FKBP1A

Summary

FKBP1A (FKBP prolyl isomerase 1A, HGNC:3711) is a protein-coding gene on chromosome 20p13, encoding Peptidyl-prolyl cis-trans isomerase FKBP1A (P62942). Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. It is a selective cancer dependency (DepMap: 21.5% of cell lines).

The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. The protein is a cis-trans prolyl isomerase that binds the immunosuppressants FK506 and rapamycin. It interacts with several intracellular signal transduction proteins including type I TGF-beta receptor. It also interacts with multiple intracellular calcium release channels, and coordinates multi-protein complex formation of the tetrameric skeletal muscle ryanodine receptor. In mouse, deletion of this homologous gene causes congenital heart disorder known as noncompaction of left ventricular myocardium. Multiple alternatively spliced variants, encoding the same protein, have been identified. The human genome contains five pseudogenes related to this gene, at least one of which is transcribed.

Source: NCBI Gene 2280 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 15 total — 2 pathogenic
• Druggable target: yes — 7 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 21.5% of screened cell lines
• MANE Select transcript: NM_000801

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3711
Approved symbol	FKBP1A
Name	FKBP prolyl isomerase 1A
Location	20p13
Locus type	gene with protein product
Status	Approved
Aliases	FKBP-12, FKBP12, PKC12, PPIASE, FKBP12C
Ensembl gene	ENSG00000088832
Ensembl biotype	protein_coding
OMIM	186945
Entrez	2280

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 11 protein_coding, 4 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000381715, ENST00000381719, ENST00000381724, ENST00000400137, ENST00000439640, ENST00000460490, ENST00000474657, ENST00000474726, ENST00000612074, ENST00000614856, ENST00000618612, ENST00000677078, ENST00000677335, ENST00000677533, ENST00000677937, ENST00000678136, ENST00000678325, ENST00000678408, ENST00000679195, ENST00000904223, ENST00000915649, ENST00000915650

RefSeq mRNA: 3 — MANE Select: NM_000801 NM_000801, NM_001199786, NM_054014

CCDS: CCDS13014, CCDS74688

Canonical transcript exons

ENST00000400137 — 5 exons

Exon	Start	End
ENSE00001107838	1392834	1392881
ENSE00001561754	1392962	1393054
ENSE00001872186	1368978	1370072
ENSE00003563011	1372076	1372240
ENSE00003602918	1375491	1375603

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 99.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 88.1703 / max 892.9210, expressed in 1818 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
186013	114.2079	1828
186012	84.9824	1818
186011	3.0130	1550
186009	0.1749	71

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	99.36	gold quality
monocyte	CL:0000576	99.19	gold quality
upper lobe of left lung	UBERON:0008952	99.18	gold quality
mononuclear cell	CL:0000842	99.16	gold quality
leukocyte	CL:0000738	99.15	gold quality
right lobe of thyroid gland	UBERON:0001119	99.10	gold quality
omental fat pad	UBERON:0010414	99.10	gold quality
left lobe of thyroid gland	UBERON:0001120	99.09	gold quality
peritoneum	UBERON:0002358	99.08	gold quality
nucleus accumbens	UBERON:0001882	99.04	gold quality
upper lobe of lung	UBERON:0008948	99.01	gold quality
colonic epithelium	UBERON:0000397	98.97	gold quality
rectum	UBERON:0001052	98.92	gold quality
smooth muscle tissue	UBERON:0001135	98.85	gold quality
left uterine tube	UBERON:0001303	98.85	gold quality
metanephros cortex	UBERON:0010533	98.85	gold quality
mucosa of transverse colon	UBERON:0004991	98.84	gold quality
body of uterus	UBERON:0009853	98.84	gold quality
stromal cell of endometrium	CL:0002255	98.82	gold quality
left adrenal gland	UBERON:0001234	98.75	gold quality
right adrenal gland	UBERON:0001233	98.73	gold quality
left adrenal gland cortex	UBERON:0035825	98.73	gold quality
right adrenal gland cortex	UBERON:0035827	98.69	gold quality
right ovary	UBERON:0002118	98.68	gold quality
granulocyte	CL:0000094	98.64	gold quality
cortical plate	UBERON:0005343	98.64	gold quality
islet of Langerhans	UBERON:0000006	98.57	gold quality
left coronary artery	UBERON:0001626	98.57	gold quality
lower esophagus mucosa	UBERON:0035834	98.53	gold quality
transverse colon	UBERON:0001157	98.52	gold quality

Single-cell (SCXA)

Detected in 34 experiment(s), a significant marker in 23.

Experiment	Marker?	Max mean expression
E-HCAD-11	yes	2190.10
E-MTAB-8410	yes	2167.86
E-MTAB-6701	yes	2163.65
E-HCAD-15	yes	1945.42
E-MTAB-8322	yes	1832.76
E-MTAB-9906	yes	1733.32
E-GEOD-135922	yes	1387.66
E-GEOD-125970	yes	1297.70
E-MTAB-8271	yes	1257.02
E-MTAB-10553	yes	1179.82
E-HCAD-4	yes	72.02
E-HCAD-1	yes	60.07
E-GEOD-134144	yes	50.43
E-HCAD-10	yes	45.77
E-CURD-122	yes	45.74

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI1, SP3, STAT5A

miRNA regulators (miRDB)

168 targeting FKBP1A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-8485	100.00	77.57	4731
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-570-3P	99.96	72.41	4910

