HSPD1

Summary

HSPD1 (heat shock protein family D (Hsp60) member 1, HGNC:5261) is a protein-coding gene on chromosome 2q33.1, encoding 60 kDa heat shock protein, mitochondrial (P10809). Chaperonin implicated in mitochondrial protein import and macromolecular assembly. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

This gene encodes a member of the chaperonin family. The encoded mitochondrial protein may function as a signaling molecule in the innate immune system. This protein is essential for the folding and assembly of newly imported proteins in the mitochondria. This gene is adjacent to a related family member and the region between the 2 genes functions as a bidirectional promoter. Several pseudogenes have been associated with this gene. Two transcript variants encoding the same protein have been identified for this gene. Mutations associated with this gene cause autosomal recessive spastic paraplegia 13.

Source: NCBI Gene 3329 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary spastic paraplegia 13 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 10
• Clinical variants (ClinVar): 355 total — 3 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 37
• Druggable target: yes — 27 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_002156

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5261
Approved symbol	HSPD1
Name	heat shock protein family D (Hsp60) member 1
Location	2q33.1
Locus type	gene with protein product
Status	Approved
Aliases	GroEL, HSP60
Ensembl gene	ENSG00000144381
Ensembl biotype	protein_coding
OMIM	118190
Entrez	3329

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 32 protein_coding, 6 nonsense_mediated_decay, 5 retained_intron

ENST00000345042, ENST00000388968, ENST00000418022, ENST00000426480, ENST00000428204, ENST00000430176, ENST00000439605, ENST00000440114, ENST00000452200, ENST00000461097, ENST00000476746, ENST00000486181, ENST00000491249, ENST00000676933, ENST00000677403, ENST00000677454, ENST00000677792, ENST00000677913, ENST00000678170, ENST00000678545, ENST00000678621, ENST00000678761, ENST00000678969, ENST00000679291, ENST00000858497, ENST00000858498, ENST00000858499, ENST00000858500, ENST00000858501, ENST00000915116, ENST00000915117, ENST00000915118, ENST00000915119, ENST00000915120, ENST00000954435, ENST00000954436, ENST00000954437, ENST00000954438, ENST00000954439, ENST00000954440, ENST00000954441, ENST00000954442, ENST00000954443

RefSeq mRNA: 2 — MANE Select: NM_002156 NM_002156, NM_199440

CCDS: CCDS33357

Canonical transcript exons

ENST00000388968 — 12 exons

Exon	Start	End
ENSE00001005145	197487858	197488036
ENSE00001302446	197493324	197493492
ENSE00001307330	197494157	197494250
ENSE00001328194	197490197	197490296
ENSE00001730653	197499782	197499840
ENSE00001905363	197486584	197487198
ENSE00003554524	197494657	197494752
ENSE00003582492	197495294	197495376
ENSE00003603043	197498675	197498850
ENSE00003612003	197489002	197489247
ENSE00003640919	197497140	197497392
ENSE00003650174	197488317	197488491

Expression profiles

Bgee: expression breadth ubiquitous, 217 present calls, max score 99.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 198.0413 / max 2893.5574, expressed in 1823 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
33082	157.2920	1819
33083	40.4978	1805
33081	0.1301	45
33080	0.1213	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	99.85	gold quality
right adrenal gland	UBERON:0001233	99.65	gold quality
right adrenal gland cortex	UBERON:0035827	99.64	gold quality
left adrenal gland	UBERON:0001234	99.59	gold quality
left adrenal gland cortex	UBERON:0035825	99.53	gold quality
ventricular zone	UBERON:0003053	99.32	gold quality
adrenal cortex	UBERON:0001235	99.24	gold quality
body of pancreas	UBERON:0001150	99.12	gold quality
colonic epithelium	UBERON:0000397	99.05	gold quality
mucosa of transverse colon	UBERON:0004991	99.05	gold quality
ganglionic eminence	UBERON:0004023	99.00	gold quality
rectum	UBERON:0001052	98.97	gold quality
right lobe of liver	UBERON:0001114	98.95	gold quality
adrenal gland	UBERON:0002369	98.93	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	98.73	gold quality
left ovary	UBERON:0002119	98.71	gold quality
vermiform appendix	UBERON:0001154	98.69	gold quality
right ovary	UBERON:0002118	98.56	gold quality
smooth muscle tissue	UBERON:0001135	98.54	gold quality
adenohypophysis	UBERON:0002196	98.54	gold quality
cortical plate	UBERON:0005343	98.54	gold quality
omental fat pad	UBERON:0010414	98.46	gold quality
islet of Langerhans	UBERON:0000006	98.45	gold quality
peritoneum	UBERON:0002358	98.39	gold quality
body of stomach	UBERON:0001161	98.38	gold quality
right uterine tube	UBERON:0001302	98.38	gold quality
transverse colon	UBERON:0001157	98.35	gold quality
anterior cingulate cortex	UBERON:0009835	98.31	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.20	gold quality
metanephros cortex	UBERON:0010533	98.18	gold quality

Single-cell (SCXA)

Detected in 26 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	3783.16
E-ENAD-21	yes	1819.99
E-MTAB-10042	yes	1585.14
E-CURD-7	yes	1424.55
E-HCAD-4	yes	160.40
E-MTAB-6701	yes	117.17
E-HCAD-6	yes	42.23
E-HCAD-1	yes	34.60
E-GEOD-135922	yes	29.44
E-GEOD-125970	yes	24.81
E-CURD-122	yes	23.44
E-MTAB-9067	yes	22.99
E-GEOD-130148	yes	10.26
E-MTAB-9801	yes	6.10
E-MTAB-10137	no	4073.33

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, GATA3, IRF6, MYC, NFKB, POU5F1, RELA, RUNX3

miRNA regulators (miRDB)

77 targeting HSPD1, 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-190A-3P	100.00	80.35	5520
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-3941	99.86	70.54	2735
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-497-3P	99.61	69.71	1990

