FKBP4

Summary

FKBP4 (FKBP prolyl isomerase 4, HGNC:3720) is a protein-coding gene on chromosome 12p13.33, encoding Peptidyl-prolyl cis-trans isomerase FKBP4 (Q02790). Immunophilin protein with PPIase and co-chaperone activities.

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. This encoded protein is a cis-trans prolyl isomerase that binds to the immunosuppressants FK506 and rapamycin. It has high structural and functional similarity to FK506-binding protein 1A (FKBP1A), but unlike FKBP1A, this protein does not have immunosuppressant activity when complexed with FK506. It interacts with interferon regulatory factor-4 and plays an important role in immunoregulatory gene expression in B and T lymphocytes. This encoded protein is known to associate with phytanoyl-CoA alpha-hydroxylase. It can also associate with two heat shock proteins (hsp90 and hsp70) and thus may play a role in the intracellular trafficking of hetero-oligomeric forms of the steroid hormone receptors. This protein correlates strongly with adeno-associated virus type 2 vectors (AAV) resulting in a significant increase in AAV-mediated transgene expression in human cell lines. Thus this encoded protein is thought to have important implications for the optimal use of AAV vectors in human gene therapy. The human genome contains several non-transcribed pseudogenes similar to this gene.

Source: NCBI Gene 2288 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Moderate, GenCC)
• GWAS associations: 10
• Clinical variants (ClinVar): 62 total
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002014

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3720
Approved symbol	FKBP4
Name	FKBP prolyl isomerase 4
Location	12p13.33
Locus type	gene with protein product
Status	Approved
Aliases	FKBP59, FKBP52
Ensembl gene	ENSG00000004478
Ensembl biotype	protein_coding
OMIM	600611
Entrez	2288

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 16 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000001008, ENST00000538622, ENST00000539181, ENST00000540260, ENST00000543037, ENST00000543769, ENST00000544366, ENST00000630279, ENST00000904913, ENST00000904914, ENST00000904915, ENST00000928151, ENST00000928152, ENST00000958550, ENST00000958553, ENST00000958555, ENST00000958556, ENST00000958557, ENST00000958558

RefSeq mRNA: 1 — MANE Select: NM_002014 NM_002014

CCDS: CCDS8512

Canonical transcript exons

ENST00000001008 — 10 exons

Exon	Start	End
ENSE00000713109	2798706	2798826
ENSE00000713111	2799088	2799244
ENSE00000713118	2800392	2800577
ENSE00000713120	2801117	2801356
ENSE00000802791	2794970	2795244
ENSE00000802792	2803151	2805423
ENSE00003463512	2800039	2800122
ENSE00003604211	2799850	2799940
ENSE00003687749	2797138	2797282
ENSE00003784122	2797729	2797871

Expression profiles

Bgee: expression breadth ubiquitous, 302 present calls, max score 98.04.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 69.9544 / max 789.6549, expressed in 1820 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123444	68.0758	1820
123443	0.9058	546
123445	0.3930	183
123448	0.2318	46
123447	0.1947	75
123446	0.1162	44
123450	0.0372	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	98.04	gold quality
cerebellar hemisphere	UBERON:0002245	98.02	gold quality
cerebellar cortex	UBERON:0002129	98.00	gold quality
cerebellum	UBERON:0002037	97.73	gold quality
lower esophagus mucosa	UBERON:0035834	97.43	gold quality
ventricular zone	UBERON:0003053	97.22	gold quality
mucosa of transverse colon	UBERON:0004991	96.92	gold quality
islet of Langerhans	UBERON:0000006	96.52	gold quality
endometrium epithelium	UBERON:0004811	96.52	gold quality
ganglionic eminence	UBERON:0004023	96.37	gold quality
cortical plate	UBERON:0005343	96.27	gold quality
esophagus mucosa	UBERON:0002469	96.24	gold quality
right frontal lobe	UBERON:0002810	96.15	gold quality
body of pancreas	UBERON:0001150	95.96	gold quality
left testis	UBERON:0004533	95.92	gold quality
right testis	UBERON:0004534	95.91	gold quality
olfactory bulb	UBERON:0002264	95.81	gold quality
Brodmann (1909) area 10	UBERON:0013541	95.78	gold quality
cingulate cortex	UBERON:0003027	95.62	gold quality
anterior cingulate cortex	UBERON:0009835	95.58	gold quality
body of stomach	UBERON:0001161	95.53	gold quality
pancreas	UBERON:0001264	95.52	gold quality
hypothalamus	UBERON:0001898	95.45	gold quality
embryo	UBERON:0000922	95.43	gold quality
paraflocculus	UBERON:0005351	95.39	gold quality
skin of abdomen	UBERON:0001416	95.37	gold quality
prefrontal cortex	UBERON:0000451	95.33	gold quality
right lobe of thyroid gland	UBERON:0001119	95.32	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.23	gold quality
adult mammalian kidney	UBERON:0000082	95.21	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-7407	yes	564.34
E-MTAB-9067	yes	21.52
E-MTAB-10042	yes	14.84
E-MTAB-9388	yes	10.95
E-CURD-112	yes	9.23
E-MTAB-7008	no	580.15
E-MTAB-7606	no	319.72
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, HOPX, HOXA10, HSF1, IRF4, MYC

miRNA regulators (miRDB)

96 targeting FKBP4, 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-6127	100.00	66.76	2188
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-6763-5P	99.76	64.68	1767

Literature-anchored findings (GeneRIF, showing 40)

