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
CFBProteaseyes3.4.21.47Sushi_SCR_CCP_dom, Trypsin_dom, Peptidase_S1A
SH2D2AScaffold/PPInoSH2, SH2D2A_SH2, SH2_dom_sf
SLC1A2Other/UnknownnoNa-dicarboxylate_symporter, Na-dicarboxylate_symporter_CS, Na:dicarbo_symporter_sf
SS18Other/UnknownnoSS18_N
STAT3Transcription factornoSH2, STAT, p53-like_TF_DNA-bd_sf
STAT4Transcription factornoSH2, STAT, p53-like_TF_DNA-bd_sf
BTNL2Antibody/ImmunoglobulinyesIg_C1-set, Ig_sub, Ig-like_dom
SUOXEnzyme (other)yes1.8.3.1OxRdtase_Mopterin-bd_dom, Cyt_B5-like_heme/steroid-bd, MoCF_OxRdtse_dimer
TBX21Transcription factornoTF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS
TCF7Other/UnknownnoHMG_box_dom, CTNNB1-bd_N, TCF/LEF
TGOther/UnknownnoThyroglobulin_1, CarbesteraseB, Tyr-kin_ephrin_A/B_rcpt-like
TLR3Other/UnknownnoTIR_dom, Cys-rich_flank_reg_C, Leu-rich_rpt
TNFRSF14Other/UnknownnoTNFR/NGFR_Cys_rich_reg, TNFR_14, TNFRSF14/UL144_N
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
TNXBAntibody/ImmunoglobulinyesEGF, Fibrinogen_a/b/g_C_dom, FN3_dom
TPOComplementyes1.11.1.8EGF-type_Asp/Asn_hydroxyl_site, Sushi_SCR_CCP_dom, EGF
EIPR1Scaffold/PPInoWD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS
TYK2Kinaseyes2.7.10.2FERM_domain, Prot_kinase_dom, SH2
VAV3Scaffold/PPInoDH_dom, SH2, GDS_CDC24_CS
IKZF3Transcription factornoZnf_C2H2_type, Znf_C2H2_sf, Ikaros_C2H2-ZF
TIMMDC1Other/UnknownnoTIMMDC1
PRRC2AOther/UnknownnoBAT2_N, PRRC2
BACH2Transcription factornoBTB/POZ_dom, bZIP_Maf, bZIP
PLEKHA1Scaffold/PPInoPH_domain, PH-like_dom_sf, PI-Interact_SigTrans_Reg
EDARADDOther/UnknownnoDeath_dom, DEATH-like_dom_sf, EDARADD
C1QTNF6Other/UnknownnoC1q_dom, Collagen, Tumour_necrosis_fac-like_dom
CLEC2DOther/UnknownnoC-type_lectin-like, C-type_lectin-like/link_sf, CTDL_fold
CAMK4Kinaseyes2.7.11.17Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
MMEL1Proteaseyes3.4.24.B14Peptidase_M13, Peptidase_M13_N, Peptidase_M13_C
QRFPRGPCRyesGPCR_Rhodpsn, NPY_rcpt, GPCR_Rhodpsn_7TM
CCR6GPCRyesGPCR_Rhodpsn, Chemokine_rcpt, Chemokine_CCR6
ELMO1Scaffold/PPInoPH_domain, ELMO_dom, ARM-like
TRIM31Transcription factornoZnf_B-box, Znf_RING, Znf_RING/FYVE/PHD
CARD9Other/UnknownnoCARD, DEATH-like_dom_sf, CARD_CARD9
ACAP1Scaffold/PPInoArfGAP_dom, PH_domain, Ankyrin_rpt
ZMIZ1Transcription factornoZnf_MIZ, Znf_RING/FYVE/PHD, ZMIZ1_N
CD247Other/UnknownnoPhos_immunorcpt_sig_ITAM, CD3_zeta/IgE_Fc_rcpt_gamma, T-cell_CD3_zeta
CD226Antibody/ImmunoglobulinyesIg_sub2, Ig_sub, Ig-like_dom
CD80Antibody/ImmunoglobulinyesIg_sub, Ig-like_dom, Ig_V-set
CEP43Other/UnknownnoLisH, FOP_dimerisation-dom_N
PRICKLE1Transcription factornoZnf_LIM, PET_domain, PET_prickle
CD86Antibody/ImmunoglobulinyesIg_sub, Ig-like_dom, Ig_V-set
FNBP1Scaffold/PPInoFCH_dom, SH3_domain, HR1_rho-bd
PSORS1C1Other/UnknownnoSEEK1
ANKRD30AScaffold/PPInoAnkyrin_rpt, Ankyrin_rpt-contain_sf, CC144C-like_CC_dom
ARID5BOther/UnknownnoARID_dom, ARID5B_ARID/BRIGHT_DNA-bd, ARID_dom_sf
SBK1KinaseyesProt_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