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• These detoxification results represent the first evidence that Prosbeta2 plays a role in the detoxification of DM, which may provide new idea and target for studying the molecular mechanisms of insect resistance (PMID:26850132)
• H9724, a monoclonal antibody to Borrelia burgdorferi’s flagellin, binds within live neuroblastoma cells, a potential role in peptide hormone signaling in an autoimmune pathogenesis of the neuropathy of Lyme disease. (PMID:11860186)
• promoter polymorphism of the IL-6 gene is associated with levels of antibodies to 60-kDa heat-shock proteins (PMID:11862386)
• Hereditary spastic paraplegia SPG13 is associated with a mutation in the gene encoding the mitochondrial chaperonin Hsp60 (HSPD1) (PMID:11898127)
• Gene expression of HSP1 was down-regulated during early apoptosis in human hepatoma cells exposed to Paeoniae Radix in vitro. (PMID:12215374)
• A regulatory role for human HSP60 autoreactivity is demonstrated by DNA vaccine therapy of rat adjuvant arthritis that results in increased T cell proliferation and variable changes in cytokine production. (PMID:12218165)
• HSP60 reactivity showed no apparent difference between normal and neoplastic odontogenic epithelium (PMID:12406306)
• HLA-E can present a peptide derived from the signal sequence of human hsp60. (PMID:12461076)
• The genome structure of this gene has been established. (PMID:12483302)
• Deficiency of chaperonin 60 in Down’s syndrome. A quantitative analysis by Western blots showed a marked reduction of Cpn60 per equal amount of total protein in DS cells to an average of 35% of normal. (PMID:12515899)
• Maturation of murine bone marrow-derived dendritic cells is strongly induced by human HSP60 and paralleled by release of Th1-promoting cytokines. (PMID:12594256)
• The recombinant protein does not induce the release of tumor necrosis factor alpha from murine macrophages (PMID:12686536)
• the host factor, Hsp60, is essential for in vivo hepatitis B virus replication, and the mechanism of Hsp60 is probably through an activation of HBV pol by Hsp60 (PMID:12869561)
• Evidence of elevated anti-HSP60 reactivity in the serum of patients with tic disorder supports HSP60 as an autoantigen and implicates the involvement of autoimmunity in tic disorders. (PMID:12965262)
• A regulatory HSP60 peptide specifically recognized by the T cells of DNA-vaccinated rats is successfully used as an effective vaccine to inhibit the development of adjuvant arthritis in rats. (PMID:14500649)
• A novel association between anti-heat shock protein 65 autoantibodies and occurrence of postoperative atrial fibrillation. (PMID:15249499)
• The perioperative kinetics of HSP60 in serum may result from suppressed protein synthesis caused by a reduced energy charge of hepatocytes during early reperfusion in liver transplantation. (PMID:15251360)
• T cell immunity to Hsp70 and Hsp90, like Hsp60-specific immunity, can modulate arthritogenic response in adjuvant arthritis. Regulatory mechanisms induced by Hsp60, Hsp70, and Hsp90 are reinforced by an immune network that connects their reactivities. (PMID:15529360)
• Hsp10 exerts anti-inflammatory activity by inhibiting Toll-like receptor signaling possibly by interacting with extracellular Hsp60 (PMID:15546885)
• The HSP60 is a mitochondrial chaperonin, highly preserved during evolution, responsible of protein folding. Its function is strictly dependent on HSP10 in both prokaryotic and eukaryotic elements. (PMID:15590416)
• A defined region of HSP60 (amino acids 354-365) is involved in lipopolysaccharide (LPS) binding, thereby implicating a physiological role of human HSP60 as an LPS-binding protein. (PMID:15661886)
• a decrease of Hsp60 in the cytoplasmic fraction of dilated cardiomyopathy-affected left ventricles was observed; at the same time an increase in P450 2E1 expression in dilated hearts’ cytoplasmic fractions was observed (PMID:15763499)
• Overall, we found clear evidence for the occurrence of HSP60 on the surface of stressed HUVECs in a very similar patchy distribution pattern in living and fixed cells (PMID:15784682)
• Atherosclerotic plaques harbor in vivo-activated CD4+ T cells that recognize the human 60-kDa HSP and become target for both autoreactive T cells and cross-reactive T cells to Chlamydia pneumoniae 60-kDa HSP via a mechanism of molecular mimicry. (PMID:15879154)
• Mortalin and HSP60 interact both in vivo and in vitro, and that the N-terminal region of mortalin is involved in these interactions. (PMID:15957980)
• Autoantibodies recognizing amino acid residues 288 to 366 of HSP60 induce atherosclerosis via the mechanisms of autoimmune reactions to HSP60 expressed on arterial endothelial cells, which can be prevented by F(ab)2 segments derived from these antibodies (PMID:16116071)
• human HSP60 induced naive mouse B cells to proliferate and to secrete IL-10 and IL-6 and up-regulate their expression of MHC class II and accessory molecules (PMID:16148103)
• The 14-3-3 protein forms molecular complex with Hsp60 and PrPC in human CNS under physiological conditions, and this complex might become disintegrated in pathologic process of prion diseases. (PMID:16215457)
• HSP60 and HSP10 are expressed in large bowel carcinomas with lymph node metastases (PMID:16253146)
• Our study provides the first prospective data confirming an association between high levels of sHSP60 and early carotid atherosclerosis. (PMID:16254226)
• Hsp60 is an important target for anti-endothelial antibodies; such an interaction contributes to pathogenic effects, especially in vasculitis-associated systemic autoimmune disease (PMID:16320351)
• With HSP60, results from cell-lines correlated with clinical results, indicating that this model can be used for dissection of mechanisms involved in transformation to androgen resistance and assignment of protein markers in prostate cancer. (PMID:16705742)
• HSP60 is a potent inducer of venous smooth muscle cell (VSMC) proliferation; HSP60 uses TLR2 as well as TLR4 to cause its mitogenic effect on VSMCs (PMID:16843693)
• Mitochondrial heat shock protein 60 is able to neutralize the inhibition of electron transport complex IV by amyloid beta-protein. (PMID:16887805)
• Investigation of single-nucleotide variations in the Hsp60 gene and their disease-causing potential. (PMID:17072495)
• Yersinia Hsp60-specific T cells of one patient cross-reacted directly with human Hsp60 (PMID:17075864)
• dysregulated expression of DHX32 might lead to as of yet unknown changes in mitochondrial homeostasis manifested by cytoplasmic redistribution of the molecular chaperon Hsp60 (PMID:17174952)
• A negative association between Hsp60 in plasma, and seropositivity for three microbial agents which are risk factors for cardiovascular disease, suggest a protective effect of circulating stress protein Hsp60. (PMID:17202307)
• Plasminogen bound to hsps 27, 60, and 70 and Angiostatin predominantly bound to hsp 27 and to hsp 70 in a concentration- and kringle-dependent manner. (PMID:17206383)
• found that the function of the p.Gln461Glu heat shock protein 60 was mildly compromised. The c.1381C > G mutation likely represents a novel low-penetrance HSP allele. (PMID:17420924)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	hspd1	ENSDARG00000056160
mus_musculus	Hspd1	ENSMUSG00000025980
rattus_norvegicus	Hspd1	ENSRNOG00000014525
rattus_norvegicus	Hspd1l1	ENSRNOG00000065120
drosophila_melanogaster	Hsp60B	FBGN0011244
drosophila_melanogaster	Hsp60A	FBGN0015245
drosophila_melanogaster	Hsp60C	FBGN0031728
drosophila_melanogaster	Hsp60D	FBGN0032525
caenorhabditis_elegans		WBGENE00002025

Paralogs (13): PIKFYVE (ENSG00000115020), CCT4 (ENSG00000115484), TCP1 (ENSG00000120438), MKKS (ENSG00000125863), CCT6B (ENSG00000132141), CCT7 (ENSG00000135624), CCT6A (ENSG00000146731), CCT5 (ENSG00000150753), CCT8 (ENSG00000156261), CCT3 (ENSG00000163468), CCT2 (ENSG00000166226), BBS12 (ENSG00000181004), CCT8L2 (ENSG00000198445)

Protein

Protein identifiers

60 kDa heat shock protein, mitochondrial — P10809 (reviewed: P10809)

Alternative names: 60 kDa chaperonin, Chaperonin 60, Heat shock protein 60, Heat shock protein family D member 1, HuCHA60, Mitochondrial matrix protein P1, P60 lymphocyte protein

All UniProt accessions (16): P10809, A0A024R3X4, A0A7I2V2X6, A0A7I2V369, A0A7I2V599, A0A7I2V5K3, A0A7I2V5M1, A0A7I2YQ71, A0A7I2YQK6, C9J0S9, C9JCQ4, C9JL19, C9JL25, E7ESH4, E7EXB4, F8WBB1

UniProt curated annotations — full annotation on UniProt →

Function. Chaperonin implicated in mitochondrial protein import and macromolecular assembly. Together with Hsp10, facilitates the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix. The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back-to-back double ring. In a cyclic reaction, Hsp60 ring complexes bind one unfolded substrate protein per ring, followed by the binding of ATP and association with 2 heptameric rings of the co-chaperonin Hsp10. This leads to sequestration of the substrate protein in the inner cavity of Hsp60 where, for a certain period of time, it can fold undisturbed by other cell components. Synchronous hydrolysis of ATP in all Hsp60 subunits results in the dissociation of the chaperonin rings and the release of ADP and the folded substrate protein.

