PPID

Summary

PPID (peptidylprolyl isomerase D, HGNC:9257) is a protein-coding gene on chromosome 4q32.1, encoding Peptidyl-prolyl cis-trans isomerase D (Q08752). PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding.

The protein encoded by this gene is a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate the folding of proteins. This protein has been shown to possess PPIase activity and, similar to other family members, can bind to the immunosuppressant cyclosporin A.

Source: NCBI Gene 5481 — RefSeq curated summary.

At a glance

• Gene–disease (curated): stutter disorder (Limited, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 70 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005038

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9257
Approved symbol	PPID
Name	peptidylprolyl isomerase D
Location	4q32.1
Locus type	gene with protein product
Status	Approved
Aliases	CYP-40, CypD
Ensembl gene	ENSG00000171497
Ensembl biotype	protein_coding
OMIM	601753
Entrez	5481

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 nonsense_mediated_decay

ENST00000307720, ENST00000507213, ENST00000512699, ENST00000877682, ENST00000877683, ENST00000914201, ENST00000914202, ENST00000914203, ENST00000953196

RefSeq mRNA: 1 — MANE Select: NM_005038 NM_005038

CCDS: CCDS3801

Canonical transcript exons

ENST00000307720 — 10 exons

Exon	Start	End
ENSE00001126597	158715562	158715684
ENSE00001126604	158717012	158717200
ENSE00001126610	158719180	158719286
ENSE00001126616	158721343	158721483
ENSE00001170868	158709127	158709824
ENSE00001170876	158723204	158723396
ENSE00003478463	158713119	158713260
ENSE00003500279	158710628	158710670
ENSE00003652118	158715297	158715403
ENSE00003694349	158710762	158710848

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 96.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.2845 / max 553.9949, expressed in 1807 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54615	31.2845	1807

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	96.58	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.43	gold quality
gastrocnemius	UBERON:0001388	96.25	gold quality
muscle of leg	UBERON:0001383	96.13	gold quality
mucosa of transverse colon	UBERON:0004991	95.73	gold quality
adrenal tissue	UBERON:0018303	95.71	gold quality
muscle organ	UBERON:0001630	95.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.19	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.61	gold quality
right adrenal gland	UBERON:0001233	94.58	gold quality
right adrenal gland cortex	UBERON:0035827	94.58	gold quality
rectum	UBERON:0001052	94.56	gold quality
body of tongue	UBERON:0011876	94.50	gold quality
skeletal muscle tissue	UBERON:0001134	94.46	gold quality
heart left ventricle	UBERON:0002084	94.34	gold quality
biceps brachii	UBERON:0001507	94.33	gold quality
cardiac ventricle	UBERON:0002082	94.28	gold quality
pons	UBERON:0000988	94.21	gold quality
jejunum	UBERON:0002115	94.11	gold quality
left adrenal gland	UBERON:0001234	94.09	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.07	gold quality
body of pancreas	UBERON:0001150	94.03	gold quality
cerebellar hemisphere	UBERON:0002245	93.85	gold quality
islet of Langerhans	UBERON:0000006	93.83	gold quality
cerebellar cortex	UBERON:0002129	93.79	gold quality
vastus lateralis	UBERON:0001379	93.75	gold quality
left adrenal gland cortex	UBERON:0035825	93.68	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.60	gold quality
tibialis anterior	UBERON:0001385	93.56	gold quality
transverse colon	UBERON:0001157	93.54	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.59
E-ENAD-17	no	434.57

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, MYC

miRNA regulators (miRDB)

22 targeting PPID, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-10524-5P	99.05	66.08	963
HSA-MIR-4711-3P	98.97	66.87	1020
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-758-3P	98.42	68.60	1122
HSA-MIR-4684-5P	98.29	67.99	1650
HSA-MIR-4457	98.09	67.12	1274
HSA-MIR-12120	98.05	68.44	1768

Literature-anchored findings (GeneRIF, showing 17)

• cyclophilin D suppresses apoptotic cell death via a mitochondrial hexokinase II-dependent mechanism in cancer cells (PMID:16551620)
• CyP40 chaperone function then, is localized within the linker that forms a binding cleft with potential to accommodate non-native substrates (PMID:16650407)
• CyP40 is found in the cell nucleus after 3-methylchloranthrene treatment and appears to promote the dioxin response element binding form of the AhR/Arnt heterodimer. (PMID:18708059)
• CypD-mediated mitochondrial permeability transition pore is directly linked to the cellular and synaptic perturbations observed in the pathogenesis of Alzheimer’s disease. (PMID:18806802)
• Cyclophilin D interacts with Bcl2 and exerts an anti-apoptotic effect (PMID:19228691)
• Data show that disruption of FKBP51 and Cyp40 in AI C4-2 cells caused only a small reduction in proliferation. (PMID:20023700)
• this is the first report establishing an important role for Cyp40 in lymphoma. (PMID:22681779)
• The Photorhabdus toxins TccC3 and TccC5 interacted with Hsp90, FKBP51, Cyp40 and CypA, suggesting a role of these host cell factors in translocation and/or refolding of the ADP-ribosyltransferases. (PMID:24138221)
• Cyp40 binds to C2I in vitro and in intact cells, it also interacts with the enzyme components of iota toxin and CDT, suggesting a common principle for this toxin family. (PMID:25058685)
• cyclophilin-D protein could increase oxidative stress and cause endothelial cell injury and apoptosis. cyclophilin-D protein is the key factor in reactive oxygen species-induced mitochondrial damage, leading to apoptosis of endothelial cells. (PMID:25966197)
• The thermodynamics of binding of Cyp-40 to Hsp90 shows remarkable temperature sensitivity in the physiological temperature range. (PMID:26330616)
• Data show that cyclophilin 40 (CyP40) interacts with and dissolves amyloids forming proteins tau and alpha-synuclein aggregates. (PMID:28654636)
• These findings provided novel insights into the role of a CypD-dependent mitochondrial pathway. (PMID:31089403)
• Cyclophilin D-mediated Mitochondrial Permeability Transition Regulates Mitochondrial Function. (PMID:36915987)
• Cyclophilin D in Mitochondrial Dysfunction: A Key Player in Neurodegeneration? (PMID:37627330)
• CypD induced ROS output promotes intracranial aneurysm formation and rupture by 8-OHdG/NLRP3/MMP9 pathway. (PMID:37717465)
• Elevations in the Mitochondrial Matrix Protein Cyclophilin D Correlate With Reduced Parvalbumin Expression in the Prefrontal Cortex of Patients With Schizophrenia. (PMID:38412332)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppid	ENSDARG00000038835
mus_musculus	Ppid	ENSMUSG00000027804
rattus_norvegicus	Ppid	ENSRNOG00000027408
rattus_norvegicus	Ppidl1	ENSRNOG00000037230
caenorhabditis_elegans		WBGENE00021201