65 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
granulocyte14
male germ line stem cell (sensu Vertebrata) in testis9
blood7
primordial germ cell in gonad7
lymph node7
sperm5
left testis5
monocyte5
Brodmann (1909) area 234
sural nerve4
ventricular zone4
jejunal mucosa4
spleen4
right testis4
leukocyte4
mononuclear cell4
adrenal tissue3
right adrenal gland3
right adrenal gland cortex3
middle temporal gyrus3

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
CFB134broadmarkerright lobe of liver, liver, gall bladder
SH2D2A166broadmarkergranulocyte, male germ line stem cell (sensu Vertebrata) in testis, blood
SLC1A2227broadmarkerendothelial cell, entorhinal cortex, Brodmann (1909) area 23
SS18291ubiquitousmarkeradrenal tissue, right adrenal gland cortex, right adrenal gland
STAT3301ubiquitousmarkertype B pancreatic cell, pericardium, lower lobe of lung
STAT4201broadmarkergranulocyte, sperm, middle temporal gyrus
BTNL2106yessural nerve, ventricular zone, primordial germ cell in gonad
SUOX267ubiquitousmarkerright lobe of liver, right adrenal gland, right adrenal gland cortex
TBX21149broadmarkergranulocyte, blood, male germ line stem cell (sensu Vertebrata) in testis
TCF7279ubiquitousmarkerthymus, olfactory bulb, periodontal ligament
TG169tissue_specificmarkerright lobe of thyroid gland, left lobe of thyroid gland, thyroid gland
TLR3232ubiquitousmarkerjejunal mucosa, palpebral conjunctiva, placenta
TNFRSF14134ubiquitousmarkergranulocyte, spleen, right uterine tube
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
TNXB134ubiquitousmarkerapex of heart, right adrenal gland cortex, right adrenal gland
TPO132tissue_specificmarkerleft lobe of thyroid gland, thyroid gland, right lobe of thyroid gland
EIPR1249ubiquitousmarkerprefrontal cortex, adenohypophysis, nucleus accumbens
TYK2288ubiquitousmarkergranulocyte, right hemisphere of cerebellum, adenohypophysis
VAV3258ubiquitousmarkertongue squamous epithelium, renal medulla, esophagus squamous epithelium
IKZF3155broadmarkergranulocyte, lymph node, epithelium of nasopharynx
TIMMDC1259ubiquitousmarkerleft ventricle myocardium, cardiac muscle of right atrium, myocardium
PRRC2A134ubiquitousmarkerright testis, left testis, ventricular zone
BACH2237ubiquitousmarkercortical plate, sural nerve, epithelium of nasopharynx
PLEKHA1280ubiquitousmarkerupper leg skin, sperm, Brodmann (1909) area 23
EDARADD147broadmarkerislet of Langerhans, sural nerve, male germ line stem cell (sensu Vertebrata) in testis
C1QTNF6170ubiquitousmarkerdecidua, right uterine tube, stromal cell of endometrium
CLEC2D194broadmarkergranulocyte, calcaneal tendon, spleen

Protein interactions among cohort

Intra-cohort edges: 40.