Subunit / interactions. Homoheptamer arranged in a ring structure. The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back-to-back double ring. Interacts with 2 heptameric Hsp10 rings to form the symmetrical football complex. Interacts with HRAS. Interacts with ATAD3A. Interacts with ETFBKMT and EEF1AKMT3. Interacts with MFHAS1. (Microbial infection) Interacts with hepatitis B virus/HBV protein X. (Microbial infection) Interacts with HTLV-1 protein p40tax.

Subcellular location. Mitochondrion matrix.

Disease relevance. Spastic paraplegia 13, autosomal dominant (SPG13) [MIM:605280] A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. The disease is caused by variants affecting the gene represented in this entry. Leukodystrophy, hypomyelinating, 4 (HLD4) [MIM:612233] A severe autosomal recessive hypomyelinating leukodystrophy. Clinically characterized by infantile-onset rotary nystagmus, progressive spastic paraplegia, neurologic regression, motor impairment, profound intellectual disability. Death usually occurs within the first two decades of life. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the chaperonin (HSP60) family.

Isoforms (2)

UniProt ID	Names	Canonical?
P10809-1	1	yes
P10809-2	2

RefSeq proteins (2): NP_002147, NP_955472 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001844	Cpn60/GroEL	Family
IPR002423	Cpn60/GroEL/TCP-1	Family
IPR018370	Chaperonin_Cpn60_CS	Conserved_site
IPR027409	GroEL-like_apical_dom_sf	Homologous_superfamily
IPR027410	TCP-1-like_intermed_sf	Homologous_superfamily
IPR027413	GROEL-like_equatorial_sf	Homologous_superfamily

Pfam: PF00118

UniProt features (113 total): modified residue 44, strand 25, helix 23, turn 5, sequence conflict 5, binding site 4, splice variant 2, sequence variant 2, transit peptide 1, chain 1, cross-link 1

Structure

Experimental structures (PDB)

31 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9SHG	ELECTRON MICROSCOPY	1.91
9SHH	ELECTRON MICROSCOPY	2.11
9SHJ	ELECTRON MICROSCOPY	2.18
9SHI	ELECTRON MICROSCOPY	2.19
9ES2	ELECTRON MICROSCOPY	2.44
8G7L	ELECTRON MICROSCOPY	2.5
9SHL	ELECTRON MICROSCOPY	2.5
9ES0	ELECTRON MICROSCOPY	2.58
8G7N	ELECTRON MICROSCOPY	2.7
9ES4	ELECTRON MICROSCOPY	2.91
9SHK	ELECTRON MICROSCOPY	2.91
9ES1	ELECTRON MICROSCOPY	2.95
9H5S	ELECTRON MICROSCOPY	2.98
9ES6	ELECTRON MICROSCOPY	3
6MRC	ELECTRON MICROSCOPY	3.08
9H5U	ELECTRON MICROSCOPY	3.14
4PJ1	X-RAY DIFFRACTION	3.15
8G7M	ELECTRON MICROSCOPY	3.2
9ES3	ELECTRON MICROSCOPY	3.28
8G7J	ELECTRON MICROSCOPY	3.4
8G7O	ELECTRON MICROSCOPY	3.4
8U39	ELECTRON MICROSCOPY	3.4
9H5T	ELECTRON MICROSCOPY	3.44
7AZP	ELECTRON MICROSCOPY	3.5
7L7S	ELECTRON MICROSCOPY	3.5
9ES5	ELECTRON MICROSCOPY	3.5
6HT7	X-RAY DIFFRACTION	3.7
8G7K	ELECTRON MICROSCOPY	3.8
6MRD	ELECTRON MICROSCOPY	3.82
9H5V	ELECTRON MICROSCOPY	3.96

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10809-F1	88.21	0.70

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 (4): 75; 111–115; 440; 520

Post-translational modifications (45): 82, 82, 87, 90, 91, 125, 125, 130, 133, 133, 133, 156, 191, 191, 202, 202, 205, 205, 218, 218 …

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1268020	Mitochondrial protein import
R-HSA-8869496	TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation
R-HSA-9837999	Mitochondrial protein degradation
R-HSA-9841251	Mitochondrial unfolded protein response (UPRmt)

MSigDB gene sets: 646 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GOBP_REGULATION_OF_CELL_ACTIVATION, AGGAAGC_MIR5163P, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP, GOBP_POSITIVE_REGULATION_OF_MACROPHAGE_ACTIVATION, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_RESPONSE_TO_COLD, GOBP_POSITIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_RESPONSE_TO_PEPTIDE, RORA1_01, GOBP_B_CELL_ACTIVATION, GOCC_SECRETORY_GRANULE

GO Biological Process (30): MyD88-dependent toll-like receptor signaling pathway (GO:0002755), positive regulation of T cell mediated immune response to tumor cell (GO:0002842), protein folding (GO:0006457), ‘de novo’ protein folding (GO:0006458), response to unfolded protein (GO:0006986), apoptotic mitochondrial changes (GO:0008637), response to cold (GO:0009409), positive regulation of interferon-alpha production (GO:0032727), positive regulation of type II interferon production (GO:0032729), positive regulation of interleukin-10 production (GO:0032733), positive regulation of interleukin-12 production (GO:0032735), positive regulation of interleukin-6 production (GO:0032755), mitochondrial unfolded protein response (GO:0034514), protein refolding (GO:0042026), B cell proliferation (GO:0042100), T cell activation (GO:0042110), B cell activation (GO:0042113), positive regulation of macrophage activation (GO:0043032), negative regulation of apoptotic process (GO:0043066), protein import into mitochondrial intermembrane space (GO:0045041), isotype switching to IgG isotypes (GO:0048291), protein stabilization (GO:0050821), positive regulation of T cell activation (GO:0050870), chaperone-mediated protein complex assembly (GO:0051131), protein maturation (GO:0051604), biological process involved in interaction with symbiont (GO:0051702), cellular response to interleukin-7 (GO:0098761), negative regulation of execution phase of apoptosis (GO:1900118), positive regulation of execution phase of apoptosis (GO:1900119), positive regulation of cytokine production (GO:0001819)