Paralogs (22): PPIE (ENSG00000084072), PPIL2 (ENSG00000100023), PPIF (ENSG00000108179), PPWD1 (ENSG00000113593), NKTR (ENSG00000114857), PPIL4 (ENSG00000131013), PPIL1 (ENSG00000137168), PPIG (ENSG00000138398), CWC27 (ENSG00000153015), PPIB (ENSG00000166794), PPIC (ENSG00000168938), PPIH (ENSG00000171960), PPIL6 (ENSG00000185250), PPIA (ENSG00000196262), PPIAL4G (ENSG00000236334), PPIL3 (ENSG00000240344), PPIAL4A (ENSG00000263353), PPIAL4H (ENSG00000270339), PPIAL4E (ENSG00000271567), PPIAL4F (ENSG00000279782), PPIAL4C (ENSG00000288867), PPIAL4D (ENSG00000289549)

Protein

Protein identifiers

Peptidyl-prolyl cis-trans isomerase D — Q08752 (reviewed: Q08752)

Alternative names: 40 kDa peptidyl-prolyl cis-trans isomerase, Cyclophilin-40, Cyclophilin-related protein, Rotamase D

All UniProt accessions (4): Q08752, E5KN55, H0Y8J0, H0Y969

UniProt curated annotations — full annotation on UniProt →

Function. PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding. Proposed to act as a co-chaperone in HSP90 complexes such as in unligated steroid receptors heterocomplexes. Different co-chaperones seem to compete for association with HSP90 thus establishing distinct HSP90-co-chaperone-receptor complexes with the potential to exert tissue-specific receptor activity control. May have a preference for estrogen receptor complexes and is not found in glucocorticoid receptor complexes. May be involved in cytoplasmic dynein-dependent movement of the receptor from the cytoplasm to the nucleus. May regulate MYB by inhibiting its DNA-binding activity. Involved in regulation of AHR signaling by promoting the formation of the AHR:ARNT dimer; the function is independent of HSP90 but requires the chaperone activity. Involved in regulation of UV radiation-induced apoptosis. Promotes cell viability in anaplastic lymphoma kinase-positive anaplastic large-cell lymphoma (ALK+ ALCL) cell lines. (Microbial infection) May be involved in hepatitis C virus (HCV) replication and release.

Subunit / interactions. Identified in ESR1 or NR3C1/GCR steroid receptor-chaperone complexes. Found in HSP90 chaperone complexes with kinase clients LCK or EIF2AK1. Two monomers associate with one HSP90 homodimer. Interacts with HSP90AA1. Interacts with HSP90AB1; PPID and FKBP4 compete for binding to HSP90AB1 and the interaction is mutually exclusive with the PPID:HSPA8 interaction. Interacts with HSPA8; PPID and STIP1 but not FKBP4 compete for binding to HSPA8 and the interaction is mutually exclusive with the PPID:HSP90AB1 interaction. Interacts with S100A1 and S100A2; the interactions dissociate the PPID:HSP90AA1 interaction. Interacts with S100A6. Interacts with MYB, ILF2, XRCC6, RACK1 and RPS3. Interacts with cytoplasmic dynein 1 intermediate chain (DYNC1I1 or DYNC1I2).

Subcellular location. Cytoplasm. Nucleus. Nucleolus. Nucleoplasm.

Tissue specificity. Widely expressed.

Activity regulation. Less sensitive to inhibition by cyclosporin A than is CYP-18.

Similarity. Belongs to the cyclophilin-type PPIase family. PPIase D subfamily.

