TRAP1

Summary

TRAP1 (TNF receptor associated protein 1, HGNC:16264) is a protein-coding gene on chromosome 16p13.3, encoding Heat shock protein 75 kDa, mitochondrial (Q12931). Chaperone that expresses an ATPase activity.

This gene encodes a mitochondrial chaperone protein that is member of the heat shock protein 90 (HSP90) family. The encoded protein has ATPase activity and interacts with tumor necrosis factor type I. This protein may function in regulating cellular stress responses. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 10131 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic disease (Strong, GenCC)
• Clinical variants (ClinVar): 345 total — 1 pathogenic, 1 likely-pathogenic
• Druggable target: yes — 9 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_016292

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16264
Approved symbol	TRAP1
Name	TNF receptor associated protein 1
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	HSP75, HSP90L
Ensembl gene	ENSG00000126602
Ensembl biotype	protein_coding
OMIM	606219
Entrez	10131

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 11 protein_coding, 5 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000246957, ENST00000538171, ENST00000570403, ENST00000570514, ENST00000571011, ENST00000571538, ENST00000571804, ENST00000573872, ENST00000574175, ENST00000574494, ENST00000574941, ENST00000575671, ENST00000575707, ENST00000575854, ENST00000576106, ENST00000576335, ENST00000576788, ENST00000900180, ENST00000900181, ENST00000900182, ENST00000923089, ENST00000923090, ENST00000923091

RefSeq mRNA: 2 — MANE Select: NM_016292 NM_001272049, NM_016292

CCDS: CCDS10508, CCDS61824

Canonical transcript exons

ENST00000246957 — 18 exons

Exon	Start	End
ENSE00000865681	3661987	3662132
ENSE00000865683	3662882	3662967
ENSE00000865684	3663424	3663562
ENSE00000865686	3664274	3664459
ENSE00000865688	3665971	3666118
ENSE00000865693	3672700	3672820
ENSE00001321393	3658037	3658230
ENSE00002655290	3717421	3717524
ENSE00003498623	3676036	3676145
ENSE00003515726	3689055	3689137
ENSE00003525576	3675324	3675397
ENSE00003558742	3671722	3671791
ENSE00003570078	3690827	3690985
ENSE00003588290	3685996	3686136
ENSE00003643641	3658793	3658865
ENSE00003656993	3674339	3674494
ENSE00003679903	3677498	3677658
ENSE00003683439	3679719	3679790

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 80.3122 / max 567.8417, expressed in 1823 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156043	66.1522	1822
156044	14.1600	1703

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	98.03	gold quality
right uterine tube	UBERON:0001302	97.99	gold quality
gastrocnemius	UBERON:0001388	97.39	gold quality
triceps brachii	UBERON:0001509	97.20	gold quality
muscle of leg	UBERON:0001383	97.19	gold quality
gluteal muscle	UBERON:0002000	97.11	gold quality
right lobe of liver	UBERON:0001114	96.98	gold quality
muscle organ	UBERON:0001630	96.76	gold quality
skeletal muscle organ	UBERON:0014892	96.76	gold quality
body of pancreas	UBERON:0001150	96.68	gold quality
apex of heart	UBERON:0002098	96.47	gold quality
skin of leg	UBERON:0001511	96.45	gold quality
skin of abdomen	UBERON:0001416	96.31	gold quality
cortical plate	UBERON:0005343	96.17	gold quality
islet of Langerhans	UBERON:0000006	96.15	gold quality
mucosa of stomach	UBERON:0001199	96.07	gold quality
heart left ventricle	UBERON:0002084	96.05	gold quality
pancreas	UBERON:0001264	95.97	gold quality
metanephros cortex	UBERON:0010533	95.93	gold quality
cardiac ventricle	UBERON:0002082	95.90	gold quality
left ovary	UBERON:0002119	95.85	gold quality
vastus lateralis	UBERON:0001379	95.81	gold quality
quadriceps femoris	UBERON:0001377	95.77	gold quality
right ovary	UBERON:0002118	95.72	gold quality
skeletal muscle tissue	UBERON:0001134	95.70	gold quality
pancreatic ductal cell	CL:0002079	95.69	silver quality
esophagus mucosa	UBERON:0002469	95.67	gold quality
ectocervix	UBERON:0012249	95.66	gold quality
prefrontal cortex	UBERON:0000451	95.61	gold quality
endocervix	UBERON:0000458	95.55	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	13.10
E-MTAB-9388	yes	7.75
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

Literature-anchored findings (GeneRIF, showing 40)

