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Atlas / Gene / TYK2

TYK2

gene
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Also known as JTK1

Summary

TYK2 (tyrosine kinase 2, HGNC:12440) is a protein-coding gene on chromosome 19p13.2, encoding Non-receptor tyrosine-protein kinase TYK2 (P29597). Non-membrane spanning protein tyrosine kinase involved in numerous cytokines and interferons signaling, which regulates cell growth, development, cell migration, innate and adaptive immunity.

This gene encodes a member of the tyrosine kinase and, more specifically, the Janus kinases (JAKs) protein families. This protein associates with the cytoplasmic domain of type I and type II cytokine receptors and promulgate cytokine signals by phosphorylating receptor subunits. It is also a component of both the type I and type III interferon signaling pathways. As such, it may play a role in anti-viral immunity. A mutation in this gene has been associated with Immunodeficiency 35.

Source: NCBI Gene 7297 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): immunodeficiency 35 (Strong, GenCC)
  • GWAS associations: 56 (top 2% of genes corpus-wide)
  • Clinical variants (ClinVar): 1,164 total — 26 pathogenic, 21 likely-pathogenic (top 3% of genes corpus-wide)
  • Expression (HPA): Low tissue specificity — highest in pituitary gland, vagina, blood vessel
  • GTEx eGene: eQTL in 37 tissues, sQTL in 27 (q < 0.05)
  • Phenotypes (HPO): 7
  • Drug target: yes — 7 curated mechanism-of-action drugs, 6 via a complex or family; 72 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
  • Approved drugs (ChEMBL mechanism of action): 4 — Deucravacitinib, Deuruxolitinib Phosphate, Filgotinib, +1 more
  • Approved drugs acting on a complex or family including it: 2 — Peficitinib, Tofacitinib Citrate (Janus Kinase (JAK))
  • Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.63 (unconstrained)
  • MANE Select transcript: NM_003331
  • Interaction hub: 2,250 STRING partners (top 5% of genes corpus-wide)

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:12440
Approved symbolTYK2
Nametyrosine kinase 2
Location19p13.2
Locus typegene with protein product
StatusApproved
AliasesJTK1
Ensembl geneENSG00000105397
Ensembl biotypeprotein_coding
OMIM176941
Entrez7297

Gene structure

Transcript identifiers

Ensembl transcripts: 64 — 25 protein_coding, 23 nonsense_mediated_decay, 11 retained_intron, 5 protein_coding_CDS_not_defined

MANE Select: ENST00000525621

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 3, TSL 3: 9, TSL 4: 2, TSL 5: 1

ENST00000525621, ENST00000524462, ENST00000524470, ENST00000525220, ENST00000525824, ENST00000525976, ENST00000527481, ENST00000529317, ENST00000529370, ENST00000529739, ENST00000530220, ENST00000530560, ENST00000530829, ENST00000531620, ENST00000531836, ENST00000533334, ENST00000534228, ENST00000699354, ENST00000699355, ENST00000699356, ENST00000699357, ENST00000699358, ENST00000699359, ENST00000699360, ENST00000699361, ENST00000699362, ENST00000699363, ENST00000699364, ENST00000699365, ENST00000699366, ENST00000699367, ENST00000699368, ENST00000699369, ENST00000699370, ENST00000699371, ENST00000907161, ENST00000907162, ENST00000907163, ENST00000913938, ENST00000955973, ENST00000955974, ENST00000955975, ENST00000955976, ENST00000955977, ENST00000955978, ENST00000973704, ENST00000973705, ENST00000973706, ENST00001029329, ENST00001029330, ENST00001029331, ENST00001029332, ENST00001029333, ENST00001029334, ENST00001029335, ENST00001029336, ENST00001029337, ENST00001029339, ENST00001029340, ENST00001029341, ENST00001071933, ENST00001071934, ENST00001071935, ENST00001135476

RefSeq mRNA: 13 — MANE Select: NM_003331 NM_001385197, NM_001385198, NM_001385199, NM_001385200, NM_001385201, NM_001385202, NM_001385203, NM_001385204, NM_001385205, NM_001385206, NM_001385207, NM_001406461, NM_003331

CCDS: CCDS12236, CCDS92513

Canonical transcript exons

ENST00000525621 — 25 exons

ExonStartEnd
ENSE000006761821035776410357918
ENSE000006761851036151110361598
ENSE000006761871036207810362181
ENSE000006761881036226410362456
ENSE000006761891036254910362657
ENSE000006761901036461410364771
ENSE000006761911036485110365048
ENSE000006761921036551710365898
ENSE000006761951036805510368202
ENSE000006761981036829510368418
ENSE000021697991038038010380572
ENSE000021789841037961510379779
ENSE000021802821037821410378426
ENSE000027838741035404210354234
ENSE000034797011036641710366580
ENSE000034891481036177010361955
ENSE000034977651035800310358138
ENSE000035164621035292610353098
ENSE000035282481035451210354609
ENSE000035900141035656810356718
ENSE000035959261035352810353646
ENSE000036441971035917510359302
ENSE000036466241035053310350968
ENSE000036569061035105210351162
ENSE000037856011035243410352551

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.2469 / max 490.8687, expressed in 1814 samples.

Highest expression (Bgee): granulocyte, hemisphere of cerebellum, adenohypophysis, cerebellar hemisphere, metanephros cortex.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TYK2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 37 tissues and its splicing (sQTL) in 27 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 64 significant tissue × QTL associations:

TissueQTLq-valueSlopeLead variant
Skin Sun Exposed Lower legsqtl7.2e-23+1.9119:10353864:C:T
Adipose Visceral Omentumsqtl4.2e-21+1.8819:10353864:C:T
Whole Bloodeqtl1.3e-18+0.1219:10354011:A:G
Thyroidsqtl2.9e-18+1.9619:10353864:C:T
Nerve Tibialsqtl6.5e-18-0.9019:10359299:A:C
Spleensqtl8.0e-17+2.5719:10353864:C:T
Adipose Subcutaneouseqtl1.4e-15+0.1819:10354011:A:G
Cells Cultured fibroblastseqtl1.1e-14-0.2419:10380684:T:G
Artery Tibialsqtl9.0e-14-0.7719:10359299:A:C
Nerve Tibialeqtl4.7e-13+0.1419:10354011:A:G
Skin Not Sun Exposed Suprapubicsqtl1.4e-12-0.8019:10414696:G:A
Brain Cerebellar Hemisphereeqtl8.9e-12+0.2419:10354011:A:G
Thyroideqtl9.7e-12+0.1619:10354011:A:G
Brain Cerebellumeqtl1.4e-11+0.2819:10354011:A:G
Skin Not Sun Exposed Suprapubiceqtl1.7e-11+0.1519:10354011:A:G
Spleeneqtl4.9e-11+0.2319:10354011:A:G
Adrenal Glandeqtl9.9e-11+0.4219:10349293:G:A
Skin Sun Exposed Lower legeqtl1.7e-09+0.1419:10349293:G:A
Whole Bloodsqtl1.5e-08-1.1819:10355556:C:T
Esophagus Muscularissqtl5.7e-08+1.7419:10353864:C:T

FANTOM5 promoters

7 alternative TSS:

Promoter IDTPM avgSamples expressed
17912313.72551802
1791247.40591745
1791190.4025153
1791220.3533119
1791180.165680
1791200.104739
1791170.089460

Top tissues by expression

showing 100 of 299 tissues by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
granulocyteCL:000009499.24gold quality
right hemisphere of cerebellumUBERON:001489098.28gold quality
adenohypophysisUBERON:000219698.20gold quality
cerebellar hemisphereUBERON:000224598.08gold quality
metanephros cortexUBERON:001053398.08gold quality
cerebellar cortexUBERON:000212997.98gold quality
right lobe of thyroid glandUBERON:000111997.97gold quality
spleenUBERON:000210697.94gold quality
small intestine Peyer’s patchUBERON:000345497.90gold quality
right uterine tubeUBERON:000130297.89gold quality
right lobe of liverUBERON:000111497.85gold quality
nerveUBERON:000102197.84gold quality
tibial nerveUBERON:000132397.84gold quality
right ovaryUBERON:000211897.84gold quality
apex of heartUBERON:000209897.79gold quality
left lobe of thyroid glandUBERON:000112097.78gold quality
upper lobe of left lungUBERON:000895297.74gold quality
endocervixUBERON:000045897.53gold quality
left ovaryUBERON:000211997.49gold quality
mucosa of transverse colonUBERON:000499197.45gold quality
left uterine tubeUBERON:000130397.41gold quality
pituitary glandUBERON:000000797.36gold quality
minor salivary glandUBERON:000183097.35gold quality
body of uterusUBERON:000985397.34gold quality
monocyteCL:000057697.33gold quality
right lungUBERON:000216797.32gold quality
mucosa of stomachUBERON:000119997.26gold quality
body of stomachUBERON:000116197.14gold quality
skin of legUBERON:000151197.12gold quality
leukocyteCL:000073897.11gold quality
right adrenal gland cortexUBERON:003582797.11gold quality
transverse colonUBERON:000115797.10gold quality
mononuclear cellCL:000084297.09gold quality
body of pancreasUBERON:000115097.09gold quality
ectocervixUBERON:001224997.05gold quality
right adrenal glandUBERON:000123396.97gold quality
skin of abdomenUBERON:000141696.96gold quality
C1 segment of cervical spinal cordUBERON:000646996.91gold quality
omental fat padUBERON:001041496.91gold quality
olfactory segment of nasal mucosaUBERON:000538696.89gold quality
peritoneumUBERON:000235896.87gold quality
lower esophagus mucosaUBERON:003583496.85gold quality
lymph nodeUBERON:000002996.77gold quality
thyroid glandUBERON:000204696.74gold quality
left adrenal gland cortexUBERON:003582596.70gold quality
upper lobe of lungUBERON:000894896.61gold quality
right frontal lobeUBERON:000281096.58gold quality
left adrenal glandUBERON:000123496.55gold quality
muscle layer of sigmoid colonUBERON:003580596.55gold quality
right coronary arteryUBERON:000162596.54gold quality
small intestineUBERON:000210896.43gold quality
bloodUBERON:000017896.37gold quality
adipose tissue of abdominal regionUBERON:000780896.36gold quality
esophagogastric junction muscularis propriaUBERON:003584196.22gold quality
stromal cell of endometriumCL:000225596.14gold quality
lower esophagusUBERON:001347396.09gold quality
adrenal cortexUBERON:000123596.08gold quality
lower esophagus muscularis layerUBERON:003583396.08gold quality
left coronary arteryUBERON:000162696.03gold quality
right atrium auricular regionUBERON:000663196.03gold quality
ascending aortaUBERON:000149695.98gold quality
hindlimb stylopod muscleUBERON:000425295.96gold quality
descending thoracic aortaUBERON:000234595.93gold quality
thoracic aortaUBERON:000151595.92gold quality
cerebellumUBERON:000203795.90gold quality
colonic epitheliumUBERON:000039795.80gold quality
gall bladderUBERON:000211095.74gold quality
stomachUBERON:000094595.72gold quality
coronary arteryUBERON:000162195.56gold quality
adrenal glandUBERON:000236995.50gold quality
aortaUBERON:000094795.44gold quality
esophagusUBERON:000104395.43gold quality
tibial arteryUBERON:000761095.24gold quality
popliteal arteryUBERON:000225095.23gold quality
spinal cordUBERON:000224095.22gold quality
esophagus mucosaUBERON:000246995.19gold quality
mouth mucosaUBERON:000372995.19gold quality
saliva-secreting glandUBERON:000104495.06gold quality
amygdalaUBERON:000187694.95gold quality
fundus of stomachUBERON:000116094.91gold quality
cardiac atriumUBERON:000208194.91gold quality
tonsilUBERON:000237294.72gold quality
nucleus accumbensUBERON:000188294.67gold quality
heart left ventricleUBERON:000208494.41gold quality
vermiform appendixUBERON:000115494.36gold quality
vaginaUBERON:000099694.29gold quality
subcutaneous adipose tissueUBERON:000219094.27gold quality
caudate nucleusUBERON:000187394.24gold quality
rectumUBERON:000105294.17gold quality
sural nerveUBERON:001548894.17gold quality
intestineUBERON:000016094.15gold quality
zone of skinUBERON:000001494.13gold quality
sigmoid colonUBERON:000115994.11gold quality
colonUBERON:000115594.08gold quality
putamenUBERON:000187493.99gold quality
cardiac ventricleUBERON:000208293.95gold quality
heartUBERON:000094893.83gold quality
Brodmann (1909) area 9UBERON:001354093.74gold quality
cingulate cortexUBERON:000302793.73gold quality
bone marrow cellCL:000209293.61gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes9.29

