Protein / target

Peptidyl-prolyl cis-trans isomerase FKBP1A

FKBP1AP62942Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
7
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Type I transforming growth factor beta receptor binding

Primary system

Immune system

Strongest disease association

atopic eczema

Clinical evidence · score 0.60

Therapeutic maturity

Clinically validated target

7 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

7 approved

30 linked trials

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

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.

Immune signallingGO · ReactomeMuscle contractionGO
View supporting evidence

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.

Drugs targeting this protein

3

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

Sirolimus
Narrow target profileApprovedInhibitor

FK506-binding protein 1A inhibitor

Appears in clinical studies involving blue rubber bleb nevus, Venous malformation, Gorham-Stout disease, vascular neoplasm

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

everolimus
Narrow target profileApprovedInhibitor

FK506-binding protein 1A inhibitor

Appears in clinical studies involving angiomyolipoma, tuberous sclerosis, astrocytoma (excluding glioblastoma), neuroendocrine neoplasm

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

Tacrolimus
Narrow target profileApprovedInhibitor

FK506-binding protein 1A inhibitor

Appears in clinical studies involving conjunctivitis, graft versus host disease, graft versus host disease, Eczematoid dermatitis

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

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

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

atopic eczema0.99

Clinical · overall 0.60

renal cell carcinoma0.98

Clinical · overall 0.60

kidney transplant0.98

Clinical · overall 0.59

liver transplant0.96

Clinical · overall 0.59

breast cancer0.95

Clinical · overall 0.60

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

tuberous sclerosis0.57

Clinical

graft versus host disease0.56

Clinical

neoplasm0.55

Clinical

kidney angiomyolipoma0.54

Clinical

neuroendocrine neoplasm0.53

Clinical

Show all associations
atopic eczema0.60
breast cancer0.60
renal cell carcinoma0.60
kidney transplant0.59
liver transplant0.59
tuberous sclerosis0.57
graft versus host disease0.56
neoplasm0.55
kidney angiomyolipoma0.54
neuroendocrine neoplasm0.53

Open Targets ranks 1,462 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 7 total

TEMSIROLIMUSApproval

renal cell carcinoma · mantle cell lymphoma · renal cell carcinoma

TACROLIMUS ANHYDROUSApproval

conjunctivitis · graft versus host disease · graft versus host disease

PIMECROLIMUSApproval

atopic eczema · atopic eczema · Eczematoid dermatitis

EVEROLIMUSApproval

angiomyolipoma · tuberous sclerosis · astrocytoma (excluding glioblastoma)

ZOTAROLIMUSApproval

coronary artery disorder

SIROLIMUSApproval

blue rubber bleb nevus · Venous malformation · Gorham-Stout disease

TACROLIMUSApproval

conjunctivitis · graft versus host disease · graft versus host disease

Tractability

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

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.

Show remaining trials (24)

TERMINATED · via everolimus · NCT01009957

COMPLETED · via Sirolimus · NCT02487485

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

breast cancerModerately supported
0.74
agreement 0.590.90
Clinical87%Literature13%

Open Targets aggregate 0.60 · 2 independent evidence families

atopic eczemaModerately supported
0.74
agreement 0.590.90
Clinical100%Literature0%

Open Targets aggregate 0.60 · 2 independent evidence families

renal cell carcinomaModerately supported
0.73
agreement 0.580.89
Clinical99%Literature1%

Open Targets aggregate 0.60 · 2 independent evidence families

kidney transplantModerately supported
0.73
agreement 0.570.90
Clinical100%

Open Targets aggregate 0.59 · 1 independent evidence family

liver transplantModerately supported
0.72
agreement 0.560.89
Clinical100%

Open Targets aggregate 0.59 · 1 independent evidence family

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. 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 underlying per-type scores are shown above so the calculation can be checked.

What's happening now

60

Recent activity around this target, drawn from one canonical event stream. Every item is reached through 3 drugs that target this protein, so each event is news about that drug rather than about the protein directly.

  1. Industry development2026-07-23
    Autism-Like Traits in Mice Improved After Single Rapamycin Dose

    GEN News · news · via Sirolimus

  2. Trial status changed2026-07-22

    Phase I Study of the Pan-ERBB Inhibitor Neratinib Given in Combination With Everolimus, Palbociclib, or Trametinib in Advanced Cancer Subjects With EGFR Mutation/Amplification, HER2 Mutation/Amplification, or HER3/4 Mutation or KRAS Mutation

    Status changed to Terminated · ClinicalTrials.gov · via everolimus

  3. Regulatory approval2026-06-30

    Approval: EVEROLIMUS (ANDA219464)

    fda · regulatory · fda · via everolimus

  4. Label change2025-05-07

    Label change: TACROLIMUS (ANDA090402)

    fda · regulatory · fda · via Tacrolimus

  5. 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

  6. 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

  7. New publication2023-11-02
    Rapamycin extenuates experimental colitis by modulating the gut microbiota.

    Journal of gastroenterology and hepatology · 2023 · 20 citations · Europe PMC · via Sirolimus

  8. New publication2023-10-25
    Autophagy and autophagy signaling in Epilepsy: possible role of autophagy activator.

    Molecular medicine (Cambridge, Mass.) · 2023 · 39 citations · Europe PMC · via Sirolimus

  9. 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

  10. 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

  11. New publication2023-07-06
    Gut microbiome modulates tacrolimus pharmacokinetics through the transcriptional regulation of ABCB1.

    Microbiome · 2023 · 42 citations · Europe PMC · via Tacrolimus

  12. New publication2023-06-20
    The PI3K-Akt-mTOR and Associated Signaling Pathways as Molecular Drivers of Immune-Mediated Inflammatory Skin Diseases: Update on Therapeutic Strategy Using Natural and Synthetic Compounds.

    Cells · 2023 · 98 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.