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 21.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• It is likely that in FKBP12-ligand complexes, tryptophan 59 provides added binding energy at the active site at the expense of protein stability, a characteristic common to other proteins. (PMID:12600203)
• folding and kinetics of human FKBP12 (PMID:12850152)
• the central binding site for the 12 kDa FK506-binding protein of type-3 ryanodine receptor, encompassing the critical valine proline motif, plays a crucial role in the modulation of the Ca2+ release properties (PMID:14970260)
• experimental data on the stability of FKBP12 are reported for the effects of three environmental variables: pH, salt, and macromolecular crowding (PMID:15992823)
• The spinal horn neurons stained with anti-FKBP 12 antibody was significantly decreased in the motor neuron disease cases compared to that in controls. (PMID:16036432)
• FKBP12 accelerated the aggregation of alpha-synuclein in vitro. (PMID:16410343)
• These findings indicate a new inhibitory function of FKBP12 as an adaptor molecule for the Smad7-Smurf1 complex to regulate the duration of the activin signal through activin type I receptors. (PMID:16720724)
• characterization of the stability, binding and enzymatic properties of three FK506 binding proteins (FKBP-12) differing only by the length and sequence of their N-terminus (PMID:16908189)
• Data show that insertion of a chaperone domain from E. coli SlyD converts human FKBP12 into a powerful catalyst of protein folding. (PMID:17397867)
• FKBP12.0-RyR2 interaction can regulate the gain of excitation-contraction coupling in cardiomyocytes (PMID:17872463)
• FKBP12 is predominantly present during early neointima formation, while mature neointimal atheromas show a relatively low expression without confinement to luminal areas. (PMID:17962721)
• fndings suggest that the peptidyl-prolyl isomerase activity requires only the hydrophobic cavity that captures the Pro-containing peptide (PMID:18029417)
• We investigated in detail the effect of FKBP12 on early aggregation and on fibril formation of wild-type, A53T and A30P alpha-SYN. FKBP12 has a much smaller effect on the fibril formation of these two clinical mutants of alpha-SYN. (PMID:18346205)
• CCI-779 inhibits mTOR signaling through an FKBP12-independent mechanism that leads to profound translational repression in cancer cells. (PMID:18413763)
• our results suggest that FKBP12 may be involved in neuronal or astrocytic cytoskeletal organization and in the abnormal metabolism of tau protein in Alzheimer’s disease damaged neurons (PMID:19414059)
• FKBP12 is the most important PPIase modulating alpha-SYN aggregation and validate the protein as an interesting drug target for Parkinson disease (PMID:21652707)
• The study provides biochemical evidence of the interaction between FKBP12 and RYR1, RYR3 and IP3R. (PMID:22100703)
• Results suggest that FKBP12 forms an endogenous inhibitor of EGFR phosphorylation directly involved in control of cellular EGFR activity (as in carcinoma). (PMID:22103444)
• These data corroborate other studies suggesting that mutations in FKBP12 and FKBP12.6 genes are not commonly related to cardiac diseases. (PMID:22236651)
• N-terminal and central domain elements are closely apposed near the FKBP12 binding site within the RyR1 three-dimensional structure. (PMID:23585572)
• The K44V mutation selectively reduces the line-broadening in the 40’s loop, verifying that at least three distinct conformational transitions underlie the line-broadening processes of FKBP12. (PMID:23688288)
• the association of FKBP12 with OPRM1 attenuates the phosphorylation of the receptor and triggers the recruitment and activation of PKCepsilon. (PMID:24113748)
• the structural basis of the slow resonance doubling transition of FKBP12 and the more rapid conformational linebroadening transition in the 80’s loop to gain insight into how these effects are propagated through the protein structure (PMID:24405377)
• FKBP12 regulates the localization and processing of amyloid precursor protein in human cell lines. (PMID:24499793)
• FKBP12 inhibits RyR1 and FKBP12 E31Q/D32N/W59F mutant activates RyR1 in vitro. (PMID:24559985)
• Enhanced plasticity in the active site of FKBP12.6 is likely to contribute to marked attenuation in the spatial extent of the residues that exhibit doubling of their amide resonances compared with those of the homologous FKBP12. (PMID:24598733)
• peptidyl prolyl cis-trans isomerase activity of FKBP12 probably plays a role in inhibition of receptor phosphorylation. (PMID:24607931)
• Selectivity within the FKBP family, in particular selective inhibition of FKBP12 or FKBP51, is possible. FKBP51 is a pharmacologically tractable target for stress-related disorders. (PMID:25615537)
• Ultra-fast Shape Recognition with Atom Types–the discovery of novel bioactive small molecular scaffolds for FKBP12 and 11betaHSD1. (PMID:25659145)
• RyRs have been identified as important targets of FKBP12 and FKBP12.6, members of the immunophilin family (PMID:26009182)
• How phosphorylation of RyR affects channel activity and whether proteins such as the FK-506 binding proteins (FKBP12 and FKBP12.6) are involved in heart failure (PMID:26009186)
• Findings indicate that mutant huntingtin (mHTT) aggregates can be transformed into benign species by isomerase FKBP12. (PMID:26450664)
• FKBP12 binding is required for full Met activation and everolimus can inhibit Met (PMID:27223077)
• Electrostatic effects on the folding stability of FKBP12 (PMID:27381026)
• Specifically tested on two model systems, the power of iSPOT is demonstrated to accurately predict the structures of a large protein-protein complex (TGFbeta-FKBP12) and a multidomain nuclear receptor homodimer (HNF-4alpha), based on the structures of individual components of the complexes. (PMID:27496803)
• These results identify a novel function for FKBP12 in downregulating MDM2, which directly enhances sensitivity of cancer cells to chemotherapy and nutlin-3 treatment. (PMID:27617579)
• Data show that FKBP12 (FK506 binding protein 1A)conformational transition Is coupled to histidine tautomerization. (PMID:27936610)
• ubiquitylation destabilizes the fold of two proteins, FKBP12 and FABP4 (PMID:27991582)
• These findings of this study suggested that FKBP12 is linked to the accumulation of alpha-SYN and phosphorylated tau protein in alpha-synucleinopathies. FKBP12 may play important roles in the pathogenesis of alpha-synucleinopathies. (PMID:29246765)
• this study examined the effect of the suppressor FKBP12 on the signal transduction of a further 14 ALK2 mutations associated with fibrodysplasia ossificans progressiva or diffuse intrinsic pontine glioma. (PMID:29551750)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fkbp1a	ENSMUSG00000032966
rattus_norvegicus	Fkbp1a	ENSRNOG00000008822
drosophila_melanogaster	Fkbp12	FBGN0013954
caenorhabditis_elegans		WBGENE00001429
caenorhabditis_elegans	fkb-5	WBGENE00001430

Paralogs (18): FKBP4 (ENSG00000004478), FKBP6 (ENSG00000077800), FKBP7 (ENSG00000079150), FKBP5 (ENSG00000096060), FKBP3 (ENSG00000100442), FKBP8 (ENSG00000105701), FKBP14 (ENSG00000106080), FKBP15 (ENSG00000119321), FKBP1B (ENSG00000119782), FKBP9 (ENSG00000122642), TTC9 (ENSG00000133985), FKBP11 (ENSG00000134285), FKBP10 (ENSG00000141756), TTC9C (ENSG00000162222), FKBP2 (ENSG00000173486), TTC9B (ENSG00000174521), FKBP1C (ENSG00000198225), FKBPL (ENSG00000204315)

Protein

Protein identifiers

Peptidyl-prolyl cis-trans isomerase FKBP1A — P62942 (reviewed: P62942)

Alternative names: 12 kDa FK506-binding protein, Calstabin-1, FK506-binding protein 1A, Immunophilin FKBP12, Rotamase

All UniProt accessions (8): P62942, A0A087WTS4, A0A087WZM5, A0A7I2V3S6, F6T7Q3, Q1JUQ3, Q1JUQ5, Q5W0X3

UniProt curated annotations — full annotation on 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.

Subunit / interactions. Interacts with TGFBR1; prevents TGFBR1 phosphorylation by TGFBR2 and stabilizes it in the inactive conformation. Interacts with ACVR1B and SMAD7. Identified in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1). Interacts directly with RYR2 and RYR3. Interacts with GLMN; rapamycin and FK506 abolish the interaction with GLMN in a dose dependent manner. Interacts directly with RYR1.

Subcellular location. Cytoplasm. Cytosol. Sarcoplasmic reticulum membrane.

Activity regulation. Inhibited by both FK506 and rapamycin.

Similarity. Belongs to the FKBP-type PPIase family. FKBP1 subfamily.

RefSeq proteins (3): NP_000792, NP_001186715, NP_463460 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001179	PPIase_FKBP_dom	Domain
IPR046357	PPIase_dom_sf	Homologous_superfamily
IPR050689	FKBP-type_PPIase	Family

Pfam: PF00254

Enzyme classification (BRENDA):

• EC 5.2.1.8 — peptidylprolyl isomerase (BRENDA: 69 organisms, 374 substrates, 222 inhibitors, 24 Km, 30 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
N-SUCCINYL-ALA-GLU-(TRANS)-PRO-PHE-4-NITROANILID	0.17–0.7	5
N-SUCCINYL-ALA-ALA-(CIS)-PRO-PHE-4-NITROANILIDE	0.104–0.814	2
RNASE T1	0.0004–0.0006	2
SUCCINYL-ALA-ALA-PRO-PHE 4-NITROANILIDE	0.451–1.247	2
SUCCINYL-ALA-LYS-PRO-PHE-4-NITROANILIDE	0.585–0.788	2
ALA-GLY-PSI[CS-N]-PRO-PHE-4-NITROANILIDE	0.53	1
N-SUCCINYL-ALA-LEU-(CIS)-PRO-PHE-4-NITROANILIDE	0.059	1
SUCCINYL-ALA-GLU-PRO-PHE-7-AMIDO-4-METHYLCOUMARI	0.12	1
TRYWNAKMK-(CIS)-PFIFGA	2	1
SUCCINYL-ALA-ALA-(CIS)-PRO-LYS-4-METHYLCOUMARIN-	—	0
SUCCINYL-ALA-ALA-(CIS)-PRO-PHE 4-METHYLCOUMARIN	—	0

Catalyzed reactions (Rhea), 1 shown:

• [protein]-peptidylproline (omega=180) = [protein]-peptidylproline (omega=0) (RHEA:16237)

UniProt features (20 total): strand 7, helix 3, turn 3, modified residue 2, sequence conflict 2, initiator methionine 1, chain 1, domain 1

Structure

Experimental structures (PDB)