RefSeq proteins (1): NP_005029* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002130	Cyclophilin-type_PPIase_dom	Domain
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR020892	Cyclophilin-type_PPIase_CS	Conserved_site
IPR029000	Cyclophilin-like_dom_sf	Homologous_superfamily

Pfam: PF00160

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 (25 total): mutagenesis site 10, sequence variant 4, modified residue 3, repeat 3, region of interest 2, initiator methionine 1, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q08752-F1	96.51	0.94

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 (3): 198, 5, 171

Mutagenesis-validated functional residues (10):

Position	Phenotype
227	abolishes interaction with hsp90ab1 and impairs interaction with hspa8.
231	abolishes interaction with hsp90ab1 and impairs interaction with hspa8.
234	impairs interaction with hsp90ab1 and hspa8.
274	impairs interaction with hsp90ab1 and hspa8.
278	abolishes interaction with hsp90ab1.
284	impairs interaction with hsp90ab1 and hspa8.
285	impairs interaction with hsp90ab1 and hspa8.
308	abolishes interaction with hsp90ab1 and impairs interaction with hspa8.
312	abolishes interaction with hsp90ab1 and impairs interaction with hspa8.
329	impairs interaction with hsp90ab1.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8939211	ESR-mediated signaling

MSigDB gene sets: 186 (showing top): chr4q32, GOBP_CELLULAR_RESPONSE_TO_UV, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_POSITIVE_REGULATION_OF_VIRAL_GENOME_REPLICATION, PUJANA_CHEK2_PCC_NETWORK, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_REGULATION_OF_PROTEIN_SECRETION, MUELLER_PLURINET, GOBP_PROTEIN_MATURATION, WATANABE_RECTAL_CANCER_RADIOTHERAPY_RESPONSIVE_UP, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_CDC25_UP, GROSS_HYPOXIA_VIA_HIF1A_UP, HESS_TARGETS_OF_HOXA9_AND_MEIS1_UP

GO Biological Process (12): negative regulation of transcription by RNA polymerase II (GO:0000122), protein folding (GO:0006457), apoptotic process (GO:0006915), protein transport (GO:0015031), viral release from host cell (GO:0019076), lipid droplet organization (GO:0034389), positive regulation of apoptotic process (GO:0043065), positive regulation of viral genome replication (GO:0045070), positive regulation of protein secretion (GO:0050714), protein-containing complex assembly (GO:0065003), cellular response to UV-A (GO:0071492), protein peptidyl-prolyl isomerization (GO:0000413)

GO Molecular Function (9): peptidyl-prolyl cis-trans isomerase activity (GO:0003755), transcription factor binding (GO:0008134), cyclosporin A binding (GO:0016018), nuclear estrogen receptor binding (GO:0030331), Hsp70 protein binding (GO:0030544), heat shock protein binding (GO:0031072), Hsp90 protein binding (GO:0051879), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), cilium (GO:0005929)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signaling by Nuclear Receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein binding	2
binding	2
heat shock protein binding	2
nuclear lumen	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
cellular process	1
protein maturation	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
viral process	1
viral life cycle	1
exit from host cell	1
organelle organization	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
viral genome replication	1
regulation of viral genome replication	1
positive regulation of viral process	1
protein secretion	1
regulation of protein secretion	1
positive regulation of protein transport	1
positive regulation of secretion by cell	1
cellular component assembly	1
protein-containing complex organization	1
cellular response to UV	1
response to UV-A	1
peptidyl-proline modification	1
cis-trans isomerase activity	1
catalytic activity, acting on a protein	1
nuclear receptor binding	1
protein-folding chaperone binding	1
catalytic activity	1

Protein interactions and networks

STRING

3186 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPID	HSP90AA1	P07900	997
PPID	HSP90AB1	P08238	997
PPID	HSPA4	P34932	970
PPID	ATP5PO	P48047	940
PPID	VDAC1	P21796	931
PPID	TP53	P04637	907
PPID	PPIA	P05092	900
PPID	FKBP4	Q02790	878
PPID	STIP1	P31948	870
PPID	CDC37	Q16543	855
PPID	ESR1	P03372	826
PPID	PTGES3	Q15185	760
PPID	AGO1	Q9UL18	756
PPID	HSPA8	P11142	712
PPID	SPG7	Q9UQ90	671

IntAct

84 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ATP5PO	PPID	psi-mi:“MI:0915”(physical association)	0.600
ATP5PO	PPID	psi-mi:“MI:0407”(direct interaction)	0.600
PPID	UROD	psi-mi:“MI:0915”(physical association)	0.590
PPID	RACK1	psi-mi:“MI:0407”(direct interaction)	0.590
PPID	RACK1	psi-mi:“MI:0915”(physical association)	0.590
PPID	ILF2	psi-mi:“MI:0407”(direct interaction)	0.590
PPID	ILF2	psi-mi:“MI:0915”(physical association)	0.590
RPS3	PPID	psi-mi:“MI:0407”(direct interaction)	0.590
PPID	RPS3	psi-mi:“MI:0915”(physical association)	0.590
XRCC6	PPID	psi-mi:“MI:0407”(direct interaction)	0.590
PPID	XRCC6	psi-mi:“MI:0915”(physical association)	0.590
XRCC6	PPID	psi-mi:“MI:0915”(physical association)	0.590
ILF2	PPID	psi-mi:“MI:0915”(physical association)	0.590
RACK1	PPID	psi-mi:“MI:0915”(physical association)	0.590
RPS3	PPID	psi-mi:“MI:0915”(physical association)	0.590
PPID	APP	psi-mi:“MI:0407”(direct interaction)	0.580
PPID	APP	psi-mi:“MI:0914”(association)	0.580
PPID	APP	psi-mi:“MI:0403”(colocalization)	0.580
ATP5PO	APP	psi-mi:“MI:0915”(physical association)	0.540
AKIRIN2	RGPD3	psi-mi:“MI:0914”(association)	0.530
TMA16	TNPO2	psi-mi:“MI:0914”(association)	0.530
FGF9	PPID	psi-mi:“MI:0914”(association)	0.530
PPID	APP	psi-mi:“MI:0407”(direct interaction)	0.520
	PPID	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (137): TRIM27 (Two-hybrid), HSP90AA1 (Reconstituted Complex), PPID (Affinity Capture-MS), PPID (Affinity Capture-RNA), PKM (Co-fractionation), PPID (Co-fractionation), PPID (Co-fractionation), PPID (Co-fractionation), PSMD12 (Co-fractionation), SF1 (Co-fractionation), PPID (Affinity Capture-MS), PPID (Affinity Capture-Western), PPID (Affinity Capture-MS), PPID (Affinity Capture-MS), UROD (Affinity Capture-MS)