GO Molecular Function (20): lipopolysaccharide binding (GO:0001530), p53 binding (GO:0002039), DNA replication origin binding (GO:0003688), single-stranded DNA binding (GO:0003697), RNA binding (GO:0003723), double-stranded RNA binding (GO:0003725), ATP binding (GO:0005524), high-density lipoprotein particle binding (GO:0008035), isomerase activity (GO:0016853), ATP hydrolysis activity (GO:0016887), enzyme binding (GO:0019899), ubiquitin protein ligase binding (GO:0031625), apolipoprotein binding (GO:0034185), apolipoprotein A-I binding (GO:0034186), obsolete unfolded protein binding (GO:0051082), protein-folding chaperone binding (GO:0051087), cysteine-type endopeptidase activator activity (GO:0140608), ATP-dependent protein folding chaperone (GO:0140662), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (19): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial matrix (GO:0005759), early endosome (GO:0005769), cytosol (GO:0005829), plasma membrane (GO:0005886), clathrin-coated pit (GO:0005905), cell surface (GO:0009986), membrane (GO:0016020), coated vesicle (GO:0030135), secretory granule (GO:0030141), protein-containing complex (GO:0032991), lipopolysaccharide receptor complex (GO:0046696), extracellular exosome (GO:0070062), sperm midpiece (GO:0097225), sperm plasma membrane (GO:0097524), migrasome (GO:0140494)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Protein localization	1
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1
Metabolism of proteins	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
positive regulation of cytokine production	4
protein binding	4
protein folding	2
apoptotic process	2
lymphocyte activation	2
ATP-dependent activity	2
cytoplasm	2
intracellular membrane-bounded organelle	2
membrane	2
endomembrane system	2
toll-like receptor signaling pathway	1
T cell mediated immune response to tumor cell	1
positive regulation of T cell mediated immunity	1
positive regulation of immune response to tumor cell	1
regulation of T cell mediated immune response to tumor cell	1
cellular process	1
protein maturation	1
response to topologically incorrect protein	1
mitochondrion organization	1
response to stress	1
response to temperature stimulus	1
positive regulation of type I interferon production	1
interferon-alpha production	1
regulation of interferon-alpha production	1
type II interferon production	1
regulation of type II interferon production	1
interleukin-10 production	1
regulation of interleukin-10 production	1
interleukin-12 production	1
regulation of interleukin-12 production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
cellular response to unfolded protein	1
B cell activation	1
lymphocyte proliferation	1
positive regulation of leukocyte activation	1
macrophage activation	1
regulation of macrophage activation	1
regulation of apoptotic process	1

Protein interactions and networks

STRING

5778 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HSPD1	HSPE1	P61604	999
HSPD1	TLR4	O00206	995
HSPD1	TLR2	O60603	967
HSPD1	HSPA9	P30036	924
HSPD1	TST	Q16762	918
HSPD1	GRPEL1	Q9HAV7	916
HSPD1	CLPB	Q9H078	892
HSPD1	APP	P05067	883
HSPD1	HSP90AA1	P07900	856
HSPD1	HSP90AB1	P08238	855
HSPD1	LALBA	P00709	852
HSPD1	GLUL	P15104	845
HSPD1	TCP1	P17987	834
HSPD1	HSPA4	P34932	830
HSPD1	CLPP	Q16740	813

IntAct

697 interactions, top by confidence:

A	B	Type	Score
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
HSPD1	LZTS2	psi-mi:“MI:0915”(physical association)	0.780
LZTS2	HSPD1	psi-mi:“MI:0915”(physical association)	0.780
HMG20A	KDM1A	psi-mi:“MI:0914”(association)	0.730
PPP2R1B	STRN	psi-mi:“MI:0914”(association)	0.730
DARS2	HSPD1	psi-mi:“MI:0915”(physical association)	0.730
HSPD1	TMCC2	psi-mi:“MI:0915”(physical association)	0.720
HSPD1	CEP70	psi-mi:“MI:0915”(physical association)	0.720
TMCC2	HSPD1	psi-mi:“MI:0915”(physical association)	0.720
CEP70	HSPD1	psi-mi:“MI:0915”(physical association)	0.720
CFTR	XPO1	psi-mi:“MI:0914”(association)	0.710
HSPD1	NUDT19	psi-mi:“MI:0914”(association)	0.710
HSPD1	SAMD3	psi-mi:“MI:0915”(physical association)	0.670
USE1	NBAS	psi-mi:“MI:0914”(association)	0.640
IFT88	IFT56	psi-mi:“MI:0914”(association)	0.640
MRPS30	GTPBP10	psi-mi:“MI:0914”(association)	0.640

BioGRID (1401): HSPD1 (Affinity Capture-MS), HSPD1 (Affinity Capture-MS), KRTAP5-9 (Two-hybrid), KRT31 (Two-hybrid), RGS20 (Two-hybrid), TMCC2 (Two-hybrid), CEP70 (Two-hybrid), LZTS2 (Two-hybrid), KRT40 (Two-hybrid), SAMD3 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), HSPD1 (Affinity Capture-RNA), HSPD1 (Affinity Capture-RNA)

ESM2 similar proteins: A2SCV1, A4W5N8, A8AMQ6, A9N3Z7, B0SXR2, B2FIU9, B2ICU4, B3PLM6, B4SKL8, B4TF80, B4TSC6, B5BKF4, B5FFY0, B5R005, B5R991, C0Q6A2, O02649, O33500, O66026, O74261, P0A1D4, P10809, P18687, P19882, P29185, P29197, P31081, P50140, P63038, P63039, Q05045, Q05046, Q07WX7, Q0AS40, Q15PD3, Q2RWV4, Q2Y6I6, Q39727, Q43298, Q48EI5

Diamond homologs: A4YRI5, A4YS25, A4Z0U1, A5ECI7, A5EG60, A5EM76, A5VBQ6, A5VTU1, A6U6I5, A6U7N0, A6U901, A6UM48, A6X3D0, A7HQQ0, A8I5R5, A8ILV4, A9HK37, A9HPH6, A9MDV1, A9WXQ0, B0SXR2, B2ICU4, B2SCZ4, B6IU98, B8ER20, B9K1Y8, C0RKD5, O02649, O60008, O74261, P0CB35, P10809, P18687, P25420, P29185, P29197, P30779, P31081, P35469, P35470

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RUNX3	“down-regulates quantity by repression”	HSPD1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 206 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
Activation of AMPK downstream of NMDARs	5	13.3×	1e-03
Centrosome maturation	7	12.4×	2e-04
Aggrephagy	7	12.2×	2e-04
Nuclear Envelope (NE) Reassembly	5	10.2×	4e-03
DNA Damage Recognition in GG-NER	5	10.0×	4e-03
Mitotic G2-G2/M phases	11	9.8×	5e-06
G2/M Transition	11	9.8×	5e-06
Loss of Nlp from mitotic centrosomes	8	8.9×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
cellular response to UV	7	11.2×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	5
Uncertain significance	180
Likely benign	112
Benign	23

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
17557	NM_002156.5(HSPD1):c.292G>A (p.Val98Ile)	Pathogenic
17558	NM_002156.5(HSPD1):c.86A>G (p.Asp29Gly)	Pathogenic
561192	NM_002156.5(HSPD1):c.1381C>G (p.Gln461Glu)	Pathogenic
214550	NM_002156.5(HSPD1):c.397A>G (p.Lys133Glu)	Likely pathogenic
2630153	NM_002156.5(HSPD1):c.188T>C (p.Ile63Thr)	Likely pathogenic
3767209	NM_002156.5(HSPD1):c.185T>C (p.Val62Ala)	Likely pathogenic
816623	NM_002156.5(HSPD1):c.139T>G (p.Leu47Val)	Likely pathogenic
986925	NM_002156.5(HSPD1):c.329G>T (p.Gly110Val)	Likely pathogenic

SpliceAI

3125 predictions. Top by Δscore:

Variant	Effect	Δscore
2:197487853:TTTA:T	donor_loss	1.0000
2:197487854:TTA:T	donor_loss	1.0000
2:197487855:TACCT:T	donor_loss	1.0000
2:197487856:ACC:A	donor_loss	1.0000
2:197487857:C:A	donor_loss	1.0000
2:197488308:A:C	donor_gain	1.0000
2:197488313:TTAC:T	donor_loss	1.0000
2:197488337:G:C	donor_gain	1.0000
2:197488487:CCAAC:C	acceptor_gain	1.0000
2:197488488:CAAC:C	acceptor_gain	1.0000
2:197488488:CAACC:C	acceptor_gain	1.0000
2:197488489:AAC:A	acceptor_gain	1.0000
2:197488490:AC:A	acceptor_gain	1.0000
2:197488491:CC:C	acceptor_gain	1.0000
2:197488492:C:CA	acceptor_loss	1.0000
2:197488492:C:CC	acceptor_gain	1.0000
2:197488492:C:T	acceptor_gain	1.0000
2:197488997:GTTAC:G	donor_loss	1.0000
2:197489001:C:CG	donor_loss	1.0000
2:197489243:AACAC:A	acceptor_gain	1.0000
2:197489244:ACAC:A	acceptor_gain	1.0000
2:197489245:CAC:C	acceptor_gain	1.0000
2:197489245:CACC:C	acceptor_gain	1.0000
2:197489246:AC:A	acceptor_gain	1.0000
2:197489247:CC:C	acceptor_gain	1.0000
2:197489248:C:CA	acceptor_loss	1.0000
2:197489248:C:CC	acceptor_gain	1.0000
2:197489251:C:CT	acceptor_gain	1.0000
2:197489252:A:T	acceptor_gain	1.0000
2:197490195:A:AC	donor_gain	1.0000

AlphaMissense

3743 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:197487865:G:T	P521Q	1.000
2:197488404:C:G	G435R	1.000
2:197488415:G:T	A431D	1.000
2:197488427:G:T	A427D	1.000
2:197488428:C:G	A427P	1.000
2:197488433:A:G	L425P	1.000
2:197488436:G:T	A424D	1.000
2:197488437:C:G	A424P	1.000
2:197488438:A:C	D423E	1.000
2:197488438:A:T	D423E	1.000
2:197489012:G:T	A402D	1.000
2:197489039:C:G	R393P	1.000
2:197490239:T:A	R309S	1.000
2:197490239:T:G	R309S	1.000
2:197490249:C:T	G306D	1.000
2:197490251:A:C	F305L	1.000
2:197490251:A:T	F305L	1.000
2:197490252:A:C	F305C	1.000
2:197490253:A:G	F305L	1.000
2:197493336:A:G	L286P	1.000
2:197493370:C:G	A275P	1.000
2:197494192:C:A	G222V	1.000
2:197494192:C:T	G222D	1.000
2:197494193:C:G	G222R	1.000
2:197494698:C:G	A189P	1.000
2:197494715:C:T	G183D	1.000
2:197494737:C:G	A176P	1.000
2:197494748:G:T	A172D	1.000
2:197494749:C:G	A172P	1.000
2:197497220:G:T	A116D	1.000

dbSNP variants (sampled 300 via entrez): RS1000014618 (2:197500984 A>G), RS1000170100 (2:197498572 C>G,T), RS1000356953 (2:197491000 G>A), RS1000506744 (2:197486088 ATTCTT>A), RS1000601756 (2:197496805 G>A,T), RS1000721409 (2:197502009 A>G), RS1001084650 (2:197492349 TCTG>T), RS1001301186 (2:197495062 T>C), RS1001577817 (2:197488868 CA>C,CAA), RS1001688656 (2:197496624 T>C), RS1001857571 (2:197499666 CGCGGTGCGGA>C), RS1001857591 (2:197500559 C>T), RS1001926320 (2:197501487 G>A,T), RS1002130353 (2:197487049 G>C), RS1002270363 (2:197491362 G>A)

Disease associations

OMIM: gene MIM:118190 | disease phenotypes: MIM:612233, MIM:605280, MIM:303350, MIM:312080

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary spastic paraplegia 13	Strong	Autosomal dominant
hypomyelinating leukodystrophy 4	Strong	Autosomal recessive

Mondo (5): hypomyelinating leukodystrophy 4 (MONDO:0012824), hereditary spastic paraplegia 13 (MONDO:0011532), hereditary spastic paraplegia (MONDO:0019064), leukodystrophy (MONDO:0019046), intellectual disability (MONDO:0001071)

Orphanet (6): Pelizaeus-Merzbacher-like disease (Orphanet:280270), Pelizaeus-Merzbacher-like disease due to HSPD1 mutation (Orphanet:280288), Autosomal dominant spastic paraplegia type 13 (Orphanet:100994), Hereditary spastic paraplegia (Orphanet:685), Leukodystrophy (Orphanet:68356), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

37 total (30 of 37 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000012	Urinary urgency
HP:0000020	Urinary incontinence
HP:0000365	Hearing impairment
HP:0000486	Strabismus
HP:0000510	Rod-cone dystrophy
HP:0000639	Nystagmus
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001258	Spastic paraplegia
HP:0001263	Global developmental delay
HP:0001266	Choreoathetosis
HP:0001347	Hyperreflexia
HP:0001371	Flexion contracture
HP:0001761	Pes cavus
HP:0002061	Lower limb spasticity
HP:0002064	Spastic gait
HP:0002104	Apnea
HP:0002151	Increased circulating lactate concentration
HP:0002166	Impaired vibration sensation in the lower limbs
HP:0002187	Profound intellectual disability
HP:0002191	Progressive spasticity
HP:0002415	Leukodystrophy
HP:0002421	Poor head control
HP:0002599	Head titubation
HP:0002650	Scoliosis
HP:0002839	Urinary bladder sphincter dysfunction
HP:0003219	Ethylmalonic aciduria
HP:0003487	Babinski sign

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002539_41	Schizophrenia	2.000000e-11
GCST004521_180	Autism spectrum disorder or schizophrenia	3.000000e-11
GCST004521_275	Autism spectrum disorder or schizophrenia	7.000000e-09
GCST006803_21	Schizophrenia	4.000000e-13
GCST010698_25	Subcortical volume (min-P)	2.000000e-08
GCST010699_24	Brain morphology (min-P)	1.000000e-09
GCST010700_25	Cortical thickness (MOSTest)	2.000000e-10
GCST010701_25	Cortical surface area (MOSTest)	2.000000e-37
GCST010702_65	Subcortical volume (MOSTest)	1.000000e-11
GCST010703_197	Brain morphology (MOSTest)	1.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D015419	Spastic Paraplegia, Hereditary	C10.500.300.820; C10.574.500.495.820; C10.668.829.800.300.820; C16.131.666.300.820; C16.320.400.375.820
C567390	Leukodystrophy, Hypomyelinating, 4 (supp.)
C537485	Spastic paraplegia 13, autosomal dominant (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4106131 (PROTEIN COMPLEX), CHEMBL4721 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

27 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 744,896 (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
CHEMBL1042	CHOLECALCIFEROL	4	64,162
CHEMBL1200712	EVANS BLUE	4	24,260
CHEMBL1200787	PHENOXYBENZAMINE HYDROCHLORIDE	4	2,483
CHEMBL1265	ADAPALENE	4	12,179
CHEMBL1536	ERGOCALCIFEROL	4	35,524
CHEMBL1801800	METABROMSALAN	4	6,102
CHEMBL290106	BITHIONOL	4	6,439
CHEMBL38	TRETINOIN	4	194,008
CHEMBL388590	BENZBROMARONE	4	8,245
CHEMBL3989697	RIBOFLAVIN 5’-PHOSPHATE SODIUM	4	53
CHEMBL456	ETHACRYNIC ACID	4	20,004
CHEMBL496	HEXACHLOROPHENE	4	26,164
CHEMBL506247	TANNIC ACID	4	25,753
CHEMBL590	MENADIONE	4	21,034
CHEMBL6067487	IVERMECTIN	4
CHEMBL64894	GENTIAN VIOLET	4	111,449
CHEMBL704	MESALAMINE	4	52,574
CHEMBL140	CURCUMIN	3	93,882
CHEMBL2003538	CETYLPYRIDINIUM CHLORIDE	3	3,733
CHEMBL265502	SURAMIN	3	36,848
CHEMBL297453	EPIGALOCATECHIN GALLATE	3
CHEMBL12131	CLOSANTEL	2
CHEMBL15192	LAPACHONE	2
CHEMBL221753	BENZETHONIUM CHLORIDE	2
CHEMBL287542	RAFOXANIDE	2
CHEMBL33845	DICHLOROPHEN	2
CHEMBL295316	PLUMBAGIN	1