• suppression of the expression of TRAP1 in mitochondria might play an important role in the induction of apoptosis caused via formation of ROS (PMID:15292218)
• TRAP1 might play a role in protecting mitochondria against damaging stimuli via decrease of reactive oxygen species generation (PMID:16927372)
• PINK1 protects against oxidative-stress-induced cell death by suppressing cytochrome c release from mitochondria, and this protective action of PINK1 depends on its kinase activity to phosphorylate TRAP1. (PMID:17579517)
• TRAP-1 protects cells from oxidative stress and apoptosis (PMID:17853063)
• Hsp75 can provide protection against ischemia-like in vitro injury (PMID:18091755)
• analysis of the ATPase cycle of the mitochondrial Hsp90 analog Trap1 (PMID:18287101)
• mitochondrial ribosomal protein S12 3’-UTR interacts specifically with TRAP1 (tumor necrosis factor receptor-associated protein1), hnRNPM4 (heterogeneous nuclear ribonucleoprotein M4), Hsp70 and Hsp60 (heat shock proteins 70 and 60), and alpha-tubulin (PMID:18790094)
• Data show that mtDNA variability is able to influence the cellular response to heat stress by modulating both the transcription of HSP60 and 75 and their intra-mitochondrial protein levels. (PMID:18815895)
• TRAP1, a novel mitochondrial chaperone responsible for multi-drug resistance and protection from apoptotis in human colorectal carcinoma cells. (PMID:19217207)
• TRAP1 works synergistically with tumor necrosis factor receptor 1 (TNFR1) to modulate expression of the cell adhesion molecule N-cadherin, and alters inter-cellular adhesion of neuronal cells. (PMID:19490362)
• These data identify TRAP-1 as a novel mitochondrial survival factor differentially expressed in localized and metastatic prostate cancer compared with normal prostate. (PMID:19948822)
• In many tumors TRAP1 may activate proliferation whilst inhibiting metastatic spread. (PMID:20471161)
• up-regulated in prostate cancer tissue (PMID:20499060)
• Depletion of TRAP1 by short hairpin RNA in colorectal carcinoma cells lowered Sorcin levels in mitochondria, whereas the depletion of Sorcin by small interfering RNA increased TRAP1 degradation. (PMID:20647321)
• Mitochondria could be a potential regulator of the unfolded protein response in the endoplasmic reticulum via mitochondrial TRAP1. (PMID:21338643)
• HSP75 likely reduces the hypertrophy and fibrosis induced by pressure overload through blocking TAK/P38, JNK, and AKT signaling pathways (PMID:21381076)
• TRAP-1-directed compartmentalized protein folding is broadly exploited in cancer. (PMID:21878357)
• The proposed TRAP1 network has an impact in vivo, as it is conserved in human colorectal cancers, is controlled by ER-localized TRAP1 interacting with TBP7 and provides a novel model of the ER-mitochondria crosstalk. (PMID:21979464)
• alpha-Synuclein toxicity is intimately connected to mitochondrial dysfunction and that toxicity reduction in fly and rat primary neurons and human cell lines can be achieved using overexpression of the mitochondrial chaperone TRAP1 (PMID:22319455)
• Immunohistochemical evaluation of TRAP1 together with ERalpha provides significant prognostic information. TRAP1 alone is significantly associated with chemotherapy response and overall survival. (PMID:22978347)
• Mitochondria TRAP-1 affects the lymph node metastasis in colorectal cancer, and may be a potential biomarker for LNM and a prognostic factor in CRC. (PMID:23139614)
• Early mesangial nephritis initiates a cascade of inflammatory signals that lead to up-regulation of Trap1 and a consequent down-regulation of renal DNaseI by transcriptional interference. (PMID:23273922)
• TRAP1 controls mitochondrial fusion/fission balance through Drp1 and Mff expression. (PMID:23284813)
• Overexpression of TRAP1 is able to mitigate Pink1 but not parkin loss-of-function phenotypes. (PMID:23525905)
• TRAP1 binds to and inhibits succinate dehydrogenase (SDH), the complex II of the respiratory chain. (PMID:23747254)
• Mitochondrial Hsp90 and TRAP-1 are global regulators of tumor metabolic reprogramming, including oxidative phosphorylation, and are required for disease maintenance. (PMID:23842546)
• This study demonstrates for the first time that TRAP1 is associated with ribosomes and with several translation factors in colon carcinoma cells. (PMID:24113185)
• Identify mutations in TRAP1 as highly likely causing CAKUT or VACTERL association with CAKUT. (PMID:24152966)
• High TRAP1 expression is associated with resistance to anthracyclins in breast carcinoma. (PMID:24297638)
• TRAP1 controls NSCLC proliferation, apoptosis, and mitochondrial function, and its status has prognostic potential in NSCLC. (PMID:24567527)
• study shows that TRAP1 was overexpressed in most patients with ESCC, and caused an increase in antiapoptosis potency (PMID:24754231)
• TRAP1-dependent regulation of p70S6K is involved in the attenuation of protein synthesis and cell migration: relevance in human colorectal tumors (PMID:24962791)
• The article summarizes the central regulatory function of TRAP1 with homeostatic roles at the crossroad between different kinds of cell functions/metabolism during the transformation process or, possibly, during normal development. [review] (PMID:24990602)
• dual HSP90/TRAP1 inhibitor HSP990 showed activity against the TRAP1 network and high cytostatic potential in BRAF-mutated colorectal carcinoma cells (PMID:25239454)
• TRAP1 expression was associated with increased risk of lymph node metastasis, while high TRAP1 expression correlated with poor prognosis in esophageal squamous cell cancer. (PMID:25438697)
• Oxidative stress in ulcerative colitis could lead to the increase of cytoprotective protein TRAP1, which in turn could promote cancer progression by preventing or protecting the oxidative damaged epithelial cells from undergoing apoptosis. (PMID:25493016)
• crystal structure of the mitochondrial Hsp90, TRAP1, revealed an extension of the N-terminal beta-strand previously shown to cross between protomers in the closed state (PMID:25531069)
• Our findings demonstrate that SDH inhibition by TRAP1 is oncogenic not only by inducing pseudohypoxia, but also by protecting tumor cells from oxidative stress (PMID:25564869)
• The combined presence of pain, fatigue and nausea is strongly associated with p.Ile253Val (OR 7.5, P = 0.0001) and with two other interacting variants (OR 18, P = 0.0005). (PMID:26022780)
• a correlation between TRAP1 and AKT expression is found in vivo in human colorectal tumours. These results provide new insights into TRAP1 role in the regulation of cell migration in cancer cells, tumour progression and metastatic mechanisms. (PMID:26071104)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	trap1	ENSDARG00000024317
mus_musculus	Trap1	ENSMUSG00000005981
rattus_norvegicus	Trap1	ENSRNOG00000005418
drosophila_melanogaster	Trap1	FBGN0026761
caenorhabditis_elegans		WBGENE00020110

Paralogs (3): HSP90AA1 (ENSG00000080824), HSP90AB1 (ENSG00000096384), HSP90B1 (ENSG00000166598)

Protein

Protein identifiers

Heat shock protein 75 kDa, mitochondrial — Q12931 (reviewed: Q12931)

Alternative names: Heat shock protein family C member 5, TNFR-associated protein 1, Tumor necrosis factor type 1 receptor-associated protein

All UniProt accessions (9): Q12931, A0A140VJY2, I3L0K7, I3L0P6, I3L239, I3L253, I3L2D5, I3L3L4, I3L4L7

UniProt curated annotations — full annotation on UniProt →

Function. Chaperone that expresses an ATPase activity. Involved in maintaining mitochondrial function and polarization, downstream of PINK1 and mitochondrial complex I. Is a negative regulator of mitochondrial respiration able to modulate the balance between oxidative phosphorylation and aerobic glycolysis. The impact of TRAP1 on mitochondrial respiration is probably mediated by modulation of mitochondrial SRC and inhibition of SDHA.

Subunit / interactions. Binds to the intracellular domain of tumor necrosis factor type 1 receptor. Binds to RB1. Interacts with SRC. Interacts with SDHA.

Subcellular location. Mitochondrion. Mitochondrion inner membrane. Mitochondrion matrix.

Tissue specificity. Found in skeletal muscle, liver, heart, brain, kidney, pancreas, lung, placenta and bladder. Expression is highly reduced in bladder cancer and renal cell carcinoma specimens compared to healthy tissues, but it is increased in other type of tumors.