ESM2 similar proteins: A0MTA1, A1YES6, A1YFZ3, A2T6Y4, A2T7I6, A5WVX1, B4FAT0, O54747, O94903, P0A2X3, P0A2X4, P13051, P23196, P26882, P27695, P28339, P28340, P28352, P36776, P43138, P52431, P97283, P97931, Q08752, Q08DF7, Q0J705, Q0V9S0, Q16775, Q32LH4, Q3B7M2, Q3T0G5, Q3TIU4, Q4P1V1, Q4R5U5, Q4R6C1, Q59HJ6, Q5R4Z1, Q5XIP6, Q5ZI23, Q653S9

Diamond homologs: A0A075B759, A0A075B767, A0A0B4J2A2, A0A0R0H9T5, A4FV72, F5H284, O00060, O49886, P0C1H7, P0C1H8, P0C1I1, P0C1I2, P0C1I7, P0C1I8, P0CP78, P0CP79, P0DN26, P0DN37, P10111, P14088, P14832, P14851, P17742, P18253, P21568, P21569, P22011, P24525, P25007, P25719, P26882, P29117, P30404, P30405, P34790, P34791, P34887, P35627, P52009, P52010

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 80 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
Signaling by BRAF and RAF1 fusions	5	16.4×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1324 predictions. Top by Δscore:

Variant	Effect	Δscore
4:158710668:AGCC:A	acceptor_loss	1.0000
4:158710669:GCC:G	acceptor_loss	1.0000
4:158710670:CCTT:C	acceptor_gain	1.0000
4:158710671:C:CC	acceptor_gain	1.0000
4:158710671:C:G	acceptor_loss	1.0000
4:158710672:T:A	acceptor_loss	1.0000
4:158710672:T:C	acceptor_gain	1.0000
4:158710673:T:C	acceptor_gain	1.0000
4:158710673:T:TC	acceptor_gain	1.0000
4:158710677:T:C	acceptor_gain	1.0000
4:158710677:T:TC	acceptor_gain	1.0000
4:158713114:CTTA:C	donor_loss	1.0000
4:158713115:TTA:T	donor_loss	1.0000
4:158713116:TA:T	donor_loss	1.0000
4:158713117:A:T	donor_loss	1.0000
4:158713118:CCT:C	donor_gain	1.0000
4:158713256:CGTAT:C	acceptor_gain	1.0000
4:158715291:TATTA:T	donor_loss	1.0000
4:158715292:ATTAC:A	donor_loss	1.0000
4:158715293:TTACC:T	donor_loss	1.0000
4:158715294:TA:T	donor_loss	1.0000
4:158715295:ACC:A	donor_loss	1.0000
4:158715296:CC:C	donor_loss	1.0000
4:158715400:CTAC:C	acceptor_gain	1.0000
4:158715401:TAC:T	acceptor_gain	1.0000
4:158715554:GTACT:G	donor_loss	1.0000
4:158715556:ACTC:A	donor_loss	1.0000
4:158715558:TCA:T	donor_loss	1.0000
4:158715559:CA:C	donor_loss	1.0000
4:158715560:A:AC	donor_gain	1.0000

AlphaMissense

2448 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:158709742:A:C	F369L	0.993
4:158709742:A:T	F369L	0.993
4:158709744:A:G	F369L	0.993
4:158719273:A:C	F80L	0.984
4:158719273:A:T	F80L	0.984
4:158719275:A:G	F80L	0.984
4:158719222:A:C	S97R	0.980
4:158719222:A:T	S97R	0.980
4:158719224:T:G	S97R	0.980
4:158717177:G:C	S119R	0.978
4:158717177:G:T	S119R	0.978
4:158717179:T:G	S119R	0.978
4:158717138:A:C	F132L	0.977
4:158717138:A:T	F132L	0.977
4:158717140:A:G	F132L	0.977
4:158719204:A:C	F103L	0.975
4:158719204:A:T	F103L	0.975
4:158719206:A:G	F103L	0.975
4:158717087:A:C	F149L	0.967
4:158717087:A:T	F149L	0.967
4:158717089:A:G	F149L	0.967
4:158721425:A:C	F48L	0.967
4:158721425:A:T	F48L	0.967
4:158721427:A:G	F48L	0.967
4:158709743:A:C	F369C	0.966
4:158721345:C:G	R75P	0.965
4:158721428:A:C	N47K	0.965
4:158721428:A:T	N47K	0.965
4:158721423:C:G	R49P	0.962
4:158723232:G:C	F19L	0.957

dbSNP variants (sampled 300 via entrez): RS1000035951 (4:158714926 G>A), RS1000114774 (4:158720751 G>A), RS1001116968 (4:158708802 G>A), RS1001686275 (4:158712957 T>C), RS1001706671 (4:158723483 C>T), RS1001759030 (4:158723660 G>C), RS1001788168 (4:158719004 T>C), RS1001861849 (4:158719360 C>T), RS1002038671 (4:158722467 T>C), RS1002067566 (4:158725296 C>T), RS1002090972 (4:158722684 A>G,T), RS1002116028 (4:158713329 G>A,C), RS10021213 (4:158722629 T>A,C), RS1002472099 (4:158716479 C>T), RS1002501785 (4:158716822 G>A)