• activation of the Wnt pathway and mutation of the tcf-4 gene in hepatocellular carcinoma (HCC) (PMID:12603528)
• Data show that FK506-binding protein 52(FKBP52) selectively potentiates hormone-dependent reporter gene activation, and this potentiation is readily blocked by co-expression of the closely related FKBP51. (PMID:12606580)
• Promoter constructs with only 143 bp of upstream sequence contain a CAAT motif sequence and consensus binding sites for Sp1, heat-shock factor, and MYC-MAX. The sequence maintained high activity when transfected. (PMID:12782134)
• FKBP52 is a component of the copper efflux machinery, and in so, may also promote neuroprotection from copper toxicity (PMID:15133031)
• Data report the crystal structures of two overlapped fragments of FK506-binding protein 52 and the heterocomplex of glucocorticoid receptors with heat-shock proteins 90. (PMID:15159550)
• FK506-binding proteins 51 and 52 differentially regulate dynein interaction and nuclear translocation of the glucocorticoid receptor (PMID:15591061)
• FKBP52 is an AR folding factor that has critically important physiological roles in some male reproductive tissues (PMID:15831525)
• results suggest that FKBP52 plays an important role in the regulation of TRPV5 and thus in the process of Ca(2+) reabsorption (PMID:16352746)
• FKBP52 is an essential regulator of PR-A action in the uterus. (PMID:16873445)
• FKBP52 may play a role in growth and development of male genitalia, since it is expressed in genital skin of prepubertal boys; however, alterations in the sequence and in expression of the FKBP4 gene are not a common cause of non-syndromic hypospadias. (PMID:17343741)
• phosphorylation of the FK linker appears to be an important regulatory determinant of FKBP52-mediated potentiation of steroid receptor activity (PMID:17717070)
• immunophilin ligands can protect neurons from Ca(2+)-induced cell death by modulating Ca(2+) channels and promote neurite outgrowth via FKBP52 binding (PMID:18162540)
• Data show that the loss of FKBP52 encourages the growth of endometriotic lesions with increased inflammation, cell proliferation, and angiogenesis. (PMID:18988805)
• Increased FKBP4 expression of correlated to HIV(+)major depressive disorder(MDD) but not to HIV without MDD (PMID:19199039)
• knockdown of FKBP4 gene, coding for the immunophilin FKBP52, inhibited cortisol-activated glucocorticoid receptor nuclear translocation (PMID:19545546)
• Resutls show that three of five autoantibodies, FKBP52, PPIA, and PRDX2, showed significantly increased reactivity in primary breast cancer and CIS compared with healthy controls. (PMID:19584157)
• FKBP52 mediates stimulus-dependent TRPC1 gating through isomerization, which is required for chemotropic turning of neuronal growth cones to midline axon guidance of commissural interneurons in the developing spinal cord. (PMID:19945390)
• Data show that FKBP52, which is abundant in brain, binds directly and specifically to Tau, especially in its hyperphosphorylated form. (PMID:20133804)
• RET51/FKBP52 complex is involved in Parkinson disease. (PMID:20442138)
• these results provide evidence that FKBP5 transcriptional dysregulation together with FKBP4 as its functional antagonist are implicated in biological features of major depressive disorder symptoms in human immunodeficiency virus-infected individuals. (PMID:20726698)
• Transgenic overexpression of HSP56 does not result in cardiac hypertrophy nor protect from ischaemia/reperfusion injury. (PMID:20932935)
• Aimed to discover markers of drug resistance in breast cancer before neoadjuvant chemotherapy. Found FKBP4 and S100A9 might be putative prediction markers in discriminating the drug resistant group from the drug sensitive group of breast cancer patients. (PMID:22074005)
• FKBP52 expression level is abnormally low in frontal cortex of Alzheimer’s disease compared to controls. (PMID:22233767)
• involved in the induction of decidualization (PMID:22279148)
• This study does not confirm a role for genetic variants in the SFRS3 and FKBP4 genes in the pathogenesis of corticosteroid-induced ocular hypertension. (PMID:22921020)
• The guinea pig GR-specific mutations within the H1-H3 loop confer global changes within the GR-Hsp90 complex that favor FKBP51 repression over FKBP52 potentiation. (PMID:23686112)
• FKBP4, p23, and Aha1 cooperatively regulate the progression of hAgo2 through the chaperone cycle. (PMID:23741051)
• FKBP52 appears to be an endogenous candidate that directly interacts with the pathogenic Tau-P301L and modulates its function in vitro and in vivo (PMID:24623856)
• Molecular chaperone activity and biological regulatory actions of the TPR-domain immunophilins FKBP51 and FKBP52 (PMID:24694367)
• Despite their substantial structural similarity, in both the beta3 bulge and the beta4-beta5 loop, the FK1 domain of FKBP51 undergoes significantly populated conformational transitions that appear to be suppressed in FKBP52. (PMID:24749623)
• The biological action of NF-kappaB in different cell types could be positively regulated by a high FKBP52/FKBP51 expression ratio. (PMID:25104352)
• identify a novel steroid-responsive FKBP52-dependent pathway suppressing the expression and activity of tryptophan-2,3-dioxygenase (PMID:25132599)
• FKBP51 is the major target accounting for the neuritotrophic effect of neuroimmunophilin ligands. Selectivity against the homolog FKBP52 is essential for optimal neuritotrophic efficacy. (PMID:25615537)
• FKBP4 was not differentially expressed in PTSD patients with low HPA axis reactivity compared to PTSD patients with high HPA axis reactivity. (PMID:25745955)
• The Hsp90-associated FKBP52 cochaperone has become increasingly associated with aberrant steroid hormone receptor signaling in disease. [review] (PMID:25986565)
• FKBP52 seems to be disrupted in preeclampsia and intrauterine growth restriction pregnancies (PMID:26065228)
• FKBP52 and beta-catenin interact directly in vitro. FKBP52 promotes beta-catenin interaction with androgen receptor signaling. (PMID:26207810)
• The capacity FKBP52 to oligomerize Tau is not linked to its peptidyl-prolyl isomerase activity. (PMID:26903089)
• FKBP52 could be abnormally released from NFTs negative neurons in AD brains in correlation with the early pathologic Tau-D(421) neuronal accumulation. (PMID:27479154)
• Results provide a molecular mechanism by which FKBP52 modulates telomerase activity by promoting dynein-dynactin-dependent nuclear import of hTERT. (PMID:27503910)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fkbp4	ENSDARG00000008447
mus_musculus	Fkbp4	ENSMUSG00000030357
rattus_norvegicus	Fkbp4	ENSRNOG00000006444
caenorhabditis_elegans		WBGENE00001429
caenorhabditis_elegans	fkb-5	WBGENE00001430

Paralogs (18): FKBP6 (ENSG00000077800), FKBP7 (ENSG00000079150), FKBP1A (ENSG00000088832), 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 FKBP4 — Q02790 (reviewed: Q02790)

Alternative names: 51 kDa FK506-binding protein, 52 kDa FK506-binding protein, 59 kDa immunophilin, FK506-binding protein 4, FKBP59, HSP-binding immunophilin, Immunophilin FKBP52, Rotamase

All UniProt accessions (5): Q02790, F5H120, F5H1U3, H0YFG2, H0YG86

UniProt curated annotations — full annotation on UniProt →

Function. Immunophilin protein with PPIase and co-chaperone activities. Component of steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). May play a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors between cytoplasm and nuclear compartments. The isomerase activity controls neuronal growth cones via regulation of TRPC1 channel opening. Also acts as a regulator of microtubule dynamics by inhibiting MAPT/TAU ability to promote microtubule assembly. May have a protective role against oxidative stress in mitochondria.