Hub genes (top 10 by interactor count)

SymbolInteractor count
STAT310,108
LRRK27,628
TLR34,305
TYK23,932
CTLA43,863
ATG16L13,843
PNPT13,741
IFIH13,706
CD863,672
CD803,664

Intra-cohort edges

ABSources
ADCY7PNPT1biogrid_interaction
ADGRL2ATG16L1intact
ANKRD55BACH2intact
ANKRD55MACIRstring_interaction
ARID5BRTKN2string_interaction
ATG16L1TCF7intact
ATG16L1TNFSF15string_interaction
BACH2C1QTNF6string_interaction
BACH2TCF7string_interaction
CARD9IFIH1string_interaction
CCR6CEP43string_interaction
CCR6CLEC2Dstring_interaction
CCR6RNASET2string_interaction
CD226NCR3string_interaction
CD247NCR3string_interaction
CD40LGCD80string_interaction
CD40LGCD86string_interaction
CD80CD86biogrid_interaction, intact, string_interaction
CD80CTLA4biogrid_interaction, intact, string_interaction
CD86CTLA4biogrid_interaction, intact, string_interaction
CEP43RNASET2string_interaction
CLEC2DCLECL1string_interaction
CLEC2DIL23Rstring_interaction
CTLA4TNFSF18string_interaction
CTLA4TPOstring_interaction
IFIH1TLR3string_interaction
IL23RSTAT4string_interaction
IL23RTBX21string_interaction
IL23RTYK2string_interaction
STAT3TYK2string_interaction
STAT4TBX21string_interaction
STAT4TYK2string_interaction
TBX21TCF7string_interaction
TCF7ZMIZ1biogrid_interaction
TGTPOstring_interaction
TNFRSF14TNFRSF6Bstring_interaction
TNFRSF14TNFSF15string_interaction
TNFRSF14TNFSF18string_interaction
TNFRSF6BTNFSF15biogrid_interaction, intact, string_interaction
TNFSF15TNFSF18string_interaction

Structural data

PDB: 46 · AlphaFold-only: 28 · No structure: 1

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
TYK2P2959752
LRRK2Q5S00744
CD247P2096338
CFBP0075126
CTLA4P1641022
TLR3O1545520
ELMO1Q9255618
ATG16L1Q676U516
PNPT1Q8TCS811
IFIH1Q9BYX49
TNFRSF14Q929568
TNFRSF6BO954078
CD40LGP299658
CARD9Q9H2578
SLC1A2P430047
TNFSF15O951507
TNFSF18Q9UNG27
ACAP1Q150277
CD86P420817
STAT3P407636
CLEC2DQ9UHP76
CD80P336816
NCR3O149314
IL23RQ5VWK54
TGP012663
TNXBP221053
BACH2Q9BYV92
QRFPRQ96P652
TRIM31Q9BZY92
CD226Q157622

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
MMEL1Q495T690.34
PLGRKTQ9HBL789.60
EIPR1Q53HC989.26
STAT4Q1476586.87
BTNL2Q9UIR085.97
CYTL1Q9NRR185.86
TPOP0720284.00
SLC25A27O9584780.95
SBK1Q52WX277.87
C1QTNF6Q9BXI977.42
ADCY7P5182877.32
EDARADDQ8WWZ373.81
SPATA13Q96N9672.49
TIMMDC1Q9NPL872.08
RTKN2Q8IZC470.33
ANKRD55Q3KP4463.43
TBX21Q9UL1761.95
SH2D2AQ9NP3161.87
TCF7P3640258.11
MACIRQ96GV958.00
PRICKLE1Q96MT355.55
PSORS1C1Q9UIG555.10
LRRC36Q1X8D755.05
CLECL1Q8IZS753.91
IKZF3Q9UKT948.06
C12orf42Q96LP644.43
PRRC2AP4863440.07
ZNF365Q70YC430.21