Disease associations

OMIM: gene MIM:601753 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
stutter disorder	Limited	Autosomal dominant

Mondo (1): stutter disorder (MONDO:0000723)

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST006249_17	Serum metabolite levels	5.000000e-12
GCST006249_83	Serum metabolite levels	2.000000e-12
GCST006585_2337	Blood protein levels	2.000000e-50
GCST008595_152	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1697657 (SINGLE PROTEIN), CHEMBL3885544 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 168,247 (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

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
CRV431	Inhibition	8.55	pIC50
cyclosporin A	Inhibition	8.0	pIC50

Binding affinities (BindingDB)

20 measured of 25 human assays (25 total across all organisms); most potent 20 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[(4-aminophenyl)methyl]-3-[2-[2-(2-methylsulfanylphenyl)pyrrolidin-1-yl]-2-oxoethyl]urea	IC50	650 nM	US-8901295: Inhibitors of cyclophilins and uses thereof
1-[(4-aminophenyl)methyl]-3-[4-methylsulfanyl-1-[2-(2-methylsulfanylphenyl)pyrrolidin-1-yl]-1-oxobutan-2-yl]urea	IC50	660 nM	US-8901295: Inhibitors of cyclophilins and uses thereof
1-[(4-aminophenyl)methyl]-3-[2-[2-(2-bromophenyl)pyrrolidin-1-yl]-2-oxoethyl]urea	IC50	760 nM	US-8901295: Inhibitors of cyclophilins and uses thereof
1-[(4-aminophenyl)methyl]-3-[1-[2-(2-methylsulfanylphenyl)pyrrolidin-1-yl]-1-oxopropan-2-yl]urea	IC50	1100 nM	US-8901295: Inhibitors of cyclophilins and uses thereof
1-[(4-aminophenyl)methyl]-3-[2-[2-(2-methoxyphenyl)pyrrolidin-1-yl]-2-oxoethyl]urea	IC50	1200 nM	US-8901295: Inhibitors of cyclophilins and uses thereof
1-[(4-aminophenyl)methyl]-3-[2-(2-naphthalen-1-ylpyrrolidin-1-yl)-2-oxoethyl]urea	IC50	1400 nM	US-8901295: Inhibitors of cyclophilins and uses thereof
CHEMBL4471175	IC50	2800 nM
1-[(4-aminophenyl)methyl]-3-[4-methyl-1-[2-(2-methylsulfanylphenyl)pyrrolidin-1-yl]-1-oxopentan-2-yl]urea	IC50	3000 nM	US-8901295: Inhibitors of cyclophilins and uses thereof
2-[(4-aminophenyl)methylcarbamoylamino]-N-ethyl-N-phenylmethoxyacetamide	IC50	4800 nM	US-8901295: Inhibitors of cyclophilins and uses thereof
ethyl 2-[(4-aminophenyl)methylcarbamoylamino]acetate	IC50	6100 nM	US-8901295: Inhibitors of cyclophilins and uses thereof
1-[(4-aminophenyl)methyl]-3-[2-[2-(2-chlorophenyl)pyrrolidin-1-yl]-2-oxoethyl]urea	IC50	6200 nM	US-8901295: Inhibitors of cyclophilins and uses thereof
2-[(2S,7R)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]decan-4-yl]-N-[(4-nitrophenyl)methyl]acetamide	IC50	105000 nM	US-9975902: Compounds for the inhibition of cyclophilins and uses thereof
N-[1-(4-aminophenyl)cyclopropyl]-2-[(1R,2R,6S,7S)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]decan-4-yl]acetamide	IC50	105000 nM	US-9975902: Compounds for the inhibition of cyclophilins and uses thereof
2-[(1S,2R,7R)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]decan-4-yl]-N-[(5-ethyl-4-oxo-1,2,3,6-tetrahydro-1,5-benzodiazocin-8-yl)methyl]acetamide	IC50	105000 nM	US-9975902: Compounds for the inhibition of cyclophilins and uses thereof
N-[2-(4-aminophenyl)ethyl]-2-(1,3-dioxo-3a,4,5,6,7,7a-hexahydroisoindol-2-yl)acetamide	IC50	105000 nM	US-9975902: Compounds for the inhibition of cyclophilins and uses thereof
N-[(4-aminophenyl)methyl]-2-(1,3-dioxo-3a,4,5,6,7,7a-hexahydro-4,7-epoxyisoindol-2-yl)acetamide	IC50	105000 nM	US-9975902: Compounds for the inhibition of cyclophilins and uses thereof
2-[(1S,2S,6R,7R)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]decan-4-yl]-N-[2-(1,2,3,4-tetrahydroquinolin-6-yl)ethyl]acetamide	IC50	105000 nM	US-9975902: Compounds for the inhibition of cyclophilins and uses thereof
2-[(2S,7R)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]decan-4-yl]-N-[2-(4-nitrophenyl)ethyl]acetamide	IC50	105000 nM	US-9975902: Compounds for the inhibition of cyclophilins and uses thereof
2-[(1S,2S,6R,7R)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]decan-4-yl]-N-[1-(2-ethyl-3-oxo-4H-1,4-benzoxazin-7-yl)ethyl]acetamide	IC50	105000 nM	US-9975902: Compounds for the inhibition of cyclophilins and uses thereof
CHEMBL4444722	IC50	490000 nM