Subunit / interactions. Homodimer. Interacts with GLMN. Associates with HSP90AA1 and HSP70 in steroid hormone receptor complexes. Also interacts with peroxisomal phytanoyl-CoA alpha-hydroxylase (PHYH). Interacts with NR3C1 and dynein. Interacts with HSF1 in the HSP90 complex. Associates with tubulin. Interacts with MAPT/TAU. Interacts (via TPR domain) with S100A1, S100A2 and S100A6; the interaction is Ca(2+) dependent. Interaction with S100A1 and S100A2 (but not with S100A6) leads to inhibition of FKBP4-HSP90 interaction. Interacts with dynein; causes partially NR3C1 transport to the nucleus.

Subcellular location. Cytoplasm. Cytosol. Mitochondrion. Nucleus. Cytoskeleton. Cell projection. Axon.

Tissue specificity. Widely expressed.

Post-translational modifications. Phosphorylation by CK2 results in loss of HSP90 binding activity.

Activity regulation. Inhibited by FK506.

Domain organisation. The PPIase activity is mainly due to the first PPIase FKBP-type domain (1-138 AA). The C-terminal region (AA 375-458) is required to prevent tubulin polymerization. The chaperone activity resides in the C-terminal region, mainly between amino acids 264 and 400. The TPR repeats mediate mitochondrial localization.

RefSeq proteins (1): NP_002005* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001179	PPIase_FKBP_dom	Domain
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR013105	TPR_2	Repeat
IPR019734	TPR_rpt	Repeat
IPR046357	PPIase_dom_sf	Homologous_superfamily
IPR050754	FKBP4/5/8-like	Family

Pfam: PF00254, PF00515, PF07719

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (63 total): strand 17, helix 15, modified residue 9, turn 6, region of interest 3, repeat 3, chain 2, compositionally biased region 2, domain 2, initiator methionine 1, cross-link 1, sequence variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
4LAY	X-RAY DIFFRACTION	1.7
4DRJ	X-RAY DIFFRACTION	1.8
4LAV	X-RAY DIFFRACTION	1.8
1Q1C	X-RAY DIFFRACTION	1.9
4LAX	X-RAY DIFFRACTION	2.01
6RCY	X-RAY DIFFRACTION	2.3
1N1A	X-RAY DIFFRACTION	2.4
4LAW	X-RAY DIFFRACTION	2.4
1P5Q	X-RAY DIFFRACTION	2.8
1QZ2	X-RAY DIFFRACTION	3
4TW8	X-RAY DIFFRACTION	3
8FFV	ELECTRON MICROSCOPY	3.01

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q02790-F1	90.82	0.85

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 (10): 1, 2, 143, 220, 282, 373, 436, 451, 453, 441

Mutagenesis-validated functional residues (1):

Position	Phenotype
67–68	decreased catalytic activity toward trpc1.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-3371497	HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand
R-HSA-3371568	Attenuation phase
R-HSA-8939211	ESR-mediated signaling
R-HSA-9018519	Estrogen-dependent gene expression
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-3371453	Regulation of HSF1-mediated heat shock response
R-HSA-3371511	HSF1 activation
R-HSA-3371571	HSF1-dependent transactivation

MSigDB gene sets: 336 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, ELVIDGE_HYPOXIA_DN, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_CELLULAR_RESPONSE_TO_LIPID, PAL_PRMT5_TARGETS_UP, GOBP_TRANSITION_METAL_ION_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_POLYMERIZATION, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, HSIAO_HOUSEKEEPING_GENES, GOBP_NEUROGENESIS, PID_REG_GR_PATHWAY, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS

GO Biological Process (12): protein folding (GO:0006457), steroid hormone receptor complex assembly (GO:0006463), copper ion transport (GO:0006825), embryo implantation (GO:0007566), negative regulation of neuron projection development (GO:0010977), androgen receptor signaling pathway (GO:0030521), prostate gland development (GO:0030850), negative regulation of microtubule polymerization or depolymerization (GO:0031111), negative regulation of microtubule polymerization (GO:0031115), protein-containing complex localization (GO:0031503), male sex differentiation (GO:0046661), reproductive structure development (GO:0048608)

GO Molecular Function (13): RNA binding (GO:0003723), peptidyl-prolyl cis-trans isomerase activity (GO:0003755), ATP binding (GO:0005524), GTP binding (GO:0005525), FK506 binding (GO:0005528), protein-macromolecule adaptor activity (GO:0030674), heat shock protein binding (GO:0031072), copper-dependent protein binding (GO:0032767), nuclear glucocorticoid receptor binding (GO:0035259), tau protein binding (GO:0048156), phosphoprotein binding (GO:0051219), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (14): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), microtubule (GO:0005874), protein-containing complex (GO:0032991), neuronal cell body (GO:0043025), axonal growth cone (GO:0044295), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), nucleus (GO:0005634), cytoskeleton (GO:0005856), axon (GO:0030424), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Cellular response to heat stress	3
Cellular responses to stress	1
HSF1-dependent transactivation	1
Signaling by Nuclear Receptors	1
ESR-mediated signaling	1
SARS-CoV Infections	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
protein binding	4
cytoplasm	3
multicellular organism development	2
purine ribonucleoside triphosphate binding	2
intracellular membrane-bounded organelle	2
cellular process	1
protein maturation	1
protein-containing complex assembly	1
transition metal ion transport	1
female pregnancy	1
reproductive process	1
regulation of neuron projection development	1
neuron projection development	1
negative regulation of cell projection organization	1
nuclear receptor-mediated steroid hormone signaling pathway	1
urogenital system development	1
reproductive structure development	1
gland development	1
microtubule polymerization or depolymerization	1
regulation of microtubule polymerization or depolymerization	1
negative regulation of cytoskeleton organization	1
negative regulation of microtubule polymerization or depolymerization	1
regulation of microtubule polymerization	1
negative regulation of protein polymerization	1
microtubule polymerization	1
negative regulation of supramolecular fiber organization	1
macromolecule localization	1
sex differentiation	1
developmental process involved in reproduction	1
anatomical structure development	1
reproductive system development	1
nucleic acid binding	1
cis-trans isomerase activity	1
catalytic activity, acting on a protein	1
adenyl ribonucleotide binding	1
guanyl ribonucleotide binding	1
macrolide binding	1
molecular adaptor activity	1
nuclear receptor binding	1