112 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
2PPN	X-RAY DIFFRACTION	0.92
2PPP	X-RAY DIFFRACTION	0.94
6YF3	X-RAY DIFFRACTION	1
6YF2	X-RAY DIFFRACTION	1.03
8X6P	X-RAY DIFFRACTION	1.05
6YF1	X-RAY DIFFRACTION	1.12
8CHM	X-RAY DIFFRACTION	1.12
4N19	X-RAY DIFFRACTION	1.2
8PDF	X-RAY DIFFRACTION	1.2
9LYG	X-RAY DIFFRACTION	1.26
2PPO	X-RAY DIFFRACTION	1.29
7U8D	X-RAY DIFFRACTION	1.39
9DTW	X-RAY DIFFRACTION	1.39
8CHL	X-RAY DIFFRACTION	1.4
6I1S	X-RAY DIFFRACTION	1.52
6YF0	X-RAY DIFFRACTION	1.55
8CHK	X-RAY DIFFRACTION	1.55
1BKF	X-RAY DIFFRACTION	1.6
6VCU	X-RAY DIFFRACTION	1.69
8CHJ	X-RAY DIFFRACTION	1.7
1FKB	X-RAY DIFFRACTION	1.7
1FKF	X-RAY DIFFRACTION	1.7
1FKJ	X-RAY DIFFRACTION	1.7
2DG3	X-RAY DIFFRACTION	1.7
2DG4	X-RAY DIFFRACTION	1.7
2DG9	X-RAY DIFFRACTION	1.7
4IPX	X-RAY DIFFRACTION	1.7
8CHI	X-RAY DIFFRACTION	1.7
1FKD	X-RAY DIFFRACTION	1.72
2FKE	X-RAY DIFFRACTION	1.72

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62942-F1	96.30	0.99

Functional residue map

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

Post-translational modifications (2): 53, 53

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-166208	mTORC1-mediated signalling
R-HSA-2025928	Calcineurin activates NFAT
R-HSA-2173789	TGF-beta receptor signaling activates SMADs
R-HSA-2173791	TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)
R-HSA-3656535	TGFBR1 LBD Mutants in Cancer
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-9692916	SARS-CoV-1 activates/modulates innate immune responses

MSigDB gene sets: 468 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_MUSCLE_TISSUE_DEVELOPMENT, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_HEART_TRABECULA_MORPHOGENESIS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, KAAB_FAILED_HEART_ATRIUM_DN, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, TTTGTAG_MIR520D, CHUNG_BLISTER_CYTOTOXICITY_DN, AAGCCAT_MIR135A_MIR135B, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP

GO Biological Process (18): heart morphogenesis (GO:0003007), protein folding (GO:0006457), ‘de novo’ protein folding (GO:0006458), regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion (GO:0010881), regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion (GO:0014809), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), regulation of protein localization (GO:0032880), negative regulation of activin receptor signaling pathway (GO:0032926), protein refolding (GO:0042026), T cell activation (GO:0042110), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), regulation of immune response (GO:0050776), protein maturation (GO:0051604), ventricular cardiac muscle tissue morphogenesis (GO:0055010), heart trabecula formation (GO:0060347), supramolecular fiber organization (GO:0097435), regulation of amyloid precursor protein catabolic process (GO:1902991), amyloid fibril formation (GO:1990000)

GO Molecular Function (12): peptidyl-prolyl cis-trans isomerase activity (GO:0003755), transforming growth factor beta receptor binding (GO:0005160), calcium channel regulator activity (GO:0005246), macrolide binding (GO:0005527), FK506 binding (GO:0005528), signaling receptor inhibitor activity (GO:0030547), type I transforming growth factor beta receptor binding (GO:0034713), transmembrane transporter binding (GO:0044325), I-SMAD binding (GO:0070411), activin receptor binding (GO:0070697), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (9): cytoplasm (GO:0005737), cytosol (GO:0005829), terminal cisterna (GO:0014802), membrane (GO:0016020), sarcoplasmic reticulum (GO:0016529), Z disc (GO:0030018), sarcoplasmic reticulum membrane (GO:0033017), cytoplasmic side of membrane (GO:0098562), ryanodine receptor complex (GO:1990425)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Signaling by TGF-beta Receptor Complex	2
MTOR signalling	1
Downstream signaling events of B Cell Receptor (BCR)	1
Loss of Function of TGFBR1 in Cancer	1
SARS-CoV Infections	1
SARS-CoV-1-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein folding	2
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	2
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	2
protein metabolic process	2
binding	2
sarcoplasmic reticulum	2
heart development	1
animal organ morphogenesis	1
cellular process	1
protein maturation	1
regulation of cardiac muscle contraction by calcium ion signaling	1
regulation of skeletal muscle contraction by calcium ion signaling	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
intracellular protein localization	1
regulation of localization	1
activin receptor signaling pathway	1
regulation of activin receptor signaling pathway	1
lymphocyte activation	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
regulation of immune system process	1
immune response	1
regulation of response to stimulus	1
gene expression	1
cardiac ventricle morphogenesis	1
ventricular cardiac muscle tissue development	1
cardiac muscle tissue morphogenesis	1
cardiac chamber morphogenesis	1
trabecula formation	1
heart trabecula morphogenesis	1
cellular component organization	1
amyloid precursor protein catabolic process	1
regulation of protein metabolic process	1
supramolecular fiber organization	1
cis-trans isomerase activity	1
catalytic activity, acting on a protein	1
cytokine receptor binding	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

62 interactions, top by confidence:

A	B	Type	Score
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
MTOR	FKBP1A	psi-mi:“MI:0407”(direct interaction)	0.790
FKBP1A	MTOR	psi-mi:“MI:0915”(physical association)	0.790
MTOR	FKBP1A	psi-mi:“MI:2364”(proximity)	0.790
MTOR	FKBP1A	psi-mi:“MI:0915”(physical association)	0.790
FKBP1A	MTOR	psi-mi:“MI:2364”(proximity)	0.790
RYR1	FKBP1A	psi-mi:“MI:0915”(physical association)	0.700
FKBP1A	RYR1	psi-mi:“MI:0915”(physical association)	0.700
TGFBR1	FKBP1A	psi-mi:“MI:0407”(direct interaction)	0.590
TGFBR1	FKBP1A	psi-mi:“MI:0915”(physical association)	0.590
SMAD7	FKBP1A	psi-mi:“MI:0915”(physical association)	0.580
FKBP1A	SMAD7	psi-mi:“MI:0915”(physical association)	0.580
FKBP1A	AHSP	psi-mi:“MI:0915”(physical association)	0.560
AHSP	FKBP1A	psi-mi:“MI:0915”(physical association)	0.560
APP	FKBP1A	psi-mi:“MI:0915”(physical association)	0.560
FKBP1A	rep	psi-mi:“MI:0915”(physical association)	0.510
rep	FKBP1A	psi-mi:“MI:0915”(physical association)	0.510
FKBP1A	ACVR1B	psi-mi:“MI:0915”(physical association)	0.510
ACVR1B	FKBP1A	psi-mi:“MI:0915”(physical association)	0.510
FKBP1A	RPS9	psi-mi:“MI:0915”(physical association)	0.400
RyR1	FKBP1A	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (170): MTOR (Co-crystal Structure), MID1 (Two-hybrid), SF3B4 (Two-hybrid), AHSP (Two-hybrid), CTBP1 (Co-fractionation), FKBP1A (Co-fractionation), FKBP1A (Co-fractionation), FKBP1A (Co-fractionation), FKBP1A (Co-fractionation), FKBP1A (Co-fractionation), FKBP1A (Co-fractionation), FKBP1A (Co-fractionation), FKBP1A (Co-fractionation), FKBP1A (Co-fractionation), FKBP1A (Co-fractionation)