ChEMBL bioactivities

59 potent at pChembl≥5 of 76 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.59	Ki	2.58	nM	CYCLOSPORINE
8.44	IC50	3.6	nM	CYCLOSPORINE
8.40	IC50	4	nM	CHEMBL4470490
8.15	Ki	7	nM	CYCLOSPORINE
8.09	Ki	8.2	nM	CYCLOSPORINE
7.92	Ki	12	nM	CHEMBL1688203
7.89	Kd	13	nM	CYCLOSPORINE
7.52	Kd	30	nM	CYCLOSPORINE
7.47	Ki	34	nM	CYCLOSPORINE
7.22	IC50	60	nM	CHEMBL4470490
7.00	Ki	99	nM	CHEMBL3799661
7.00	Kd	101	nM	CHEMBL1688203
6.83	Kd	149	nM	CHEMBL3805631
6.72	IC50	190	nM	CHEMBL4466871
6.72	Kd	191.4	nM	CHEMBL5653589
6.72	ED50	191.4	nM	CHEMBL5653589
6.64	Kd	230	nM	CHEMBL3798755
6.39	Kd	410	nM	CHEMBL3799661
6.22	IC50	600	nM	CHEMBL4464178
6.19	IC50	640	nM	CHEMBL3647433
6.18	IC50	660	nM	CHEMBL3647436
6.13	IC50	735	nM	CHEMBL4547673
6.02	Ki	950	nM	CHEMBL3799597
5.96	IC50	1100	nM	CHEMBL3647432
5.96	IC50	1100	nM	CHEMBL3647435
5.92	Kd	1200	nM	CHEMBL3799597
5.88	Ki	1330	nM	CHEMBL3805631
5.87	IC50	1350	nM	CHEMBL4464178
5.85	IC50	1400	nM	CHEMBL3647431
5.83	IC50	1490	nM	CHEMBL3805631
5.82	IC50	1500	nM	CHEMBL4464825
5.82	IC50	1500	nM	CHEMBL5558181
5.77	IC50	1700	nM	CHEMBL4520315
5.77	IC50	1700	nM	CHEMBL4451136
5.70	IC50	2000	nM	CHEMBL4464825
5.70	Ki	2000	nM	CHEMBL1557710
5.62	IC50	2420	nM	CHEMBL2017129
5.58	Ki	2600	nM	CHEMBL3799875
5.55	Kd	2800	nM	CHEMBL3798755
5.55	IC50	2800	nM	CHEMBL4471175
5.54	Ki	2900	nM	CHEMBL3647424
5.52	IC50	3000	nM	CHEMBL3647434
5.52	Ki	3000	nM	CHEMBL5275318
5.52	Ki	3000	nM	CHEMBL2006156
5.46	IC50	3500	nM	CHEMBL4540033
5.44	IC50	3600	nM	CHEMBL4453162
5.39	IC50	4100	nM	CHEMBL4563478
5.31	Ki	4900	nM	CHEMBL3797905
5.29	Kd	5120	nM	CHEMBL3798305
5.27	Kd	5400	nM	CHEMBL3799575