Similarity. Belongs to the heat shock protein 90 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q12931-1	1	yes
Q12931-2	2

RefSeq proteins (2): NP_001258978, NP_057376* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001404	Hsp90_fam	Family
IPR003594	HATPase_dom	Domain
IPR020568	Ribosomal_Su5_D2-typ_SF	Homologous_superfamily
IPR020575	Hsp90_N	Domain
IPR036890	HATPase_C_sf	Homologous_superfamily
IPR037196	HSP90_C	Homologous_superfamily

Pfam: PF00183, PF13589

UniProt features (96 total): helix 32, strand 28, modified residue 11, turn 8, binding site 5, sequence conflict 5, sequence variant 4, transit peptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

24 structures.

PDB	Method	Resolution (Å)
7U8V	X-RAY DIFFRACTION	1.45
7C7B	X-RAY DIFFRACTION	1.5
7U8X	X-RAY DIFFRACTION	1.6
7C04	X-RAY DIFFRACTION	1.7
7U8W	X-RAY DIFFRACTION	1.71
5F3K	X-RAY DIFFRACTION	1.82
5F5R	X-RAY DIFFRACTION	1.85
7ULK	X-RAY DIFFRACTION	2.34
5Y3N	X-RAY DIFFRACTION	2.4
5HPH	X-RAY DIFFRACTION	2.43
7C05	X-RAY DIFFRACTION	2.59
5Y3O	X-RAY DIFFRACTION	2.7
4Z1F	X-RAY DIFFRACTION	2.7
4Z1H	X-RAY DIFFRACTION	2.9
7C7C	X-RAY DIFFRACTION	3
7U8U	X-RAY DIFFRACTION	3.06
4Z1G	X-RAY DIFFRACTION	3.1
7KLV	ELECTRON MICROSCOPY	3.1
7KCL	ELECTRON MICROSCOPY	3.14
6XG6	ELECTRON MICROSCOPY	3.2
7KCK	ELECTRON MICROSCOPY	3.26
4Z1I	X-RAY DIFFRACTION	3.3
7KCM	ELECTRON MICROSCOPY	3.43
7KLU	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12931-F1	86.28	0.63

Functional residue map

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

Ligand- & substrate-binding residues (5): 119; 158; 171; 205; 402

Post-translational modifications (11): 262, 324, 332, 424, 431, 466, 494, 568, 170, 174, 194

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-611105	Respiratory electron transport
R-HSA-71403	Citric acid cycle (TCA cycle)

MSigDB gene sets: 215 (showing top): ATF_B, SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP, RORA1_01, GOBP_NEGATIVE_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, CREBP1_Q2, TGACCTY_ERR1_Q2, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_TRANSLATION, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_REACTIVE_OXYGEN_SPECIES_BIOSYNTHETIC_PROCESS, SCHUHMACHER_MYC_TARGETS_UP, GOBP_PROTEIN_MATURATION

GO Biological Process (5): protein folding (GO:0006457), translational attenuation (GO:0009386), negative regulation of cellular respiration (GO:1901856), negative regulation of reactive oxygen species biosynthetic process (GO:1903427), negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide (GO:1903751)

GO Molecular Function (9): RNA binding (GO:0003723), tumor necrosis factor receptor binding (GO:0005164), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), protein kinase binding (GO:0019901), obsolete unfolded protein binding (GO:0051082), ATP-dependent protein folding chaperone (GO:0140662), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (7): nucleoplasm (GO:0005654), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial intermembrane space (GO:0005758), mitochondrial matrix (GO:0005759), membrane (GO:0016020), intracellular organelle lumen (GO:0070013)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Aerobic respiration and respiratory electron transport	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ATP-dependent activity	2
cellular anatomical structure	2
cellular process	1
protein maturation	1
regulation of translation	1
negative regulation of metabolic process	1
regulation of cellular respiration	1
cellular respiration	1
negative regulation of biosynthetic process	1
reactive oxygen species biosynthetic process	1
regulation of reactive oxygen species biosynthetic process	1
negative regulation of reactive oxygen species metabolic process	1
intrinsic apoptotic signaling pathway in response to hydrogen peroxide	1
negative regulation of hydrogen peroxide-mediated programmed cell death	1
negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	1
regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide	1
nucleic acid binding	1
tumor necrosis factor receptor superfamily binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
kinase binding	1
protein folding chaperone	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
nuclear lumen	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrial envelope	1
organelle envelope lumen	1
mitochondrion	1
intracellular organelle lumen	1
intracellular organelle	1
organelle lumen	1

Protein interactions and networks

STRING

4485 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRAP1	PINK1	Q9BXM7	724
TRAP1	EXTL3	O43909	718
TRAP1	EXTL1	Q92935	714
TRAP1	EXT1	Q16394	697
TRAP1	PPIF	P30405	672
TRAP1	EXT2	Q93063	663
TRAP1	DNASE1	P24855	615
TRAP1	SRI	P30626	611
TRAP1	TNF	P01375	589
TRAP1	DNAJB1	P25685	555
TRAP1	HSPA9	P30036	549
TRAP1	HSP90AB1	P08238	540
TRAP1	HSP90AA1	P07900	537
TRAP1	CDC37	Q16543	504
TRAP1	BAG2	O95816	499

IntAct

180 interactions, top by confidence:

A	B	Type	Score
APC	CTNNB1	psi-mi:“MI:0914”(association)	0.960
CDK5	FIBP	psi-mi:“MI:0914”(association)	0.840
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
CDK9	AIP	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CDK4	HSP90AA1	psi-mi:“MI:0914”(association)	0.640
PINK1	TRAP1	psi-mi:“MI:0915”(physical association)	0.600
PINK1	TRAP1	psi-mi:“MI:0407”(direct interaction)	0.600
SYNGAP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
AKAP12	HSPA12A	psi-mi:“MI:0914”(association)	0.530
PRKACB	VAPB	psi-mi:“MI:0914”(association)	0.530
HSD17B10	TRAP1	psi-mi:“MI:0915”(physical association)	0.500
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
HSCB	NDUFS8	psi-mi:“MI:0914”(association)	0.460
	TRAP1	psi-mi:“MI:0915”(physical association)	0.400
SYTL4	TRAP1	psi-mi:“MI:0915”(physical association)	0.400
TRAP1	HSPA9	psi-mi:“MI:0915”(physical association)	0.400
TRAP1	ACTB	psi-mi:“MI:0915”(physical association)	0.400
Bles03		psi-mi:“MI:0915”(physical association)	0.400
YWHAZ	TRAP1	psi-mi:“MI:0915”(physical association)	0.400
TRAP1	PTGER4	psi-mi:“MI:0915”(physical association)	0.370
TRAP1	FXR1	psi-mi:“MI:0915”(physical association)	0.370
TPM3	TRAP1	psi-mi:“MI:0915”(physical association)	0.370
TRAP1	ESX1	psi-mi:“MI:0915”(physical association)	0.370
SIRT4	VWA8	psi-mi:“MI:0914”(association)	0.350
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
Ppp6r1	PPP6C	psi-mi:“MI:0914”(association)	0.350