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 550. Enrichment computed across 139 evidence-associated genes (101 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 101 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Interleukin-23 signaling675.4×2e-08STAT3, STAT4, TYK2, IL23R, IL12B, JAK2
Interleukin-35 Signalling547.1×1e-05STAT3, STAT4, TYK2, JAK1, JAK2
TNFs bind their physiological receptors623.4×3e-05TNFRSF14, TNFRSF6B, TNFSF15, TNFSF18, EDARADD, LTA
Interleukin-10 signaling716.1×3e-05STAT3, TYK2, CD80, CD86, IL10, IL12B, JAK1
Interleukin-4 and Interleukin-13 signaling99.2×6e-05STAT3, TYK2, IL23R, IL10, IL12B, IRF4, ITGAM, JAK1 (+1 more)
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling98.6×9e-05CD80, CD86, PIK3R5, TRAT1, ERBB3, FLT3, FYN, IER3 (+1 more)
Interleukin-21 signaling445.2×9e-05STAT3, STAT4, IL21, JAK1
Interleukin-27 signaling441.1×1e-04STAT3, TYK2, JAK1, JAK2
Interleukin-6 signaling437.7×2e-04STAT3, TYK2, JAK1, JAK2
Interleukin-20 family signaling520.9×2e-04STAT3, STAT4, TYK2, JAK1, JAK2
Interleukin-12 signaling520.2×2e-04STAT4, TYK2, IL12B, JAK1, JAK2
Cytokine Signaling in Immune system124.8×3e-04STAT3, STAT4, CD40LG, CD80, CD86, SH2B3, IRF3, IRF4 (+4 more)
Constitutive Signaling by Aberrant PI3K in Cancer78.8×6e-04CD80, CD86, PIK3R5, TRAT1, ERBB3, FLT3, FYN
Interleukin-2 family signaling425.1×6e-04STAT3, STAT4, JAK1, JAK2
Signaling by CSF3 (G-CSF)422.6×9e-04STAT3, TYK2, JAK1, JAK2
Signaling by Interleukins95.7×9e-04STAT3, STAT4, CD80, CD86, IRF4, ITGAM, JAK1, JAK2 (+1 more)
Interleukin-6 family signaling342.4×0.001STAT3, JAK1, JAK2
Co-inhibition by CTLA4420.6×0.001CD80, CD86, CTLA4, FYN
Interleukin-37 signaling420.6×0.001STAT3, IL18R1, SMAD3, PTPN2
Nef and signal transduction337.7×0.001ELMO1, CD247, FYN
Interleukin-12 family signaling418.8×0.001STAT3, STAT4, JAK1, JAK2
MAPK1 (ERK2) activation333.9×0.002TYK2, JAK1, JAK2
Inactivation of CSF3 (G-CSF) signaling417.4×0.002STAT3, TYK2, JAK1, JAK2
Interleukin receptor SHC signaling416.1×0.002IL2RA, IL5, JAK1, JAK2
MAPK3 (ERK1) activation330.8×0.002TYK2, JAK1, JAK2
CD28 dependent PI3K/Akt signaling415.6×0.002CD80, CD86, PIK3R5, FYN
Co-stimulation by CD28415.1×0.003CD80, CD86, CTLA4, FYN
PIP3 activates AKT signaling85.3×0.003CD80, CD86, PIK3R5, TRAT1, ERBB3, FLT3, FYN, INS
Interferon gamma signaling67.5×0.003TRIM31, HLA-DQA1, IRF3, IRF4, JAK1, JAK2
CD28 dependent Vav1 pathway326.1×0.003CD80, CD86, FYN