PubChem BioAssay actives

52 with measured affinity, of 118 total; 31 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
cyclosporine	1300180: Binding affinity to human recombinant cyclophilin D by surface plasmon resonance analysis	ki	0.0026	uM
1-[[(1R,9R,10S)-10-hydroxy-12-oxa-8-azatricyclo[7.3.1.02,7]trideca-2(7),3,5-trien-4-yl]methyl]-3-[2-[(2R)-2-(2-methylsulfanylphenyl)pyrrolidin-1-yl]-2-oxoethyl]urea	1566290: Inhibition of CypD (unknown origin) PPIase activity using N-Suc-AAPF-p-nitroanilide as substrate preincubated with enzyme for 10 mins followed by chymotrypsin addition and further incubation for 4 mins followed by substrate addition	ic50	0.0040	uM
5-[[4-[(E,4R,5R)-5-[(2S,5S,11S,14S,17S,20S,23R,26S,29S,32S)-5-ethyl-1,7,10,16,20,23,25,28,31-nonamethyl-11,17,26,29-tetrakis(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33-undecaoxo-14,32-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacont-2-yl]-5-hydroxy-4-methylpent-1-enyl]phenyl]methylcarbamoyl]-2-(3-hydroxy-6-oxoxanthen-9-yl)benzoic acid	580951: Inhibition of Cyclophilin 40 PPIase activity	ki	0.0120	uM
1-[(4-aminophenyl)methyl]-3-[(2S)-4-methylsulfanyl-1-[(2S)-2-(2-methylsulfanylphenyl)pyrrolidin-1-yl]-1-oxobutan-2-yl]urea	1296457: Inhibition of Cyclophilin D (unknown origin) activity preincubated for 15 mins followed Suc-AAPF-pNA substrate addition by chymotrypsin coupled based spectrophotometry assay	ki	0.0990	uM
2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methyl-N-(4-sulfamoylphenyl)-1,3-thiazole-5-carboxamide	1300180: Binding affinity to human recombinant cyclophilin D by surface plasmon resonance analysis	kd	0.1490	uM
1-[(5-ethyl-4-oxo-1,2,3,6-tetrahydro-1,5-benzodiazocin-8-yl)methyl]-3-[2-[(2R)-2-(2-methylsulfanylphenyl)pyrrolidin-1-yl]-2-oxoethyl]urea	1566289: Displacement of fluorescein labelled cyclosporine A derivative from human recombinant CypD (30 to 207 residues) expressed in Escherichia coli cells incubated for 90 mins by fluorescence polarization assay	ic50	0.1900	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149042: Binding affinity to human PPID incubated for 45 mins by Kinobead based pull down assay	kd	0.1914	uM
1-[(4-aminophenyl)methyl]-3-[2-[(2R)-2-(2-methylsulfanylphenyl)pyrrolidin-1-yl]-2-oxoethyl]urea	1566287: Binding affinity to CypD (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.2300	uM
2-(3,5-dioxo-4-azatricyclo[5.2.1.02,6]decan-4-yl)-N-(1,2,3,4-tetrahydroquinolin-6-ylmethyl)acetamide	1566290: Inhibition of CypD (unknown origin) PPIase activity using N-Suc-AAPF-p-nitroanilide as substrate preincubated with enzyme for 10 mins followed by chymotrypsin addition and further incubation for 4 mins followed by substrate addition	ic50	0.6000	uM
2-[(1S,2R,6S,7R)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]decan-4-yl]-N-[[(1R,9R,10S)-10-hydroxy-12-oxa-8-azatricyclo[7.3.1.02,7]trideca-2(7),3,5-trien-4-yl]methyl]acetamide	1566289: Displacement of fluorescein labelled cyclosporine A derivative from human recombinant CypD (30 to 207 residues) expressed in Escherichia coli cells incubated for 90 mins by fluorescence polarization assay	ic50	0.7350	uM
1-[(4-aminophenyl)methyl]-3-[2-[(2R)-2-(2-bromophenyl)pyrrolidin-1-yl]-2-oxoethyl]urea	1296457: Inhibition of Cyclophilin D (unknown origin) activity preincubated for 15 mins followed Suc-AAPF-pNA substrate addition by chymotrypsin coupled based spectrophotometry assay	ki	0.9500	uM
N’-cyclopentyl-N-[2-[(1R,9R,10S)-10-hydroxy-12-oxa-8-azatricyclo[7.3.1.02,7]trideca-2(7),3,5-trien-4-yl]ethyl]oxamide	1566290: Inhibition of CypD (unknown origin) PPIase activity using N-Suc-AAPF-p-nitroanilide as substrate preincubated with enzyme for 10 mins followed by chymotrypsin addition and further incubation for 4 mins followed by substrate addition	ic50	1.5000	uM
N,N’-bis(3-carbamoyl-4,5-dimethylthiophen-2-yl)pentanediamide	2084031: Inhibition of GST-tagged human CYP40 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	1.5000	uM
1-[[(1S,9S,10S)-10-hydroxy-12-oxa-8-azatricyclo[7.3.1.02,7]trideca-2(7),3,5-trien-4-yl]methyl]-3-[2-[(2R)-2-(2-methylsulfanylphenyl)pyrrolidin-1-yl]-2-oxoethyl]urea	1566289: Displacement of fluorescein labelled cyclosporine A derivative from human recombinant CypD (30 to 207 residues) expressed in Escherichia coli cells incubated for 90 mins by fluorescence polarization assay	ic50	1.7000	uM
2-[(1S,2S,6R,7R)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]decan-4-yl]-N-[[(1R,9R,10S)-10-hydroxy-12-oxa-8-azatricyclo[7.3.1.02,7]trideca-2(7),3,5-trien-4-yl]methyl]acetamide	1566289: Displacement of fluorescein labelled cyclosporine A derivative from human recombinant CypD (30 to 207 residues) expressed in Escherichia coli cells incubated for 90 mins by fluorescence polarization assay	ic50	1.7000	uM
N-[2,3-bis(furan-2-yl)quinoxalin-6-yl]pyrrolidine-1-carboxamide	1949528: Binding affinity to CypD (unknown origin)	ki	2.0000	uM
2,3-dihydro-1H-inden-1-yl-[5-(5-fluoro-2-hydroxy-3-nitrophenyl)-2-hydroxy-3-nitrophenyl]methanone	1799858: PPIase Assay from Article 10.1021/bi9007287: “Isoform-specific inhibition of cyclophilins.”	ki	2.4200	uM