BioGRID (551): TRAP1 (Affinity Capture-RNA), TRAP1 (Affinity Capture-MS), TRAP1 (Affinity Capture-MS), TRAP1 (Affinity Capture-MS), TRAP1 (Affinity Capture-MS), ALDOA (Co-fractionation), ALDOC (Co-fractionation), COQ3 (Co-fractionation), COX6B1 (Co-fractionation), DUT (Co-fractionation), GAPDH (Co-fractionation), GLRX (Co-fractionation), IQGAP1 (Co-fractionation), LTA4H (Co-fractionation), PRDX5 (Co-fractionation)

ESM2 similar proteins: A1A4J8, A6H784, D3ZS74, D4A6D7, E9QBI7, O42899, O43819, O60341, O75880, P00258, P10109, P23833, P24483, P30048, P38072, Q05B51, Q0VCH8, Q12931, Q2KHU5, Q2NKY8, Q2TBI4, Q3ULF4, Q4VAE3, Q5EA41, Q5REY3, Q5RH02, Q5SUC9, Q69ZP3, Q6DKK2, Q6PI78, Q6ZQ88, Q7ZUC7, Q8BMS4, Q8JZQ2, Q8LAL0, Q8N490, Q8VCL2, Q920A7, Q95N00, Q96HS1

Diamond homologs: A0KL53, A1A8D9, A1ANS1, A1AWE2, A1BFP7, A1JNB3, A1S564, A1TZH7, A1W3A1, A1WXE4, A3QF50, A4SEX9, A4SLY0, A4TPA5, A4XV81, A5IBL1, A5UB42, A5UFQ9, A6T5N6, A6V7J7, A6VML2, A7MJW4, A7ZIN3, A7ZXD1, A8AJX0, A8FX83, A8GAV2, A8H2R4, A9KGQ8, A9MW88, A9NB44, B0USJ0, B1IZC1, B7VII6, C3K6N7, P0A6Z3, P0A6Z4, P0A6Z5, P44516, P54649

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PINK1	“up-regulates activity”	TRAP1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 210 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial electron transport, NADH to ubiquinone	7	13.5×	4e-04
autophagosome maturation	7	13.2×	4e-04
mitophagy	6	10.3×	7e-03
JNK cascade	7	10.2×	2e-03
mitochondrion organization	10	8.2×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	181
Likely benign	86
Benign	43

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1457650	NC_000016.9:g.(?3711968)(3781958_?)del	Pathogenic
2445209	Single allele	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

4589 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:3677599:A:C	F201L	1.000
16:3677599:A:T	F201L	1.000
16:3677601:A:G	F201L	1.000
16:3679735:G:T	A176D	1.000
16:3671754:G:C	S401R	0.999
16:3671754:G:T	S401R	0.999
16:3671756:T:G	S401R	0.999
16:3674488:A:G	W299R	0.999
16:3674488:A:T	W299R	0.999
16:3677511:A:G	W231R	0.999
16:3677511:A:T	W231R	0.999
16:3677591:C:T	G204D	0.999
16:3677597:C:T	G202E	0.999
16:3677606:C:T	G199D	0.999
16:3679738:A:T	I175N	0.999
16:3689083:A:T	V101D	0.999
16:3689115:G:C	F90L	0.999
16:3689115:G:T	F90L	0.999
16:3689116:A:G	F90S	0.999
16:3689117:A:G	F90L	0.999
16:3666003:C:G	G451R	0.998
16:3671752:C:G	R402P	0.998
16:3671755:C:A	S401I	0.998
16:3677587:G:C	F205L	0.998
16:3677587:G:T	F205L	0.998
16:3677589:A:G	F205L	0.998
16:3677592:C:G	G204R	0.998
16:3677598:C:G	G202R	0.998
16:3677598:C:T	G202R	0.998
16:3679790:C:G	D158H	0.998

dbSNP variants (sampled 300 via entrez): RS1000014150 (16:3664791 G>A), RS1000037666 (16:3712667 G>A), RS1000049710 (16:3684477 C>A,T), RS1000066591 (16:3664919 T>C), RS1000100129 (16:3684126 A>G,T), RS1000173047 (16:3696597 C>T), RS1000183657 (16:3717989 G>A), RS1000201768 (16:3716403 C>T), RS1000228915 (16:3698996 C>T), RS1000246934 (16:3704203 G>T), RS1000360297 (16:3692504 A>G,T), RS1000383226 (16:3661254 T>C), RS1000407754 (16:3694931 G>C), RS1000411367 (16:3692301 T>A), RS1000458988 (16:3668599 C>CT)

Disease associations

OMIM: gene MIM:606219 | disease phenotypes: MIM:180849, MIM:192350, MIM:610805

GenCC curated gene-disease

Disease	Classification	Inheritance
syndromic disease	Strong	Autosomal recessive

Mondo (5): Rubinstein-Taybi syndrome (MONDO:0019188), VACTERL/vater association (MONDO:0008642), Rubinstein-Taybi syndrome due to CREBBP mutations (MONDO:0008393), congenital anomaly of kidney and urinary tract (MONDO:0019719), syndromic disease (MONDO:0002254)

Orphanet (4): Rubinstein-Taybi syndrome (Orphanet:783), VACTERL/VATER association (Orphanet:887), Rubinstein-Taybi syndrome due to CREBBP mutations (Orphanet:353277), Renal or urinary tract malformation (Orphanet:93545)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D012415	Rubinstein-Taybi Syndrome	C05.116.099.370.797; C05.660.207.850; C10.597.606.360.700; C16.131.077.804; C16.131.260.790; C16.131.621.207.850; C16.320.180.790
D013577	Syndrome	C23.550.288.500
C566906	Cakut (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1075132 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

9 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 328,006 (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
CHEMBL109480	TANESPIMYCIN	3	3,645
CHEMBL2103879	GANETESPIB	3	2,075
CHEMBL1229093	MITOQUINONE CATION	2	303
CHEMBL14249	ADENOSINE TRIPHOSPHATE	2	287,353
CHEMBL200102	PU-H71	2	221
CHEMBL252164	LUMINESPIB	2	1,800
CHEMBL278315	GELDANAMYCIN	2	30,673
CHEMBL467399	BIIB021	2	1,606
CHEMBL2419346	CUDC-305	1	330

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — Heat shock proteins

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
luminespib	Inhibition	7.8	pIC50

ChEMBL bioactivities

148 potent at pChembl≥5 of 173 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.24	Kd	5.8	nM	CHEMBL1910764
8.23	Kd	5.9	nM	CHEMBL2419342
8.00	Kd	10	nM	CHEMBL4126250
7.80	Ki	16	nM	LUMINESPIB
7.42	IC50	38	nM	LUMINESPIB
7.42	IC50	37.7	nM	GANETESPIB
7.40	Kd	40	nM	CHEMBL5633903
7.40	Kd	40	nM	CHEMBL5633816
7.29	IC50	51	nM	GANETESPIB
7.29	Kd	51.8	nM	CHEMBL2419341
7.24	IC50	58	nM	CHEMBL4866705
7.21	Ki	62	nM	BIIB021
7.21	IC50	62.4	nM	CHEMBL4863672
7.20	IC50	63.5	nM	CHEMBL4864922
7.18	IC50	65.8	nM	CHEMBL4869481
7.18	IC50	66	nM	CHEMBL4869481
7.12	IC50	76.6	nM	CHEMBL4879021
7.10	IC50	79	nM	CHEMBL4068596
7.10	Kd	80	nM	CHEMBL5633571
7.09	IC50	81.5	nM	CHEMBL4866958
7.08	IC50	82.7	nM	CHEMBL4876871
7.05	IC50	90	nM	BIIB021
7.05	IC50	89.9	nM	CHEMBL4863988
7.05	Kd	90	nM	CHEMBL5632075
7.05	Kd	90	nM	CHEMBL5633012
7.00	IC50	100	nM	CHEMBL4871630
6.86	IC50	138	nM	CHEMBL4080323
6.84	IC50	143	nM	CHEMBL4068596
6.80	Kd	160	nM	CHEMBL5631806
6.77	IC50	170	nM	CHEMBL4857569
6.75	IC50	178	nM	CHEMBL4860652
6.72	IC50	192	nM	PU-H71
6.70	IC50	200	nM	CHEMBL3360305
6.69	IC50	205	nM	PU-H71
6.64	IC50	230	nM	CHEMBL4850126
6.64	Kd	230	nM	CHEMBL5633174
6.62	Kd	240	nM	PU-H71
6.61	IC50	243	nM	CHEMBL4846028
6.59	Ki	255	nM	CHEMBL1230584
6.59	IC50	257	nM	PU-H71
6.57	Kd	270	nM	CHEMBL6162105
6.53	IC50	296	nM	CHEMBL4870087
6.49	Ki	326	nM	CHEMBL3104859
6.48	IC50	330.6	nM	PU-H71
6.48	IC50	332	nM	CHEMBL4864235
6.48	IC50	331	nM	CHEMBL4854861
6.47	IC50	339	nM	CHEMBL4867384
6.46	Kd	350	nM	CHEMBL5631336
6.44	Kd	360	nM	CHEMBL5633431
6.43	IC50	373	nM	CHEMBL5266569

PubChem BioAssay actives

124 with measured affinity, of 318 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
5-[[3-[6-amino-8-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]purin-9-yl]propyl-propan-2-ylcarbamothioyl]amino]-2-(3-hydroxy-6-oxoxanthen-9-yl)benzoic acid	767755: Binding affinity to recombinant human Trap-1 by fluorescence polarization assay	kd	0.0058	uM
5-[3-[6-amino-8-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]purin-9-yl]propylcarbamothioylamino]-2-(3-hydroxy-6-oxoxanthen-9-yl)benzoic acid	767755: Binding affinity to recombinant human Trap-1 by fluorescence polarization assay	kd	0.0059	uM
4-N-(diaminomethylidene)-1-N-[5-(2,4-dihydroxy-5-propan-2-ylphenyl)-3-(ethylcarbamoyl)-1,2-oxazol-4-yl]benzene-1,4-dicarboxamide	1497390: Inhibition of FITC-geldanamycin binding to recombinant human N-terminal His6-tagged TRAP1 (60 to 704 residues) expressed in Escherichia coli BL21-CodonPlus-RIL by fluorescence anisotropy method	kd	0.0100	uM
5-(2,4-dihydroxy-5-propan-2-ylphenyl)-N-ethyl-4-[4-(morpholin-4-ylmethyl)phenyl]-1,2-oxazole-3-carboxamide	1063122: Binding affinity to human recombinant TRAP1 after 3 hrs by fluorescence polarization assay	ki	0.0160	uM
3-(2,4-dihydroxy-5-propan-2-ylphenyl)-4-(1-methylindol-5-yl)-1H-1,2,4-triazol-5-one	1653907: Inhibition of TRAP1 (unknown origin)	ic50	0.0377	uM
3-[[2-[2-hydroxy-5-(4-methoxy-1,3-dihydroisoindole-2-carbonyl)benzoyl]-1,3-dihydroisoindol-5-yl]oxy]propyl-triphenylphosphanium	2135531: Binding affinity to TRAP1 (unknown origin) assessed as dissociation constant incubated for 24 hrs by fluorescence polarization assay	kd	0.0400	uM
[3-(1,3-dihydroisoindole-2-carbonyl)-4-hydroxyphenyl]-(4-methoxy-1,3-dihydroisoindol-2-yl)methanone	2135531: Binding affinity to TRAP1 (unknown origin) assessed as dissociation constant incubated for 24 hrs by fluorescence polarization assay	kd	0.0400	uM
24-[2-[4-[[(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-9-carbamoyloxy-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-19-yl]amino]butylamino]-2-oxoethyl]-5,5,27,27-tetramethyl-16-oxa-20-aza-12-azoniaheptacyclo[15.11.0.03,15.04,12.06,11.020,28.021,26]octacosa-1(28),2,4(12),6(11),7,9,21(26),22,24-nonaene-8-sulfonate	767755: Binding affinity to recombinant human Trap-1 by fluorescence polarization assay	kd	0.0518	uM
2-amino-9-[(4-bromo-2-fluorophenyl)methyl]-6-chloro-7H-purin-8-one	1765850: Inhibition of PU-H71-FITC3 binding to recombinant full length TRAP1 (unknown origin) incubated for 2 hrs by fluorescence polarization assay	ic50	0.0580	uM
6-chloro-9-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]purin-2-amine	1063122: Binding affinity to human recombinant TRAP1 after 3 hrs by fluorescence polarization assay	ki	0.0620	uM
2-amino-6-chloro-9-[(2-fluoro-4-methylphenyl)methyl]-7H-purin-8-one	1765850: Inhibition of PU-H71-FITC3 binding to recombinant full length TRAP1 (unknown origin) incubated for 2 hrs by fluorescence polarization assay	ic50	0.0624	uM
2-amino-6-chloro-9-[(3,4-dichlorophenyl)methyl]-7H-purine-8-thione	1765850: Inhibition of PU-H71-FITC3 binding to recombinant full length TRAP1 (unknown origin) incubated for 2 hrs by fluorescence polarization assay	ic50	0.0635	uM
2-amino-9-[(6-bromo-1,3-benzodioxol-5-yl)methyl]-6-chloro-7H-purin-8-one	1765850: Inhibition of PU-H71-FITC3 binding to recombinant full length TRAP1 (unknown origin) incubated for 2 hrs by fluorescence polarization assay	ic50	0.0658	uM
2-amino-6-chloro-9-[(3,4-dichlorophenyl)methyl]-7H-purin-8-one	1765850: Inhibition of PU-H71-FITC3 binding to recombinant full length TRAP1 (unknown origin) incubated for 2 hrs by fluorescence polarization assay	ic50	0.0766	uM
1-[(6-bromo-1,3-benzodioxol-5-yl)methyl]-4-chloropyrazolo[5,4-d]pyrimidin-6-amine	1451173: Inhibition of FITC3-labeled PU-H71 binding to recombinant human N-terminal His6-tagged TRAP1 (60 to 561 residues) expressed in Escherichia coli BL21(DE3) after 24 hrs by fluorescence polarization assay	ic50	0.0790	uM
[3-(1,3-dihydroisoindole-2-carbonyl)-4-hydroxyphenyl]-(4-ethoxy-1,3-dihydroisoindol-2-yl)methanone	2135531: Binding affinity to TRAP1 (unknown origin) assessed as dissociation constant incubated for 24 hrs by fluorescence polarization assay	kd	0.0800	uM
2-amino-4-chloro-7-[(3,4-dichlorophenyl)methyl]-5H-pyrrolo[2,3-d]pyrimidin-6-one	1765850: Inhibition of PU-H71-FITC3 binding to recombinant full length TRAP1 (unknown origin) incubated for 2 hrs by fluorescence polarization assay	ic50	0.0815	uM
2-amino-6-chloro-9-[(2-fluoro-4-methylphenyl)methyl]-7H-purine-8-thione	1765850: Inhibition of PU-H71-FITC3 binding to recombinant full length TRAP1 (unknown origin) incubated for 2 hrs by fluorescence polarization assay	ic50	0.0827	uM
2-amino-4-chloro-7-[(2-fluoro-4-methylphenyl)methyl]-5H-pyrrolo[2,3-d]pyrimidin-6-one	1765850: Inhibition of PU-H71-FITC3 binding to recombinant full length TRAP1 (unknown origin) incubated for 2 hrs by fluorescence polarization assay	ic50	0.0899	uM
[3-[5-[3-(dimethylamino)propoxy]-1,3-dihydroisoindole-2-carbonyl]-4-hydroxyphenyl]-(4-methoxy-1,3-dihydroisoindol-2-yl)methanone	2135531: Binding affinity to TRAP1 (unknown origin) assessed as dissociation constant incubated for 24 hrs by fluorescence polarization assay	kd	0.0900	uM
[3-[5-[2-(dimethylamino)ethoxy]-1,3-dihydroisoindole-2-carbonyl]-4-hydroxyphenyl]-(4-methoxy-1,3-dihydroisoindol-2-yl)methanone	2135531: Binding affinity to TRAP1 (unknown origin) assessed as dissociation constant incubated for 24 hrs by fluorescence polarization assay	kd	0.0900	uM
2-amino-7-[(4-bromo-2-fluorophenyl)methyl]-4-chloro-5H-pyrrolo[2,3-d]pyrimidin-6-one	1765850: Inhibition of PU-H71-FITC3 binding to recombinant full length TRAP1 (unknown origin) incubated for 2 hrs by fluorescence polarization assay	ic50	0.1000	uM
4-chloro-1-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]pyrazolo[5,4-d]pyrimidin-6-amine	1451173: Inhibition of FITC3-labeled PU-H71 binding to recombinant human N-terminal His6-tagged TRAP1 (60 to 561 residues) expressed in Escherichia coli BL21(DE3) after 24 hrs by fluorescence polarization assay	ic50	0.1380	uM
3-[[2-[5-(4-fluoro-1,3-dihydroisoindole-2-carbonyl)-2-hydroxybenzoyl]-1,3-dihydroisoindol-5-yl]oxy]propyl-triphenylphosphanium	2135531: Binding affinity to TRAP1 (unknown origin) assessed as dissociation constant incubated for 24 hrs by fluorescence polarization assay	kd	0.1600	uM
2-amino-6-chloro-9-[[2-chloro-5-(trifluoromethyl)phenyl]methyl]-7H-purin-8-one	1765850: Inhibition of PU-H71-FITC3 binding to recombinant full length TRAP1 (unknown origin) incubated for 2 hrs by fluorescence polarization assay	ic50	0.1700	uM
2-amino-6-chloro-9-[(2,6-difluoro-4-methoxyphenyl)methyl]-7H-purine-8-thione	1765850: Inhibition of PU-H71-FITC3 binding to recombinant full length TRAP1 (unknown origin) incubated for 2 hrs by fluorescence polarization assay	ic50	0.1780	uM
8-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine	1765850: Inhibition of PU-H71-FITC3 binding to recombinant full length TRAP1 (unknown origin) incubated for 2 hrs by fluorescence polarization assay	ic50	0.1920	uM
(7R)-2-amino-7-[4-fluoro-2-(6-methoxy-2-pyridinyl)phenyl]-4-methyl-7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one	1497388: Inhibition of recombinant human N-terminal His6-tagged TRAP1 (60 to 704 residues) ATPase activity expressed in Escherichia coli BL21-CodonPlus-RIL after overnight incubation by BioMol green dye-based assay	ic50	0.2000	uM
2-amino-4-chloro-7-[(2,6-difluoro-3-methoxyphenyl)methyl]-5H-pyrrolo[2,3-d]pyrimidin-6-one	1765850: Inhibition of PU-H71-FITC3 binding to recombinant full length TRAP1 (unknown origin) incubated for 2 hrs by fluorescence polarization assay	ic50	0.2300	uM
(4-chloro-1,3-dihydroisoindol-2-yl)-[3-(1,3-dihydroisoindole-2-carbonyl)-4-hydroxyphenyl]methanone	2135531: Binding affinity to TRAP1 (unknown origin) assessed as dissociation constant incubated for 24 hrs by fluorescence polarization assay	kd	0.2300	uM
2-amino-6-chloro-9-[(5-chloro-2-fluorophenyl)methyl]-7H-purin-8-one	1765850: Inhibition of PU-H71-FITC3 binding to recombinant full length TRAP1 (unknown origin) incubated for 2 hrs by fluorescence polarization assay	ic50	0.2430	uM
5-[2-amino-4-chloro-7-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]pyrrolo[2,3-d]pyrimidin-5-yl]-2-methylpent-4-yn-2-ol	716073: Binding affinity at TRAP1 incubated for 16 hrs by fluorescence polarization competition assay	ki	0.2550	uM
2-amino-7-[(6-bromo-1,3-benzodioxol-5-yl)methyl]-4-chloro-5H-pyrrolo[2,3-d]pyrimidin-6-one	1765850: Inhibition of PU-H71-FITC3 binding to recombinant full length TRAP1 (unknown origin) incubated for 2 hrs by fluorescence polarization assay	ic50	0.2960	uM
[(4E,6Z,8R,9S,10E,12S,13R,14S,16R)-19-[2-(dimethylamino)ethylamino]-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl] carbamate	1063122: Binding affinity to human recombinant TRAP1 after 3 hrs by fluorescence polarization assay	ki	0.3260	uM
2-amino-4-chloro-7-[(2,3-dimethoxyphenyl)methyl]-5H-pyrrolo[2,3-d]pyrimidin-6-one	1765850: Inhibition of PU-H71-FITC3 binding to recombinant full length TRAP1 (unknown origin) incubated for 2 hrs by fluorescence polarization assay	ic50	0.3310	uM
2-amino-9-[(4-bromo-2-fluorophenyl)methyl]-6-chloro-7H-purine-8-thione	1765850: Inhibition of PU-H71-FITC3 binding to recombinant full length TRAP1 (unknown origin) incubated for 2 hrs by fluorescence polarization assay	ic50	0.3320	uM
2-amino-7-(1,3-benzodioxol-5-ylmethyl)-4-chloro-5H-pyrrolo[2,3-d]pyrimidin-6-one	1765850: Inhibition of PU-H71-FITC3 binding to recombinant full length TRAP1 (unknown origin) incubated for 2 hrs by fluorescence polarization assay	ic50	0.3390	uM
[3-(5-fluoro-1,3-dihydroisoindole-2-carbonyl)-4-hydroxyphenyl]-(4-fluoro-1,3-dihydroisoindol-2-yl)methanone	2135531: Binding affinity to TRAP1 (unknown origin) assessed as dissociation constant incubated for 24 hrs by fluorescence polarization assay	kd	0.3500	uM
[3-(4-fluoro-1,3-dihydroisoindole-2-carbonyl)-4-hydroxyphenyl]-(4-fluoro-1,3-dihydroisoindol-2-yl)methanone	2135531: Binding affinity to TRAP1 (unknown origin) assessed as dissociation constant incubated for 24 hrs by fluorescence polarization assay	kd	0.3600	uM
1-[(4-bromo-2-fluorophenyl)methyl]-4-chloropyrazolo[5,4-d]pyrimidin-6-amine	1922479: Inhibition of TRAP1 (unknown origin)	ic50	0.3730	uM
(4-bromo-1,3-dihydroisoindol-2-yl)-[3-(1,3-dihydroisoindole-2-carbonyl)-4-hydroxyphenyl]methanone	2135531: Binding affinity to TRAP1 (unknown origin) assessed as dissociation constant incubated for 24 hrs by fluorescence polarization assay	kd	0.3800	uM
2-amino-6-chloro-9-[(2,3,6-trifluorophenyl)methyl]-7H-purine-8-thione	1765850: Inhibition of PU-H71-FITC3 binding to recombinant full length TRAP1 (unknown origin) incubated for 2 hrs by fluorescence polarization assay	ic50	0.3920	uM
5-(2,4-dihydroxy-5-propan-2-ylphenyl)-N-ethyl-4-[(4-methoxybenzoyl)amino]-1,2-oxazole-3-carboxamide	1497388: Inhibition of recombinant human N-terminal His6-tagged TRAP1 (60 to 704 residues) ATPase activity expressed in Escherichia coli BL21-CodonPlus-RIL after overnight incubation by BioMol green dye-based assay	ic50	0.4000	uM
2-amino-6-chloro-9-[[4-(trifluoromethyl)phenyl]methyl]-7H-purine-8-thione	1765850: Inhibition of PU-H71-FITC3 binding to recombinant full length TRAP1 (unknown origin) incubated for 2 hrs by fluorescence polarization assay	ic50	0.4130	uM
[5-(1,3-dihydroisoindole-2-carbonyl)-2,4-dihydroxyphenyl]-(1,3-dihydroisoindol-2-yl)methanone	2135531: Binding affinity to TRAP1 (unknown origin) assessed as dissociation constant incubated for 24 hrs by fluorescence polarization assay	kd	0.4200	uM
1,3-dihydroisoindol-2-yl-(2,4-dihydroxy-5-indol-1-ylphenyl)methanone	2135531: Binding affinity to TRAP1 (unknown origin) assessed as dissociation constant incubated for 24 hrs by fluorescence polarization assay	kd	0.4200	uM
[3-[5-[3-(dimethylamino)propoxy]-1,3-dihydroisoindole-2-carbonyl]-4-hydroxyphenyl]-(4-fluoro-1,3-dihydroisoindol-2-yl)methanone	2135531: Binding affinity to TRAP1 (unknown origin) assessed as dissociation constant incubated for 24 hrs by fluorescence polarization assay	kd	0.4700	uM
(4-fluoro-1,3-dihydroisoindol-2-yl)-[4-hydroxy-3-(5-methoxy-1,3-dihydroisoindole-2-carbonyl)phenyl]methanone	2135531: Binding affinity to TRAP1 (unknown origin) assessed as dissociation constant incubated for 24 hrs by fluorescence polarization assay	kd	0.4700	uM
9-[(4-bromo-2-fluorophenyl)methyl]-6-chloropurine-2,8-diamine	1765850: Inhibition of PU-H71-FITC3 binding to recombinant full length TRAP1 (unknown origin) incubated for 2 hrs by fluorescence polarization assay	ic50	0.4770	uM
[3-[5-[2-(dimethylamino)ethoxy]-1,3-dihydroisoindole-2-carbonyl]-4-hydroxyphenyl]-(4-fluoro-1,3-dihydroisoindol-2-yl)methanone	2135531: Binding affinity to TRAP1 (unknown origin) assessed as dissociation constant incubated for 24 hrs by fluorescence polarization assay	kd	0.4900	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases expression	3
sodium arsenite	decreases expression, increases expression	3
Valproic Acid	increases methylation, affects expression, increases expression	3
perfluorooctanoic acid	decreases expression, increases expression	2
methacrylaldehyde	affects cotreatment, decreases expression, increases oxidation, increases abundance	2
bisphenol S	increases expression, affects cotreatment, decreases expression	2
Acetaminophen	decreases expression	2
Acrolein	affects cotreatment, decreases expression, increases oxidation, increases abundance	2
Benzo(a)pyrene	decreases methylation, increases expression, affects reaction	2
Cisplatin	decreases expression, decreases reaction, increases activity, increases cleavage, decreases response to substance (+2 more)	2
Doxorubicin	decreases expression, increases expression	2
Fluorouracil	affects expression, affects reaction, decreases expression	2
Hydrogen Peroxide	affects reaction, affects response to substance, decreases response to substance, increases expression	2
Ozone	affects cotreatment, decreases expression, increases oxidation, increases abundance	2
Tetrachlorodibenzodioxin	decreases expression	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	increases expression	1
bufotalin	increases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
sodium arsenate	increases expression	1
diethyl maleate	decreases expression, decreases reaction, decreases response to substance	1
cobaltous chloride	decreases expression	1
ochratoxin A	affects reaction, increases expression, decreases expression, decreases reaction	1
benzo(e)pyrene	increases methylation	1
casticin	increases expression	1
CGP 52608	affects binding, increases reaction	1
nickel acetate	affects expression	1
pinostrobin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1

ChEMBL screening assays

94 unique, capped per target: 94 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1100285	Binding	Inhibition of TRAP1	Heat shock protein 90: inhibitors in clinical trials. — J Med Chem

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A9H4	HAP1 TRAP1 (-) 1	Cancer cell line	Male
CVCL_C7DR	Abcam A-549 TRAP1 KO	Cancer cell line	Male
CVCL_C7EF	Abcam HCT 116 TRAP1 KO	Cancer cell line	Male
CVCL_C7ET	Abcam THP-1 TRAP1 KO	Cancer cell line	Male
CVCL_E2MJ	HAP1 TRAP1 (-) 2	Cancer cell line	Male
CVCL_E2MK	HAP1 TRAP1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00027456	PHASE2	COMPLETED	Leptin to Treat Severe Insulin Resistance - Pilot Study
NCT01619644	PHASE2	COMPLETED	Rubinstein-Taybi Syndrome: Functional Imaging and Therapeutic Trial
NCT04115345	PHASE1	COMPLETED	A Study of a Renal Autologous Cell Therapy (REACT) in Patients With Chronic Kidney Disease (CKD) From Congenital Anomalies of the Kidney and Urinary Tract (CAKUT).
NCT05694169	PHASE1	TERMINATED	A Study of Participants With Chronic Kidney Disease Previously Treated With REACT
NCT00213447	Not specified	COMPLETED	T Cell Response in Hypersensitivity Syndrome
NCT02240888	Not specified	COMPLETED	Vaccination in Inflammatory Rheumatic Disease (VACCIMIL). The Impact of Antirheumatic Treatment on Antibody Response
NCT02526082	Not specified	ACTIVE_NOT_RECRUITING	Long-term Follow-up of the Helsinki Businessmen Study
NCT02637518	Not specified	UNKNOWN	Comprehensive Validation of Frailty Assessment Tools in Older Adults in Different Clinical and Social Settings
NCT02971072	Not specified	COMPLETED	Neurophysiology of Weakness and Exercise in Rotator Cuff Tendinopathy
NCT02974569	Not specified	COMPLETED	Improving Symptom Self-management in Adolescents & Young Adults With Cancer
NCT03265561	Not specified	COMPLETED	Spinal Infection Management With Structural Allograft
NCT04190342	Not specified	COMPLETED	Effects of a Traditional Chinese Exercise Program on Symptom Cluster in Breast Cancer Patients
NCT04874584	Not specified	COMPLETED	Culturally Tailored Nurse Coaching Study for Cancer Symptom Management
NCT04909489	Not specified	UNKNOWN	PDR and SKYD of Dyslipidemia’s Characteristics From the Oxidative Stress Enhancement Caused by Inhibition of Serine Metabolic Pathway
NCT05218122	Not specified	UNKNOWN	Characteristics of LKDS and PBSS of KOA Based on the Enhancement of Inflammatory Response by TGF-β/Smad Pathway Inhibited
NCT05266118	Not specified	COMPLETED	Patient Reported Symptoms the First Week After Intensive Care Unit Discharge and up to Hospital Discharge
NCT05321966	Not specified	COMPLETED	The Effect of Video Training on Symptom Burden Patients Undergoing Hemodialysis Treatment
NCT05818748	Not specified	UNKNOWN	Effect Of Virtual Reality Distraction on Symptom Control and Anxiety in Children With Leukemia
NCT05837988	Not specified	UNKNOWN	Construction of Symptom Network in Maintenance Hemodialysis Patients
NCT06143436	Not specified	UNKNOWN	TCM Constitution, Pattern Types, and Disease Factors in Primary Lung Cancer.
NCT06222008	Not specified	UNKNOWN	Study on Symptom Clusters During Chemotherapy in Ovarian Cancer Patients With Different Chinese Medicine Constitution
NCT06412107	Not specified	COMPLETED	Somatic Acupressure for Symptom Cluster Management in Breast Cancer Survivors
NCT06847360	Not specified	RECRUITING	Home-based Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) for IBS Pain
NCT07281300	Not specified	RECRUITING	Mindfulness-Oriented Respiratory Distress Symptom Intervention for Lung Cancer
NCT07315672	Not specified	RECRUITING	Acupressure for Cough in Lung Cancer Survivors
NCT07479654	Not specified	NOT_YET_RECRUITING	AI-Enabled Frailty Risk Prediction in Adult Congenital Heart Disease
NCT07495358	Not specified	NOT_YET_RECRUITING	Development and Usability Evaluation of a Knowledge Graph-Based Symptom Management System for Patients With Breast Cancer Undergoing Chemotherapy
NCT07576114	Not specified	RECRUITING	Comparison of Gluteal Muscle Activation and Core Strengthening in Dead Butt Syndrome Syndrome
NCT04122742	Not specified	UNKNOWN	Diagnosis of RSTS: Identification of the Acetylation Profiles as Epigenetic Markers for Assessing Causality of CREBBP and EP300 Variants.
NCT05696912	Not specified	UNKNOWN	Functional Tests to Resolve Unsolved Rare Diseases. Rares.
NCT06740162	Not specified	RECRUITING	Physical Activity and Community EmPOWERment Project
NCT03799705	Not specified	COMPLETED	Genetic Variants in Nicotinamide Adenine Dinucleotide (NAD) Synthesis Pathway
NCT04537364	Not specified	COMPLETED	Prediction of Renal Parenchymal Damage of CAKUT
NCT06921733	Not specified	RECRUITING	Ultrasound Localization Microscopy in Patient With Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)