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

ChEMBL bioactivities

63 potent at pChembl≥5 of 170 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.39	Kd	4.098	nM	CHEMBL3752910
8.39	ED50	4.098	nM	CHEMBL3752910
6.83	Kd	147.5	nM	CHEMBL5653589
6.83	ED50	147.5	nM	CHEMBL5653589
6.77	IC50	170	nM	EVANS BLUE
6.00	IC50	1000	nM	CHEMBL4161583
5.92	IC50	1200	nM	CHEMBL1516388
5.89	IC50	1300	nM	HEXACHLOROPHENE
5.80	IC50	1600	nM	CHEMBL3115912
5.75	IC50	1800	nM	CHEMBL3115927
5.68	IC50	2100	nM	CHEMBL4167333
5.68	IC50	2100	nM	LAPACHONE
5.64	IC50	2300	nM	ADAPALENE
5.64	IC50	2300	nM	EPIGALOCATECHIN GALLATE
5.62	IC50	2400	nM	CHEMBL4169499
5.60	IC50	2500	nM	CLOSANTEL
5.55	IC50	2800	nM	CHEMBL3115921
5.55	IC50	2800	nM	RAFOXANIDE
5.55	IC50	2800	nM	CLOSANTEL
5.55	IC50	2800	nM	BITHIONOL
5.54	IC50	2900	nM	CHEMBL5483017
5.51	IC50	3100	nM	ASCORBYL PALMITATE
5.50	IC50	3200	nM	AURINTRICARBOXYLIC ACID
5.48	IC50	3300	nM	CHEMBL3115913
5.44	IC50	3600	nM	CHEMBL1632145
5.44	IC50	3600	nM	HEMATEIN
5.42	IC50	3800	nM	TANNIC ACID
5.40	IC50	4000	nM	CHEMBL78764
5.38	IC50	4200	nM	CHEMBL1632145
5.35	IC50	4500	nM	CHEMBL4160098
5.35	IC50	4500	nM	ARACHIDONIC ACID
5.33	IC50	4700	nM	CHEMBL4166077
5.33	IC50	4700	nM	CHEMBL4277733
5.31	IC50	4900	nM	CHEMBL3115911
5.31	IC50	4900	nM	PROTOPORPHYRIN
5.30	IC50	5000	nM	CHEMBL4176697
5.28	IC50	5200	nM	CHEMBL3115914
5.28	IC50	5300	nM	TRETINOIN
5.26	IC50	5500	nM	CHEMBL1632145
5.24	IC50	5800	nM	GENTIAN VIOLET
5.23	IC50	5900	nM	CHEMBL4162794
5.23	IC50	5900	nM	CHEMBL4277733
5.22	IC50	6000	nM	CETYLPYRIDINIUM CHLORIDE
5.21	IC50	6100	nM	CHEMBL4161487
5.20	IC50	6300	nM	PLUMBAGIN
5.19	IC50	6500	nM	CHEMBL4162794
5.17	IC50	6800	nM	CHEMBL4448756
5.17	IC50	6700	nM	CHEMBL4161487
5.16	IC50	6900	nM	CHEMBL4293874
5.14	IC50	7200	nM	SURAMIN