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cellAxisnTPMProtein (IHC)
Pituitary glandtissue47.8
Vaginatissue28.8medium
Corpus callosumtissue18.5
Hypothalamustissue17.2
Spinal cordtissue17.1
Substantia nigratissue16.5
Amygdalatissue16.4
Septumtissue15.7
Cerebral cortextissue15.5high
Medulla oblongatatissue15.5
Insular cortextissue15.5
Cerebellumtissue15.4high
Periaqueductal graytissue15.3
Midbraintissue14.8
Hippocampal formationtissue14.8
Thymustissue14.6
Olfactory bulbtissue14.5
Ventral forebraintissue14.3
Retrosplenial cortextissue14.2
Entorhinal cortextissue13.7
Superior colliculitissue13.5
Temporal cortextissue13.4
Thalamustissue13.2
Ponstissue13.1
Retrosplenial and cingulate cortextissue13.1
Prefrontal cortextissue13.0
Basal gangliatissue13.0not detected
Motor cortextissue12.8
Putamentissue12.8
Occipital cortextissue12.1
Pancreastissue11.9medium
Somatosensory cortextissue11.9
Lymph nodetissue10.5not detected
Choroid plexustissue9.6
Spleentissue9.1medium
Appendixtissue8.8high
Salivary glandtissue8.3high
Small intestinetissue7.7medium
Heart muscletissue7.5high
Tonsiltissue7.3medium
Skeletal muscletissue7.2medium
Parathyroid glandtissue6.9high
Colontissue6.8medium
Gallbladdertissue6.6high
Ovarytissue6.4medium
Urinary bladdertissue6.4medium
Tonguetissue6.2
Cervixtissue6.1high
Duodenumtissue6.1high
Stomach 1tissue6.0high
Lungtissue6.0high
Locus coeruleustissue5.9
Fallopian tubetissue5.7high
Placentatissue5.5medium
Bone marrowtissue5.5medium
Hippocampustissue5.1not detected
Esophagustissue4.8medium
Thyroid glandtissue4.8medium
Adrenal glandtissue4.7high
Smooth muscletissue4.3low

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (28.7), White matter (18.5), Dorsal spinal cord (17.1), Ventral spinal cord (15.7), Subiculum (14.8).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT1, STAT3

Functional genomics

gnomAD constraint: pLI 1.57e-07, LOEUF 0.626, missense Z 2.04 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000525621 — one region, missense o/e 0.86.

Literature-anchored findings (GeneRIF, showing 40)

  • Data show that Tyk2 tyrosine kinase is essential for stable cell surface expression of IFNAR1. (PMID:12554654)
  • evidence that the small GTPases RhoA and Rac1, but not Cdc42, are directly associated with Tyk2 and PI3-K in an uPA/uPAR-dependent fashion and are necessary to mediate the uPA/uPAR-directed migration via the Tyk2/PI3-K signalling complex in human VSMC (PMID:12719789)
  • Catalytically active Tyk2 is necessary for Janus kinase 2 phosphorylation and association with the platelet-activating factor receptor. (PMID:14500680)
  • In the IFN signaling pathway leading to STAT activation, both JAK1 and TYK2 are essential, whereas NF-kappaB activation requires only TYK2. (PMID:15883164)
  • Janus kinase Tyk2 and the transcription factor Stat3 serve as downstream components in the signaling cascade resulting in upregulation of C5aR expression (PMID:15944400)
  • mutations in the JAK1 and Tyk2 genes may be identified as initial molecular defects in human cancers and autoimmune diseases (PMID:16239216)
  • catalytic activation of Tyk2 is not essential for IFNAR1 internalization, but is required for ligand-induced IFNAR1 serine phosphorylation, ubiquitination and efficient lysosomal proteolysis (PMID:16551269)
  • Tyk2 mutation is not associated with essential thrombocythaemia (PMID:17011030)
  • study showed association to systemic lupus erythematosus from individual SNPs and haplotypes in TYK2 (PMID:17384181)
  • suggest a novel function for Tyk2 as an important modulator of the urokinase-directed vascular smooth muscle cell functional behaviour at the place of injury (PMID:17548050)
  • These results suggest that Tyk2 signaling in prostate cancer cells facilitate invasion of these cells, and interference with this signaling may be a potential therapeutic pathway. (PMID:17920038)
  • protein tyrosine kinase TYK2 genes were found significantly upregulated in the cases with progressive sarcoidosis. (PMID:17937105)
  • The Stat3-activating Tyk2 V678F mutant does not up-regulate signaling through the type I interferon receptor but confers ligand hypersensitivity to a homodimeric receptor (PMID:18456658)
  • Tyk2 contributes to both the regulation of total IFNAR1 levels as well as the regulation of the cell surface density of this receptor chain. (PMID:18474601)
  • when type I IFN is added to primary human fibroblasts following MV infection, the tyrosine phosphorylation of the Janus kinase Tyk2 is specifically blocked, thereby preventing the subsequent activation of downstream STAT1 and STAT2 (PMID:19254804)
  • TYK2 may be a multiple sclerosis susceptibility factor (PMID:19293837)
  • TYK2 is not a genetic risk factor for systemic lupus erythematosus in a Japanese population suggesting that there is an ethnic difference in the susceptibility genes for this disease. (PMID:19440814)
  • The IFN pathway genes IRF5 and TYK2 may act epistatically in increasing risk for systemic lupus erythematosus (PMID:19567624)
  • TYK2 and STAT3 are genetic determinants of Crohn’s disease in the Japanese population. (PMID:19653082)
  • Studies have demonstrated that mutations in STAT3 and TYK2 genes result in Hyper-IgE syndrome (HIES. (PMID:19717292)
  • rs2304256 associated with increased risk of discoid lupus erythematosus (PMID:19758313)
  • Single-nucleotide polymorphism in TYK2 gene is confirmed to be associated with multiple sclerosis. (PMID:19888296)
  • Studies indicate that the highest T1D association was at marker rs2304256 (odds ratio (OR) = 0.86; 95%CI = 0.82-0.90) in the TYK2 gene 19p13.2See TYK2 gene at chromosome 19p13.2. (PMID:19966805)
  • Here, the authors report the crystal structures of TYK2, a first in class structure, and JAK3 in complex with PAN-JAK inhibitors CP-690550 and CMP-6, both of which bind in the ATP-binding cavities of both JAK isozymes. (PMID:20478313)
  • Siva-1 forms a functional complex with Tyk2 and participates in the transduction of signals that inhibit B lymphocyte growth. (PMID:20727854)
  • This meta-analysis demonstrates that autoimmune and inflammatory diseases is associated with TYK2 gene rs34536443 and rs2304256 polymorphisms, but not rs280523, rs280519, rs12720270 and rs12720356. (PMID:21140222)
  • Tyk2 deficiency and clinical manifestations of hyper IgE syndromes (Review) (PMID:21178271)
  • Data suggest that TYK2 polymorphisms were not associated with systemic lupus erythematosus in Hong Kong Chinese, but that rs2304256 and rs12720270 may be associated with photosensitivity and discoid rash. (PMID:21196586)
  • The rs34536443 variant effect on multiple sclerosis susceptibility might be mediated by deviating T lymphocyte differentiation toward a Th2 phenotype. (PMID:21354972)
  • The consequent effect of SOCS1 inhibition of Tyk2 not only results in a reduced IFN response because of inhibition of Tyk2 kinase-mediated STAT signaling but also negatively impacts IFNAR1 surface expression, which is stabilized by Tyk2. (PMID:21757742)
  • infection of airway epithelial cells with hMPV decreased cellular level of Janus tyrosine kinase (Jak1) and tyrosine kinase 2 (Tyk2) (PMID:21949722)
  • Association analysis identified five SLE susceptibility genes reaching genome-wide levels of significance : NCF2 ,IKZF1 ,IRF8 ,IFIH1 , and TYK2 (PMID:22046141)
  • data highlight the role of TYK2 downregulation in breast cancer cell de-differentitation and initiation of regional metastasis (PMID:22116632)
  • Studied the doubly tagged full-length construct, H6-FL-TYK-2-FLAG. In the presence of ATP and a peptide substrate, H6-FL-TYK-2-FLAG showed a marked lag in phosphopeptide product formation. TYK-2 KD showed no such lag. (PMID:22486643)
  • In our pilot study, we discovered significant changes in methylation patterns of genes IL-7, IL-13, IL-17C and TYK2 between henodialysis patients and healthy subjects (PMID:22506826)
  • The rs6445975 polymorphism of phox homology domain containing serine/threonine kinase and the rs2304256 polymorphism of tyrosine kinase 2 are associated with the development of systemic lupus erythematosus in Europeans (PMID:22592861)
  • This study demonistrated that Rs55762744 is a rare variant of modest effect on multiple sclerosis risk affecting a subset of patients. (PMID:22744673)
  • The most associated variant in primary biliary cirrhosis was in chromosome 19, a low-frequency nonsynonymous single nucleotide polymorphism in TYK2. (PMID:22961000)
  • TYK2 rs34536443 polymorphism is associated with a decreased susceptibility to endometriosis-related infertility. (PMID:23000200)
  • Two rare autoimmune disease-associated Tyk2 variants are catalytically impaired but signaling competent. (PMID:23359498)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
danio_reriotyk2ENSDARG00000020326
mus_musculusTyk2ENSMUSG00000032175
rattus_norvegicusTyk2ENSRNOG00000032948

Paralogs (32): FGR (ENSG00000000938), MATK (ENSG00000007264), BTK (ENSG00000010671), FYN (ENSG00000010810), STYK1 (ENSG00000060140), TNK2 (ENSG00000061938), TXK (ENSG00000074966), JAK2 (ENSG00000096968), ABL1 (ENSG00000097007), PTK6 (ENSG00000101213), HCK (ENSG00000101336), BMX (ENSG00000102010), CSK (ENSG00000103653), JAK3 (ENSG00000105639), FRK (ENSG00000111816), ITK (ENSG00000113263), ZAP70 (ENSG00000115085), PTK2B (ENSG00000120899), SRMS (ENSG00000125508), TEC (ENSG00000135605), BLK (ENSG00000136573), ABL2 (ENSG00000143322), FER (ENSG00000151422), JAK1 (ENSG00000162434), SYK (ENSG00000165025), PTK2 (ENSG00000169398), TNK1 (ENSG00000174292), YES1 (ENSG00000176105), FES (ENSG00000182511), LCK (ENSG00000182866), SRC (ENSG00000197122), LYN (ENSG00000254087)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1929470) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 54 distinct phenotype terms.

Mouse phenotype (MP)Records
decreased interferon-gamma secretion4
decreased circulating HDL cholesterol level1
abnormal heart morphology1
enlarged heart1
abnormal maxilla morphology1
abnormal spleen morphology1
enlarged spleen1
enlarged thymus1
abnormal ovary morphology1
increased body weight1
obese1
increased circulating free fatty acids level1
abnormal body temperature homeostasis1
decreased IgG level1
abnormal pancreas morphology1
abnormal seminal vesicle morphology1
abnormal skin morphology1
increased circulating insulin level1
abnormal T cell differentiation1
abnormal inspiratory capacity1
abnormal T cell physiology1
abnormal brown adipose tissue morphology1
abnormal cell cycle1
thrombocytopenia1
decreased susceptibility to induced arthritis1

+29 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

OrganismUniProtIdentityMethod
Pongo abeliiQ5RB2399.7%Diamond
Sus scrofaO1906495.3%Diamond
Gallus gallusQ75R6588.1%Diamond
Cyprinus carpioQ0917886.8%Diamond
Drosophila melanogasterQ8IR7944.2%Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

SymbolTypeEntrez
CDC37protein-coding11140
ICAM3protein-coding3385
PDE4Aprotein-coding5141
KEAP1protein-coding9817
MIR1181ncRNA100302213
ZGLP1protein-coding100125288
FDX2protein-coding112812
FDX2-ZGLP1ncRNA125242785
RAVER1protein-coding125950
S1PR5protein-coding53637

Protein

Protein identifiers

Non-receptor tyrosine-protein kinase TYK2 — P29597 (reviewed: P29597)

All UniProt accessions (18): A0A8V8TN50, A0A8V8TN55, A0A8V8TN89, A0A8V8TN95, A0A8V8TNM9, A0A8V8TPH2, A0A8V8TPJ0, A0A8V8TPJ3, A0A8V8TPX5, E9PM19, E9PQE9, E9PQL2, P29597, H0YCT7, H0YE24, H0YE41, K7EJR6, K7EM33

UniProt curated annotations — full annotation on UniProt →

Function. Non-membrane spanning protein tyrosine kinase involved in numerous cytokines and interferons signaling, which regulates cell growth, development, cell migration, innate and adaptive immunity. Plays both structural and catalytic roles in numerous interleukins and interferons (IFN-alpha/beta) signaling. Associates with heterodimeric cytokine receptor complexes and activates STAT family members including STAT1, STAT3, STAT4 or STAT6. The heterodimeric cytokine receptor complexes are composed of (1) a TYK2-associated receptor chain (IFNAR1, IL12RB1, IL10RB or IL13RA1), and (2) a second receptor chain associated either with JAK1 or JAK2. In response to cytokine-binding to receptors, phosphorylates and activates receptors (IFNAR1, IL12RB1, IL10RB or IL13RA1), creating docking sites for STAT members. In turn, recruited STATs are phosphorylated by TYK2 (or JAK1/JAK2 on the second receptor chain), form homo- and heterodimers, translocate to the nucleus, and regulate cytokine/growth factor responsive genes. Negatively regulates STAT3 activity by promototing phosphorylation at a specific tyrosine that differs from the site used for signaling. Involved in the oncostatin-M-mediated signaling pathway through both type I OSM receptor complex (heterodimers composed of LIFR and IL6ST) and type II OSM receptor complex (heterodimers composed of OSMR and IL6ST).

Subunit / interactions. Interacts (via FERM domain) with JAKMIP1. Interacts with PIK3R1; this interaction is important for cell migration. Interacts with MPL/TPOR. (Microbial infection) Interacts with Epstein-Barr virus protein LMP1; this interaction inhibits TYK2-mediated interferon signaling. (Microbial infection) Interacts with papillomavirus-18 protein E6; this interaction impairs JAK-STAT activation by interferon-alpha. (Microbial infection) Interacts with Epstein-Barr virus (EBV) tegument protein BGLF2; this interaction participates in the inhibition of type I IFN signaling by the virus.

Tissue specificity. Observed in all cell lines analyzed. Expressed in a variety of lymphoid and non-lymphoid cell lines.

Post-translational modifications. Phosphorylated. Phosphorylation by JAK1 at Tyr-1054 and Tyr-1055 induces kinase activation.

Disease relevance. Immunodeficiency 35 (IMD35) [MIM:611521] A primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and highly elevated serum IgE. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. The protein kinase 1 domain (also termed pseudokinase domain) mediates autoinhibition of the TYK2 kinase domain.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.

RefSeq proteins (13): NP_001372126, NP_001372127, NP_001372128, NP_001372129, NP_001372130, NP_001372131, NP_001372132, NP_001372133, NP_001372134, NP_001372135, NP_001372136, NP_001393390, NP_003322* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000299FERM_domainDomain
IPR000719Prot_kinase_domDomain
IPR000980SH2Domain
IPR001245Ser-Thr/Tyr_kinase_cat_domDomain
IPR008266Tyr_kinase_ASActive_site
IPR011009Kinase-like_dom_sfHomologous_superfamily
IPR016045Tyr_kinase_non-rcpt_TYK2_NDomain
IPR016251Tyr_kinase_non-rcpt_Jak/Tyk2Family
IPR017441Protein_kinase_ATP_BSBinding_site
IPR019749Band_41_domainDomain
IPR020635Tyr_kinase_cat_domDomain
IPR035963FERM_2Homologous_superfamily
IPR036860SH2_dom_sfHomologous_superfamily
IPR041046FERM_F2Domain
IPR041155FERM_F1Domain
IPR041381JAK1-3/TYK2_PHL_domDomain
IPR051286JAKFamily

Pfam: PF07714, PF17887, PF18377, PF18379, PF21990

Enzyme classification (BRENDA)

  • EC 2.7.10.2 — non-specific protein-tyrosine kinase (BRENDA: 41 organisms, 396 substrates, 479 inhibitors, 43 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

SubstrateKm (mM)Measurements
ATP0.014–17.6412
[KDSRC KINASE]-L-TYROSINE0.0057–0.2412
POLY(GLU4-TYR)0.018–0.65910
EEEEYIQ[DP]-8-HYDROXY-5-(N,N-DIMETHYLSULFONAMIDO0.0571
S1 PEPTIDE0.0371
EEEEY—0

Catalyzed reactions (Rhea)

  • L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (147 total): helix 49, strand 41, sequence variant 14, turn 12, modified residue 7, mutagenesis site 6, sequence conflict 6, domain 4, binding site 2, region of interest 2, compositionally biased region 2, chain 1, active site 1

Structure

Experimental structures (PDB)

showing 30 of 52 structures by resolution:

PDBTitleMethodResolution (Å)
3LXPStructural and Thermodynamic Characterization of the TYK2 and JAK3 Kinase Domains in …X-RAY DIFFRACTION1.65
8S99Crystal structure of the TYK2 pseudokinase domain in complex with compound 11X-RAY DIFFRACTION1.71
4WOVCRYSTAL STRUCTURE OF TYROSINE KINASE 2 JH2 (PSEUDO KINASE DOMAIN) COMPLEXED WITH BMS-066 …X-RAY DIFFRACTION1.8
8S9ACrystal structure of the TYK2 pseudokinase domain in complex with TAK-279X-RAY DIFFRACTION1.83
8S98Crystal structure of the TYK2 pseudokinase domain in complex with compound 8X-RAY DIFFRACTION1.87
5C03Crystal Structure of kinaseX-RAY DIFFRACTION1.9
5TKDCRYSTAL STRUCTURE OF TYROSINE KINASE 2 JH2 (PSEUDO KINASE DOMAIN) COMPLEXED WITH …X-RAY DIFFRACTION1.92
6NZECRYSTAL STRUCTURE OF TYROSINE KINASE 2 JH2 (PSEUDO KINASE DOMAIN) COMPLEXED WITH …X-RAY DIFFRACTION1.96
8TB6TYK2 JH2 bound to Compound14X-RAY DIFFRACTION1.96
6AAMCrystal structure of TYK2 in complex with peficitinibX-RAY DIFFRACTION1.98
4PO6Crystal structure of the human TYK2 FERM and SH2 domains with an IFNAR1 intracellular …X-RAY DIFFRACTION1.99
3NZ0Non-phosphorylated TYK2 kinase with CMP6X-RAY DIFFRACTION2
4GIHTyk2 (JH1) in complex with …X-RAY DIFFRACTION2
6DBKTyk2 with compound 8X-RAY DIFFRACTION2
4GVJTyk2 (JH1) in complex with adenosine di-phosphateX-RAY DIFFRACTION2.03
7UYUCrystal structure of TYK2 kinase domain in complex with compound 30X-RAY DIFFRACTION2.05
6VNSCrystal structure of TYK2 kinase with compound 13X-RAY DIFFRACTION2.09
6NZQCRYSTAL STRUCTURE OF TYROSINE KINASE 2 JH2 (PSEUDO KINASE DOMAIN) COMPLEXED WITH …X-RAY DIFFRACTION2.11
7AX4Human TYK2 pseudokinase domain (575-869) in complex with …X-RAY DIFFRACTION2.12
7UYTCrystal structure of TYK2 kinase domain in complex with compound 25X-RAY DIFFRACTION2.14
3ZONHuman TYK2 pseudokinase domain bound to a kinase inhibitorX-RAY DIFFRACTION2.15
5C01Crystal Structure of kinaseX-RAY DIFFRACTION2.15
6NSLCRYSTAL STRUCTURE OF TYROSINE KINASE 2 JH2 (PSEUDO KINASE DOMAIN) COMPLEXED WITH …X-RAY DIFFRACTION2.15
6VNVCrystal structure of TYK2 kinase with compound 14X-RAY DIFFRACTION2.15
6X8FCrystal structure of TYK2 with Compound 11X-RAY DIFFRACTION2.15
7UYRCrystal structure of TYK2 kinase domain in complex with compound 12X-RAY DIFFRACTION2.15
7UYSCrystal structure of TYK2 kinase domain in complex with compound 16X-RAY DIFFRACTION2.15
8EXNCrystal structure of PTP1B D181A/Q262A phosphatase domain with TYK2 activation loop …X-RAY DIFFRACTION2.15
4PY1Crystal structure of Tyk2 in complex with compound 15 …X-RAY DIFFRACTION2.16
6VNXCrystal structure of TYK2 kinase with compound 19X-RAY DIFFRACTION2.18

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P29597-F182.690.53

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Tyr protein kinases, Predicted intracellular proteins, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes, Primary immunodeficiency

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol

Antibody reliability (HPA): IH uncertain · IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1)

PositionRole
1023proton acceptor

Ligand- & substrate-binding residues (2)

PositionRole
903–911ATP
930ATP

Post-translational modifications (7)

TypePositions
Phosphotyrosine292, 604, 1054, 1055
Phosphoserine499, 525, 884

Mutagenesis-validated functional residues (6)

PositionPhenotype
930complete loss of catalytic activity.
1023complete loss of catalytic activity.
1054reduces basal catalytic activity and abolishes ifn-dependent activation.
1055reduces basal catalytic activity and abolishes ifn-dependent activation.
1145does not affect phosphorylation state and enzymatic activity.
1176does not affect phosphorylation state and enzymatic activity.

Function

Pathways and Gene Ontology

Reactome pathways

13 curated (TAS) of 41; 14 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

41 pathways:

IDPathwayEvidence
R-HSA-9833109Evasion by RSV of host interferon responses ⚕curated
R-HSA-9679191Potential therapeutics for SARS ⚕curated
R-HSA-9705671SARS-CoV-2 activates/modulates innate and adaptive immune responses ⚕curated
R-HSA-9725370Signaling by ALK fusions and activated point mutants ⚕curated
R-HSA-6788467IL-6-type cytokine receptor ligand interactionscurated
R-HSA-909733Interferon alpha/beta signalingcurated
R-HSA-6783783Interleukin-10 signalingcurated
R-HSA-8854691Interleukin-20 family signalingcurated
R-HSA-8984722Interleukin-35 Signallingcurated
R-HSA-6785807Interleukin-4 and Interleukin-13 signalingcurated
R-HSA-112411MAPK1 (ERK2) activationcurated
R-HSA-110056MAPK3 (ERK1) activationcurated
R-HSA-449836Other interleukin signalingcurated
R-HSA-1643685Disease ⚕—
R-HSA-5663202Diseases of signal transduction by growth factor receptors and second messengers ⚕—
R-HSA-5663205Infectious disease ⚕—
R-HSA-9833110RSV-host interactions ⚕—
R-HSA-9820952Respiratory Syncytial Virus Infection Pathway ⚕—
R-HSA-9679506SARS-CoV Infections ⚕—
R-HSA-9694516SARS-CoV-2 Infection ⚕—
R-HSA-9705683SARS-CoV-2-host interactions ⚕—
R-HSA-9700206Signaling by ALK in cancer ⚕—
R-HSA-9824446Viral Infection Pathways ⚕—
R-HSA-9958825Activation of STAT3 by cadherin engagementelectronic
R-HSA-1280215Cytokine Signaling in Immune system—
R-HSA-168256Immune System—
R-HSA-9705462Inactivation of CSF3 (G-CSF) signalingelectronic
R-HSA-913531Interferon Signaling—
R-HSA-447115Interleukin-12 family signaling—
R-HSA-9020591Interleukin-12 signalingelectronic
R-HSA-9020933Interleukin-23 signalingelectronic
R-HSA-9020956Interleukin-27 signalingelectronic
R-HSA-6783589Interleukin-6 family signaling—
R-HSA-1059683Interleukin-6 signalingelectronic
R-HSA-5683057MAPK family signaling cascades—
R-HSA-5684996MAPK1/MAPK3 signaling—
R-HSA-112409RAF-independent MAPK1/3 activation—
R-HSA-912694Regulation of IFNA/IFNB signalingelectronic
R-HSA-162582Signal Transduction—
R-HSA-9674555Signaling by CSF3 (G-CSF)electronic
R-HSA-449147Signaling by Interleukins—

MSigDB gene sets: 318 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_REGULATION_OF_CELL_ACTIVATION, REACTOME_INTERLEUKIN_6_SIGNALING, MYAATNNNNNNNGGC_UNKNOWN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, GNF2_BNIP2, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_RESPONSE_TO_TYPE_I_INTERFERON, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, RIZKI_TUMOR_INVASIVENESS_3D_DN

GO Biological Process (19): protein phosphorylation (GO:0006468), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), cell population proliferation (GO:0008283), cytokine-mediated signaling pathway (GO:0019221), cell differentiation (GO:0030154), intracellular signal transduction (GO:0035556), interleukin-12-mediated signaling pathway (GO:0035722), interleukin-5-mediated signaling pathway (GO:0038043), interleukin-23-mediated signaling pathway (GO:0038155), positive regulation of T cell proliferation (GO:0042102), regulation of receptor signaling pathway via JAK-STAT (GO:0046425), regulation of alpha-beta T cell activation (GO:0046634), type II interferon-mediated signaling pathway (GO:0060333), type I interferon-mediated signaling pathway (GO:0060337), growth hormone receptor signaling pathway via JAK-STAT (GO:0060397), interleukin-10-mediated signaling pathway (GO:0140105), positive regulation of protein localization to nucleus (GO:1900182), regulation of cell-cell adhesion (GO:0022407), regulation of multicellular organismal process (GO:0051239)

GO Molecular Function (9): protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), growth hormone receptor binding (GO:0005131), ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (10): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasmic side of plasma membrane (GO:0009898), extrinsic component of plasma membrane (GO:0019897), extrinsic component of cytoplasmic side of plasma membrane (GO:0031234), extracellular exosome (GO:0070062), cytoskeleton (GO:0005856), membrane (GO:0016020)

Reactome top-level categories

12 top-level categories:

CategoryPathways
Signaling by Interleukins4
Interleukin-12 family signaling4
Interleukin-6 family signaling2
RAF-independent MAPK1/3 activation2
Interferon Signaling1
Interferon alpha/beta signaling1
Cytokine Signaling in Immune system1
SARS-CoV Infections1
Signaling by CSF3 (G-CSF)1
SARS-CoV-2-host interactions1
Signaling by ALK in cancer1
RSV-host interactions1

GO top-level categories

57 GO namespaces:

CategoryTerms
cytokine-mediated signaling pathway4
cellular anatomical structure3
intracellular anatomical structure2
interferon-mediated signaling pathway2
plasma membrane2
phosphorylation1
protein modification process1
cell surface receptor signaling pathway via STAT1
cellular process1
cell surface receptor signaling pathway1
cellular response to cytokine stimulus1
cellular developmental process1
signal transduction1
cellular response to interleukin-121
T cell proliferation1
regulation of T cell proliferation1
positive regulation of lymphocyte proliferation1
positive regulation of T cell activation1
cell surface receptor signaling pathway via JAK-STAT1
regulation of receptor signaling pathway via STAT1
alpha-beta T cell activation1
regulation of T cell activation1
cellular response to type II interferon1
cellular response to type I interferon1
growth hormone receptor signaling pathway1
protein localization to nucleus1
regulation of protein localization to nucleus1
positive regulation of protein localization1
regulation of cell adhesion1
cell-cell adhesion1
multicellular organismal process1
regulation of biological process1
protein kinase activity1
protein tyrosine kinase activity1
cytokine receptor binding1
hormone receptor binding1
adenyl ribonucleotide binding1
purine ribonucleoside triphosphate binding1
anion binding1
nucleoside phosphate binding1
heterocyclic compound binding1
kinase activity1
phosphotransferase activity, alcohol group as acceptor1
catalytic activity, acting on a protein1
binding1
transferase activity, transferring phosphorus-containing groups1
catalytic activity1
intracellular membrane-bounded organelle1
cytoplasm1
membrane1
cell periphery1
cytoplasmic side of membrane1
extrinsic component of membrane1
cytoplasmic side of plasma membrane1
extrinsic component of plasma membrane1
extracellular vesicle1
intracellular membraneless organelle1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 13 of 38 annotations. The rest are phylogenetic / computational / electronic (IEA).

13 experimentally-supported GO terms:

GO termNSEvidence
cell surface receptor signaling pathway via JAK-STATBPdirect assay
interleukin-10-mediated signaling pathwayBPdirect assay
interleukin-12-mediated signaling pathwayBPdirect assay
interleukin-23-mediated signaling pathwayBPdirect assay
positive regulation of protein localization to nucleusBPdirect assay
type I interferon-mediated signaling pathwayBPdirect assay
type II interferon-mediated signaling pathwayBPdirect assay
cytoplasmCCdirect assay
extracellular exosomeCChigh-throughput assay
nucleusCCdirect assay
growth hormone receptor bindingMFphysical interaction
non-membrane spanning protein tyrosine kinase activityMFdirect assay
protein tyrosine kinase activityMFdirect assay

Protein interactions and networks

STRING

showing 15 of 2,250 interactions by confidence (×1000):

Protein AProtein BPartner UniProtScore
TYK2STAT2P52630915
TYK2IFNA13P01562884
TYK2STAT4Q14765877
TYK2STAT1P42224877
TYK2STAT3P40763859
TYK2IFNAR1P17181847
TYK2IL12RB1P42701827
TYK2IRF9Q00978818
TYK2IFNGP01579790
TYK2IFNGR2P38484766
TYK2IFNAR2P48551763
TYK2IFNGR1P15260757
TYK2JAK1P23458754
TYK2IL23RQ5VWK5752
TYK2STAT5BP51692740

IntAct

Human interaction partners of TYK2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

23 partners by confidence:

PartnerInteraction typeMIscoreRecords
KHDRBS2physical association0.7807
FHL3physical association0.7206
HNRNPKphysical association0.6707
STAT2physical association0.6402
AGR2physical association0.5605
IFNAR1direct interaction0.5604
AKAP8Lphysical association0.5603
CYSRT1physical association0.5603
GOLGA6L9physical association0.5603
KHDRBS3physical association0.5603
KRT31physical association0.5603
KRT40physical association0.5603
KRTAP6-3physical association0.5603
PRDM5physical association0.5603
TP53BP2physical association0.5603
TRAF4physical association0.5603
HSP90AB1physical association0.5202
JAK2physical association0.4002
PRKCAphysical association0.4001
PTPN1physical association0.4001
DNM2physical association0.3701
TK1physical association0.3701
UBE2Fphysical association0.3701

BioGRID (211 interactions; top human partners by supporting records): IFNAR1 (Reconstituted Complex; 7 records), SIVA1 (Two-hybrid; 4 records), COPS5 (Affinity Capture-Western; 3 records), EFNB2 (Affinity Capture-MS; 3 records), FHL3 (Two-hybrid; 3 records), HNRNPK (Two-hybrid; 3 records), KHDRBS2 (Two-hybrid; 3 records), LRRC46 (Affinity Capture-MS; 3 records), RNF13 (Affinity Capture-MS; 3 records), SOCS1 (Affinity Capture-MS; 3 records), C16orf71 (Affinity Capture-MS; 2 records), CD79A (Affinity Capture-MS; 2 records), CDH8 (Affinity Capture-MS; 2 records), EIF2AK2 (Affinity Capture-Western; 2 records), FYN (Affinity Capture-Western; 2 records)

SIGNOR signaling

showing 21 of 27 signaling interactions:

AEffectBMechanism
IL13RA1up-regulatesTYK2binding
PTPN6down-regulatesTYK2
IFNLR1up-regulatesTYK2binding
PTPN1“down-regulates activity”TYK2dephosphorylation
TYK2up-regulatesDUSP3phosphorylation
TYK2“up-regulates activity”IFNAR1phosphorylation
JAK1up-regulatesTYK2phosphorylation
IL15RAup-regulatesTYK2
TYK2up-regulatesSTAT3phosphorylation
IFNAR“up-regulates activity”TYK2binding
TYK2“up-regulates activity”“ISGF3 complex”phosphorylation
TYK2“up-regulates activity”STAT2phosphorylation
TYK2“up-regulates activity”STAT4phosphorylation
TYK2“down-regulates activity”KLF10phosphorylation
TYK2“up-regulates activity”TYK2phosphorylation
IL10RBup-regulatesTYK2binding
IFNB1up-regulatesTYK2
IL23Rup-regulatesTYK2binding
IL22RA1up-regulatesTYK2binding
PTPRC“down-regulates activity”TYK2dephosphorylation
TYK2“up-regulates activity”STAT1phosphorylation

Protein complexes (CORUM) (7)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

7 complexes by size:

ComplexSubunitsMembers
★ JAK2-PAFR-TYK2 complex3JAK2, PTAFR, TYK2
★ IFNAR1-IFNAR2-TYK2 complex3IFNAR1, IFNAR2, TYK2
★ IFNAR1-STAT1alpha-TYK2 complex3IFNAR1, STAT1, TYK2
★ PTPN6-TYK2 complex2TYK2, PTPN6
★ PTAFR-TYK2 complex2PTAFR, TYK2
★ PDGFRB-TYK2 complex2PDGFRB, TYK2
★ GHR-TYK2 complex2GHR, TYK2

Disease & clinical

Genetic variants

Variant evidence for TYK2: 1,164 ClinVar records (47 pathogenic / likely pathogenic); 56 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

1,164 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic26
Likely pathogenic21
Uncertain significance509
Likely benign445
Benign67

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 47 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant IDHGVSClassificationReviewSubmitters
225508NM_003331.5(TYK2):c.209_212del (p.Cys70fs)Pathogeniccriteria provided, multiple submitters, no conflicts4
1425910NM_003331.5(TYK2):c.2393G>A (p.Trp798Ter)Pathogeniccriteria provided, multiple submitters, no conflicts2
224888NM_003331.5(TYK2):c.1912C>T (p.Arg638Ter)Pathogeniccriteria provided, single submitter2
1069417NM_003331.5(TYK2):c.2573C>G (p.Ser858Ter)Pathogeniccriteria provided, single submitter1
2022602NM_003331.5(TYK2):c.1148dup (p.Thr384fs)Pathogeniccriteria provided, single submitter1
2704548NM_003331.5(TYK2):c.2488C>T (p.Gln830Ter)Pathogeniccriteria provided, single submitter1
2761990NM_003331.5(TYK2):c.2920_2941del (p.Leu974fs)Pathogeniccriteria provided, single submitter1
2764448NM_003331.5(TYK2):c.424C>T (p.Gln142Ter)Pathogeniccriteria provided, single submitter1
2911814NM_003331.5(TYK2):c.463C>T (p.Gln155Ter)Pathogeniccriteria provided, single submitter1
3619403NM_003331.5(TYK2):c.905del (p.Asp302fs)Pathogeniccriteria provided, single submitter1
3659006NM_003331.5(TYK2):c.2873_2874insTGTA (p.Ile959fs)Pathogeniccriteria provided, single submitter1
3684066NM_003331.5(TYK2):c.1507C>T (p.Arg503Ter)Pathogeniccriteria provided, single submitter1
3720074NM_003331.5(TYK2):c.3013C>T (p.Gln1005Ter)Pathogeniccriteria provided, single submitter1
4722157NM_003331.5(TYK2):c.3229_3230insC (p.Lys1077fs)Pathogeniccriteria provided, single submitter1
4802964NM_003331.5(TYK2):c.2739_2758dup (p.Asn920fs)Pathogeniccriteria provided, single submitter1

Per-variant reference — Sugi Variant

Explore TYK2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 25 predictions of 2,330):

Position(s)EffectΔscoreSites
19:10350969acceptor_loss1.0000
19:10353099acceptor_loss1.0000
19:10354040–10354041donor_loss1.00005
19:10354235–10354236acceptor_loss1.00003
19:10356536donor_gain1.0000
19:10358001–10358002donor_loss1.00005
19:10358045donor_gain1.0000
19:10358139acceptor_loss1.00002
19:10359181donor_gain1.0000
19:10361599–10361600acceptor_loss1.00005

AlphaMissense

2,116 missense substitutions predicted likely pathogenic (of 7,753 scored), across 550 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

ResidueLikely-pathogenic substitutionsMean am_pathogenicityMax am_pathogenicity
M101190.8860.980
M97890.8830.983
N102880.9940.997
D104180.9940.999
D102380.9930.999
D108380.9890.996
H102180.9840.996
F104280.9750.993
F116280.9550.992
F90880.9510.999
F108780.9370.990
D42180.9190.962
H73280.9050.975
D79680.8960.971
D91780.8870.975
F58180.8850.986
F65580.8830.979
F10980.8680.960
F85980.8640.980
D75980.8450.916

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

CancerPrognosticp-value
Kidney Renal Clear Cell Carcinoma (TCGA)unfavorable5.44e-11
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)favorable5.22e-05
Pancreatic Adenocarcinoma (TCGA)favorable0.000174

Disease associations

OMIM: gene MIM:176941 | disease phenotypes: MIM:611521 (Immunodeficiency 35)

GenCC curated gene-disease

1 curated gene-disease records:

DiseaseClassificationInheritanceRecords
immunodeficiency 35StrongAutosomal recessive3

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (2 panels, 2 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

2 panels:

PanelRating
COVID-19 researchgreen
Primary immunodeficiency or monogenic inflammatory bowel diseasegreen

Mondo (1): immunodeficiency 35 (MONDO:0012682)

Orphanet (1): Susceptibility to infection due to TYK2 deficiency (Orphanet:331226)

HPO phenotypes

7 phenotypes (HPO-id order):

HPOTerm
HP:0000007Autosomal recessive inheritance
HP:0002205Recurrent respiratory infections
HP:0002721Immunodeficiency
HP:0002841Recurrent fungal infections
HP:0003212Increased circulating IgE concentration
HP:0004429Recurrent viral infections
HP:0011274Recurrent mycobacterial infections

GWAS associations

showing 30 of 56 associations:

StudyTraitp-value
GCST90002400_714Plateletcrit8e-35
GCST005527_19Psoriasis9e-31
GCST90002402_62Platelet count1e-30
GCST004627_92Lymphocyte count2e-25
GCST005752_123Systemic lupus erythematosus2e-25
GCST90002388_224Lymphocyte count1e-23
GCST007400_39Systemic lupus erythematosus5e-23
GCST001725_60Inflammatory bowel disease2e-18
GCST009873_14Autoimmune traits (pleiotropy)2e-17
GCST90002389_259Lymphocyte percentage of white cells5e-17
GCST003268_25Psoriasis vulgaris1e-16
GCST011956_222Systemic lupus erythematosus1e-16
GCST002318_108Rheumatoid arthritis5e-16
GCST006959_126Rheumatoid arthritis5e-16
GCST007932_110Medication use (thyroid preparations)1e-15
GCST006048_47Rheumatoid arthritis (ACPA-positive)3e-15
GCST90002389_258Lymphocyte percentage of white cells3e-15
GCST90002399_156Neutrophil percentage of white cells3e-15
GCST005536_16Type 1 diabetes4e-15
GCST005531_112Multiple sclerosis2e-14
GCST005568_38Rheumatoid arthritis (ACPA-positive)2e-14
GCST003156_27Systemic lupus erythematosus1e-13
GCST90002388_225Lymphocyte count2e-13
GCST004132_58Crohn’s disease3e-13
GCST005569_39Rheumatoid arthritis3e-13
GCST003155_22Systemic lupus erythematosus4e-13
GCST004603_94Platelet count7e-13
GCST010571_73Autoimmune thyroid disease8e-13
GCST000879_36Crohn’s disease1e-12
GCST005581_42Primary biliary cirrhosis1e-12

EFO canonical traits (from GWAS)

8 canonical traits:

EFO IDTrait name
EFO:1001494psoriasis vulgaris
EFO:0004309platelet count
EFO:0004587lymphocyte count
EFO:0007990neutrophil percentage of leukocytes
EFO:0009933Thyroid preparation use measurement
EFO:0004346neuroimaging measurement
EFO:0007993lymphocyte percentage of leukocytes
EFO:0007985platelet crit

MeSH disease descriptors

1 disease descriptors:

DescriptorNameTree numbers
C566928Tyrosine Kinase 2 Deficiency *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (6): CHEMBL2363062 (PROTEIN FAMILY), CHEMBL3301390 (PROTEIN COMPLEX), CHEMBL3301391 (PROTEIN COMPLEX), CHEMBL3301392 (PROTEIN COMPLEX), CHEMBL3553 (SINGLE PROTEIN), CHEMBL6066058 (PROTEIN-PROTEIN INTERACTION)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the TYK2 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

7 curated-mechanism drugs:

DrugModalityMax phase
DEUCRAVACITINIBSmall molecule4
DEURUXOLITINIB PHOSPHATESmall molecule4
FILGOTINIBSmall molecule4
UPADACITINIB HEMIHYDRATESmall molecule4
BREPOCITINIBSmall molecule3
CERDULATINIBSmall molecule2
ROPSACITINIBSmall molecule2

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes TYK2 — the drug acts on the assembly or class, not necessarily on this subunit alone.

6 drugs via a complex or family:

DrugTarget (ChEMBL)MembersMax phase
PEFICITINIBJanus Kinase (JAK)44
TOFACITINIB CITRATEJanus Kinase (JAK)44
DELGOCITINIBJanus Kinase (JAK)43
GUSACITINIBJanus Kinase (JAK)42
IZENCITINIBJanus Kinase (JAK)42
NEZULCITINIBJanus Kinase (JAK)42

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 329,715 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 72 molecules by phase:

MoleculeNamePhasePatents
CHEMBL4435170DEUCRAVACITINIB4776
CHEMBL3301607FILGOTINIB43,101
CHEMBL3622821UPADACITINIB42,949
CHEMBL3655081ABROCITINIB41,145
CHEMBL1289926AXITINIB416,510
CHEMBL2105759BARICITINIB47,117
CHEMBL288441BOSUTINIB412,869
CHEMBL4596392CRAVACITINIB425
CHEMBL601719CRIZOTINIB415,133
CHEMBL5416410DASATINIB4674
CHEMBL553ERLOTINIB4109,860
CHEMBL1287853FEDRATINIB43,770
CHEMBL941IMATINIB4113,105
CHEMBL1852688INFIGRATINIB42,298
CHEMBL1834657INFIGRATINIB PHOSPHATE4330
CHEMBL608533MIDOSTAURIN47,641
CHEMBL1078178MOMELOTINIB43,649
CHEMBL502835NINTEDANIB48,978
CHEMBL2035187PACRITINIB43,544
CHEMBL477772PAZOPANIB416,241
CHEMBL3137308PEFICITINIB4
CHEMBL1789941RUXOLITINIB4
CHEMBL1795071RUXOLITINIB PHOSPHATE4
CHEMBL535SUNITINIB4
CHEMBL221959TOFACITINIB4
CHEMBL2103743TOFACITINIB CITRATE4
CHEMBL4297477BREPOCITINIB3
CHEMBL428690ALVOCIDIB3
CHEMBL3137331DEFACTINIB3
CHEMBL4297507DELGOCITINIB3
CHEMBL522892DOVITINIB3
CHEMBL3622820ITACITINIB3
CHEMBL603469LESTAURTINIB3
CHEMBL4116008CERDULATINIB2
CHEMBL4459585ROPSACITINIB2
CHEMBL495727AT-92832
CHEMBL4066193ATINVICITINIB2
CHEMBL1231124AZD-14802
CHEMBL3545215BMS-9115432
CHEMBL4094440BMS-9193732
CHEMBL1614713CC-4012
CHEMBL1967878CENISERTIB2
CHEMBL3039513DECERNOTINIB2
CHEMBL482968ENMD-20762
CHEMBL1230609FORETINIB2
CHEMBL2107823GANDOTINIB2
CHEMBL4577523GOLIDOCITINIB2
CHEMBL4594275GUSACITINIB2
CHEMBL4594441IFIDANCITINIB2
CHEMBL1980297ILORASERTIB2
CHEMBL4650343IZENCITINIB2
CHEMBL4447181LONDAMOCITINIB2
CHEMBL4802163NEZULCITINIB2
CHEMBL4303389NS-0182
CHEMBL2103874OCLACITINIB2
CHEMBL521851PICTILISIB2
CHEMBL475251R-4062
CHEMBL558752RAF-2652
CHEMBL1230165SILMITASERTIB2
CHEMBL3301606SOLCITINIB2

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Janus kinase (JakA) family

Most potent curated ligand interactions (55 total), top 25:

LigandActionAffinityParameter
deucravacitinibInhibition10.7pKi
BMS-986202Inhibition10.7pKi
izencitinibInhibition10.0pKi
soficitinibInhibition9.3pIC50
cerdulatinibInhibition9.3pIC50
SJ988497Binding9.27pKd
vexicitinibInhibition9.09pIC50
JAK inhibitor IInhibition9.0pIC50
embricitinibInhibition8.83pIC50
SDC-1801Inhibition8.72pIC50
cadefrecitinibInhibition8.64pIC50
nezulcitinibInhibition8.6pKi
nomelcitinibInhibition8.6pIC50
GDC-0214Inhibition8.5pKi
compound 29 [Moslin et al., 2017]Inhibition8.4pIC50
peficitinibInhibition8.3pIC50
fadeucravacitinibInhibition8.24pIC50
OB756Inhibition8.14pIC50
lorpucitinibInhibition8.13pIC50
TYK2 inhibitor 14lInhibition8.05pIC50
SAR-20347Inhibition7.89pIC50
zotiraciclibInhibition7.85pIC50
ropsacitinibInhibition7.82pIC50
momelotinibInhibition7.7pIC50
ilginatinibInhibition7.66pIC50

Binding affinities (BindingDB)

4546 measured of 6076 human assays (6100 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
6-(cyclopropanecarbonylamino)-4-[3-(5-dicyclopropylphosphoryl-1-methylpyrazol-3-yl)-2-methoxyanilino]pyridazine-3-carboxamideKD0.004 nMUS-20260001898: Heteroaryl compounds as inhibitors of TYK2/JAK1, composition and application thereof
CHEMBL4460368KI0.015 nM
CHEMBL4442827KI0.018 nM
CHEMBL4571920KI0.024 nM
CHEMBL4439957KI0.035 nM
3-fluoro-2-[4-[3-(3-hydroxy-3-methylpiperidin-1-yl)pyrazol-1-yl]-5-oxo-6,7-dihydropyrrolo[3,4-b]pyridin-2-yl]benzonitrileKI0.05 nMUS-10781204: TYK2 inhibitors and uses thereof
3-fluoro-2-[4-[3-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]pyrazol-1-yl]-5-oxo-6,7-dihydropyrrolo[3,4-b]pyridin-2-yl]benzonitrileKI0.05 nMUS-10781204: TYK2 inhibitors and uses thereof
3-fluoro-2-[4-[3-(3-hydroxypyrrolidin-1-yl)pyrazol-1-yl]-5-oxo-6,7-dihydropyrrolo[3,4-b]pyridin-2-yl]benzonitrileKI0.05 nMUS-10781204: TYK2 inhibitors and uses thereof
3-fluoro-2-[4-[3-[(3S)-3-hydroxypyrrolidin-1-yl]pyrazol-1-yl]-5-oxo-6,7-dihydropyrrolo[3,4-b]pyridin-2-yl]benzonitrileKI0.05 nMUS-10781204: TYK2 inhibitors and uses thereof
2-[4-[3-[3-amino-3-(trifluoromethyl)piperidin-1-yl]pyrazol-1-yl]-5-oxo-6,7-dihydropyrrolo[3,4-b]pyridin-2-yl]-3-fluorobenzonitrileKI0.05 nMUS-10781204: TYK2 inhibitors and uses thereof
3-fluoro-2-[4-[3-[(3R)-3-hydroxy-3-(trifluoromethyl)piperidin-1-yl]pyrazol-1-yl]-5-oxo-6,7-dihydropyrrolo[3,4-b]pyridin-2-yl]benzonitrileKI0.05 nMUS-10781204: TYK2 inhibitors and uses thereof
2-[4-[3-(1,4-dioxa-7-azaspiro[4.4]nonan-7-yl)pyrazol-1-yl]-5-oxo-6,7-dihydropyrrolo[3,4-b]pyridin-2-yl]-3-fluorobenzonitrileKI0.05 nMUS-10781204: TYK2 inhibitors and uses thereof
2-[4-[3-[(3S)-3-amino-3-(trifluoromethyl)piperidin-1-yl]pyrazol-1-yl]-5-oxo-6,7-dihydropyrrolo[3,4-b]pyridin-2-yl]-3-fluorobenzonitrileKI0.05 nMUS-10781204: TYK2 inhibitors and uses thereof
2-[4-[3-[(3R)-3-amino-3-(trifluoromethyl)piperidin-1-yl]pyrazol-1-yl]-5-oxo-6,7-dihydropyrrolo[3,4-b]pyridin-2-yl]-3-fluorobenzonitrileKI0.05 nMUS-10781204: TYK2 inhibitors and uses thereof
2-[4-[3-[(3R,4S)-3,4-dihydroxypiperidin-1-yl]pyrazol-1-yl]-5-oxo-6,7-dihydropyrrolo[3,4-b]pyridin-2-yl]-3-fluorobenzonitrileKI0.05 nMUS-10781204: TYK2 inhibitors and uses thereof
3-fluoro-2-[5-oxo-4-[3-(5-oxo-1,4-diazepan-1-yl)pyrazol-1-yl]-6,7-dihydropyrrolo[3,4-b]pyridin-2-yl]benzonitrileKI0.05 nMUS-10781204: TYK2 inhibitors and uses thereof
3-fluoro-2-[4-[3-(3-morpholin-4-ylpiperidin-1-yl)pyrazol-1-yl]-5-oxo-6,7-dihydropyrrolo[3,4-b]pyridin-2-yl]benzonitrileKI0.05 nMUS-10781204: TYK2 inhibitors and uses thereof
3-fluoro-2-[4-[3-[(2S,3R)-3-hydroxy-2-methylpyrrolidin-1-yl]pyrazol-1-yl]-5-oxo-6,7-dihydropyrrolo[3,4-b]pyridin-2-yl]benzonitrileKI0.05 nMUS-10781204: TYK2 inhibitors and uses thereof
3-fluoro-2-[4-[3-(4-fluoro-3-hydroxypiperidin-1-yl)pyrazol-1-yl]-5-oxo-6,7-dihydropyrrolo[3,4-b]pyridin-2-yl]benzonitrileKI0.05 nMUS-10781204: TYK2 inhibitors and uses thereof
2-[4-[3-[(3S,4R)-3,4-dihydroxy-3-methylpiperidin-1-yl]pyrazol-1-yl]-5-oxo-6,7-dihydropyrrolo[3,4-b]pyridin-2-yl]-3-fluorobenzonitrileKI0.05 nMUS-10781204: TYK2 inhibitors and uses thereof
3-fluoro-2-[5-oxo-4-[3-[(5S)-1-oxo-2,7-diazaspiro[4.4]nonan-7-yl]pyrazol-1-yl]-6,7-dihydropyrrolo[3,4-b]pyridin-2-yl]benzonitrileKI0.05 nMUS-10781204: TYK2 inhibitors and uses thereof
3-fluoro-2-[4-[3-[(3S,4R)-4-fluoro-3-hydroxypiperidin-1-yl]pyrazol-1-yl]-5-oxo-6,7-dihydropyrrolo[3,4-b]pyridin-2-yl]benzonitrileKI0.05 nMUS-10781204: TYK2 inhibitors and uses thereof
3-fluoro-2-[4-[3-(3-hydroxy-2,2-dimethylpyrrolidin-1-yl)pyrazol-1-yl]-5-oxo-6,7-dihydropyrrolo[3,4-b]pyridin-2-yl]benzonitrileKI0.05 nMUS-10781204: TYK2 inhibitors and uses thereof
3-fluoro-2-[4-[3-[(1R,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl]pyrazol-1-yl]-5-oxo-6,7-dihydropyrrolo[3,4-b]pyridin-2-yl]benzonitrileKI0.05 nMUS-10781204: TYK2 inhibitors and uses thereof
3-fluoro-2-[4-[3-[(3S,4R)-3-hydroxy-4-methoxy-3-methylpiperidin-1-yl]pyrazol-1-yl]-5-oxo-6,7-dihydropyrrolo[3,4-b]pyridin-2-yl]benzonitrileKI0.05 nMUS-10781204: TYK2 inhibitors and uses thereof
3-fluoro-2-[4-[3-[(3R,4S)-3-hydroxy-4-methoxy-3-methylpiperidin-1-yl]pyrazol-1-yl]-5-oxo-6,7-dihydropyrrolo[3,4-b]pyridin-2-yl]benzonitrileKI0.05 nMUS-10781204: TYK2 inhibitors and uses thereof
3-fluoro-2-[4-[(5-morpholin-4-yl-2-pyridinyl)amino]-5-oxo-6,7-dihydropyrrolo[3,4-b]pyridin-2-yl]benzonitrileKI0.051 nMUS-10196390: TYK2 inhibitors and uses thereof
[2-[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-3-yl]-3,4,6,7-tetrahydroimidazo[4,5-c]pyridin-5-yl]-(4-piperidin-1-ylpiperidin-1-yl)methanoneKD0.069 nMUS-10882859: Kinase inhibitors
CHEMBL4434711KI0.07 nM
N-[3-[(3-fluorophenyl)sulfonylmethyl]cyclobutyl]-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amineIC500.077 nMUS-10966980: Pyrrolo[2,3-d]pyrimidine derivatives
[2-[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-3-yl]-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridin-6-yl]-(4-propan-2-ylpiperazin-1-yl)methanoneKI0.08 nMUS-10208040: Fused imidazo-piperidine JAK inhibitors
1,4-dimethyl-5-[[3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl]methylsulfonyl]pyridin-2-oneIC500.088 nMUS-10966980: Pyrrolo[2,3-d]pyrimidine derivatives
CHEMBL4443010KI0.091 nM
N-[3-[(4,4-difluoro-1,3-dihydroisoquinolin-2-yl)sulfonylmethyl]cyclobutyl]-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amineIC500.109 nMUS-10966980: Pyrrolo[2,3-d]pyrimidine derivatives
[2-[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-3-yl]-3,4,6,7-tetrahydroimidazo[4,5-c]pyridin-5-yl]-morpholin-4-ylmethanoneKD0.11 nMUS-10882859: Kinase inhibitors
N-[3-(3,4-dihydro-1H-pyrrolo[1,2-a]pyrazin-2-ylsulfonylmethyl)cyclobutyl]-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amineIC500.114 nMUS-10966980: Pyrrolo[2,3-d]pyrimidine derivatives
CHEMBL4435047KI0.12 nM
CHEMBL4293907KI0.13 nM
CHEMBL4438107KI0.13 nM
1-methyl-5-[[3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl]methylsulfonyl]pyridin-2-oneIC500.135 nMUS-10966980: Pyrrolo[2,3-d]pyrimidine derivatives
CHEMBL4474801KI0.14 nM
CHEMBL4561123KI0.15 nM
N-methyl-N-[3-[(4-methyl-3-pyridinyl)sulfonylmethyl]cyclobutyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amineIC500.153 nMUS-10966980: Pyrrolo[2,3-d]pyrimidine derivatives
N-[3-(benzenesulfonylmethyl)cyclobutyl]-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amineIC500.168 nMUS-10966980: Pyrrolo[2,3-d]pyrimidine derivatives
N-[3-[(3,3-difluorocyclobutyl)sulfonylmethyl]cyclobutyl]-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amineIC500.185 nMUS-10966980: Pyrrolo[2,3-d]pyrimidine derivatives
CHEMBL4784391IC500.19 nM
2-[4-[4-[(2R)-2-hydroxypropyl]-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-3-yl]cyclohexyl]acetonitrileIC500.2 nMUS-10294226: Small molecule inhibitors of the JAK family of kinases
N-[(1S,2R)-2-fluorocyclopropyl]-5-[[1-(3-fluoro-2-pyridinyl)-2-oxo-3-pyridinyl]amino]-7-(methylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamideKD0.2 nMUS-12221453: Substituted pyrazolo[5′,1′:2,3]pyrimido[5,4-b][1,4]oxazines as TYK2 inhibitors
N-[(1S,2R)-2-fluorocyclopropyl]-7-(methylamino)-5-[(2-oxo-1-pyridin-2-yl-3-pyridinyl)amino]pyrazolo[1,5-a]pyrimidine-3-carboxamideKD0.2 nMUS-12221453: Substituted pyrazolo[5′,1′:2,3]pyrimido[5,4-b][1,4]oxazines as TYK2 inhibitors
N-[(1S,2S)-2-methoxycyclobutyl]-7-(methylamino)-5-[1-(2-morpholin-4-ylethyl)pyrrolo[2,3-b]pyridin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamideKD0.2 nMUS-12221453: Substituted pyrazolo[5′,1′:2,3]pyrimido[5,4-b][1,4]oxazines as TYK2 inhibitors

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
11.00IC500.01nMCHEMBL5427107
10.82Ki0.015nMCHEMBL4460368
10.80IC500.016nMCHEMBL5427277
10.74Ki0.018nMCHEMBL4442827
10.74IC500.018nMCHEMBL5422022
10.72Kd0.019nMCHEMBL5433700
10.72Kd0.019nMCHEMBL5424497
10.70Ki0.02nMDEUCRAVACITINIB
10.70Ki0.02nMBMS-986202
10.66Kd0.022nMCHEMBL5424894
10.64Kd0.023nMCHEMBL5398548
10.64Kd0.023nMCHEMBL5424894
10.62Ki0.024nMCHEMBL4571920
10.59IC500.026nMCHEMBL5416227
10.59IC500.026nMCHEMBL5418288
10.57IC500.027nMCHEMBL5420349
10.55Kd0.028nMCHEMBL5419627
10.48Kd0.033nMCHEMBL5407138
10.47Kd0.034nMCHEMBL5430689
10.46Ki0.035nMCHEMBL4439957
10.42IC500.038nMCHEMBL5417355
10.41Kd0.039nMCHEMBL5415951
10.30IC500.05nMCHEMBL5437122
10.30IC500.05nMCHEMBL5440225
10.30Ki0.05nMCHEMBL6048102
10.30Ki0.05nMCHEMBL5879865
10.30Ki0.05nMCHEMBL6028729
10.30Ki0.05nMCHEMBL5994009
10.30Ki0.05nMCHEMBL5981476
10.30Ki0.05nMCHEMBL5819557
10.30Ki0.05nMCHEMBL5807669
10.30Ki0.05nMCHEMBL5985265
10.30Ki0.05nMCHEMBL5840367
10.30Ki0.05nMCHEMBL5805686
10.30Ki0.05nMCHEMBL5785787
10.30Ki0.05nMCHEMBL5935458
10.30Ki0.05nMCHEMBL5816231
10.30Ki0.05nMCHEMBL5943374
10.30Ki0.05nMCHEMBL5923101
10.30Ki0.05nMCHEMBL5995806
10.30Ki0.05nMCHEMBL5879376
10.30Ki0.05nMCHEMBL5931775
10.30Ki0.05nMCHEMBL5817496
10.30Ki0.05nMCHEMBL6021065
10.30Ki0.05nMCHEMBL5794881
10.30Ki0.05nMCHEMBL5976818
10.29Ki0.051nMCHEMBL5200655
10.28IC500.053nMCHEMBL5418288
10.22Ki0.06nMCHEMBL4561663
10.22IC500.06nMCHEMBL5412034

PubChem BioAssay actives

2433 with measured affinity, of 4766 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
6-[[1-(1,5-dimethylpyrazol-3-yl)-2-oxo-3-pyridinyl]amino]-N-[(1R,2S)-2-fluorocyclopropyl]-8-(methylamino)imidazo[1,2-b]pyridazine-3-carboxamide1603362: Inhibition of fluorescein-labeled kinase tracer binding to His-TVMV-fused TYK2 JH2 domain (575 to 869 residues) (unknown origin) measured after 90 mins by HTRF assayki<0.0001uM
N-[(1R,2S)-2-fluorocyclopropyl]-8-(methylamino)-6-[[1-(6-methylpyridazin-3-yl)-2-oxo-3-pyridinyl]amino]imidazo[1,2-b]pyridazine-3-carboxamide1603362: Inhibition of fluorescein-labeled kinase tracer binding to His-TVMV-fused TYK2 JH2 domain (575 to 869 residues) (unknown origin) measured after 90 mins by HTRF assayki<0.0001uM
Deucravacitinib1534892: Inhibition of TYK2 in human Jurkat cells assessed as reduction in IFN-alpha stimulated TYK2 phosphorylation by caspase3/7 reagent-based Western blot analysiski<0.0001uM
N-[(1S,2S)-2-methoxycyclobutyl]-7-(methylamino)-5-[[1-[(3R)-oxan-3-yl]-2-oxo-3-pyridinyl]amino]pyrazolo[1,5-a]pyrimidine-3-carboxamide1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression systemkd<0.0001uM
N-[(1R,2R)-2-methoxycyclobutyl]-7-(methylamino)-5-[(2-oxo-1-pyridin-2-yl-3-pyridinyl)amino]pyrazolo[1,5-a]pyrimidine-3-carboxamide2011264: Binding affinity to TYK2 JH2 (unknown origin) assessed as dissociation constantkd<0.0001uM
N-[(1S,2S)-2-methoxycyclobutyl]-7-(methylamino)-5-[(2-oxo-1-pyridin-2-yl-3-pyridinyl)amino]pyrazolo[1,5-a]pyrimidine-3-carboxamide1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression systemkd<0.0001uM
N-[(1S,2S)-2-methoxycyclobutyl]-7-(methylamino)-5-[[1-(6-methyl-3-pyridinyl)-2-oxo-3-pyridinyl]amino]pyrazolo[1,5-a]pyrimidine-3-carboxamide1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression systemkd<0.0001uM
5-[[1-(3-fluoro-2-pyridinyl)-2-oxo-3-pyridinyl]amino]-N-[(1R,2R)-2-methoxycyclobutyl]-7-(methylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression systemkd<0.0001uM
5-[[1-(3-fluoro-2-pyridinyl)-2-oxo-3-pyridinyl]amino]-N-[(1S,2S)-2-hydroxycyclobutyl]-7-(methylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression systemkd<0.0001uM
5-[[1-(5-fluoro-3-pyridinyl)-2-oxo-3-pyridinyl]amino]-N-[(1S,2S)-2-methoxycyclobutyl]-7-(methylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression systemkd<0.0001uM
N-[(1S,2S)-2-methoxycyclobutyl]-7-(methylamino)-5-[[1-(oxan-4-yl)-2-oxo-3-pyridinyl]amino]pyrazolo[1,5-a]pyrimidine-3-carboxamide1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression systemkd<0.0001uM
5-[[1-(3-fluoro-2-pyridinyl)-2-oxo-3-pyridinyl]amino]-N-[[1-(hydroxymethyl)cyclopropyl]methyl]-7-(methylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression systemkd<0.0001uM
N-cyclopropyl-5-[(2-methoxy-3-pyridinyl)amino]-7-(methylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression systemkd<0.0001uM
N-[(1S,2S)-2-methoxycyclobutyl]-7-(methylamino)-5-[(2-oxo-1-pyridin-3-yl-3-pyridinyl)amino]pyrazolo[1,5-a]pyrimidine-3-carboxamide1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression systemkd<0.0001uM
N-[(1S,2S)-2-methoxycyclobutyl]-7-(methylamino)-5-[(2-oxo-1-propan-2-yl-3-pyridinyl)amino]pyrazolo[1,5-a]pyrimidine-3-carboxamide1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression systemkd<0.0001uM
5-[[1-(3-fluoro-2-pyridinyl)-2-oxo-3-pyridinyl]amino]-N-[(1R,2S)-2-hydroxycyclobutyl]-7-(methylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression systemkd<0.0001uM
5-[[1-[1-(2-fluoroethyl)piperidin-4-yl]-2-oxo-3-pyridinyl]amino]-N-[(1S,2S)-2-methoxycyclobutyl]-7-(methylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression systemkd<0.0001uM
N-[(1S,2S)-2-methoxycyclobutyl]-7-(methylamino)-5-[[1-(4-methyl-1,3-oxazol-2-yl)-2-oxo-3-pyridinyl]amino]pyrazolo[1,5-a]pyrimidine-3-carboxamide1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression systemkd<0.0001uM
N-[(1S,2S)-2-methoxycyclobutyl]-7-(methylamino)-5-[[1-(1,3-oxazol-2-yl)-2-oxo-3-pyridinyl]amino]pyrazolo[1,5-a]pyrimidine-3-carboxamide1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression systemkd<0.0001uM
N-[(1S,2S)-2-methoxycyclobutyl]-7-(methylamino)-5-[[1-[(3S)-oxan-3-yl]-2-oxo-3-pyridinyl]amino]pyrazolo[1,5-a]pyrimidine-3-carboxamide1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression systemkd<0.0001uM
5-[[1-(3-fluoro-2-pyridinyl)-2-oxo-3-pyridinyl]amino]-N-[(1S,2S)-2-methoxycyclopropyl]-7-(methylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression systemkd<0.0001uM
N-[(1R,2R)-2-methoxycyclobutyl]-5-[[1-(4-methoxycyclohexyl)-2-oxo-3-pyridinyl]amino]-7-(methylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression systemkd<0.0001uM
N-[(1R,2R)-2-methoxycyclobutyl]-7-(methylamino)-5-[[1-(2-methyl-1,3-oxazol-5-yl)-2-oxo-3-pyridinyl]amino]pyrazolo[1,5-a]pyrimidine-3-carboxamide1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression systemkd<0.0001uM
5-[[1-(5-fluoro-2-pyridinyl)-2-oxo-3-pyridinyl]amino]-N-[(1R,2R)-2-methoxycyclobutyl]-7-(methylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression systemkd<0.0001uM
N-[(1R,2R)-2-methoxycyclobutyl]-7-(methylamino)-5-[[1-(4-methyl-1,3-oxazol-5-yl)-2-oxo-3-pyridinyl]amino]pyrazolo[1,5-a]pyrimidine-3-carboxamide1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression systemkd<0.0001uM
N-[(1S,2S)-2-methoxycyclobutyl]-7-(methylamino)-5-[[1-(oxetan-3-yl)-2-oxo-3-pyridinyl]amino]pyrazolo[1,5-a]pyrimidine-3-carboxamide1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression systemkd<0.0001uM
N-[(1S,2S)-2-methoxycyclobutyl]-5-[[1-(3-methoxycyclobutyl)-2-oxo-3-pyridinyl]amino]-7-(methylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression systemkd<0.0001uM
N-[(1S)-2,2-difluorocyclobutyl]-5-[[1-(3-fluoro-2-pyridinyl)-2-oxo-3-pyridinyl]amino]-7-(methylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression systemkd<0.0001uM
5-[[1-(3-fluoro-2-pyridinyl)-2-oxo-3-pyridinyl]amino]-7-(methylamino)-N-[(1R,2R)-2-(trideuteriomethoxy)cyclobutyl]pyrazolo[1,5-a]pyrimidine-3-carboxamide1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression systemkd<0.0001uM
6-(azetidine-1-carbonylamino)-4-[2-methoxy-3-(1-methyl-1,2,4-triazol-3-yl)anilino]-N-methylpyridazine-3-carboxamide2029526: Binding affinity to human wild-type partial length TYK2 JH2 (G556 to D888 residues) expressed in mammalian expression system by KINOMEscan assaykd<0.0001uM
(11R)-4-methoxy-11-methyl-18-(methylamino)-9-oxa-2,12,16,20,21-pentazatetracyclo[12.5.2.13,7.017,21]docosa-1(20),3,5,7(22),14,16,18-heptaen-13-one2029546: Binding affinity to TYK2 JH2 (unknown origin)kd<0.0001uM
N-[(1R,2S)-2-fluorocyclopropyl]-6-[[1-(5-fluoro-2-pyridinyl)-2-oxo-3-pyridinyl]amino]-8-(methylamino)imidazo[1,2-b]pyridazine-3-carboxamide1603362: Inhibition of fluorescein-labeled kinase tracer binding to His-TVMV-fused TYK2 JH2 domain (575 to 869 residues) (unknown origin) measured after 90 mins by HTRF assayki<0.0001uM
N-[(1R,2S)-2-fluorocyclopropyl]-6-[[1-(6-fluoro-2-pyridinyl)-2-oxo-3-pyridinyl]amino]-8-(methylamino)imidazo[1,2-b]pyridazine-3-carboxamide1603362: Inhibition of fluorescein-labeled kinase tracer binding to His-TVMV-fused TYK2 JH2 domain (575 to 869 residues) (unknown origin) measured after 90 mins by HTRF assayki<0.0001uM
6-(cyclopropanecarbonylamino)-4-[3-(5-fluoropyrimidin-2-yl)-2-methoxyanilino]-N-(trideuteriomethyl)pyridine-3-carboxamide1744162: Inhibition of TYK2 JH2 domain (unknown origin) by HTRF assay based Morrison titration analysiski<0.0001uM
6-[(2-cyclopropylacetyl)amino]-4-[[3-methoxy-4-(1-methyl-1,2,4-triazol-3-yl)-2-pyridinyl]amino]-N-(trideuteriomethyl)pyridazine-3-carboxamide2011975: Displacement of fluorescein-labeled kinase tracer from His-TVMV-TYK2 JH2 (575 to 869 residues) (unknown origin) measured after 90 mins by HTRF assayic50<0.0001uM
6-[[5-(3-hydroxyazetidin-1-yl)-2-pyridinyl]amino]-4-[2-methoxy-3-(1-methyl-1,2,4-triazol-3-yl)anilino]-N-(trideuteriomethyl)pyridazine-3-carboxamide2029526: Binding affinity to human wild-type partial length TYK2 JH2 (G556 to D888 residues) expressed in mammalian expression system by KINOMEscan assaykd<0.0001uM
N-[4-[(6-methylsulfonyl-2-pyridinyl)amino]-5-pyridin-2-yl-2-pyridinyl]acetamide2029556: Inhibition of TYK2 JH2 (561 to 860 residues) (unknown origin) by HTRF assayic50<0.0001uM
N-[4-(3-methylsulfonylanilino)-5-pyridin-2-yl-2-pyridinyl]acetamide2029556: Inhibition of TYK2 JH2 (561 to 860 residues) (unknown origin) by HTRF assayic50<0.0001uM
6-(cyclopropanecarbonylamino)-4-[3-[[4-[[(2S)-1,4-dioxan-2-yl]methylamino]phenyl]carbamoyl]-2-methoxyanilino]-N-(trideuteriomethyl)pyridazine-3-carboxamide1875749: Binding affinity to T7-tagged TYK2 JH2 (unknown origin) expressed in Escherichia coli BL21 cells incubated for 1 hr by qPCR analysiskd<0.0001uM
N-[5-(5-fluoro-2-pyridinyl)-4-[(4-methoxy-6-methylsulfonyl-2-pyridinyl)amino]-2-pyridinyl]acetamide2029556: Inhibition of TYK2 JH2 (561 to 860 residues) (unknown origin) by HTRF assayic50<0.0001uM
N-[5-[5-(2-hydroxypropan-2-yl)-2-pyridinyl]-4-[(4-methoxy-6-methylsulfonyl-2-pyridinyl)amino]-2-pyridinyl]acetamide2029556: Inhibition of TYK2 JH2 (561 to 860 residues) (unknown origin) by HTRF assayic50<0.0001uM
N-[5-(2,2-dimethyl-3H-[1,4]dioxino[2,3-b]pyridin-6-yl)-4-[(4-methoxy-6-methylsulfonyl-2-pyridinyl)amino]-2-pyridinyl]acetamide2029556: Inhibition of TYK2 JH2 (561 to 860 residues) (unknown origin) by HTRF assayic50<0.0001uM
N-[4-[[4-(2-methoxyethoxy)-6-methylsulfonyl-2-pyridinyl]amino]-5-pyridin-2-yl-2-pyridinyl]acetamide2029556: Inhibition of TYK2 JH2 (561 to 860 residues) (unknown origin) by HTRF assayic50<0.0001uM
(13R,17R)-24-(methylamino)-7-(trideuteriomethyl)-12-oxa-2,5,6,7,18,22,26,27-octazahexacyclo[18.5.2.13,10.04,8.013,17.023,27]octacosa-1(26),3,5,8,10(28),20,22,24-octaen-19-one2029546: Binding affinity to TYK2 JH2 (unknown origin)kd<0.0001uM
6-(cyclopropanecarbonylamino)-4-[2-methoxy-3-[5-[[4-(methylsulfonimidoyl)piperazin-1-yl]methyl]-1,2,4-oxadiazol-3-yl]anilino]-N-(trideuteriomethyl)pyridazine-3-carboxamide2029526: Binding affinity to human wild-type partial length TYK2 JH2 (G556 to D888 residues) expressed in mammalian expression system by KINOMEscan assaykd<0.0001uM
2-(4-amino-2-methoxyphenyl)-7-(cyclopropanecarbonylamino)-N-methyl-1H-pyrrolo[2,3-d]pyridazine-4-carboxamide2011272: Binding affinity to human recombinant TYK2 (556 to 871 residues) incubated for 10 hrs by microplate reader based analysiskd<0.0001uM
6-(cyclopropanecarbonylamino)-4-[2-methoxy-3-[5-(methylsulfonimidoyl)-4,6-dihydropyrrolo[3,4-c]pyrazol-2-yl]anilino]-N-(trideuteriomethyl)pyridazine-3-carboxamide2029526: Binding affinity to human wild-type partial length TYK2 JH2 (G556 to D888 residues) expressed in mammalian expression system by KINOMEscan assaykd<0.0001uM
6-[[2-(2,6-difluorophenyl)-5-oxo-6,7-dihydropyrrolo[3,4-b]pyridin-4-yl]amino]-N-ethylpyridine-3-carboxamide1851014: Inhibition of TYK2 JH1 domain (unknown origin) measured in presence of 10 uM ATPki0.0001uM
3-fluoro-2-[4-[(5-morpholin-4-yl-2-pyridinyl)amino]-5-oxo-6,7-dihydropyrrolo[3,4-b]pyridin-2-yl]benzonitrile1851014: Inhibition of TYK2 JH1 domain (unknown origin) measured in presence of 10 uM ATPki0.0001uM
2-(2,6-difluorophenyl)-4-[[5-(4,4-difluoropiperidin-1-yl)-2-pyridinyl]amino]-6,7-dihydropyrrolo[3,4-b]pyridin-5-one1851014: Inhibition of TYK2 JH1 domain (unknown origin) measured in presence of 10 uM ATPki0.0001uM

CTD chemical–gene interactions

50 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
bisphenol Adecreases methylation, affects cotreatment2
sodium arsenitedecreases expression, increases abundance2
aristolochic acid Iincreases expression1
FR900359decreases phosphorylation1
bisphenol Fdecreases methylation1
moringinincreases expression1
6-hydroxy-3-O-methylkaempferol 6-O-glucopyranosideincreases expression, increases reaction, increases phosphorylation, decreases reaction1
triphenyl phosphateaffects expression1
2,4,5,2’,4’,5’-hexachlorobiphenylincreases phosphorylation1
beta-lapachonedecreases expression1
isoquercitrinaffects expression1
cobaltous chloridedecreases expression1
perfluorooctanoic aciddecreases expression1
di-n-butylphosphoric acidaffects expression1
10-decarbamoylmitomycin Cdecreases phosphorylation1
perfluorooctane sulfonic aciddecreases expression1
perfluoro-n-nonanoic aciddecreases expression1
corosolic acidincreases expression1
2-palmitoylglycerolincreases expression1
obeticholic aciddecreases expression1
perfluorohexanesulfonic aciddecreases expression1
ICG 001increases expression1
ON 01910decreases phosphorylation1
ponatinibdecreases activity1
4-acetylantroquinonol Bdecreases expression1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acidincreases expression1
Interferon alpha-2increases expression, increases reaction, increases phosphorylation, decreases reaction1
Temozolomideincreases expression1
Decitabineaffects cotreatment, decreases expression1
Arsenic Trioxideaffects cotreatment, decreases expression1

ChEMBL screening assays

1083 unique, capped per target: 1043 binding, 39 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1218226BindingInhibition of JAK-mediated interferon-gamma/anisomycin-induced Stat1 phosphorylation in human U937 cells by Phospho-Flow cytometryHigh-content single-cell drug screening with phosphospecific flow cytometry. — *Nat Chem Biol*
CHEMBL1963765FunctionalPUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: TYK2PubChem BioAssay data set
CHEMBL4685312ADMETInhibition of recombinant human N-terminal GST-tagged TYK2 cytoplasmic domain (833 to 1187 residues) expressed in baculovirus expression system using TK-substrate-biotin preincubated for 5 mins followed by substrate addition and measured afDesign, synthesis, and pharmacological evaluation of 4- or 6-phenyl-pyrimidine derivatives as novel and selective Janus kinase 3 inhibitors. — *Eur J Med Chem*

Cellosaurus cell lines

13 cell lines: 9 cancer cell line, 3 transformed cell line, 1 factor-dependent cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_B3KHAbcam HEK293T TYK2 KOTransformed cell lineFemale
CVCL_D8D7Ubigene A-549 TYK2 KOCancer cell lineMale
CVCL_D8XWUbigene HCT 116 TYK2 KOCancer cell lineMale
CVCL_D9V7Ubigene HEK293 TYK2 KOTransformed cell lineFemale
CVCL_E0SHUbigene HeLa TYK2 KOCancer cell lineFemale
CVCL_F4VCHyCyte Ba/F3 stable cell line for hTYK2 overexpressionFactor-dependent cell line
CVCL_TV30HAP1 TYK2 (-) 1Cancer cell lineMale
CVCL_TV31HAP1 TYK2 (-) 2Cancer cell lineMale
CVCL_TV32HAP1 TYK2 (-) 3Cancer cell lineMale
CVCL_TV33HAP1 TYK2 (-) 4Cancer cell lineMale

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 250 trials:

NCTPhaseStatusTitle
NCT00001542Phase 4COMPLETEDFluconazole Prophylaxis of Thrush in AIDS
NCT00144157Phase 4COMPLETEDOpen Label Study of NVP+CBV Treatment in Women Who Have Received sdNVP for the pMTCT of HIV
NCT00162643Phase 4UNKNOWNPI Vs. NNRTI Based Therapy for HIV Advanced Disease
NCT00273988Phase 4COMPLETEDPharmacokinetic Study of Interaction Between Nevirapine and Methadone in HIV-1 Infected, Opioid-dependent Adults
NCT00981318Phase 4TERMINATEDPilot Assessment of Lopinavir/Ritonavir and Maraviroc
NCT01086878Phase 4COMPLETEDSafety of Cotrimoxazole in HIV- and HAART-exposed Infants
NCT01090102Phase 4COMPLETEDMesalamine to Reduce T Cell Activation in HIV Infection
NCT01147042Phase 4TERMINATEDBiochemical Response to Interferon-Gamma in Subjects With Specific Gene Mutation in Chronic Granulomatous Disease
NCT01230580Phase 4UNKNOWNProtease Inhibitor Monotherapy Versus Ongoing Triple-therapy in the Long Term Management of HIV Infection (PIVOT)
NCT01465958Phase 4COMPLETEDPharmacokinetics, Safety, and Tolerability of Subcutaneous GAMUNEX-C in Pediatric Subjects With Primary Immunodeficiency
NCT02274662Phase 4COMPLETEDExpanded Access Protocol Thymus Transplantation
NCT02348177Phase 4COMPLETEDPharmacokinetics of Lopinavir/Ritonavir Superboosting in Infants and Young Children Co-infected With HIV and TB
NCT02396979Phase 4COMPLETEDIntervention of HIV, Drug Use and the Criminal Justice System in Malaysia
NCT02490956Phase 4UNKNOWNDiagnostic Immunization With Rabies Vaccine in Patients With PID
NCT02503293Phase 4COMPLETEDA Study to Compare Quality of Life and Satisfaction in Primary Immunodeficient Patients Treated With Subcutaneous Injections of Gammanorm® 165 mg/mL Administered With Two Different Delivery Devices: Injections Using Pump or Rapid Push
NCT02881437Phase 4COMPLETEDIgG Level in Primary Immunodeficiency Switching From Standard SCIG to Every Other Week HyQvia
NCT03033745Phase 4COMPLETEDSafety and Tolerability of Higher Infusion Parameters of IgPro20 (Hizentra) in Subjects With Primary Immunodeficiency (PID)
NCT03677557Phase 4UNKNOWNSafety, Tolerability, Patient Satisfaction and Cost of 16.5% Subcutaneous Immunoglobulin (Cutaquig®) Treatment
NCT04192487Phase 4COMPLETEDEffects of Crofelemer on the Gut Microbiome in Healthy Volunteers and in HIV+ Patients With Non-Infectious Diarrhea
NCT04566692Phase 4COMPLETEDA Study to Evaluate IGSC 20% Biweekly Dosing in Treatment-Experienced Participants and Loading/Maintenance Dosing in Treatment-Naïve Participants With Primary Immunodeficiency
NCT05493969Phase 4UNKNOWNEfficacy and Tolerability of DTG Plus 3TC in HIV Infected Adults With Virologically Suppression and TDF Toxicity
NCT06576024Phase 4COMPLETEDImmunogenicity and Safety of Inactivated Hepatitis A Vaccine in HIV-infected People
NCT06634641Phase 4RECRUITINGClozapine-related Immunodeficiency in Parkinsons Disease
NCT07076446Phase 4COMPLETEDAn Open-label, Multicenter Study to Assess the Pharmacokinetics (PK), Safety, and Tolerability of Subcutaneous IgPro20 in Immunoglobulin (IG) Treatment-naïve Participants With Primary Immunodeficiency (PID)
NCT00000118Phase 3COMPLETEDGanciclovir Implant Study for Cytomegalovirus Retinitis
NCT00000134Phase 3COMPLETEDStudies of the Ocular Complications of AIDS (SOCA)–Cytomegalovirus Retinitis Retreatment Trial (CRRT)
NCT00000590Phase 3COMPLETEDAnti-HIV Immunoglobulin (HIVIG) in Prevention of Maternal-Fetal HIV Transmission (Pediatric ACTG Protocol 185)
NCT00001267Phase 3COMPLETEDA Randomized Pilot Study for the Treatment of AIDS or AIDS Related Complex With an Alternating or Simultaneous Combination Regimen of AZT and 2’,3’-Dideoxyinosine
NCT00001646Phase 3COMPLETEDVoriconazole vs. Amphotericin B in the Treatment of Invasive Aspergillosis
NCT00144183Phase 3COMPLETEDA Study of Single Dose Nevirapine (NVP) Combined With Combivir® for the Prevention of Mother to Child Transmission (pMTCT) - Treatment Options Preservation Study (TOPS)
NCT00243568Phase 3WITHDRAWNVicriviroc, a CCR5 Inhibitor, Added to an Optimized Antiretroviral Therapy for Previously Treated HIV (VICTOR-E2) (Study P04285
NCT00278954Phase 3COMPLETEDEfficacy, Safety and Pharmacokinetics of Gammaplex in Primary Immunodeficiency Diseases.
NCT00474370Phase 3COMPLETEDVicriviroc in HIV-Treatment Experienced Subjects (Study P04889AM8)(COMPLETED)
NCT00478231Phase 3COMPLETEDMulticenter, Safety Study Of Maraviroc
NCT00523211Phase 3COMPLETEDVicriviroc in HIV-Treatment Experienced Subjects (Study P04405AM5)
NCT00698334Phase 3COMPLETEDEfficacy of Thrice Weekly Directly Observed Treatment, Short-course (DOTS) in HIV-associated Tuberculosis
NCT00966160Phase 3COMPLETEDCD4 Cell Recovery in HIV-1 Patients Comparing 2 Treatment Regimes
NCT01363011Phase 3COMPLETEDCobicistat-containing Highly Active Antiretroviral Regimens in HIV-1 Infected Patients With Mild to Moderate Renal Impairment
NCT01440569Phase 3COMPLETEDSafety and Efficacy of Cobicistat-boosted Darunavir in HIV Infected Adults
NCT01475838Phase 3COMPLETEDStudy to Evaluate Switching From Regimens Consisting of a Ritonavir-boosted Protease Inhibitor Plus Emtricitabine/Tenofovir Fixed-Dose Combination to the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF Single-Tablet Regimen in Virologically Suppressed, HIV-1 Infected Patients
NCT01495702Phase 3COMPLETEDStudy to Evaluate Switching From Regimens Consisting of a Nonnucleoside Reverse Transcriptase Inhibitor Plus Emtricitabine and Tenofovir DF to the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF Single-Tablet Regimen in Virologically Suppressed, HIV-1 Infected Patients
NCT01533259Phase 3COMPLETEDOpen-Label Pilot Study to Evaluate Switching From a Regimen Consisting of Raltegravir Plus Emtricitabine/Tenofovir DF Fixed-Dose Combination to the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF Single-Tablet Regimen in Virologically Suppressed, HIV-1 Infected Patients
NCT01581593Phase 3COMPLETEDEfficacy and Safety Study of Kedrion IVIG 10% to Treat Subjects With Primary Immunodeficiency (PID)
NCT01705574Phase 3COMPLETEDSafety and Efficacy of E/C/F/TDF Versus RTV-Boosted ATV Plus FTC/TDF in HIV-1 Infected, Antiretroviral Treatment-Naive Women
NCT01967940Phase 3COMPLETEDEfficacy of Tenofovir Alafenamide Versus Placebo Added to a Failing Regimen Followed by Treatment With Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Plus Atazanavir in HIV-1 Positive, Antiretroviral Treatment-Experienced Adults
NCT01968551Phase 3COMPLETEDPhase 3 Open-Label Study to Evaluate Switching From Optimized Stable Antiretroviral Regimens Containing Darunavir to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Fixed Dose Combination (FDC) Plus Darunavir (DRV) in Treatment Experienced HIV-1 Positive Adults
NCT01985373Phase 3COMPLETEDPharmacokinetics and Safety of IVIG Nanogam 100 mg/ml
NCT02269163Phase 3COMPLETEDStudy of ProMetic BioTherapeutics Immune Globulin Intravenous (Human) 10%
NCT02604810Phase 3COMPLETEDSafety and Pharmacokinetics of IGSC 20% in Subjects With Primary Immunodeficiency
NCT02806986Phase 3COMPLETEDEfficacy, Pharmacokinetics, Safety, and Tolerability of IGSC 20% in Subjects With Primary Immunodeficiency
NCT03814798Phase 3WITHDRAWNStudy Evaluating IGSC 20% Flexible Dosing in Treatment-Experienced and Treatment-Naive Subjects With Primary Immunodeficiency
NCT03907241Phase 3COMPLETEDCLINICAL PHASE III STUDY TO MONITOR THE SAFETY, TOLERABILITY AND EFFICACY OF SUBCUTANEOUS HUMAN IMMUNOGLOBULIN (OCTANORM) IN PATIENTS WITH PRIMARY IMMUNODEFICIENCY DISEASES, INCLUDING (BUT NOT LIMITED TO) THOSE WHO HAVE COMPLETED THE SCGAM-01 TRIAL
NCT04561115Phase 3COMPLETEDA Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Immune Globulin (Human) 10% (Gamunex-C) PEG Process (IVIG-PEG) Compared to Gamunex-C in Participants With Primary Humoral Immunodeficiency
NCT04738812Phase 3COMPLETEDDetermination of Adequate Tuberculosis Regimen in Patients Hospitalized With HIV-associated Severe Immune Suppression
NCT04836260Phase 3UNKNOWNPreemptive Use of Convalescent Plasma for High-risk Patients With COVID-19
NCT06954441Phase 3RECRUITINGV-IMMUNE: A Novel Immunoglobulin Therapy for Immunodeficiency
NCT06980480Phase 3RECRUITINGA Study of Gammagard Liquid (Immune Globulin Infusion, 10%) to Prevent Infections in Adults With Multiple Myeloma
NCT00000587Phase 2COMPLETEDErythropoietin for Anemia Due to Zidovudine in Human Immunodeficiency Virus Infection
NCT00001354Phase 2COMPLETEDInterleukin-2 Therapy for HIV Infection - Supplemental Procedures
NCT00001475Phase 2COMPLETEDHome Treatment of HIV-Infected Patients With Interleukin-2 With or Without a Tumor Necrosis Factor Antagonist

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for TYK2 across ~30M SureChEMBL compounds — explore on Sugi Predict.

About this page

Built deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source. Provided for research and reference, not medical advice or a diagnosis. Data may be incomplete, especially for rare conditions. Consult a qualified clinician.

Generated
Atlas version
v1.13.0
BioBTree
v2.17.0

Sources 99

This page pulls from 99 datasets indexed by BioBTree:

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