ESM2 similar proteins: O04287, O42123, O42993, O94746, P0A0W2, P0A0W3, P0C1J3, P0CP94, P0CP95, P0CY37, P18203, P20080, P20081, P26883, P28725, P28870, P48375, P56989, P62942, P62943, P68106, P68107, P97534, Q13526, Q2U316, Q2UPT7, Q38931, Q43207, Q4HZB8, Q4R383, Q4W9R2, Q4WHX4, Q4WLV6, Q554J3, Q5ATN7, Q5BIN5, Q5VVH2, Q62658, Q6BX45, Q6CF41

Diamond homologs: A6QQ71, D3ZQF4, F6PHZ6, O42123, O42993, O46638, O54998, O75344, O94746, P0A0W2, P0A0W3, P0C1J3, P0C1J4, P0C1J5, P0C1J6, P0CP94, P0CP95, P0CP96, P0CP97, P18203, P20080, P20081, P26883, P26884, P26885, P27124, P28870, P30416, P30417, P32472, P44760, P45523, P45878, P48375, P54397, P56989, P57599, P62942, P62943, P65764

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
FKBP1A	“down-regulates activity”	TGFBR1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 47 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
heart development	5	10.1×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	7
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
58943	GRCh38/hg38 20p13(chr20:89939-1770567)x1	Pathogenic
816099	GRCh37/hg19 20p13(chr20:61568-2269777)x1	Pathogenic

SpliceAI

751 predictions. Top by Δscore:

Variant	Effect	Δscore
20:1372107:T:A	donor_gain	1.0000
20:1392829:CTCA:C	donor_loss	1.0000
20:1392830:TCACC:T	donor_loss	1.0000
20:1392831:CACC:C	donor_loss	1.0000
20:1392832:ACCGG:A	donor_loss	1.0000
20:1392954:CTACT:C	donor_loss	1.0000
20:1392957:CTCA:C	donor_loss	1.0000
20:1392958:TCA:T	donor_loss	1.0000
20:1392959:CACCG:C	donor_loss	1.0000
20:1392960:A:C	donor_loss	1.0000
20:1392961:CCGT:C	donor_gain	1.0000
20:1372236:CTCAT:C	acceptor_gain	0.9900
20:1375485:GCATA:G	donor_loss	0.9900
20:1375486:CATA:C	donor_loss	0.9900
20:1375487:ATAC:A	donor_loss	0.9900
20:1375488:TA:T	donor_loss	0.9900
20:1375489:ACCTG:A	donor_loss	0.9900
20:1375490:C:T	donor_loss	0.9900
20:1375490:CCTG:C	donor_loss	0.9900
20:1392827:GACTC:G	donor_loss	0.9900
20:1392828:ACT:A	donor_loss	0.9900
20:1392828:ACTCA:A	donor_loss	0.9900
20:1392832:A:AC	donor_gain	0.9900
20:1392833:C:CC	donor_gain	0.9900
20:1392833:C:CT	donor_gain	0.9900
20:1392953:ACTAC:A	donor_loss	0.9900
20:1392955:TAC:T	donor_loss	0.9900
20:1392956:AC:A	donor_loss	0.9900
20:1392957:C:CG	donor_loss	0.9900
20:1392958:T:TC	donor_loss	0.9900

AlphaMissense

700 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:1372139:G:C	F100L	0.996
20:1372139:G:T	F100L	0.996
20:1372141:A:G	F100L	0.996
20:1375570:G:A	S40F	0.996
20:1375578:A:C	F37L	0.996
20:1375578:A:T	F37L	0.996
20:1375580:A:G	F37L	0.996
20:1372146:A:T	L98H	0.995
20:1375574:A:G	S39P	0.995
20:1372209:A:T	I77K	0.994
20:1375511:A:G	W60R	0.994
20:1375511:A:T	W60R	0.994
20:1375542:A:C	F49L	0.994
20:1375542:A:T	F49L	0.994
20:1375544:A:G	F49L	0.994
20:1392834:C:A	G29W	0.994
20:1372222:C:G	A73P	0.993
20:1375502:C:A	G63W	0.993
20:1375513:C:T	G59D	0.993
20:1375514:C:G	G59R	0.993
20:1372153:C:G	A96P	0.992
20:1372227:T:G	Q71P	0.992
20:1375502:C:G	G63R	0.992
20:1375502:C:T	G63R	0.992
20:1375603:C:T	G29E	0.992
20:1372194:G:T	A82D	0.991
20:1392840:A:G	Y27H	0.991
20:1372140:A:G	F100S	0.990
20:1372180:C:A	G87W	0.990
20:1372146:A:G	L98P	0.989

dbSNP variants (sampled 300 via entrez): RS1000139687 (20:1373916 A>C), RS1000211315 (20:1374282 T>C), RS1000263220 (20:1369701 TAAAATA>T), RS1000279976 (20:1388866 A>G), RS1000291365 (20:1388610 G>A), RS1000306276 (20:1375878 G>A,C), RS1000358406 (20:1375504 T>A), RS1000468790 (20:1382210 A>C), RS1000632733 (20:1381906 T>G), RS1000777030 (20:1394626 A>G), RS1001228797 (20:1394415 A>G,T), RS1001237576 (20:1383556 TCC>T), RS1001283877 (20:1390313 C>T), RS1001312018 (20:1370647 C>T), RS1001348351 (20:1376972 A>G)

Disease associations

OMIM: gene MIM:186945 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008058_144	Estimated glomerular filtration rate	9.000000e-15

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (6): CHEMBL1902 (SINGLE PROTEIN), CHEMBL2221341 (PROTEIN COMPLEX), CHEMBL4106135 (PROTEIN COMPLEX), CHEMBL4296136 (PROTEIN-PROTEIN INTERACTION), CHEMBL4296662 (PROTEIN COMPLEX), CHEMBL6193812 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

7 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 539,039 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL160	CYCLOSPORINE	4	168,247
CHEMBL269732	TACROLIMUS ANHYDROUS	4	95,168
CHEMBL3989887	TACROLIMUS	4	1,981
CHEMBL413	SIROLIMUS	4	172,798
CHEMBL625	THIABENDAZOLE	4	58,476
CHEMBL123292	CYCLOHEXIMIDE	2	39,732
CHEMBL350775	BIRICODAR	2	2,637

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Peptidyl-prolyl cis/trans isomerases

Most potent curated ligand interactions (6 total), top 6:

Ligand	Action	Affinity	Parameter
sirolimus	Inhibition	9.7	pKi
tacrolimus	Inhibition	9.4	pKi
zotarolimus	Binding	8.55	pIC50
pimecrolimus	Inhibition	8.22	pIC50
SLF	Inhibitor	6.94	pIC50
cycloheximide	Inhibition	5.47	pIC50

Binding affinities (BindingDB)