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 129 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
immune response228.0×5e-11TCF7, TNFRSF14, TNFSF15, TYK2, CCR6, CD80, CD86, NCR3 (+14 more)
positive regulation of T cell proliferation1020.1×4e-08BTNL2, CD40LG, TYK2, CD80, CD86, IL23R, CLECL1, IL12B (+2 more)
positive regulation of type II interferon production1017.4×1e-07TLR3, TYK2, CD226, IL23R, IL12B, IL18R1, IL21, JAK2 (+2 more)
adaptive immune response149.1×1e-07TNFRSF14, TNFSF18, CAMK4, CD247, CD86, CTLA4, CX3CR1, ERAP2 (+6 more)
positive regulation of interleukin-17 production732.7×3e-07TYK2, CARD9, IL23R, NOD2, IL12B, IL21, JAK2
positive regulation of T-helper 17 type immune response554.4×4e-06TYK2, CARD9, IL23R, IL12B, JAK2
interleukin-23-mediated signaling pathway487.1×9e-06STAT3, TYK2, IL23R, JAK2
negative regulation of T cell receptor signaling pathway719.9×9e-06BTNL2, CD80, CD86, CTLA4, FYN, PTPN2, PTPN22
cellular response to virus812.4×4e-05TLR3, TYK2, IFIH1, IL21, IRF3, JAK1, JAK2, SMAD3
cell surface receptor signaling pathway via JAK-STAT715.8×4e-05STAT3, STAT4, TYK2, IL23R, IL12B, JAK1, JAK2
interleukin-12-mediated signaling pathway458.1×5e-05STAT4, TYK2, IL12B, JAK2
positive regulation of interleukin-10 production618.7×8e-05STAT3, CD40LG, NOD2, IL12B, IL21, IRF4
growth hormone receptor signaling pathway via JAK-STAT447.5×1e-04STAT3, TYK2, JAK1, JAK2
T cell costimulation617.4×1e-04TNFRSF14, CD40LG, CD80, CD86, EFNB2, FYN
signal transduction243.0×1e-04SH2D2A, STAT3, TG, TLR3, TNFSF15, TNFSF18, EDARADD, CAMK4 (+16 more)
positive regulation of natural killer cell proliferation443.5×1e-04TYK2, IL23R, IL12B, JAK2
interleukin-10-mediated signaling pathway443.5×1e-04STAT3, TYK2, IL10, JAK1
positive regulation of canonical NF-kappaB signal transduction116.2×1e-04STAT3, TLR3, TNFSF15, CD40LG, CARD9, CX3CR1, LURAP1L, NOD2 (+3 more)
positive regulation of tumor necrosis factor production89.5×1e-04STAT3, TLR3, CARD9, LRRK2, IFIH1, NOD2, IL12B, JAK2
natural killer cell activation522.5×1e-04NCR3, FYN, IL12B, IL18R1, RASGRP1
negative regulation of T cell proliferation615.4×1e-04TNFRSF14, CD80, CD86, CTLA4, IL10, IL2RA
positive regulation of cytokine production involved in inflammatory response521.1×2e-04STAT3, TLR3, CARD9, NOD2, IRF3
negative regulation of T cell activation520.4×2e-04CD80, CD86, CTLA4, FYN, PTPN22
positive regulation of granulocyte macrophage colony-stimulating factor production430.7×4e-04CARD9, CD80, IL23R, IL12B
positive regulation of NK T cell proliferation365.3×4e-04TYK2, IL12B, JAK2
defense response to virus105.4×9e-04TLR3, TRIM31, CARD9, IFIH1, ATG16L1, IFITM2, IL12B, IL21 (+2 more)
positive regulation of T cell receptor signaling pathway423.8×0.001CD226, CD80, CD86, TRAT1
interleukin-2-mediated signaling pathway349.0×0.001STAT3, IL2RA, JAK1
positive regulation of tyrosine phosphorylation of STAT protein422.7×0.001TNFSF18, FLT3, IL21, JAK2
type I interferon-mediated signaling pathway513.3×0.001TYK2, IFIH1, IFITM2, IRF3, JAK1

Therapeutics

Drug target analysis

Approved (phase 4): 10 · Phase ≥3: 11 · Phased (≥1): 12 · Undrugged: 63

Druggability breadth: 76 of 139 evidence-associated genes (55%) 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
CFBIPTACOPAN
STAT3MOMELOTINIB
TPOPROPYLTHIOURACIL
TYK2FEDRATINIB
IKZF3POMALIDOMIDE
CAMK4RUXOLITINIB
CCR6TEGASEROD MALEATE
SBK1AFATINIB
LRRK2PONATINIB
CX3CR1FLUOXETINE HYDROCHLORIDE

Top cohort targets by molecule count

SymbolMoleculesMax phase
TYK2724
LRRK2424
STAT3184
CAMK4144
SBK1144
CX3CR184
IKZF354
TPO34
CCR634
SLC1A223

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
IPTACOPAN4CFB
MOMELOTINIB4STAT3, TYK2
NITAZOXANIDE4STAT3
NICLOSAMIDE4STAT3
DIGOXIN4STAT3
BARICITINIB4STAT3, TYK2
DIGITOXIN4STAT3
DEUCRAVACITINIB4STAT3, TYK2
PROPYLTHIOURACIL4TPO
FEDRATINIB4LRRK2, SBK1, TYK2
RUXOLITINIB4CAMK4, LRRK2, SBK1, TYK2
TOFACITINIB4LRRK2, TYK2
UPADACITINIB4TYK2
FILGOTINIB4TYK2
ABROCITINIB4TYK2
AXITINIB4LRRK2, TYK2
RUXOLITINIB PHOSPHATE4TYK2
INFIGRATINIB PHOSPHATE4TYK2
INFIGRATINIB4TYK2
PACRITINIB4TYK2
TOFACITINIB CITRATE4LRRK2, TYK2
BOSUTINIB4LRRK2, TYK2
PEFICITINIB4TYK2
CRAVACITINIB4TYK2
PAZOPANIB4TYK2
NINTEDANIB4CAMK4, LRRK2, SBK1, TYK2
SUNITINIB4CAMK4, LRRK2, SBK1, TYK2
DASATINIB4SBK1, TYK2
ERLOTINIB4LRRK2, SBK1, TYK2
CRIZOTINIB4SBK1, TYK2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 9.

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

SymbolAssaysType breakdown
STAT31,319Binding:1304, Functional:12, Unclassified:2, ADMET:1
TYK21,083Binding:1043, Functional:39, ADMET:1
LRRK2809Binding:799, ADMET:7, Functional:3
CAMK4342Binding:342
IKZF3101Binding:100, Functional:1
SBK197Binding:97
SLC1A290Binding:84, Functional:6
CCR660Functional:33, Binding:27
TLR355Binding:52, Functional:3
CFB33Binding:33
QRFPR26Binding:13, Functional:13
CX3CR126Binding:19, Functional:7
STAT420Binding:20
ADCY716Binding:14, Functional:2
IL23R13Binding:13
TPO12Binding:12
CD40LG8Binding:8
TCF77Binding:7
ELMO16Binding:6
BACH23Binding:3
MMEL12Binding:2
CEP432Binding:2
SH2D2A1Binding:1
PRRC2A1Binding:1
PLEKHA11Binding:1
IFIH11Binding:1
CTLA41Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
CFB3.4.21.47alternative-complement-pathway C3/C5 convertase
SUOX1.8.3.1sulfite oxidase
TPO1.11.1.8, 3.6.1.52iodide peroxidase, diphosphoinositol-polyphosphate diphosphatase
TYK22.7.10.2non-specific protein-tyrosine kinase
CAMK42.7.11.17Ca2+/calmodulin-dependent protein kinase
MMEL13.4.24.B14
RNASET24.6.1.19ribonuclease T2
PNPT12.7.7.8polyribonucleotide nucleotidyltransferase
ADCY74.6.1.1adenylate cyclase

Cohort genes with high screening signal

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

SymbolChEMBL assays
STAT31,319
TYK21,083
IKZF3101
CAMK4342
LRRK2809

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)
IPTACOPAN4CFB
MOMELOTINIB4STAT3, TYK2
NITAZOXANIDE4STAT3
NICLOSAMIDE4STAT3
DIGOXIN4STAT3
BARICITINIB4STAT3, TYK2
DIGITOXIN4STAT3
DEUCRAVACITINIB4STAT3, TYK2
PROPYLTHIOURACIL4TPO
FEDRATINIB4LRRK2, SBK1, TYK2
RUXOLITINIB4CAMK4, LRRK2, SBK1, TYK2
TOFACITINIB4LRRK2, TYK2
UPADACITINIB4TYK2
FILGOTINIB4TYK2
ABROCITINIB4TYK2
AXITINIB4LRRK2, TYK2
RUXOLITINIB PHOSPHATE4TYK2
INFIGRATINIB PHOSPHATE4TYK2
INFIGRATINIB4TYK2
PACRITINIB4TYK2
TOFACITINIB CITRATE4LRRK2, TYK2
BOSUTINIB4LRRK2, TYK2
PEFICITINIB4TYK2
CRAVACITINIB4TYK2
PAZOPANIB4TYK2
NINTEDANIB4CAMK4, LRRK2, SBK1, TYK2
SUNITINIB4CAMK4, LRRK2, SBK1, TYK2
DASATINIB4SBK1, TYK2
ERLOTINIB4LRRK2, SBK1, TYK2
CRIZOTINIB4SBK1, TYK2

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)10CFB, STAT3, TPO, TYK2, IKZF3, CAMK4, CCR6, SBK1, LRRK2, CX3CR1
BPhased (≥1) drug, not yet approved2SLC1A2, ELMO1
CDruggable family + PDB, no drug11SUOX, TNXB, QRFPR, CD226, CD80, CD86, ADGRL2, NCR3, IL23R, RNASET2 (+1 more)
DDruggable family + AlphaFold only, no drug4BTNL2, MMEL1, SLC25A27, ADCY7
EDifficult family or no structure, no drug48SH2D2A, SS18, STAT4, TBX21, TCF7, TG, TLR3, TNFRSF14, TNFRSF6B, TNFSF15 (+38 more)