Protein interactions and networks

STRING

2850 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FKBP4	HSP90AA1	P07900	998
FKBP4	HSP90AB1	P08238	998
FKBP4	HSPA4	P34932	996
FKBP4	PHLPP1	O60346	992
FKBP4	NR3C1	P04150	954
FKBP4	DNAJB1	P25685	949
FKBP4	AKT1	P31749	913
FKBP4	PTGES3	Q15185	910
FKBP4	AHSA1	O95433	895
FKBP4	GLMN	Q92990	895
FKBP4	STIP1	P31948	891
FKBP4	PGR	P06401	885
FKBP4	PPID	Q08752	878
FKBP4	HSPA8	P11142	864
FKBP4	CDC37	Q16543	801

IntAct

286 interactions, top by confidence:

A	B	Type	Score
IKBKB	CHUK	psi-mi:“MI:0914”(association)	0.960
PRKAG1	PRKAB2	psi-mi:“MI:0914”(association)	0.940
FKBP4	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.790
HSP90AB1	FKBP4	psi-mi:“MI:0407”(direct interaction)	0.790
FKBP4	HSP90AB1	psi-mi:“MI:0914”(association)	0.790
FKBP4	HSP90AA1	psi-mi:“MI:0914”(association)	0.780
FKBP4	S100a1	psi-mi:“MI:0407”(direct interaction)	0.750
S100a1	FKBP4	psi-mi:“MI:0407”(direct interaction)	0.750
FKBP4	GLMN	psi-mi:“MI:0915”(physical association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
HSP90AA1	CHUK	psi-mi:“MI:0914”(association)	0.670
FKBP4	MAPT	psi-mi:“MI:0407”(direct interaction)	0.630
GABARAP	IPO5	psi-mi:“MI:0914”(association)	0.590
FKBP4	LIMK2	psi-mi:“MI:0407”(direct interaction)	0.590
PHLPP1	USP12	psi-mi:“MI:0914”(association)	0.570
CHEK2	PPM1G	psi-mi:“MI:0914”(association)	0.560
ORF	EIF3F	psi-mi:“MI:0914”(association)	0.560
EGFR	FKBP4	psi-mi:“MI:0915”(physical association)	0.550
FKBP4	EGFR	psi-mi:“MI:0915”(physical association)	0.550
MGME1	WDHD1	psi-mi:“MI:0914”(association)	0.530
GRB2	ARHGEF35	psi-mi:“MI:0914”(association)	0.530
ILK	ILVBL	psi-mi:“MI:0914”(association)	0.530
HSP90AA1	USP19	psi-mi:“MI:0914”(association)	0.530
NPB	CST4	psi-mi:“MI:0914”(association)	0.530
GLMN	MGST3	psi-mi:“MI:0914”(association)	0.530

BioGRID (413): FKBP4 (Affinity Capture-MS), FKBP4 (Reconstituted Complex), HSP90AA1 (Reconstituted Complex), HSPA4 (Reconstituted Complex), MAPT (Affinity Capture-Western), FKBP4 (Affinity Capture-Western), Mapt (Affinity Capture-Western), FKBP4 (Two-hybrid), FKBP4 (Affinity Capture-Western), FKBP4 (Affinity Capture-MS), PLS1 (Co-fractionation), PRKAB1 (Co-fractionation), FKBP4 (Affinity Capture-MS), FKBP4 (Proximity Label-MS), FKBP4 (Affinity Capture-MS)

ESM2 similar proteins: A0A0P0VG31, A0A2H5Q1B8, A4K2V0, A8XHX1, F1RBN2, O14085, O14217, P19878, P27124, P30416, Q02790, Q06AN9, Q07617, Q13217, Q13451, Q15785, Q20683, Q27968, Q32NU8, Q3KRD5, Q3ZBR5, Q5JNB5, Q5RF88, Q5U2X2, Q5ZI13, Q5ZKQ3, Q64378, Q68FQ7, Q6AZT2, Q6ES52, Q6NU95, Q7XJS0, Q7ZU45, Q80ZX8, Q91YW3, Q91Z38, Q95L05, Q99614, Q9CYG7, Q9D706

Diamond homologs: A5IGB8, G0SC91, O04287, O08437, O42123, O42993, O46638, O94746, O95302, P0A0W2, P0A0W3, P0A9L3, P0A9L4, P0C1B0, P0C1J3, P0C1J5, P0C1J6, P0C1J7, P0CP94, P0CP95, P0CP96, P0CP97, P18203, P20081, P26623, P26884, P26885, P27124, P28870, P30416, P31106, P38911, P44760, P45523, P45878, P48375, P51752, P53605, P54397, P56989

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
SRMS	“down-regulates activity”	FKBP4	phosphorylation
PTPN2	down-regulates	FKBP4	dephosphorylation
FKBP4	“up-regulates activity”	AR	binding
CSNK2A1	“down-regulates activity”	FKBP4	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 215 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Assembly and cell surface presentation of NMDA receptors	9	15.5×	4e-06
Activation of AMPK downstream of NMDARs	6	15.5×	2e-04
Aggrephagy	7	11.8×	2e-04
Selective autophagy	6	11.4×	1e-03
Neurexins and neuroligins	8	10.7×	2e-04
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	8	10.5×	2e-04
Activation of NMDA receptors and postsynaptic events	8	10.0×	2e-04
MTOR signalling	5	9.0×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	8	24.1×	7e-07
regulation of postsynaptic membrane neurotransmitter receptor levels	8	20.5×	2e-06
protein localization to synapse	5	19.8×	7e-04
receptor clustering	6	19.4×	2e-04
cellular response to nerve growth factor stimulus	5	12.1×	5e-03
mitotic spindle organization	8	11.3×	2e-04
establishment of protein localization	5	11.2×	6e-03
establishment of cell polarity	5	9.9×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1314 predictions. Top by Δscore:

Variant	Effect	Δscore
12:2795227:G:GT	donor_gain	1.0000
12:2795242:AAGGT:A	donor_loss	1.0000
12:2795243:AGG:A	donor_loss	1.0000
12:2795244:GGT:G	donor_loss	1.0000
12:2795245:GT:G	donor_loss	1.0000
12:2795246:T:G	donor_loss	1.0000
12:2797133:CCCA:C	acceptor_loss	1.0000
12:2797134:CCAG:C	acceptor_loss	1.0000
12:2797135:CA:C	acceptor_loss	1.0000
12:2797136:A:AG	acceptor_gain	1.0000
12:2797136:A:C	acceptor_loss	1.0000
12:2797137:G:GA	acceptor_gain	1.0000
12:2797137:GGTC:G	acceptor_gain	1.0000
12:2797282:GGTA:G	donor_loss	1.0000
12:2797283:GTA:G	donor_loss	1.0000
12:2797284:T:G	donor_loss	1.0000
12:2797727:AGG:A	acceptor_gain	1.0000
12:2797727:AGGG:A	acceptor_gain	1.0000
12:2797728:GGG:G	acceptor_gain	1.0000
12:2797728:GGGG:G	acceptor_gain	1.0000
12:2797728:GGGGA:G	acceptor_gain	1.0000
12:2797870:AGG:A	donor_loss	1.0000
12:2797872:G:C	donor_loss	1.0000
12:2797873:T:G	donor_loss	1.0000
12:2798791:GC:G	donor_gain	1.0000
12:2798797:C:G	donor_gain	1.0000
12:2798811:GGTGC:G	donor_gain	1.0000
12:2798825:GG:G	donor_gain	1.0000
12:2798826:GG:G	donor_gain	1.0000
12:2798835:G:GG	donor_gain	1.0000

AlphaMissense

3030 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:2801160:G:C	R359P	1.000
12:2797196:T:A	V55D	0.999
12:2797746:T:A	W90R	0.999
12:2797746:T:C	W90R	0.999
12:2800098:A:C	K274N	0.999
12:2800098:A:T	K274N	0.999
12:2800513:T:C	L323P	0.999
12:2801146:G:C	K354N	0.999
12:2801146:G:T	K354N	0.999
12:2801156:C:A	R358S	0.999
12:2801157:G:C	R358P	0.999
12:2801168:G:C	A362P	0.999
12:2801250:C:A	A389D	0.999
12:2797172:C:A	P47H	0.998
12:2797208:G:A	G59D	0.998
12:2797231:T:C	F67L	0.998
12:2797233:T:A	F67L	0.998
12:2797233:T:G	F67L	0.998
12:2797799:C:G	C107W	0.998
12:2797866:T:C	F130L	0.998
12:2797868:T:A	F130L	0.998
12:2797868:T:G	F130L	0.998
12:2798803:C:A	P164H	0.998
12:2800051:T:A	W259R	0.998
12:2800051:T:C	W259R	0.998
12:2800053:G:C	W259C	0.998
12:2800053:G:T	W259C	0.998
12:2800106:G:A	G277D	0.998
12:2800571:T:G	C342W	0.998
12:2801144:A:C	K354Q	0.998

dbSNP variants (sampled 300 via entrez): RS1000211086 (12:2797416 T>C), RS1000218110 (12:2800551 T>G), RS1000270432 (12:2800846 G>A), RS1000478559 (12:2793565 G>T), RS1000511894 (12:2803753 G>A), RS1000826451 (12:2793108 G>A), RS1001009287 (12:2805308 G>A), RS1001461579 (12:2805731 C>T), RS1001468061 (12:2802093 G>A), RS1001622912 (12:2796535 T>C), RS1002630665 (12:2795285 G>A), RS1002680029 (12:2795486 C>A,T), RS1002780248 (12:2798462 T>C,G), RS1002983253 (12:2801915 G>GCAGA), RS1003558660 (12:2800722 C>G,T)

Disease associations

OMIM: gene MIM:600611 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Moderate	Autosomal recessive

Mondo (1): complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000337_9	Quantitative traits	2.000000e-06
GCST007429_113	Lung function (FVC)	1.000000e-14
GCST007430_49	Peak expiratory flow	2.000000e-06
GCST007432_42	FEV1	8.000000e-11
GCST010241_208	Apolipoprotein A1 levels	1.000000e-09
GCST012227_637	Hip circumference adjusted for BMI	5.000000e-09
GCST012228_544	Waist-hip index	6.000000e-10
GCST012229_152	Hip index	2.000000e-08
GCST012230_37	Waist-to-hip ratio adjusted for BMI	4.000000e-10
GCST90020091_7	Estradiol levels	4.000000e-12

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004312	vital capacity
EFO:0009718	peak expiratory flow
EFO:0004314	forced expiratory volume
EFO:0004614	apolipoprotein A 1 measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004697	estradiol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4050 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 478,582 (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
CHEMBL413	SIROLIMUS	4	172,798
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 (2 total), top 2:

Ligand	Action	Affinity	Parameter
compound 19b [PMID: 37058391]	Inhibition	6.11	pKi
SLF	Inhibitor	5.03	pIC50

ChEMBL bioactivities

81 potent at pChembl≥5 of 114 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.92	Kd	1.2	nM	CHEMBL5634031
8.38	Kd	4.2	nM	SIROLIMUS
7.92	Kd	12	nM	SIROLIMUS
7.80	IC50	16	nM	CYCLOSPORINE
7.72	Ki	18.9	nM	CHEMBL4090599
7.70	Ki	20	nM	CHEMBL321022
7.64	Kd	23	nM	TACROLIMUS ANHYDROUS
6.83	Kd	149.7	nM	TACROLIMUS ANHYDROUS
6.36	Ki	436	nM	CHEMBL5399071
6.29	Kd	513	nM	CHEMBL4871144
6.26	Kd	545.8	nM	CHEMBL5653589
6.26	ED50	545.8	nM	CHEMBL5653589
6.15	IC50	710	nM	CHEMBL2058794
6.11	Ki	775	nM	CHEMBL5396982
6.11	Ki	774	nM	CHEMBL5437245
6.10	Kd	795	nM	CHEMBL4856956
6.05	IC50	890	nM	CHEMBL2057227
6.03	Ki	936	nM	GPI-1046
6.02	Ki	950	nM	CHEMBL5414438
5.99	Ki	1030	nM	CHEMBL5399488
5.97	IC50	1070	nM	CHEMBL2059026
5.96	Kd	1100	nM	CHEMBL4643473
5.89	Kd	1300	nM	CHEMBL4645417
5.85	Kd	1400	nM	CHEMBL4858532
5.85	IC50	1409	nM	CHEMBL3623630
5.80	Kd	1600	nM	CHEMBL4636775
5.77	Ki	1690	nM	CHEMBL333448
5.67	IC50	2130	nM	CHEMBL2059029
5.67	Ki	2159	nM	CHEMBL5420939
5.66	IC50	2200	nM	CHEMBL2059237
5.61	IC50	2440	nM	CHEMBL2059029
5.58	IC50	2640	nM	CHEMBL2059237
5.58	IC50	2640	nM	CHEMBL2059239
5.56	Ki	2728	nM	CHEMBL5408325
5.55	IC50	2800	nM	CHEMBL2059024
5.54	IC50	2880	nM	CHEMBL2059238
5.54	Kd	2900	nM	CHEMBL4637863
5.54	IC50	2904	nM	CHEMBL5437245
5.52	Kd	3000	nM	CHEMBL4632451
5.52	IC50	3000	nM	CHEMBL5558644
5.52	IC50	3000	nM	CHEMBL5556796
5.52	IC50	3000	nM	CHEMBL5555524
5.52	IC50	3000	nM	CHEMBL1322226
5.50	IC50	3176	nM	CHEMBL5420939
5.47	IC50	3410	nM	CHEMBL2058796
5.46	IC50	3500	nM	CHEMBL2059034
5.46	Kd	3500	nM	CHEMBL4636527
5.45	Kd	3529	nM	CHEMBL4863989
5.43	IC50	3720	nM	CHEMBL2059035
5.41	Kd	3855	nM	CHEMBL4878667