103 measured of 103 human assays (103 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(S)-C16-(1,1-dioxidoisothiazolidin-2-yl)-C32-deoxo-rapamycin	KD	0.35 nM	US-20250223297: NOVEL RAPAMYCIN DERIVATIVES
CHEMBL4090599	KI	0.45 nM
Rapamycin C-7, analog 1	KI	0.6 nM
Rapamycin C-7, analog 4	KI	1 nM
Rapamycin C-7, analog 6a	KI	1 nM
Rapamycin C-7, analog 6b	KI	1 nM
Rapamycin C-7, analog 12	KI	1 nM
Rapamycin C-7, analog 16a	KI	1 nM
Rapamycin C-7, analog 11b	KI	1.5 nM
Rapamycin C-7, analog 10a	KI	3 nM
Rapamycin C-7, analog 5a	KI	3.5 nM
Rapamycin C-7, analog 7b	KI	3.7 nM
Rapamycin C-7, analog 5b	KI	4 nM
(1R,9S,14E,16S,19R,21S,22E,24E,26E,28S,30S,33R)-12-[(2R)-1-[(1S,3R,4R)-3,4-dihydroxycyclohexyl]propan-2-yl]-1,16-dihydroxy-28-methoxy-15,19,21,27,33-pentamethyl-11,34-dioxa-4-azatricyclo[28.3.1.04,9]tetratriaconta-14,22,24,26-tetraene-2,3,10,18-tetrone	KI	4.2 nM	US-9505773: Rapamycin analogues and their pharmaceutical use
Rapamycin C-7, analog 7a	KI	4.5 nM
Rapamycin C-7, analog 14a	KI	5 nM
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24Z,26E,28E,30S,32S,35R)-1,18-dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone	KI	5.4 nM	US-9505773: Rapamycin analogues and their pharmaceutical use
(1R,9S,14E,16S,19R,21S,22E,24E,26E,28S,30S,33R)-1,16-dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-28-methoxy-15,19,21,27,33-pentamethyl-11,34-dioxa-4-azatricyclo[28.3.1.04,9]tetratriaconta-14,22,24,26-tetraene-2,3,10,18-tetrone	KI	5.9 nM	US-9505773: Rapamycin analogues and their pharmaceutical use
Rapamycin C-7, analog 10b	KI	6 nM
(1R,9S,12S,17R,18E,20S,23S,25S,26E,28E,30E,32S,34S,37R)-1,14,20-trihydroxy-12-[(2R)-1-(4-hydroxycyclohexyl)propan-2-yl]-32-methoxy-17,19,23,25,31,37-hexamethyl-11,38-dioxa-4-azatricyclo[32.3.1.04,9]octatriaconta-18,26,28,30-tetraene-2,3,10,16,22-pentone	KI	6.5 nM	US-9505773: Rapamycin analogues and their pharmaceutical use
Rapamycin C-7, analog 9	KI	7 nM
Rapamycin C-7, analog 15a	KI	7 nM
CHEMBL4067970	KI	7 nM
CHEMBL4102121	KI	7 nM
CHEMBL4101268	KI	7 nM
CHEMBL4075704	KI	7 nM
(1R,9S,12S,14E,16S,19S,21S,22E,24E,26E,28S,30S,33R)-1,16,28-trihydroxy-12-[(2R)-1-(4-hydroxycyclohexyl)propan-2-yl]-15,19,21,27,33-pentamethyl-11,34-dioxa-4-azatricyclo[28.3.1.04,9]tetratriaconta-14,22,24,26-tetraene-2,3,10,18-tetrone	KI	7.7 nM	US-9505773: Rapamycin analogues and their pharmaceutical use
(1R,9S,14E,16S,19R,21S,22E,24E,26E,28S,30S,33R)-1,16-dihydroxy-12-[(2R)-1-(4-hydroxycyclohexyl)propan-2-yl]-28-methoxy-15,19,21,27,33-pentamethyl-11,34-dioxa-4-azatricyclo[28.3.1.04,9]tetratriaconta-14,22,24,26-tetraene-2,3,10,18-tetrone	KI	7.9 nM	US-9505773: Rapamycin analogues and their pharmaceutical use
CHEMBL4063858	KI	8.8 nM
Rapamycin C-7, analog 8a	KI	9 nM
(1R,9S,14E,16S,19R,21S,22E,24E,26E,28S,30S,33R)-1,16-dihydroxy-12-[(2R)-1-[5-(hydroxymethyl)thiophen-2-yl]propan-2-yl]-28-methoxy-15,19,21,27,33-pentamethyl-11,34-dioxa-4-azatricyclo[28.3.1.04,9]tetratriaconta-14,22,24,26-tetraene-2,3,10,18-tetrone	KI	9.5 nM	US-9505773: Rapamycin analogues and their pharmaceutical use
(1R,9S,12S,13R,14S,17R,18Z,21S,23S,24R,25S,27R)-1,14-dihydroxy-12-[(E)-1-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]prop-1-en-2-yl]-23,25-dimethoxy-13,19,21,27-tetramethyl-17-prop-2-enyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone	KI	10 nM	US-9505773: Rapamycin analogues and their pharmaceutical use
(14Z,20Z)-15-ethyl-1,16,22,24,26,28-hexahydroxy-17,19,21,27,33-pentamethyl-12-[(E)-4-methyl-5-oxohex-2-en-2-yl]-11,34-dioxa-4-azatricyclo[28.3.1.04,9]tetratriaconta-14,20-diene-2,3,10-trione	KI	10 nM	US-9505773: Rapamycin analogues and their pharmaceutical use
Rapamycin C-7, analog 11a	KI	10 nM
[(E,2S,3R)-1-(4-hydroxycyclohexyl)-2,6-dimethyl-7-oxohept-5-en-3-yl] (2R)-1-[2-[(2S,3S,6R)-2-hydroxy-6-[(2S,3E,5E,7E,9R,11R)-13-hydroxy-2-methoxy-3,9,11-trimethyl-12-oxotrideca-3,5,7-trienyl]-3-methyloxan-2-yl]-2-oxoacetyl]piperidine-2-carboxylate	KI	12 nM	US-9505773: Rapamycin analogues and their pharmaceutical use
1-(Adamantan-1-ylcarbamoyl)-piperidine-2-carboxylic acid 3-(2,4-dimethoxy-phenyl)-propyl ester	KI	12 nM
CHEMBL4068304	KI	12 nM
(1R,9S,14E,16S,19R,21S,22E,24E,26E,28S,30S,33R)-1,16-dihydroxy-28-methoxy-15,19,21,27,33-pentamethyl-12-[(2R)-1-pyridin-4-ylpropan-2-yl]-11,34-dioxa-4-azatricyclo[28.3.1.04,9]tetratriaconta-14,22,24,26-tetraene-2,3,10,18-tetrone	KI	13 nM	US-9505773: Rapamycin analogues and their pharmaceutical use
(1R,9S,12S,15S,16Z,18R,19S,21R,23S,24Z,26Z,28Z,30R,32S,35R)-30-(1,1-dioxo-1,2-thiazolidin-2-yl)-1,18-dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19-methoxy-15,17,21,23,29,35-hexamethyl-20-methylidene-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10-trione	KD	16 nM	US-20250223297: NOVEL RAPAMYCIN DERIVATIVES
(1S,9S,12S,14E,16R,17R,19R,21S,22E,24E,26E,28S,30S,33R)-1,16,17-trihydroxy-12-[(2R)-1-(4-hydroxycyclohexyl)propan-2-yl]-28-methoxy-15,19,21,27,33-pentamethyl-11,34-dioxa-4-azatricyclo[28.3.1.04,9]tetratriaconta-14,22,24,26-tetraene-3,10,18-trione	KI	18 nM	US-9505773: Rapamycin analogues and their pharmaceutical use
CHEMBL4077424	KI	19 nM
CHEMBL4073944	KI	21 nM
Rapamycin C-7, analog 13	KI	29 nM
Rapamycin C-7, analog 17a	KI	30 nM
1-(Adamantan-1-ylcarbamoyl)-piperidine-2-carboxylic acid 3-(3,4-dimethoxy-phenyl)-propyl ester	KI	32 nM
1-(3,4-dichlorophenyl)-2-{4,6-dimethoxy-12-oxo-11,17-diazatetracyclo[11.3.1.0^{2,11}.0^{3,8}]heptadeca-3(8),4,6-trien-17-yl}ethane-1,2-dione	KI	34 nM
1-{4,6-dimethoxy-12-oxo-11,17-diazatetracyclo[11.3.1.0^{2,11}.0^{3,8}]heptadeca-3(8),4,6-trien-17-yl}-2-(3,5-dimethoxyphenyl)ethane-1,2-dione	KI	34 nM
Rapamycin C-7, analog 8b	KI	38 nM
(1S,9S,14E,16S,19R,21S,22E,24E,26E,28S,30S,33R)-1,16-dihydroxy-12-[(2R)-1-(4-hydroxycyclohexyl)propan-2-yl]-28-methoxy-15,19,21,27,33-pentamethyl-11,34-dioxa-4-azatricyclo[28.3.1.04,9]tetratriaconta-14,22,24,26-tetraene-3,10,18-trione	KI	45 nM	US-9505773: Rapamycin analogues and their pharmaceutical use
1-(3-chlorophenyl)-2-{4,6-dimethoxy-12-oxo-11,17-diazatetracyclo[11.3.1.0^{2,11}.0^{3,8}]heptadeca-3(8),4,6-trien-17-yl}ethane-1,2-dione	KI	46 nM