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
STAT420TYK2
TG0TPO
CEP432CCR6
SH2D2A1—
SS180—
BTNL20—
SUOX0—
TBX210—
TCF77—
TLR355—
TNFRSF140—
TNFRSF6B0—
TNFSF150—
TNFSF180—
CD40LG8—
TNXB0—
EIPR10—
VAV30—
TIMMDC10—
PRRC2A1—
BACH23—
PLEKHA11—
EDARADD0—
C1QTNF60—
CLEC2D0—
MMEL12—
QRFPR26—
TRIM310—
CARD90—
ACAP10—

Clinical trials & evidence

Clinical trials

Clinical trials: 22.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified19
PHASE22
PHASE41

Top trials by phase / activity

NCTPhaseStatusTitle
NCT02644707PHASE4COMPLETEDSelenium Supplementation in Youths With Autoimmune Thyroiditis
NCT01129492PHASE2COMPLETEDLow-Level Laser Therapy in Chronic Autoimmune Thyroiditis
NCT03289403PHASE2COMPLETEDThe Role of Immunomodulatory Treatment in Success of ICSI in Patients With Autoimmune Thyroiditis
NCT06925399Not specifiedNOT_YET_RECRUITINGChanges in Natural Immunity in Pregnant Women With Autoimmune Thyroid Disease
NCT07453290Not specifiedNOT_YET_RECRUITINGDysregulation of the Soluble α-Klotho-FGF23 Axis in Hashimoto’s Thyroiditis: A Case-Control Study
NCT07494474Not specifiedNOT_YET_RECRUITINGRisk Assessment of Pancreatic Islet Autoimmunity in Patients With AITD
NCT00271427Not specifiedCOMPLETEDSelenium Treatment in Autoimmune Thyroiditis (AIT)
NCT02013479Not specifiedCOMPLETEDSelenium Supplementation in Autoimmune Thyroiditis
NCT02061111Not specifiedCOMPLETEDNeoThyr - the Role of Mitochondria-dysfunction in Newborns of Mothers With Autoimmune Thyroid Disease
NCT02240563Not specifiedCOMPLETEDLow Level Laser Therapy for Autoimmune Thyroiditis
NCT02307175Not specifiedCOMPLETEDA Study of 99m Tc Pertechnetate Produced in High Energy Cyclotron in Patients With Thyroid Scan Indication
NCT02318160Not specifiedCOMPLETEDOxidative Status in Children With Autoimmune Thyroiditis
NCT03048708Not specifiedCOMPLETEDThyroid in Bariatric Surgery
NCT03498417Not specifiedCOMPLETEDAnti-insulin-like Growth Factor-1 Receptor (IGF-1R) Antibodies in Graves’ Disease and Graves’ Orbitopathy
NCT04075851Not specifiedUNKNOWNThe Prevalence of Serum Thyroid Hormone Autoantibodies in Autoimmune Thyroid Diseases
NCT04600349Not specifiedCOMPLETEDIdentity Oriented Psychotrauma Therapy on Hashimoto in Adults
NCT04754607Not specifiedCOMPLETEDEffects of Low-Level Laser Therapy on Oxidative Stress Levels
NCT05544448Not specifiedCOMPLETEDIn Vitro Effect Study of Interleukin-2 Muteins on Regulatory T Cells of Patients With Different Autoimmune, Allo-immune or Inflammatory Diseases
NCT05680376Not specifiedCOMPLETEDThyroid Hormone Values and Anti-thyroid Peroxidase Antibody Positivity in Recurrent Pregnancy Loss
NCT06249074Not specifiedCOMPLETEDGluten-free Diet in Women With Autoimmune Thyroiditis
NCT06324578Not specifiedUNKNOWNPrevalence of Pre-clinical Sjögren Disease and Other Immune Disturbances in Subjects With Autoimmune Thyroiditis Disease
NCT06867913Not specifiedCOMPLETEDA Study of Selenomethionine and Myo-inositol(SOLOWAYS_TM) in Patients With Autoimmune Thyroiditis Carrying the DIO2 Thr92Ala Polymorphism

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
LEVOTHYROXINE41
CHEMBL477852001
THYROXINE01

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 68

This page pulls from 68 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityfantom5_genefantom5_promotergenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot