Protein / target

Non-receptor tyrosine-protein kinase TYK2

Encoded byTYK2P29597Homo sapiensSwiss-Prot

UniProt: P29597 Ensembl: ENSG00000105397 HGNC: HGNC:12440 NCBI Gene: 7297

Clinically validated

Therapeutic maturity

Approved medicines

Open Targets target-level

View by indication →

Clinical trials

Small-molecule tractable

Druggability

Approved Drug

Protein at a glance

Biological role

Non-membrane spanning protein tyrosine kinase

Strongest disease association

Arthritis, Rheumatoid

Via encoding gene TYK2 · Genetic evidence · score 0.93

Therapeutic position

Established drug target

Small molecules

Research activity

Emerging research

1 papers · latest 2021

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Non-membrane spanning protein tyrosine kinase involved in numerous cytokines and interferons signaling, which regulates cell growth, development, cell migration, innate and adaptive immunity.

View complete UniProt function annotation

Non-membrane spanning protein tyrosine kinase involved in numerous cytokines and interferons signaling, which regulates cell growth, development, cell migration, innate and adaptive immunity (PubMed:10542297, PubMed:10995743, PubMed:7657660, PubMed:7813427, PubMed:8232552). Plays both structural and catalytic roles in numerous interleukins and interferons (IFN-alpha/beta) signaling (PubMed:10542297). Associates with heterodimeric cytokine receptor complexes and activates STAT family members including STAT1, STAT3, STAT4 or STAT6 (PubMed:10542297, PubMed:7638186). 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 (PubMed:10542297, PubMed:25762719, PubMed:7526154, PubMed:7813427). In response to cytokine-binding to receptors, phosphorylates and activates receptors (IFNAR1, IL12RB1, IL10RB or IL13RA1), creating docking sites for STAT members (PubMed:7526154, PubMed:7657660). 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 (PubMed:10542297, PubMed:25762719, PubMed:7657660). Negatively regulates STAT3 activity by promototing phosphorylation at a specific tyrosine that differs from the site used for signaling (PubMed:29162862). 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) (PubMed:9188471)

Domains and Gene Ontology detail (33)

Domains & features

FERMSH2; atypicalProtein kinase 1Protein kinase 2

Gene Ontology

Ccytoplasm
Ccytoplasmic side of plasma membrane
Ccytosol
Cextracellular exosome
Cextrinsic component of cytoplasmic side of plasma membrane
Cextrinsic component of plasma membrane
Cnucleus
Cplasma membrane
FATP binding
Fgrowth hormone receptor binding
Fnon-membrane spanning protein tyrosine kinase activity
Fprotein tyrosine kinase activity

1187 aa · 134 kDa

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Cell proliferation & survivalGOCell migrationUniProtImmune signallingUniProt · GOKinase signallingGO

View supporting evidence

Cell proliferation & survival

·cell population proliferation

Cell migration

·Non-membrane spanning protein tyrosine kinase involved in numerous cytokines and interfe…

Immune signalling

·Non-membrane spanning protein tyrosine kinase involved in numerous cytokines and interfe…
·cytokine-mediated signaling pathway
·interleukin-10-mediated signaling pathway
·interleukin-12-mediated signaling pathway

Kinase signalling

·non-membrane spanning protein tyrosine kinase activity
·protein tyrosine kinase activity

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Approved medicines with mapped indications

1 medicine · 1 area

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Psoriasis1 medicine

deucravacitinib

10 medicines meet Open Targets' target-level approved-medicine definition; the 1 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

deucravacitinib

Narrow target profileApprovedNegative allosteric modulator

Tyrosine-protein kinase TYK2 negative allosteric modulator

Indicated for Psoriasis

Direct interaction with this protein · Only this protein recorded as a target

delgocitinib

ApprovedInhibitor

Janus Kinase (JAK) inhibitor

Acts on a complex — shared with JAK3, JAK1, JAK2 · 1 of 4 recorded protein targets

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene TYK2

Gene-level evidence surfaced through the gene TYK2that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Arthritis, Rheumatoid

0.98Well supported

Genetic evidence dominant · Open Targets 0.75

Psoriasis

0.98Well supported

Genetic evidence dominant · Open Targets 0.72

Psoriasis vulgaris

0.96Well supported

Genetic evidence dominant · Open Targets 0.71

COVID-19

0.96Well supported

Genetic evidence dominant · Open Targets 0.66

Lupus Erythematosus, Systemic

0.94Well supported

Genetic evidence dominant · Open Targets 0.63

View evidence synthesis (5)

Arthritis, RheumatoidWell supported

0.98

agreement 0.88–1.00

Genetic52%Clinical41%Literature7%

Open Targets aggregate 0.75 · 3 independent evidence families

PsoriasisWell supported

0.98

agreement 0.87–1.00

Genetic53%Clinical41%Literature6%

Open Targets aggregate 0.72 · 3 independent evidence families

Psoriasis vulgarisWell supported

0.96

agreement 0.86–1.00

Genetic54%Clinical44%Literature2%

Open Targets aggregate 0.71 · 3 independent evidence families

COVID-19Well supported

0.96

agreement 0.85–1.00

Genetic62%Clinical32%Literature6%

Open Targets aggregate 0.66 · 3 independent evidence families

Lupus Erythematosus, SystemicWell supported

0.94

agreement 0.83–1.00

Genetic61%Clinical32%Literature7%

Open Targets aggregate 0.63 · 3 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations

Arthritis, Rheumatoid0.75

Psoriasis0.72

Psoriasis vulgaris0.71

Crohn's Disease0.68

Arthritis, Psoriatic0.67

COVID-190.66

Lupus Erythematosus, Systemic0.63

Colitis, Ulcerative0.59

Dermatitis, Atopic0.58

Drug development

17 compounds recorded · 10 approved · 7 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 2 drugs that target this protein in Forefront's canonical graph (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)

BREPOCITINIBPhase 3

IZENCITINIBPhase 2 3

CERDULATINIBPhase 2 3

DELGOCITINIBApproval

TOFACITINIB CITRATEApproval

FILGOTINIB MALEATEApproval

DEUCRAVACITINIBApproval

UPADACITINIB HEMIHYDRATEApproval

PEFICITINIBPhase 3

RUXOLITINIBApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Strong

Approved Drug and Structure with Ligand support this modality.

Antibodies — Emerging

Feasibility evidence (go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (literature and database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (10)

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Med-Quality PocketSM · Druggable FamilyAB · GO CC high confPR · LiteraturePR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

Utilization of a Cutaneous Therapy In Situ MicrodevicePHASE4

NOT_YET_RECRUITING · via deucravacitinib · NCT07352566

A Phase 3, Double-blinded, Vehicle-controlled Trial to Investigate the Efficacy and Safety of Twice Daily Delgocitinib Cream in Adult Participants With Lichen Sclerosus During a 12-Week Initial Treatment Period Followed by a 40-Week Continuation Treatment PeriodPHASE3

RECRUITING · via delgocitinib · NCT07335588

Deucravacitinib-TNFi Combination Therapy for Difficult-to-Control Psoriatic DiseasePHASE4

NOT_YET_RECRUITING · via deucravacitinib · NCT07280702

Comparison of Deucravacitinib and Adalimumab for the Treatment of Relapsed Takayasu's Arteritis: The TYK-TAK TrialPHASE4

NOT_YET_RECRUITING · via deucravacitinib · NCT07013838

View all trials (26)

Correction of Psoriatic T Cell Signatures by DeucravacitinibPHASE4

RECRUITING · via deucravacitinib · NCT05858645

A Multicenter, Randomized, Double-blind, Placebo-controlled Phase 3 Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Deucravacitinib in Adolescent Participants (12 Years to Less Than 18 Years) With Moderate to Severe Plaque PsoriasisPHASE3

RECRUITING · via deucravacitinib · NCT06979453

A Phase 3b/4 Multi-center, Randomized, Open-label, Long-term Safety Study of Deucravacitinib in Comparison to Ustekinumab in Participants With Moderate-to-Severe Plaque PsoriasisPHASE3

RECRUITING · via deucravacitinib · NCT07116967

A Phase 3, Multicenter, Double-blind, Placebo-controlled, Randomized Withdrawal Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of Deucravacitinib in Children and Adolescents From 5 to Less Than 18 Years of Age With Active Juvenile Psoriatic ArthritisPHASE3

RECRUITING · via deucravacitinib · NCT06869551

A Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled and Deucravacitinib Active Comparator-controlled Study to Evaluate the Efficacy and Safety of JNJ-77242113 for the Treatment of Participants With Moderate to Severe Plaque PsoriasisPHASE3

ACTIVE_NOT_RECRUITING · via deucravacitinib · NCT06220604

ACTIVE_NOT_RECRUITING · via deucravacitinib · NCT06143878

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Deucravacitinib in Adults With Active Sjögren's Syndrome (POETYK SjS-1)PHASE3

ACTIVE_NOT_RECRUITING · via deucravacitinib · NCT05946941

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Deucravacitinib in Participants With Active Systemic Lupus Erythematosus (SLE) (POETYK SLE-1)PHASE3

ACTIVE_NOT_RECRUITING · via deucravacitinib · NCT05617677

ACTIVE_NOT_RECRUITING · via deucravacitinib · NCT05620407

A Multi-center, Randomized, Double-blind, Placebo-controlled Phase 3 Study to Evaluate the Efficacy and Safety of Deucravacitinib in Participants With Active Psoriatic Arthritis (PsA) Who Are Naïve to Biologic Disease Modifying Anti-rheumatic Drugs or Had Previously Received TNFα Inhibitor TreatmentPHASE3

ACTIVE_NOT_RECRUITING · via deucravacitinib · NCT04908189

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Deucravacitinib in Participants With Active Psoriatic Arthritis Who Are Naïve to Biologic Disease-modifying Anti-rheumatic DrugsPHASE3

ACTIVE_NOT_RECRUITING · via deucravacitinib · NCT04908202

A Multicenter, Randomized, Double-Blind Placebo-Controlled Phase 3 Study to Evaluate the Pharmacokinetics, Efficacy and Safety of Deucravacitinib (BMS-986165) in Pediatric Subjects With Moderate to Severe Plaque PsoriasisPHASE3

RECRUITING · via deucravacitinib · NCT04772079

Phase 2 Open Label Trial of Delgocitinib 20 mg/g Cream in Subjects With Frontal Fibrosing Alopecia (FFA)PHASE2

NOT_YET_RECRUITING · via delgocitinib · NCT07671157

Deucravacitinib in the Treatment of Cicatricial AlopeciasPHASE2

RECRUITING · via deucravacitinib · NCT07508488

A Pilot Study to Assess Safety and Biomarker Responses of Delgocitinib (JAK1,2,3/TYK2 Inhibitor) in Central Centrifugal Cicatricial Alopecia and Lichen PlanopilarisPHASE2

RECRUITING · via delgocitinib · NCT07487948

Vitiligo Treatment by Targeting TYK2 Mediated Responses Prospective Multicentric Double Blind Interventional StudyPHASE2

ACTIVE_NOT_RECRUITING · via deucravacitinib · NCT06327321

A 44-week Monocentric Open Study Assessing the Efficacy and Safety of Deucravacitinib in Adults With Inflammatory GenodermatosesPHASE2

RECRUITING · via deucravacitinib · NCT06136403

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of Deucravacitinib (BMS-986165) in Participants With Active Discoid and/or Subacute Cutaneous Lupus Erythematosus (DLE/SCLE)PHASE2

ACTIVE_NOT_RECRUITING · via deucravacitinib · NCT04857034

A Phase IV, Open-label, Single-group, Single-dose Study Evaluating Deucravacitinib Concentrations in the Breast Milk and Plasma of Healthy Lactating Female ParticipantsPHASE4

COMPLETED · via deucravacitinib · NCT06476834

A Phase 4 Multicenter, Randomized, Open-label, Efficacy Assessor Blinded Study of Risankizumab Compared to Deucravacitinib for the Treatment of Adult Subjects With Moderate Plaque Psoriasis Who Are Candidates for Systemic TherapyPHASE4

COMPLETED · via deucravacitinib · NCT06333860

A Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Deucravacitinib in Participants With Non-Pustular PalmoPlantar and Genital Psoriasis (Psoriatyk Special Sites)PHASE4

TERMINATED · via deucravacitinib · NCT06042920

Deucravacitinib for the Treatment of Palmoplantar PustulosisPHASE4

TERMINATED · via deucravacitinib · NCT05710185

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Effect of Deucravacitinib on Quality of Life in Participants With Plaque Psoriasis in a Community SettingPHASE4

COMPLETED · via deucravacitinib · NCT05701995

A Single Center Study to Evaluate the Effectiveness and Safety of SOTYKTU® (Deucravacitinib) in Combination With Enstilar® for Moderate to Severe Plaque PsoriasisPHASE4

COMPLETED · via deucravacitinib · NCT06329258

A Phase 3B/4, Multicenter, Randomized, Double-blind Placebo-controlled Study to Evaluate the Efficacy and Safety of Deucravacitinib in Participants With Moderate-to-severe Scalp Psoriasis (PSORIATYK SCALP)PHASE4

COMPLETED · via deucravacitinib · NCT05478499

A Phase 3, Randomized, Multicenter, Double-Blind Trial to Evaluate the Efficacy, Safety, and Tolerability of Zasocitinib (TAK-279) Compared to Deucravacitinib in Participants With Moderate-to-Severe Plaque PsoriasisPHASE3

COMPLETED · via deucravacitinib · NCT06973291

ClinicalTrials.gov via the drug-target graph.

What's happening now

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

Label change2026-06-30
Label change: DELGOCITINIB (NDA219155)
fda · regulatory · fda · via delgocitinib
Label change2026-06-30
Label change: DEUCRAVACITINIB (NDA214958)
fda · regulatory · fda · via deucravacitinib
Indication expanded2026-03-06
Indication expansion: DEUCRAVACITINIB (NDA214958)
fda · regulatory · fda · via deucravacitinib
Supplemental approval2025-10-27
Supplemental approval: DEUCRAVACITINIB (NDA214958)
fda · regulatory · fda · via deucravacitinib
Regulatory approval2025-07-23
Approval: DELGOCITINIB (NDA219155)
fda · regulatory · fda · via delgocitinib
New publication2025-04-16
Efficacy and safety of topical delgocitinib cream versus oral alitretinoin capsules in adults with severe chronic hand eczema (DELTA FORCE): a 24-week, randomised, head-to-head, phase 3 trial.
Lancet (London, England) · 2025 · 12 citations · Europe PMC · via delgocitinib
Regulatory approval2024-09-19
Approval: Anzupgo (EMA)
ema · regulatory · ema · via delgocitinib
Regulatory approval2023-03-24
Approval: Sotyktu (EMA)
ema · regulatory · ema · via deucravacitinib
Regulatory approval2022-09-09
Approval: DEUCRAVACITINIB (NDA214958)
fda · regulatory · fda · via deucravacitinib

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.

Research activity

1 papers · to 2021

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Genetic mechanisms of critical illness in COVID-19.1,129 cites

Pairo-Castineira E · Nature · 2021

Recent

Genetic mechanisms of critical illness in COVID-19.

Pairo-Castineira E · Nature · 2021

Europe PMC papers linked directly to this protein.