ChEMBL bioactivities

740 potent at pChembl≥5 of 833 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	GPI-1046
10.52	Kd	0.03	nM	CHEMBL5634031
9.89	Kd	0.13	nM	SIROLIMUS
9.70	Kd	0.2	nM	TACROLIMUS ANHYDROUS
9.70	Kd	0.2	nM	SIROLIMUS
9.70	Ki	0.2	nM	SIROLIMUS
9.68	Kd	0.21	nM	CHEMBL5935211
9.57	EC50	0.27	nM	CHEMBL5275279
9.52	Ki	0.3	nM	CHEMBL4449096
9.47	Kd	0.34	nM	CHEMBL6063426
9.40	Ki	0.4	nM	TACROLIMUS ANHYDROUS
9.40	Kd	0.4	nM	TACROLIMUS ANHYDROUS
9.40	IC50	0.4	nM	CHEMBL262778
9.35	IC50	0.45	nM	SIROLIMUS
9.35	Ki	0.45	nM	CHEMBL4090599
9.30	Ki	0.5	nM	CHEMBL151727
9.29	Kd	0.51	nM	CHEMBL5934171
9.22	Ki	0.6	nM	SIROLIMUS
9.22	IC50	0.6	nM	SIROLIMUS
9.22	IC50	0.6	nM	CHEMBL52035
9.19	Kd	0.65	nM	CHEMBL5986579
9.19	Kd	0.65	nM	CHEMBL5853787
9.19	Kd	0.65	nM	CHEMBL5897947
9.19	Kd	0.65	nM	CHEMBL5866833
9.19	Kd	0.65	nM	CHEMBL5984129
9.19	Kd	0.65	nM	CHEMBL5819479
9.19	Kd	0.65	nM	CHEMBL5994752
9.19	Kd	0.65	nM	CHEMBL5877457
9.19	Kd	0.65	nM	CHEMBL5758552
9.19	Kd	0.65	nM	CHEMBL5948930
9.19	Kd	0.65	nM	CHEMBL5838984
9.19	Kd	0.65	nM	CHEMBL5926284
9.19	Kd	0.65	nM	CHEMBL5822423
9.19	Kd	0.65	nM	CHEMBL5835485
9.19	Kd	0.65	nM	CHEMBL5891210
9.19	Kd	0.65	nM	CHEMBL5765262
9.15	Ki	0.7	nM	CHEMBL2052020
9.15	IC50	0.7	nM	CHEMBL303852
9.11	IC50	0.77	nM	CHEMBL71458
9.10	IC50	0.8	nM	CHEMBL68027
9.05	EC50	0.9	nM	TACROLIMUS ANHYDROUS
9.02	Kd	0.95	nM	CHEMBL5782802
9.00	Ki	1	nM	CHEMBL151841
9.00	Ki	1	nM	CHEMBL4276944
9.00	Ki	1	nM	CHEMBL4280369
9.00	Ki	1	nM	CHEMBL4291011
9.00	Ki	1	nM	CHEMBL4287849
9.00	Ki	1	nM	CHEMBL4291053
9.00	Ki	1	nM	CHEMBL33094
9.00	Ki	1	nM	CHEMBL54189

PubChem BioAssay actives

636 with measured affinity, of 1035 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.

Compound	Assay	Type	Value	Unit
(1R,9S,12S,15S,16E,20E,23R,24S,27R)-1-hydroxy-15,23,27-trimethyl-12-[(2R)-1-[(1S,2S,3S,4R)-2,3,4-trihydroxycyclohexyl]propan-2-yl]-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacosa-16,20-diene-2,3,10,22-tetrone	2139767: Binding affinity to human FKBP12 expressed in Escherichia coli BL21 DE3 Gold assessed as dissociation constant incubated for 30 mins by competitive fluorescence polarization assay	kd	<0.0001	uM
3-pyridin-3-ylpropyl (2S)-1-(3,3-dimethyl-2-oxopentanoyl)pyrrolidine-2-carboxylate	69102: Ability to inhibit peptidyl-prolyl isomerase (PPIase, or rotamase) activity of FK506 binding protein 12	ki	<0.0001	uM
Sirolimus	2139767: Binding affinity to human FKBP12 expressed in Escherichia coli BL21 DE3 Gold assessed as dissociation constant incubated for 30 mins by competitive fluorescence polarization assay	kd	0.0001	uM
Tacrolimus	2139767: Binding affinity to human FKBP12 expressed in Escherichia coli BL21 DE3 Gold assessed as dissociation constant incubated for 30 mins by competitive fluorescence polarization assay	kd	0.0002	uM
(1R,9S,12S,15R,16E,18R,19S,21R,23S,24E,26E,28E,30S,32S,35R)-12-[(2S)-1-[(1S,3R,4R)-4-[2-[[1-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethyl]triazol-4-yl]methoxy]ethoxy]-3-methoxycyclohexyl]propan-2-yl]-1,18-dihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone	1849962: PROTAC activity at CRBN/FKBP12 in human Jurkat cells assessed as induction of FKBP12 degradation incubated for 12 hrs by Western blot analysis	ec50	0.0003	uM
(1S,9S,12S,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-12-[(2R)-1-[(1S)-4-[2-[[1-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethyl]triazol-4-yl]methoxy]ethoxy]-3-methoxycyclohexyl]propan-2-yl]-1,18-dihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone	1934637: Induction of degradation of FKBP12 (unknown origin)	ec50	0.0003	uM
(1-phenyl-7-pyridin-3-ylheptan-4-yl) (2S)-1-[2-oxo-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carboxylate	1573005: Inhibition of His6 tagged human FKBP12 expressed in Escherichia coli BL21(DE3) cells using succinylALPF-p-nitroanilide as substrate by fluorescence polarization method	ki	0.0003	uM
(1S,5S,6R)-10-(3,5-dichlorophenyl)sulfonyl-5-(methoxymethyl)-3-(pyridin-2-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-2-one	1479799: Displacement of 5-(3-(4-(((5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-5-vinyl-3,10-diazabicyclo[4.3.1]decan-3-yl)methyl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3,10-dihydroanthracen-9-yl)benzoate from human FKBP12 after 30 mins by fluorescence polarization assay	ki	0.0004	uM
2-[(1R,2R)-4-[(E)-2-[(1R,9S,12S,13R,14S,17R,18E,21S,23S,24R,25S,27R)-17-ethyl-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-2,3,10,16-tetraoxo-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-en-12-yl]prop-1-enyl]-2-methoxycyclohexyl]oxy-N-methyl-N-(2-phenylethyl)acetamide	69106: Inhibitory binding activity against human Immunophilin-FK-506 binding protein 12	ic50	0.0004	uM
(1-phenyl-7-pyridin-3-ylheptan-4-yl) 1-[2-oxo-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carboxylate	69108: Compound was tested for its ability to inhibit FK506 binding protein 12 rotamase activity	ki	0.0005	uM
2-[(1R,2R)-4-[(E)-2-[(1R,9S,12S,13R,14S,17R,18E,21S,23S,24R,25S,27R)-17-ethyl-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-2,3,10,16-tetraoxo-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-en-12-yl]prop-1-enyl]-2-methoxycyclohexyl]oxyacetamide	69106: Inhibitory binding activity against human Immunophilin-FK-506 binding protein 12	ic50	0.0006	uM
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30R,32S,35R)-1,18-dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone	1799443: FKBP12 Assay from Article 10.1016/1074-5521(95)90264-3: “Structure-activity studies of rapamycin analogs: evidence that the C-7 methoxy group is part of the effector domain and positioned at the FKBP12-FRAP interface.”	ki	0.0006	uM
(1R,9S,12S,13R,14S,17R,18Z,20S,21S,23S,24R,25S,27R)-17-ethyl-1,14,20-trihydroxy-12-[(E)-1-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]prop-1-en-2-yl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone	69108: Compound was tested for its ability to inhibit FK506 binding protein 12 rotamase activity	ki	0.0007	uM
(1R,9S,12S,13R,17R,18E,21S,23S,24R,25S,27R)-17-ethyl-1-hydroxy-12-[(E)-1-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]prop-1-en-2-yl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone	69107: The compound was tested for binding affinity against human FK506 binding protein 12	ic50	0.0008	uM
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,32S,35R)-1,18-dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19-methoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone	1412034: Inhibition of recombinant human FKBP12 expressed in Escherichia coli using succinyl-Ala-Phe-Pro-Phe-4-nitroanilide as substrate measured after 5 to 10 mins by spectrophotometric method	ki	0.0010	uM
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30R,32S,35R)-1,18-dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19-methoxy-15,17,21,23,29,35-hexamethyl-30-methylsulfanyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone	1412034: Inhibition of recombinant human FKBP12 expressed in Escherichia coli using succinyl-Ala-Phe-Pro-Phe-4-nitroanilide as substrate measured after 5 to 10 mins by spectrophotometric method	ki	0.0010	uM
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-30-[(4-chlorophenyl)methoxy]-1,18-dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19-methoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone	1412034: Inhibition of recombinant human FKBP12 expressed in Escherichia coli using succinyl-Ala-Phe-Pro-Phe-4-nitroanilide as substrate measured after 5 to 10 mins by spectrophotometric method	ki	0.0010	uM
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30R,32S,35R)-30-[(4-chlorophenyl)methoxy]-1,18-dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19-methoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone	1799443: FKBP12 Assay from Article 10.1016/1074-5521(95)90264-3: “Structure-activity studies of rapamycin analogs: evidence that the C-7 methoxy group is part of the effector domain and positioned at the FKBP12-FRAP interface.”	ki	0.0010	uM
(2S)-1-(3,3-dimethyl-2-oxopentanoyl)-N-(3-phenylpropyl)pyrrolidine-2-carboxamide	69102: Ability to inhibit peptidyl-prolyl isomerase (PPIase, or rotamase) activity of FK506 binding protein 12	ki	0.0010	uM
1,7-diphenylheptan-4-yl 1-[2-oxo-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carboxylate	69108: Compound was tested for its ability to inhibit FK506 binding protein 12 rotamase activity	ki	0.0010	uM
(1-phenyl-7-pyridin-2-ylheptan-4-yl) 1-[2-oxo-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carboxylate	69108: Compound was tested for its ability to inhibit FK506 binding protein 12 rotamase activity	ki	0.0010	uM
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19-methoxy-15,17,21,23,29,35-hexamethyl-30-methylsulfanyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone	1412034: Inhibition of recombinant human FKBP12 expressed in Escherichia coli using succinyl-Ala-Phe-Pro-Phe-4-nitroanilide as substrate measured after 5 to 10 mins by spectrophotometric method	ki	0.0010	uM
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30R,32S,35R)-1,18-dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19-methoxy-15,17,21,23,29,35-hexamethyl-30-(1H-pyrrol-2-yl)-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone	1412034: Inhibition of recombinant human FKBP12 expressed in Escherichia coli using succinyl-Ala-Phe-Pro-Phe-4-nitroanilide as substrate measured after 5 to 10 mins by spectrophotometric method	ki	0.0015	uM
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19-methoxy-15,17,21,23,29,35-hexamethyl-30-(1H-pyrrol-2-yl)-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone	1799443: FKBP12 Assay from Article 10.1016/1074-5521(95)90264-3: “Structure-activity studies of rapamycin analogs: evidence that the C-7 methoxy group is part of the effector domain and positioned at the FKBP12-FRAP interface.”	ki	0.0015	uM
2-[3-[3-(3,4-dimethoxyphenyl)-1-[(2S)-1-[(2S)-2-(3,4,5-trimethoxyphenyl)pent-4-enoyl]piperidine-2-carbonyl]oxypropyl]phenoxy]acetic acid	141354: Binding affinity for Mutant F36V-FK506 binding protein by competitive assay based on fluorescence polarization.	ic50	0.0015	uM
(1R,9S,12S,13R,14S,17R,18E,21S,23S,24R,25S,27R)-17-ethyl-1,14-dihydroxy-12-[(E)-1-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]prop-1-en-2-yl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone	69103: Effective concentration determined was towards FK506 binding protein 12 by competitive binding assay using [3H]-dihydro FK-506 as radioligand	ec50	0.0016	uM
2-[3-[(1R)-3-(3,4-dimethoxyphenyl)-1-[(2S)-1-[(2S)-2-(3,4,5-trimethoxyphenyl)butanoyl]piperidine-2-carbonyl]oxypropyl]phenoxy]acetic acid	141354: Binding affinity for Mutant F36V-FK506 binding protein by competitive assay based on fluorescence polarization.	ic50	0.0018	uM
N-cyclohexyl-2-[(1R,2R)-4-[(E)-2-[(1R,9S,12S,13R,14S,17R,18E,21S,23S,24R,25S,27R)-17-ethyl-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-2,3,10,16-tetraoxo-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-en-12-yl]prop-1-enyl]-2-methoxycyclohexyl]oxyacetamide	69106: Inhibitory binding activity against human Immunophilin-FK-506 binding protein 12	ic50	0.0020	uM
3-phenylpropyl 1-(3,3-dimethyl-2-oxobutanoyl)piperidine-2-carboxylate	69108: Compound was tested for its ability to inhibit FK506 binding protein 12 rotamase activity	ki	0.0020	uM
phenyl N-[(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19-methoxy-15,17,21,23,29,35-hexamethyl-2,3,10,14,20-pentaoxo-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraen-30-yl]-N-hydroxycarbamate	69128: The compound was tested for binding affinity to FK506 binding protein 12 using Rapamycin as control, with an ascomycin conjugate of alkaline phosphatase in a competition binding assay	ic50	0.0021	uM
2-[(1R,2R)-4-[(E)-2-[(1R,9S,12S,13R,14S,17R,18E,21S,23S,24R,25S,27R)-17-ethyl-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-2,3,10,16-tetraoxo-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-en-12-yl]prop-1-enyl]-2-methoxycyclohexyl]oxy-N-pyridin-2-ylacetamide	69106: Inhibitory binding activity against human Immunophilin-FK-506 binding protein 12	ic50	0.0024	uM
2-[(1R,2R)-4-[(E)-2-[(1R,9S,12S,13R,14S,17R,18E,21S,23S,24R,25S,27R)-17-ethyl-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-2,3,10,16-tetraoxo-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-en-12-yl]prop-1-enyl]-2-methoxycyclohexyl]oxy-N-methyl-N-phenylacetamide	69106: Inhibitory binding activity against human Immunophilin-FK-506 binding protein 12	ic50	0.0029	uM
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30R,32S,35R)-30-(furan-2-yl)-1,18-dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19-methoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone	1799443: FKBP12 Assay from Article 10.1016/1074-5521(95)90264-3: “Structure-activity studies of rapamycin analogs: evidence that the C-7 methoxy group is part of the effector domain and positioned at the FKBP12-FRAP interface.”	ki	0.0030	uM
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-30-(furan-2-yl)-1,18-dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19-methoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone	1412034: Inhibition of recombinant human FKBP12 expressed in Escherichia coli using succinyl-Ala-Phe-Pro-Phe-4-nitroanilide as substrate measured after 5 to 10 mins by spectrophotometric method	ki	0.0030	uM
(6-phenyl-1-pyridin-3-ylhexan-3-yl) 1-[2-oxo-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carboxylate	69108: Compound was tested for its ability to inhibit FK506 binding protein 12 rotamase activity	ki	0.0030	uM
3-pyridin-3-ylpropyl 1-(3,3-dimethyl-2-oxobutanoyl)pyrrolidine-2-carboxylate	69108: Compound was tested for its ability to inhibit FK506 binding protein 12 rotamase activity	ki	0.0030	uM
[(1R)-3-(3,4-dimethoxyphenyl)-1-[3-(2-morpholin-4-ylethoxy)phenyl]propyl] (2S)-1-[(2-oxo-3H-1,3-benzothiazol-6-yl)sulfonyl]piperidine-2-carboxylate	672585: Binding affinity to FKBP12 by competitive fluorescence polarization assay	ic50	0.0030	uM
1,7-diphenylheptan-4-yl 1-(2-oxo-2-phenylacetyl)piperidine-2-carboxylate	69108: Compound was tested for its ability to inhibit FK506 binding protein 12 rotamase activity	ki	0.0030	uM
2-[(1R,2R)-4-[(E)-2-[(1R,9S,12S,13R,14S,17R,18E,21S,23S,24R,25S,27R)-17-ethyl-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-2,3,10,16-tetraoxo-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-en-12-yl]prop-1-enyl]-2-methoxycyclohexyl]oxy-N-pyridin-4-ylacetamide	69106: Inhibitory binding activity against human Immunophilin-FK-506 binding protein 12	ic50	0.0032	uM
2-[(1R,2R)-4-[(E)-2-[(1R,9S,12S,13R,14S,17R,18E,21S,23S,24R,25S,27R)-17-ethyl-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-2,3,10,16-tetraoxo-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-en-12-yl]prop-1-enyl]-2-methoxycyclohexyl]oxy-N-pyridin-3-ylacetamide	69106: Inhibitory binding activity against human Immunophilin-FK-506 binding protein 12	ic50	0.0033	uM
methyl (4S,6R)-6-[(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-2,3,10,14,20-pentaoxo-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraen-12-yl]-4-(2-hydroxyethyl)heptanoate	69125: Compound was tested in vitro for its ability to compete with immobilized FK506 for binding to biotinylated FK506 binding protein 12 in a competitive binding assay	ic50	0.0034	uM
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30R,32S,35R)-30-ethoxy-1,18-dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19-methoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone	1799443: FKBP12 Assay from Article 10.1016/1074-5521(95)90264-3: “Structure-activity studies of rapamycin analogs: evidence that the C-7 methoxy group is part of the effector domain and positioned at the FKBP12-FRAP interface.”	ki	0.0035	uM
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-30-ethoxy-1,18-dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19-methoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone	1412034: Inhibition of recombinant human FKBP12 expressed in Escherichia coli using succinyl-Ala-Phe-Pro-Phe-4-nitroanilide as substrate measured after 5 to 10 mins by spectrophotometric method	ki	0.0035	uM
methyl N-[(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30R,32S,35R)-1,18-dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19-methoxy-15,17,21,23,29,35-hexamethyl-2,3,10,14,20-pentaoxo-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraen-30-yl]carbamate	1412034: Inhibition of recombinant human FKBP12 expressed in Escherichia coli using succinyl-Ala-Phe-Pro-Phe-4-nitroanilide as substrate measured after 5 to 10 mins by spectrophotometric method	ki	0.0037	uM
methyl N-[(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19-methoxy-15,17,21,23,29,35-hexamethyl-2,3,10,14,20-pentaoxo-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraen-30-yl]carbamate	1799443: FKBP12 Assay from Article 10.1016/1074-5521(95)90264-3: “Structure-activity studies of rapamycin analogs: evidence that the C-7 methoxy group is part of the effector domain and positioned at the FKBP12-FRAP interface.”	ki	0.0037	uM
2-[3-[3-(3,4-dimethoxyphenyl)-1-[(2S)-1-[(2S)-2-(3,4,5-trimethoxyphenyl)pentanoyl]piperidine-2-carbonyl]oxypropyl]phenoxy]acetic acid	141354: Binding affinity for Mutant F36V-FK506 binding protein by competitive assay based on fluorescence polarization.	ic50	0.0038	uM
(1R,9S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30R,32S,35R)-1,18-dihydroxy-12-[(2R)-1-[(1S,2R,4R,5R)-5-hydroxy-2-bicyclo[2.2.1]heptanyl]propan-2-yl]-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone	1916673: Binding affinity to FKBP12 (unknown origin) assessed as inhibition constant	ki	0.0039	uM
2-[(1R,2R)-4-[(E)-2-[(1R,9S,12S,13R,14S,17R,18E,21S,23S,24R,25S,27R)-17-ethyl-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-2,3,10,16-tetraoxo-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-en-12-yl]prop-1-enyl]-2-methoxycyclohexyl]oxyacetic acid	69106: Inhibitory binding activity against human Immunophilin-FK-506 binding protein 12	ic50	0.0040	uM
(1R,9S,14E,16S,19R,21S,22E,24E,26E,28R,30S,33R)-12-[(2R)-1-[(1S,3R,4R)-3,4-dihydroxycyclohexyl]propan-2-yl]-1,16-dihydroxy-28-methoxy-15,19,21,27,33-pentamethyl-11,34-dioxa-4-azatricyclo[28.3.1.04,9]tetratriaconta-14,22,24,26-tetraene-2,3,10,18-tetrone	1916673: Binding affinity to FKBP12 (unknown origin) assessed as inhibition constant	ki	0.0042	uM
2-[3-[1-[(2S)-1-[(2S)-3-cyclopropyl-2-(3,4,5-trimethoxyphenyl)propanoyl]piperidine-2-carbonyl]oxy-3-(3,4-dimethoxyphenyl)propyl]phenoxy]acetic acid	141354: Binding affinity for Mutant F36V-FK506 binding protein by competitive assay based on fluorescence polarization.	ic50	0.0044	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	6
bisphenol A	affects expression, decreases expression, increases expression, affects cotreatment	4
Sirolimus	affects binding, increases activity, decreases reaction	3
arsenite	affects binding, increases reaction, increases methylation	2
sodium arsenite	decreases expression, increases expression	2
tetrachlorodian	decreases reaction, increases expression	2
chloropicrin	decreases expression	2
bisphenol AF	increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Doxorubicin	decreases expression, affects response to substance	2
Nickel	increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tacrolimus	decreases ubiquitination, decreases activity, increases reaction, affects binding, decreases reaction	2
Cadmium Chloride	increases abundance, increases expression	2
moringin	decreases expression, increases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
ochratoxin A	increases acetylation, increases expression	1
bleomycetin	increases expression	1
aflatoxin B2	decreases methylation	1
nickel sulfate	decreases expression	1
K 7174	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
zotarolimus	affects binding	1
ICG 001	decreases expression	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
abrine	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1

