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Protein / target

Peptidyl-prolyl cis-trans isomerase FKBP1A

Encoded byFKBP1AP62942Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
7
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Type I transforming growth factor beta receptor binding

Strongest disease association

Dermatitis, Atopic

Via encoding gene FKBP1A · Clinical evidence · score 0.60

Therapeutic position

Established drug target

Small molecules

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

Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand.

View complete UniProt function annotation

Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruits SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides

Subcellular location

Cytoplasm, cytosolSarcoplasmic reticulum membrane
Domains and Gene Ontology detail (38)

Domains & features

PPIase FKBP-type

Gene Ontology

  • Ccytoplasm
  • Ccytoplasmic side of membrane
  • Ccytosol
  • Cmembrane
  • Cryanodine receptor complex
  • Csarcoplasmic reticulum
  • Csarcoplasmic reticulum membrane
  • Cterminal cisterna
  • CZ disc
  • Factivin receptor binding
  • Fcalcium channel regulator activity
  • FFK506 binding

108 aa · 12 kDa

Biological roles

Reactome v97

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

Oncogenic signallingReactomeImmune signallingGO · ReactomeMuscle contractionGO
View supporting evidence

Oncogenic signalling

  • ·TGFBR1 LBD Mutants in Cancer

Immune signalling

  • ·regulation of immune response
  • ·T cell activation
  • ·SARS-CoV-1 activates/modulates innate immune responses

Muscle contraction

  • ·regulation of cardiac muscle contraction by regulation of the release of sequestered cal…
  • ·regulation of skeletal muscle contraction by regulation of release of sequestered calciu…
View underlying pathways (7)

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

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

TGFBR1RPTORMTORRYR1ACVR1PPP3R1MLST8CALM3CALML3CALML5FKBP1A

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Approved medicines with mapped indications

4 medicines · 13 areas

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.

Carcinoma, Renal Cell2 medicines
Delayed Graft Function2 medicines
Tuberous Sclerosis2 medicines
Astrocytoma1 medicine
Breast Neoplasms1 medicine
Dermatitis, Atopic1 medicine
Eczema1 medicine
Eye Diseases1 medicine
Immune System Diseases1 medicine
Lymphoma, Mantle-Cell1 medicine
Neuroendocrine Tumors1 medicine
Pancreatic Neoplasms1 medicine
Broader indication categories (1)

Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.

7 medicines meet Open Targets' target-level approved-medicine definition; the 4 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

4

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.

Sirolimus
Narrow target profileApprovedInhibitor

FK506-binding protein 1A inhibitor

Indicated for Delayed Graft Function, Eye Diseases, Tuberous Sclerosis, Neoplasms

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

everolimus
Narrow target profileApprovedInhibitor

FK506-binding protein 1A inhibitor

Indicated for Astrocytoma, Breast Neoplasms, Carcinoma, Renal Cell, Neuroendocrine Tumors

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

Tacrolimus
Narrow target profileApprovedInhibitor

FK506-binding protein 1A inhibitor

Indicated for Delayed Graft Function, Dermatitis, Atopic, Eczema, Immune System Diseases

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

temsirolimus
Narrow target profileApprovedInhibitor

FK506-binding protein 1A inhibitor

Indicated for Carcinoma, Renal Cell, Lymphoma, Mantle-Cell, Neoplasms

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

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 FKBP1A

Gene-level evidence surfaced through the gene FKBP1A that 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.

Dermatitis, Atopic
0.74Moderately supported

Clinical evidence dominant · Open Targets 0.60

Carcinoma, Renal Cell
0.73Moderately supported

Clinical evidence dominant · Open Targets 0.60

Tuberous Sclerosis
0.70Moderately supported

Clinical evidence dominant · Open Targets 0.57

Graft vs Host Disease
0.69Moderately supported

Clinical evidence dominant · Open Targets 0.56

Neoplasms
0.68Moderately supported

Clinical evidence dominant · Open Targets 0.55

View evidence synthesis (5)
Dermatitis, AtopicModerately supported
0.74
agreement 0.590.90
Clinical100%Literature0%

Open Targets aggregate 0.60 · 2 independent evidence families

Carcinoma, Renal CellModerately supported
0.73
agreement 0.580.89
Clinical99%Literature1%

Open Targets aggregate 0.60 · 2 independent evidence families

Tuberous SclerosisModerately supported
0.70
agreement 0.550.86
Clinical99%Literature1%

Open Targets aggregate 0.57 · 2 independent evidence families

Graft vs Host DiseaseModerately supported
0.69
agreement 0.540.85
Clinical100%Literature0%

Open Targets aggregate 0.56 · 2 independent evidence families

NeoplasmsModerately supported
0.68
agreement 0.530.84
Clinical87%Literature13%

Open Targets aggregate 0.55 · 2 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
Dermatitis, Atopic0.60
Carcinoma, Renal Cell0.60
Tuberous Sclerosis0.57
Graft vs Host Disease0.56
Neoplasms0.55

Drug development

7 compounds recorded · 7 approved

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 4 drugs that target this protein in Forefront's canonical graph (4 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (7)
TEMSIROLIMUSApproval
TACROLIMUS ANHYDROUSApproval
PIMECROLIMUSApproval
EVEROLIMUSApproval
ZOTAROLIMUSApproval
SIROLIMUSApproval
TACROLIMUSApproval

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 moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesEmerging

Feasibility evidence (uniprot loc med conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

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 · High-Quality PocketSM · Druggable FamilyAB · UniProt loc med confPR · LiteraturePR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

30

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.

View all trials (26)

ACTIVE_NOT_RECRUITING · via Sirolimus · NCT03150914

RECRUITING · via Tacrolimus · NCT02395497

ACTIVE_NOT_RECRUITING · via everolimus · NCT03577431

ACTIVE_NOT_RECRUITING · via Sirolimus · NCT07354620

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 3 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.

  1. Label change2026-09-02

    Label change: SIROLIMUS (NDA213312)

    fda · regulatory · fda · via Sirolimus

  2. Trial status changed2026-08-19

    A Prospective Study of Optimal Cord Selection for Haplo-Cord Transplantation: Targeting the Inherited Paternal Antigen (IPA) and Matching for the Non-Inherited Maternal Antigen (NIMA)

    Status changed to Completed · ClinicalTrials.gov · via Tacrolimus

  3. Trial status changed2026-08-11

    A Randomized, Open-label, Phase III Study of SIM0270 Combined With Everolimus Versus Treatment of Physician's Choice in Patients With CDK4/6 Inhibitors Previously Treated , ER+/HER2- Locally Advanced or Metastatic Breast Cancer

    Status changed to Active, not recruiting · ClinicalTrials.gov · via everolimus

  4. Trial results posted2026-07-30

    A Phase II, Single-Arm Study of RAD001 (Everolimus), Letrozole, and Metformin in Patients With Advanced or Recurrent Endometrial Carcinoma

    Results posted · ClinicalTrials.gov · via everolimus

  5. Label change2026-07-29

    Label change: TACROLIMUS (ANDA203740)

    fda · regulatory · fda · via Tacrolimus

  6. Trial status changed2026-07-17

    Haploidentical Allogeneic Peripheral Blood Transplantation: Clinical Trial and Laboratory Correlates Examining Checkpoint Immune Regulators' Expression

    Status changed to Completed · ClinicalTrials.gov · via Tacrolimus

  7. Regulatory approval2026-06-30

    Approval: EVEROLIMUS (ANDA219464)

    fda · regulatory · fda · via everolimus

  8. Label change2025-05-07

    Label change: TACROLIMUS (ANDA090402)

    fda · regulatory · fda · via Tacrolimus

  9. New publication2024-02-03
    Targeting PI3K/AKT/mTOR and MAPK Signaling Pathways in Gastric Cancer.

    International journal of molecular sciences · 2024 · 105 citations · Europe PMC · via Sirolimus

  10. New publication2024-02-01
    PI3K-AKT/mTOR Signaling in Psychiatric Disorders: A Valuable Target to Stimulate or Suppress?

    The international journal of neuropsychopharmacology · 2024 · 32 citations · Europe PMC · via Sirolimus

  11. New publication2023-10-02
    Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease.

    Signal transduction and targeted therapy · 2023 · 628 citations · Europe PMC · via Sirolimus

  12. New publication2023-10-01
    A novel rapamycin cream formulation improves facial angiofibromas associated with tuberous sclerosis complex: a double-blind randomized placebo-controlled trial.

    The British journal of dermatology · 2023 · 10 citations · Europe PMC · via Sirolimus

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.