PubChem BioAssay actives

78 with measured affinity, of 293 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	2139770: Binding affinity to human FKBP52 FK1 domain expressed in Escherichia coli BL21 DE3 Gold assessed as dissociation constant incubated for 30 mins by competitive fluorescence polarization assay	kd	0.0012	uM
Sirolimus	1949524: Binding affinity to FKBP52 (unknown origin)	kd	0.0042	uM
cyclosporine	223386: 50% inhibitory concentration of competitive binding against hCyp-18 PPIase activity using uncoupled assay	ic50	0.0160	uM
(1S,5S,6R)-10-(3,5-dichlorophenyl)sulfonyl-5-(methoxymethyl)-3-(pyridin-2-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-2-one	1479804: 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 FKBP52 after 30 mins by fluorescence polarization assay	ki	0.0189	uM
2-[3-[(1R)-3-(3,4-dimethoxyphenyl)-1-[(2S)-1-(3,3-dimethyl-2-oxopentanoyl)piperidine-2-carbonyl]oxypropyl]phenoxy]acetic acid	1949524: Binding affinity to FKBP52 (unknown origin)	ki	0.0200	uM
Tacrolimus	1949524: Binding affinity to FKBP52 (unknown origin)	kd	0.0230	uM
2-[3-[(1R)-1-[(2S)-1-[(2S)-2-(5-bromothiophen-2-yl)-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carbonyl]oxy-3-(3,4-dimethoxyphenyl)propyl]phenoxy]acetic acid	1987845: Binding affinity to FKBP52 (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.4360	uM
(2S,9S,12R,20R,21R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-20,21-dihydroxy-25,26-dimethoxy-11,18,23-trioxa-4-azatetracyclo[22.3.1.113,17.04,9]nonacosa-1(28),13(29),14,16,24,26-hexaene-3,10-dione	1775631: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP52 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.5130	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148390: Binding affinity to human FKBP4 incubated for 45 mins by Kinobead based pull down assay	kd	0.5458	uM
[(1R)-3-(3,4-dimethoxyphenyl)-1-[3-(2-morpholin-4-ylethoxy)phenyl]propyl] (2S)-1-(3,5-dichloro-4-hydroxyphenyl)sulfonylpiperidine-2-carboxylate	672583: Binding affinity to FKBP52 FK1 domain by competitive fluorescence polarization assay	ic50	0.7100	uM
[(1R)-3-(3,4-dimethoxyphenyl)-1-[3-(2-morpholin-4-ylethoxy)phenyl]propyl] (2S)-1-[(2S)-2-(5-chlorothiophen-2-yl)-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carboxylate	1987845: Binding affinity to FKBP52 (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.7740	uM
[(1R)-3-(3,4-dimethoxyphenyl)-1-[3-(2-morpholin-4-ylethoxy)phenyl]propyl] (2S)-1-[(2S)-2-(5-methylthiophen-2-yl)-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carboxylate	1987845: Binding affinity to FKBP52 (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.7750	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-20,21-dihydroxy-25,28-dimethoxy-11,18,23-trioxa-4-azatetracyclo[22.2.2.113,17.04,9]nonacosa-1(26),13(29),14,16,24,27-hexaene-3,10-dione	1775631: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP52 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.7950	uM
[(1R)-3-(3,4-dimethoxyphenyl)-1-[3-(2-morpholin-4-ylethoxy)phenyl]propyl] (2S)-1-[2-[(1S,2R)-1-hydroxy-2-methylcyclohexyl]-2-oxoacetyl]piperidine-2-carboxylate	672588: Binding affinity to FKBP52 FK1 domain by fluorescence polarization assay	ic50	0.8900	uM
3-pyridin-3-ylpropyl (2S)-1-(3,3-dimethyl-2-oxopentanoyl)pyrrolidine-2-carboxylate	1949524: Binding affinity to FKBP52 (unknown origin)	ki	0.9360	uM
2-[3-[(1R)-1-[(2S)-1-[(2S)-2-(5-chlorothiophen-2-yl)-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carbonyl]oxy-3-(3,4-dimethoxyphenyl)propyl]phenoxy]acetic acid	1987845: Binding affinity to FKBP52 (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.9500	uM
2-[3-[(1R)-3-(3,4-dimethoxyphenyl)-1-[(2S)-1-[(2S)-2-(5-methylthiophen-2-yl)-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carbonyl]oxypropyl]phenoxy]acetic acid	1987845: Binding affinity to FKBP52 (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	1.0300	uM
[(1R)-1-(3-aminophenyl)-3-(3,4-dimethoxyphenyl)propyl] (2S)-1-(3,3-dimethyl-2-oxopentanoyl)piperidine-2-carboxylate	672588: Binding affinity to FKBP52 FK1 domain by fluorescence polarization assay	ic50	1.0700	uM
(2S)-5-(diaminomethylideneamino)-2-[[(2S)-1-[(2S)-1-[5-(dimethylamino)naphthalen-1-yl]sulfonylpiperidine-2-carbonyl]piperidine-2-carbonyl]amino]pentanoic acid	1662027: Binding affinity to FKBP52 FK1 domain (1 to 148 residues) (unknown origin) by isothermal calorimetric analysis	kd	1.1000	uM
(2S)-5-(diaminomethylideneamino)-2-[[(2S)-2-[[(2S,4S)-1-[5-(dimethylamino)naphthalen-1-yl]sulfonyl-4-fluoropyrrolidine-2-carbonyl]amino]-4-phenylbutanoyl]amino]pentanoic acid	1662027: Binding affinity to FKBP52 FK1 domain (1 to 148 residues) (unknown origin) by isothermal calorimetric analysis	kd	1.3000	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-26,27-dimethoxy-11,18,24-trioxa-4-azatetracyclo[23.3.1.113,17.04,9]triaconta-1(29),13(30),14,16,25,27-hexaene-3,10,21-trione	1775631: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP52 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	1.4000	uM
(2S)-5-(diaminomethylideneamino)-2-[[(2S)-2-[[(2S)-1-[5-(dimethylamino)naphthalen-1-yl]sulfonylpiperidine-2-carbonyl]amino]-4-phenylbutanoyl]amino]pentanoic acid	1662027: Binding affinity to FKBP52 FK1 domain (1 to 148 residues) (unknown origin) by isothermal calorimetric analysis	kd	1.6000	uM