ChEMBL screening assays

171 unique, capped per target: 161 binding, 9 admet, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1046170	Binding	Binding affinity to FKBP-12	Structure-based design of novel human Pin1 inhibitors (I). — Bioorg Med Chem Lett
CHEMBL4363887	ADMET	Inhibition of FKBP12-mediated calcineurin activation in PMA/ionomycin stimulated human Jurkat cells transfected with NFAT-Luc assessed as NFAT reporter activity up to 10 uM pretreated for 30 mins prior to PMA/ionomycin activation measured a	One-step Heck Reaction Generates Nonimmunosuppressive FK506 Analogs for Pharmacological BMP Activation. — ACS Med Chem Lett
CHEMBL678147	Functional	Inhibitory selectivity for human FK506 binding protein 12 and human mixed lymphocyte response(MLR)	32-Ascomycinyloxyacetic acid derived immunosuppressants. Independence of immunophilin binding and immunosuppressive potency. — J Med Chem

Cellosaurus cell lines

16 cell lines: 12 cancer cell line, 2 telomerase immortalized cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C6VW	MSOD	Telomerase immortalized cell line	Female
CVCL_C6VX	MSOD-B	Telomerase immortalized cell line	Female
CVCL_D4XU	U2OS SP1 CL1	Cancer cell line	Female
CVCL_D4XV	U2OS SP1 CL2	Cancer cell line	Female
CVCL_D4XW	U2OS SP1 CL3	Cancer cell line	Female
CVCL_D4XX	U2OS SP2 CL1	Cancer cell line	Female
CVCL_D4XY	U2OS SP2 CL2	Cancer cell line	Female
CVCL_D4XZ	U2OS SP2 CL3	Cancer cell line	Female
CVCL_D4Y0	U2OS SP2 CL4	Cancer cell line	Female
CVCL_D4Y1	U2OS SP2 CL5	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.