ethyl 2-[(4-acetamidophenyl)methylcarbamoylamino]acetate	1296457: Inhibition of Cyclophilin D (unknown origin) activity preincubated for 15 mins followed Suc-AAPF-pNA substrate addition by chymotrypsin coupled based spectrophotometry assay	ki	2.6000	uM
N-[(4-aminophenyl)methyl]-2-(3,5-dioxo-4-azatricyclo[5.2.1.02,6]decan-4-yl)acetamide	1566289: Displacement of fluorescein labelled cyclosporine A derivative from human recombinant CypD (30 to 207 residues) expressed in Escherichia coli cells incubated for 90 mins by fluorescence polarization assay	ic50	2.8000	uM
ethyl 2-[(4-aminophenyl)methylcarbamoylamino]acetate	1296460: Inhibition of Cyclophilin D (unknown origin) activity in absence of detergent	ki	2.9000	uM
ethyl (3R)-1-[[2,3-bis(furan-2-yl)quinoxalin-6-yl]carbamoyl]piperidine-3-carboxylate	1949528: Binding affinity to CypD (unknown origin)	ki	3.0000	uM
3-[2,3-bis(furan-2-yl)quinoxalin-6-yl]-1,1-di(propan-2-yl)urea	1949528: Binding affinity to CypD (unknown origin)	ki	3.0000	uM
1-[2-[(2R)-2-(2-methylsulfanylphenyl)pyrrolidin-1-yl]-2-oxoethyl]-3-(1,2,3,4-tetrahydroquinolin-6-ylmethyl)urea	1566289: Displacement of fluorescein labelled cyclosporine A derivative from human recombinant CypD (30 to 207 residues) expressed in Escherichia coli cells incubated for 90 mins by fluorescence polarization assay	ic50	3.5000	uM
1-[[(1R,9R,10S)-10-hydroxy-12-oxa-8-azatricyclo[7.3.1.02,7]trideca-2(7),3,5-trien-4-yl]methyl]-3-[2-[(2S)-2-(2-methylsulfanylphenyl)pyrrolidin-1-yl]-2-oxoethyl]urea	1566289: Displacement of fluorescein labelled cyclosporine A derivative from human recombinant CypD (30 to 207 residues) expressed in Escherichia coli cells incubated for 90 mins by fluorescence polarization assay	ic50	3.6000	uM
3-(5-ethyl-4-oxo-1,2,3,6-tetrahydro-1,5-benzodiazocin-8-yl)-N-[2-[(2R)-2-(2-methylsulfanylphenyl)pyrrolidin-1-yl]-2-oxoethyl]propanamide	1566289: Displacement of fluorescein labelled cyclosporine A derivative from human recombinant CypD (30 to 207 residues) expressed in Escherichia coli cells incubated for 90 mins by fluorescence polarization assay	ic50	4.1000	uM
1-[(4-aminophenyl)methyl]-3-(2-oxo-2-pyrrolidin-1-ylethyl)urea	1296457: Inhibition of Cyclophilin D (unknown origin) activity preincubated for 15 mins followed Suc-AAPF-pNA substrate addition by chymotrypsin coupled based spectrophotometry assay	ki	4.9000	uM
ethyl (2S)-2-[(4-aminophenyl)methylcarbamoylamino]-4-methylsulfanylbutanoate	1296459: Binding affinity to Cyclophilin D (unknown origin) by isothermal titration calorimetry	kd	5.1200	uM
1-[(4-aminophenyl)methyl]-3-[2-oxo-2-[(2R)-2-phenylpyrrolidin-1-yl]ethyl]urea	1296459: Binding affinity to Cyclophilin D (unknown origin) by isothermal titration calorimetry	kd	5.4000	uM
[5-(3-amino-5-fluoro-2-hydroxyphenyl)-2-hydroxyphenyl]-(2,3-dihydro-1H-inden-1-yl)methanone	1799858: PPIase Assay from Article 10.1021/bi9007287: “Isoform-specific inhibition of cyclophilins.”	ki	6.2800	uM
ethyl (2S)-2-[(4-aminophenyl)methylcarbamoylamino]-4-methylpentanoate	1296459: Binding affinity to Cyclophilin D (unknown origin) by isothermal titration calorimetry	kd	8.8000	uM
3-[[(1R,9R,10S)-10-hydroxy-12-oxa-8-azatricyclo[7.3.1.02,7]trideca-2(7),3,5-trien-4-yl]methyl]-1-methyl-1-[2-[(2R)-2-(2-methylsulfanylphenyl)pyrrolidin-1-yl]-2-oxoethyl]urea	1566289: Displacement of fluorescein labelled cyclosporine A derivative from human recombinant CypD (30 to 207 residues) expressed in Escherichia coli cells incubated for 90 mins by fluorescence polarization assay	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	4
Air Pollutants	affects expression, increases abundance, decreases expression	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Ivermectin	affects cotreatment, decreases expression	2
Methotrexate	increases expression, affects response to substance	2
Rotenone	decreases expression, increases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
aristolochic acid I	increases expression	1
afuresertib	decreases expression	1
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
bisphenol A	decreases methylation	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	increases abundance, increases expression, affects cotreatment	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	affects binding, increases reaction	1
Antineoplastic Agents, Immunological	decreases expression, decreases response to substance	1
Sunitinib	increases expression	1
Vorinostat	increases expression	1
Acetaminophen	decreases expression	1
Cadmium	increases expression	1
Caffeine	increases phosphorylation	1
Calcium Chloride	increases expression	1
Cocaine	increases expression	1
Folic Acid	decreases expression	1
Formaldehyde	decreases expression	1

ChEMBL screening assays

23 unique, capped per target: 23 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1696288	Binding	Inhibition of Cyclophilin 40 PPIase activity	Facile synthesis of a fluorescent cyclosporin a analogue to study cyclophilin 40 and cyclophilin 18 ligands. — ACS Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2BP	Abcam HeLa PPID KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07180628	Not specified	RECRUITING	Organization and Development of Motor Cortical Circuits for Speech Production in Stuttering