ethyl 2-[4-[(2R)-2-[(1S,3S,5S)-3,5-dimethyl-2-oxocyclohexyl]-2-hydroxyethyl]-2,6-dioxopiperidin-1-yl]acetate	1949524: Binding affinity to FKBP52 (unknown origin)	ki	1.6900	uM
2-[3-[(1R)-3-(3,4-dimethoxyphenyl)-1-[(2S)-1-[2-[(1S,2R)-1-hydroxy-2-methylcyclohexyl]-2-oxoacetyl]piperidine-2-carbonyl]oxypropyl]phenoxy]acetic acid	672588: Binding affinity to FKBP52 FK1 domain by fluorescence polarization assay	ic50	2.1300	uM
2-[3-[(1R)-3-(3,4-dimethoxyphenyl)-1-[(2S)-1-[(2R)-3-morpholin-4-yl-2-(3,4,5-trimethoxyphenyl)propanoyl]piperidine-2-carbonyl]oxypropyl]phenoxy]acetic acid	1987845: Binding affinity to FKBP52 (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	2.1590	uM
2-[3-[(1R)-3-(3,4-dimethoxyphenyl)-1-[(2S)-1-[2-[(1S,2S)-1-hydroxy-2-methylcyclohexyl]-2-oxoacetyl]piperidine-2-carbonyl]oxypropyl]phenoxy]acetic acid	672588: Binding affinity to FKBP52 FK1 domain by fluorescence polarization assay	ic50	2.2000	uM
2-[3-[(1R)-3-(3,4-dimethoxyphenyl)-1-[(2S)-1-[2-[(1R,2R)-1-hydroxy-2-methylcyclohexyl]-2-oxoacetyl]piperidine-2-carbonyl]oxypropyl]phenoxy]acetic acid	672588: Binding affinity to FKBP52 FK1 domain by fluorescence polarization assay	ic50	2.6400	uM
2-[3-[(1R)-1-[(2S)-1-[(2S)-2-(5-cyanothiophen-2-yl)-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carbonyl]oxy-3-(3,4-dimethoxyphenyl)propyl]phenoxy]acetic acid	1987845: Binding affinity to FKBP52 (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	2.7280	uM
[(1R)-3-(3,4-dimethoxyphenyl)-1-[3-(2-morpholin-4-ylethoxy)phenyl]propyl] (2S)-1-(3,3-dimethyl-2-oxopentanoyl)piperidine-2-carboxylate	672588: Binding affinity to FKBP52 FK1 domain by fluorescence polarization assay	ic50	2.8000	uM
2-[3-[(1R)-3-(3,4-dimethoxyphenyl)-1-[(2S)-1-[2-[(1R,2S)-1-hydroxy-2-methylcyclohexyl]-2-oxoacetyl]piperidine-2-carbonyl]oxypropyl]phenoxy]acetic acid	672588: Binding affinity to FKBP52 FK1 domain by fluorescence polarization assay	ic50	2.8800	uM
(2S)-5-(diaminomethylideneamino)-2-[[(2S)-2-[[(2S)-1-[5-(dimethylamino)naphthalen-1-yl]sulfonylpiperidine-2-carbonyl]amino]-3,3-dimethylbutanoyl]amino]pentanoic acid	1662027: Binding affinity to FKBP52 FK1 domain (1 to 148 residues) (unknown origin) by isothermal calorimetric analysis	kd	2.9000	uM
2-[[3-cyano-4-(4-methoxyphenyl)-6-(4-methylphenyl)-2-pyridinyl]sulfanyl]-N-(5-ethyl-1,3,4-oxadiazol-2-yl)acetamide	2084022: Inhibition of GST-tagged human FKBP52 expressed in Escherichia coli BL21 (DE3) using NH2-EDASRMEEVD-COOH peptide as substrate preincubated for 15 mins followed by substrate addition measured after 15 mins by Alpha Screen assay	ic50	3.0000	uM
N-[4-[[2-[(3-methyl-7,8-dihydro-6H-cyclopenta[g]quinolin-2-yl)sulfanyl]acetyl]amino]phenyl]propanamide	2084022: Inhibition of GST-tagged human FKBP52 expressed in Escherichia coli BL21 (DE3) using NH2-EDASRMEEVD-COOH peptide as substrate preincubated for 15 mins followed by substrate addition measured after 15 mins by Alpha Screen assay	ic50	3.0000	uM
(2S)-5-(diaminomethylideneamino)-2-[[(2S)-2-[[(2S)-1-[5-(dimethylamino)naphthalen-1-yl]sulfonylpiperidine-2-carbonyl]amino]-3-pyridin-3-ylpropanoyl]amino]pentanoic acid	1662027: Binding affinity to FKBP52 FK1 domain (1 to 148 residues) (unknown origin) by isothermal calorimetric analysis	kd	3.0000	uM
ethyl 2-[[2-[[5-(3-hydroxyphenyl)-1,3,4-oxadiazol-2-yl]sulfanyl]acetyl]amino]-4,5-dimethylthiophene-3-carboxylate	2084022: Inhibition of GST-tagged human FKBP52 expressed in Escherichia coli BL21 (DE3) using NH2-EDASRMEEVD-COOH peptide as substrate preincubated for 15 mins followed by substrate addition measured after 15 mins by Alpha Screen assay	ic50	3.0000	uM
methyl 2-[[2-[[5,6-bis(furan-2-yl)-1,2,4-triazin-3-yl]sulfanyl]acetyl]amino]-4,5-dimethylthiophene-3-carboxylate	2084022: Inhibition of GST-tagged human FKBP52 expressed in Escherichia coli BL21 (DE3) using NH2-EDASRMEEVD-COOH peptide as substrate preincubated for 15 mins followed by substrate addition measured after 15 mins by Alpha Screen assay	ic50	3.0000	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	672583: Binding affinity to FKBP52 FK1 domain by competitive fluorescence polarization assay	ic50	3.4100	uM
(2S)-5-(diaminomethylideneamino)-2-[[(2S)-2-[[(2S)-1-[5-(dimethylamino)naphthalen-1-yl]sulfonylpiperidine-2-carbonyl]amino]-3-pyridin-2-ylpropanoyl]amino]pentanoic acid	1662027: Binding affinity to FKBP52 FK1 domain (1 to 148 residues) (unknown origin) by isothermal calorimetric analysis	kd	3.5000	uM
2-[3-[(1R)-3-(3,4-dimethoxyphenyl)-1-[(2S)-1-[2-[(1R,2S)-2-ethyl-1-hydroxycyclohexyl]-2-oxoacetyl]piperidine-2-carbonyl]oxypropyl]phenoxy]acetic acid	672588: Binding affinity to FKBP52 FK1 domain by fluorescence polarization assay	ic50	3.5000	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-25,26-dimethoxy-11,18,23-trioxa-4-azatetracyclo[22.3.1.113,17.04,9]nonacosa-1(28),13(29),14,16,24,26-hexaene-3,10,20-trione	1775631: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP52 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	3.5290	uM
[(1R)-3-(3,4-dimethoxyphenyl)-1-[3-(2-morpholin-4-ylethoxy)phenyl]propyl] (2S)-1-[2-[(1S,2R)-2-ethyl-1-hydroxycyclohexyl]-2-oxoacetyl]piperidine-2-carboxylate	672588: Binding affinity to FKBP52 FK1 domain by fluorescence polarization assay	ic50	3.7200	uM