PubChem BioAssay actives

60 with measured affinity, of 394 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148558: Binding affinity to human HSPD1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0041	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148558: Binding affinity to human HSPD1 incubated for 45 mins by Kinobead based pull down assay	kd	0.1475	uM
tetrasodium;4-amino-6-[[4-[4-[(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl]-3-methylphenyl]-2-methylphenyl]diazenyl]-5-hydroxynaphthalene-1,3-disulfonate	1594139: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by malachite green dye based spectrometric analysis	ic50	0.1700	uM
5-chloro-N-[4-[5-[(4-chloro-3-nitrophenyl)sulfonylamino]-1,3-benzoxazol-2-yl]phenyl]thiophene-2-sulfonamide	1362251: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by spectrometric analysis	ic50	1.0000	uM
acetic acid;7-(8-formyl-1,6,7-trihydroxy-3-methyl-5-propan-2-ylnaphthalen-2-yl)-2,3,8-trihydroxy-6-methyl-4-propan-2-ylnaphthalene-1-carbaldehyde	1594139: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by malachite green dye based spectrometric analysis	ic50	1.2000	uM
3,4,6-trichloro-2-[(2,3,5-trichloro-6-hydroxyphenyl)methyl]phenol	1594139: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by malachite green dye based spectrometric analysis	ic50	1.3000	uM
N-[4-[(E)-3-(3-nitrophenyl)prop-2-enoyl]phenyl]furan-2-carboxamide	1303884: Inhibition of human HSP60/HSP10 expressed in Escherichia coli Rosetta2(DE3) cells assessed as inhibition of denatured pig heart MDH refolding by measuring reduction in NADH production incubated for 60 mins by micro plate reader analysis	ic50	1.6000	uM
(5,7-dibromo-2-oxo-1,3-benzoxathiol-6-yl) N-methylcarbamate	1303884: Inhibition of human HSP60/HSP10 expressed in Escherichia coli Rosetta2(DE3) cells assessed as inhibition of denatured pig heart MDH refolding by measuring reduction in NADH production incubated for 60 mins by micro plate reader analysis	ic50	1.8000	uM
5-chloro-N-[2-[4-[(4-chloro-3-nitrophenyl)sulfonylamino]phenyl]-1,3-benzoxazol-5-yl]thiophene-2-sulfonamide	1362251: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by spectrometric analysis	ic50	2.1000	uM
2,2-dimethyl-3,4-dihydrobenzo[h]chromene-5,6-dione	1594139: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by malachite green dye based spectrometric analysis	ic50	2.1000	uM
Adapalene	1594139: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by malachite green dye based spectrometric analysis	ic50	2.3000	uM
[(2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromen-3-yl] 3,4,5-trihydroxybenzoate	1594139: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by malachite green dye based spectrometric analysis	ic50	2.3000	uM
5-chloro-N-[4-[5-[[4-chloro-3-(trifluoromethyl)phenyl]sulfonylamino]-1,3-benzoxazol-2-yl]phenyl]thiophene-2-sulfonamide	1362251: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by spectrometric analysis	ic50	2.4000	uM
N-[5-chloro-4-[(4-chlorophenyl)-cyanomethyl]-2-methylphenyl]-2-hydroxy-3,5-diiodobenzamide	1423480: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding after 40 to 60 mins by spectrometric analysis	ic50	2.5000	uM
2,4-dichloro-6-(3,5-dichloro-2-hydroxyphenyl)sulfanylphenol	1594139: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by malachite green dye based spectrometric analysis	ic50	2.8000	uM
N-[3-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxy-3,5-diiodobenzamide	1423480: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding after 40 to 60 mins by spectrometric analysis	ic50	2.8000	uM
1-benzyl-4-chloro-3-nitroquinolin-2-one	1303884: Inhibition of human HSP60/HSP10 expressed in Escherichia coli Rosetta2(DE3) cells assessed as inhibition of denatured pig heart MDH refolding by measuring reduction in NADH production incubated for 60 mins by micro plate reader analysis	ic50	2.8000	uM
disodium;2-(2,4,5,7-tetraiodo-3-oxido-6-oxoxanthen-9-yl)benzoate;hydrate	1594139: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by malachite green dye based spectrometric analysis	ic50	2.9000	uM
[(2S)-2-[(2R)-3,4-dihydroxy-5-oxo-2H-furan-2-yl]-2-hydroxyethyl] hexadecanoate	1594139: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by malachite green dye based spectrometric analysis	ic50	3.1000	uM
5-[(3-carboxy-4-hydroxyphenyl)-(3-carboxy-4-oxocyclohexa-2,5-dien-1-ylidene)methyl]-2-hydroxybenzoic acid	1594139: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by malachite green dye based spectrometric analysis	ic50	3.2000	uM
4-(4-hydroxy-3-nitrophenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-6-carboxylic acid	1303884: Inhibition of human HSP60/HSP10 expressed in Escherichia coli Rosetta2(DE3) cells assessed as inhibition of denatured pig heart MDH refolding by measuring reduction in NADH production incubated for 60 mins by micro plate reader analysis	ic50	3.3000	uM
4,6a,9,10-tetrahydroxy-6,7-dihydroindeno[2,1-c]chromen-3-one	1594139: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by malachite green dye based spectrometric analysis	ic50	3.6000	uM
N-[4-(1,3-benzothiazol-2-ylsulfanyl)-3-chlorophenyl]-3,5-dibromo-2-hydroxybenzamide	1303885: Inhibition of human HSP60/HSP10 expressed in Escherichia coli Rosetta2(DE3) cells assessed as reduction in denatured pig heart MDH ATPase activity by malachite green dye based assay	ic50	3.6000	uM
Tannic Acid	1594139: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by malachite green dye based spectrometric analysis	ic50	3.8000	uM
agaricic acid	1594139: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by malachite green dye based spectrometric analysis	ic50	4.0000	uM
5-chloro-N-[2-[4-[[3-(trifluoromethyl)phenyl]sulfonylamino]phenyl]-1,3-benzoxazol-5-yl]thiophene-2-sulfonamide	1362251: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by spectrometric analysis	ic50	4.5000	uM
(5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoic acid	1594139: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by malachite green dye based spectrometric analysis	ic50	4.5000	uM
5-chloro-N-[4-[5-[(3,4-dichlorophenyl)sulfonylamino]-1,3-benzoxazol-2-yl]phenyl]thiophene-2-sulfonamide	1362251: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by spectrometric analysis	ic50	4.7000	uM
N-[4-(1,3-benzothiazol-2-ylsulfanyl)phenyl]-3,5-dibromo-2-hydroxybenzamide	1423480: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding after 40 to 60 mins by spectrometric analysis	ic50	4.7000	uM
(5Z)-5-[(3,4-dihydroxyphenyl)methylidene]-3-(4-hydroxyphenyl)-2-sulfanylidene-1,3-thiazolidin-4-one	1303884: Inhibition of human HSP60/HSP10 expressed in Escherichia coli Rosetta2(DE3) cells assessed as inhibition of denatured pig heart MDH refolding by measuring reduction in NADH production incubated for 60 mins by micro plate reader analysis	ic50	4.9000	uM
3-[18-(2-carboxyethyl)-8,13-bis(ethenyl)-3,7,12,17-tetramethyl-22,23-dihydroporphyrin-2-yl]propanoic acid	1594139: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by malachite green dye based spectrometric analysis	ic50	4.9000	uM
5-chloro-N-[4-[5-[[3-(trifluoromethyl)phenyl]sulfonylamino]-1,3-benzoxazol-2-yl]phenyl]thiophene-2-sulfonamide	1362251: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by spectrometric analysis	ic50	5.0000	uM
(E)-1-(3,4-dihydroxyphenyl)-3-(4-nitrophenyl)prop-2-en-1-one	1303884: Inhibition of human HSP60/HSP10 expressed in Escherichia coli Rosetta2(DE3) cells assessed as inhibition of denatured pig heart MDH refolding by measuring reduction in NADH production incubated for 60 mins by micro plate reader analysis	ic50	5.2000	uM
tretinoin	1594139: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by malachite green dye based spectrometric analysis	ic50	5.3000	uM
gentian violet	1594139: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by malachite green dye based spectrometric analysis	ic50	5.8000	uM
5-chloro-N-[4-[5-[(5-chlorothiophen-2-yl)sulfonylamino]-1,3-benzoxazol-2-yl]phenyl]thiophene-2-sulfonamide	1362251: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by spectrometric analysis	ic50	5.9000	uM
1-hexadecylpyridin-1-ium;chloride;hydrate	1594139: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by malachite green dye based spectrometric analysis	ic50	6.0000	uM
5-chloro-N-[2-[4-[[4-chloro-3-(trifluoromethyl)phenyl]sulfonylamino]phenyl]-1,3-benzoxazol-5-yl]thiophene-2-sulfonamide	1362251: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by spectrometric analysis	ic50	6.1000	uM
5-hydroxy-2-methylnaphthalene-1,4-dione	1594139: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by malachite green dye based spectrometric analysis	ic50	6.3000	uM
tetrasodium;4-amino-6-[[4-[4-[[8-amino-5,7-bis[dihydroxy(oxido)-lambda4-sulfanyl]-1-hydroxynaphthalen-2-yl]diazenyl]-3-methoxyphenyl]-2-methoxyphenyl]diazenyl]-5-hydroxynaphthalene-1,3-disulfonate	1594139: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by malachite green dye based spectrometric analysis	ic50	6.8000	uM
N-[4-(1,3-benzothiazol-2-ylsulfanyl)-3-chlorophenyl]-3-bromo-2-hydroxybenzamide	1423480: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding after 40 to 60 mins by spectrometric analysis	ic50	6.9000	uM
8-[4-methyl-3-[(5Z)-5-[(Z)-[5-[[2-methyl-5-[(4,6,8-trisulfo-2H-naphthalen-1-ylidene)carbamoyl]cyclohexa-2,4-dien-1-ylidene]carbamoyl]cyclohexa-2,4-dien-1-ylidene]carbamoyl]iminocyclohexa-1,3-diene-1-carbonyl]iminocyclohexa-1,4-diene-1-carbonyl]imino-7H-naphthalene-1,3,5-trisulfonic acid	1594139: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by malachite green dye based spectrometric analysis	ic50	7.2000	uM
1-[2,3-bis(furan-2-yl)quinoxalin-6-yl]-3-methylurea	1303884: Inhibition of human HSP60/HSP10 expressed in Escherichia coli Rosetta2(DE3) cells assessed as inhibition of denatured pig heart MDH refolding by measuring reduction in NADH production incubated for 60 mins by micro plate reader analysis	ic50	7.4000	uM
2-(3,4-dihydroxyphenyl)-3,5,7,8-tetrahydroxychromen-4-one	1594139: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by malachite green dye based spectrometric analysis	ic50	7.5000	uM
N-[4-[(E)-3-(furan-2-yl)prop-2-enoyl]phenyl]thiophene-2-carboxamide	1303884: Inhibition of human HSP60/HSP10 expressed in Escherichia coli Rosetta2(DE3) cells assessed as inhibition of denatured pig heart MDH refolding by measuring reduction in NADH production incubated for 60 mins by micro plate reader analysis	ic50	8.2000	uM
Curcumin	1594139: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by malachite green dye based spectrometric analysis	ic50	8.3000	uM
Ethacrynic Acid	1594139: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by malachite green dye based spectrometric analysis	ic50	8.5000	uM
N-[4-[5-(benzenesulfonamido)-1,3-benzoxazol-2-yl]phenyl]-5-chlorothiophene-2-sulfonamide	1590004: Inhibition of human HSP60 expressed in Escherichia coli Rosetta 2(DE3)/human HSP10 expressed in Escherichia coli Rosetta 2(DE3) pLysS cells assessed as reduction in HSP60/HSP10-mediated denatured pig heart mitochondrial MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by spectrometric analysis	ic50	9.0000	uM
5-chloro-N-[4-[5-(thiophen-2-ylsulfonylamino)-1,3-benzoxazol-2-yl]phenyl]thiophene-2-sulfonamide	1590004: Inhibition of human HSP60 expressed in Escherichia coli Rosetta 2(DE3)/human HSP10 expressed in Escherichia coli Rosetta 2(DE3) pLysS cells assessed as reduction in HSP60/HSP10-mediated denatured pig heart mitochondrial MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by spectrometric analysis	ic50	9.1000	uM
(3,5-dibromo-4-hydroxyphenyl)-(2-ethyl-1-benzofuran-3-yl)methanone	1594139: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by malachite green dye based spectrometric analysis	ic50	9.1000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases expression, affects binding, increases reaction, decreases expression (+1 more)	7
Copper	affects binding, decreases expression, increases expression	5
Cadmium Chloride	affects expression, decreases expression, increases abundance, increases expression	5
bisphenol A	increases reaction, affects expression, decreases expression, decreases reaction, increases expression	4
Arsenic Trioxide	affects cotreatment, increases expression	4
Rotenone	decreases reaction, increases expression, affects response to substance, decreases expression, affects cotreatment	4
lead acetate	affects reaction, increases abundance, increases expression, decreases expression, affects cotreatment	3
Resveratrol	affects expression, decreases expression	3
Acetaminophen	decreases expression, increases expression	3
Acetylcysteine	increases reaction, affects cotreatment, decreases reaction, increases expression	3
Cadmium	decreases expression, increases abundance, increases expression	3
Deferoxamine	increases expression, decreases expression, decreases reaction, affects cotreatment	3
Estradiol	decreases expression, increases expression	3
Quercetin	decreases reaction, increases reaction, decreases expression, affects expression	3
Tobacco Smoke Pollution	affects expression, increases expression	3
Tretinoin	decreases expression	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
bisphenol AF	increases expression, affects cotreatment, decreases reaction	2
Air Pollutants	decreases expression, increases abundance, affects expression	2
Arsenic	increases expression, affects cotreatment, increases abundance	2
Carbonyl Cyanide m-Chlorophenyl Hydrazone	affects reaction, decreases expression, affects cotreatment	2
Dexamethasone	increases expression, decreases expression, affects cotreatment, decreases reaction	2
Doxorubicin	increases expression	2
Formaldehyde	decreases expression, increases expression	2
Glucose	decreases reaction, affects cotreatment, decreases expression	2
Ivermectin	affects cotreatment, increases expression, decreases expression	2
Ouabain	affects expression, affects binding, decreases reaction, affects localization, decreases expression	2
Paraquat	decreases expression, increases expression	2
Polyethyleneimine	affects binding, increases expression	2

ChEMBL screening assays

22 unique, capped per target: 18 binding, 2 admet, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3813272	Binding	Inhibition of human HSP60/HSP10 expressed in Escherichia coli Rosetta2(DE3) cells assessed as inhibition of denatured pig heart MDH refolding by measuring reduction in NADH production incubated for 60 mins by micro plate reader analysis	GroEL/ES inhibitors as potential antibiotics. — Bioorg Med Chem Lett
CHEMBL3859767	ADMET	Inhibition of human mitochondrial HSP60/HSP10 expressed in Escherichia coli DH5alpha/BL21 (DE3) assessed as inhibition of denatured MDH refolding preincubated for 10 mins followed by ATP addition measured after 40 to 60 mins by fluorescence	Targeting the HSP60/10 chaperonin systems of Trypanosoma brucei as a strategy for treating African sleeping sickness. — Bioorg Med Chem Lett
CHEMBL825847	Functional	In vitro Hsp60 chaperone activity in mitochondrial malate dehydrogenase (MDH) refolding assay	Structure-activity relationships of epolactaene derivatives: structural requirements for inhibition of Hsp60 chaperone activity. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07542548	PHASE4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT03961906	PHASE2	COMPLETED	Physiotherapy in Hereditary Spastic Paraplegia
NCT04768166	PHASE2	COMPLETED	Testing Miglustat Administration in Subjects With Spastic Paraplegia 11
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT06117020	PHASE1	COMPLETED	Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT02604186	PHASE2/PHASE3	COMPLETED	Effects of Botulinum Toxin Injections in Patients With Hereditary Spastic Paraplegia
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT06948019	PHASE1/PHASE2	NOT_YET_RECRUITING	Safety and Efficacy of AAV9/AP4B1 (BFB-101) For Patients With AP4B1-related Hereditary Spastic Paraplegia Type 47 (SPG47)
NCT06478238	EARLY_PHASE1	RECRUITING	Calcium Folinate Treatment of Spastic Paraplegia 56
NCT00023075	Not specified	COMPLETED	Nuclear Magnetic Spectroscopy Imaging to Evaluate Primary Lateral Sclerosis, Hereditary Spastic Paraplegia and Amyotrophic Lateral Sclerosis
NCT00136630	Not specified	COMPLETED	Natural History, Genetic Bases and Phenotype-genotype Correlations in Autosomal Dominant Spinocerebellar Degenerations
NCT00140829	Not specified	COMPLETED	SPATAX: Clinical and Genetic Analysis of Cerebellar Ataxias and Spastic Paraplegias
NCT00677768	Not specified	COMPLETED	Validation of Biomarkers in Amyotrophic Lateral Sclerosis (ALS)
NCT01568658	Not specified	ACTIVE_NOT_RECRUITING	Genetic and Physical Study of Childhood Nerve and Muscle Disorders
NCT02327845	Not specified	ENROLLING_BY_INVITATION	Phenotype, Genotype & Biomarkers in ALS and Related Disorders
NCT02852278	Not specified	COMPLETED	A Patient Centric Motor Neuron Disease Activities of Daily Living Scale
NCT02859428	Not specified	TERMINATED	Disease Natural History and Biomarkers of SPG3A, SPG4A, and SPG31
NCT03104088	Not specified	COMPLETED	Studying Cognition in SPG4
NCT03206190	Not specified	RECRUITING	The preSPG4 Study - Studying the Prodromal and Early Phase of SPG4
NCT03627416	Not specified	COMPLETED	Repetitive Transcranial Magnetic Stimulation as Therapy in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy
NCT03981276	Not specified	RECRUITING	Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders
NCT04006418	Not specified	RECRUITING	A Registered Cohort Study on Spastic Paraplegia
NCT04180098	Not specified	COMPLETED	Improving Gait Adaptability in Hereditary Spastic Paraplegia
NCT04256681	Not specified	COMPLETED	SNAP: Measurement of the Subjective Perception of the Symptom in Hereditary Spastic Paraparesis (HSP)
NCT04712812	Not specified	RECRUITING	Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia
NCT04875416	Not specified	ACTIVE_NOT_RECRUITING	Phenotype, Genotype and Biomarkers 2
NCT04912609	Not specified	COMPLETED	Trehalose Administration in Subjects With Spastic Paraplegia 11 (3AL-SPG11)