(2S,9S,12R,20S,21S)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-20,21-dihydroxy-25,26-dimethoxy-11,18,23-trioxa-4-azatetracyclo[22.3.1.113,17.04,9]nonacosa-1(28),13(29),14,16,24,26-hexaene-3,10-dione	1775631: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP52 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	3.8550	uM
2-[3-[(1R)-1-[(2S)-1-[(2S)-2-cyclohexyl-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carbonyl]oxy-3-(3,4-dimethoxyphenyl)propyl]phenoxy]acetic acid	1987845: Binding affinity to FKBP52 (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	3.8590	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-28,29-dimethoxy-11,18,23,26-tetraoxa-4-azatetracyclo[25.3.1.113,17.04,9]dotriaconta-1(31),13(32),14,16,27,29-hexaene-3,10,21-trione	1775631: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP52 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	3.8770	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-26,27-dimethoxy-11,18,24-trioxa-4-azatetracyclo[23.3.1.113,17.04,9]triaconta-1(29),13(30),14,16,25,27-hexaene-3,10,20-trione	1775631: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP52 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	4.0980	uM
2-[3-[(1R)-3-(3,4-dimethoxyphenyl)-1-[(2S)-1-[2-[(1S,2R)-2-ethyl-1-hydroxycyclohexyl]-2-oxoacetyl]piperidine-2-carbonyl]oxypropyl]phenoxy]acetic acid	672588: Binding affinity to FKBP52 FK1 domain by fluorescence polarization assay	ic50	4.2000	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-25,26-dimethoxy-11,18,23-trioxa-4-azatetracyclo[22.3.1.113,17.04,9]nonacosa-1(28),13(29),14,16,24,26-hexaene-3,10-dione	1775631: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP52 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	4.4590	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-25,28-dimethoxy-11,18,23-trioxa-4-azatetracyclo[22.2.2.113,17.04,9]nonacosa-1(26),13(29),14,16,24,27-hexaene-3,10,20-trione	1775631: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP52 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	4.6710	uM
N-[2-methyl-4-[[2-[(3-methyl-7,8-dihydro-6H-cyclopenta[g]quinolin-2-yl)sulfanyl]acetyl]amino]phenyl]propanamide	2084022: Inhibition of GST-tagged human FKBP52 expressed in Escherichia coli BL21 (DE3) using NH2-EDASRMEEVD-COOH peptide as substrate preincubated for 15 mins followed by substrate addition measured after 15 mins by Alpha Screen assay	ic50	5.0000	uM
(2S)-5-(diaminomethylideneamino)-2-[[(2S)-2-[[(2S)-1-[5-(dimethylamino)naphthalen-1-yl]sulfonylpyrrolidine-2-carbonyl]amino]-4-phenylbutanoyl]amino]pentanoic acid	1662027: Binding affinity to FKBP52 FK1 domain (1 to 148 residues) (unknown origin) by isothermal calorimetric analysis	kd	5.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, affects expression	5
Estradiol	increases expression, affects expression, affects binding	5
sodium arsenite	increases abundance, increases expression, affects expression, affects cotreatment	4
Tobacco Smoke Pollution	increases expression, affects expression	4
Formaldehyde	decreases expression, increases expression	3
Valproic Acid	affects expression, increases expression, increases methylation	3
Particulate Matter	increases expression, affects cotreatment, decreases expression, affects expression, increases reaction (+1 more)	3
Cadmium	increases expression	2
Doxorubicin	increases expression, decreases response to substance	2
Silver	increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
testosterone enanthate	affects expression	1
methylselenic acid	decreases expression	1
titanium dioxide	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization	1
2-methyl-4-isothiazolin-3-one	increases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
perfluorooctanoic acid	affects cotreatment, decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
cupric chloride	increases expression	1
coumarin	decreases phosphorylation	1
cadmium sulfate	increases expression	1
beta-methylcholine	affects expression	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	increases expression	1

ChEMBL screening assays

52 unique, capped per target: 44 binding, 7 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2061146	Binding	Binding affinity to FKBP52 FK1 domain by competitive fluorescence polarization assay	Exploration of pipecolate sulfonamides as binders of the FK506-binding proteins 51 and 52. — J Med Chem
CHEMBL4379897	ADMET	Inhibition of human full length N-terminal His-tagged/C-terminal FLAG tagged FKBP52 expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by competitive fluorescence polarization assay	A Novel Decalin-Based Bicyclic Scaffold for FKBP51-Selective Ligands. — J Med Chem
CHEMBL864156	Functional	Increase in neurite outgrowth in chick embryo dorsal root ganglion at 1 pM in presence of NGF	FK506-binding protein ligands: structure-based design, synthesis, and neurotrophic/neuroprotective properties of substituted 5,5-dimethyl-2-(4-thiazolidine)carboxylates. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1WD	Abcam A-549 FKBP4 KO	Cancer cell line	Male
CVCL_D2AS	Abcam HCT 116 FKBP4 KO	Cancer cell line	Male
CVCL_E1XF	HAP1 FKBP4 (-) 1	Cancer cell line	Male
CVCL_E1XG	HAP1 FKBP4 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder