HSPE1

Summary

HSPE1 (heat shock protein family E (Hsp10) member 1, HGNC:5269) is a protein-coding gene on chromosome 2q33.1, encoding 10 kDa heat shock protein, mitochondrial (P61604). Co-chaperonin implicated in mitochondrial protein import and macromolecular assembly. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

This gene encodes a major heat shock protein which functions as a chaperonin. Its structure consists of a heptameric ring which binds to another heat shock protein in order to form a symmetric, functional heterodimer which enhances protein folding in an ATP-dependent manner. This gene and its co-chaperonin, HSPD1, are arranged in a head-to-head orientation on chromosome 2. Naturally occurring read-through transcription occurs between this locus and the neighboring locus MOBKL3.

Source: NCBI Gene 3336 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 6 total
• Druggable target: yes — 27 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_002157

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5269
Approved symbol	HSPE1
Name	heat shock protein family E (Hsp10) member 1
Location	2q33.1
Locus type	gene with protein product
Status	Approved
Aliases	CPN10, GroES, HSP10, EPF
Ensembl gene	ENSG00000115541
Ensembl biotype	protein_coding
OMIM	600141
Entrez	3336

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000233893, ENST00000409468, ENST00000409729, ENST00000463841, ENST00000465573, ENST00000473395, ENST00000495200, ENST00000915248, ENST00000915249, ENST00000915250, ENST00000915251, ENST00000915252

RefSeq mRNA: 1 — MANE Select: NM_002157 NM_002157

CCDS: CCDS2320

Canonical transcript exons

ENST00000233893 — 4 exons

Exon	Start	End
ENSE00000803170	197503209	197503449
ENSE00001582383	197500379	197500439
ENSE00003559349	197501074	197501238
ENSE00003580189	197503039	197503128

Expression profiles

Bgee: expression breadth ubiquitous, 142 present calls, max score 99.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 74.4397 / max 1130.1496, expressed in 1815 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
24482	212.2057	1823
24481	65.3540	1814
24483	9.0857	1685

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	99.73	gold quality
right adrenal gland	UBERON:0001233	99.68	gold quality
left adrenal gland	UBERON:0001234	99.65	gold quality
right adrenal gland cortex	UBERON:0035827	99.65	gold quality
adrenal gland	UBERON:0002369	99.64	gold quality
left adrenal gland cortex	UBERON:0035825	99.64	gold quality
mucosa of transverse colon	UBERON:0004991	99.50	gold quality
right lobe of liver	UBERON:0001114	99.46	gold quality
hypothalamus	UBERON:0001898	99.32	gold quality
adult mammalian kidney	UBERON:0000082	99.30	gold quality
ventricular zone	UBERON:0003053	99.30	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.28	gold quality
adenohypophysis	UBERON:0002196	99.26	gold quality
substantia nigra	UBERON:0002038	99.24	gold quality
islet of Langerhans	UBERON:0000006	99.22	gold quality
amygdala	UBERON:0001876	99.21	gold quality
Ammon’s horn	UBERON:0001954	99.20	gold quality
cortex of kidney	UBERON:0001225	99.19	gold quality
caudate nucleus	UBERON:0001873	99.19	gold quality
endometrium	UBERON:0001295	99.18	gold quality
pituitary gland	UBERON:0000007	99.16	gold quality
nucleus accumbens	UBERON:0001882	99.16	gold quality
temporal lobe	UBERON:0001871	99.14	gold quality
putamen	UBERON:0001874	99.12	gold quality
embryo	UBERON:0000922	99.10	gold quality
rectum	UBERON:0001052	99.10	gold quality
ganglionic eminence	UBERON:0004023	99.10	gold quality
anterior cingulate cortex	UBERON:0009835	99.10	gold quality
kidney	UBERON:0002113	99.04	gold quality
metanephros cortex	UBERON:0010533	99.03	gold quality

Single-cell (SCXA)

Detected in 23 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-CURD-7	yes	853.64
E-HCAD-1	yes	49.02
E-MTAB-8410	yes	44.41
E-HCAD-5	yes	31.68
E-GEOD-134144	yes	31.55
E-CURD-122	yes	28.23
E-GEOD-135922	yes	27.52
E-GEOD-125970	yes	21.25
E-MTAB-10042	yes	14.50
E-CURD-112	yes	9.80
E-GEOD-130148	yes	6.80
E-MTAB-9801	yes	6.09
E-CURD-95	no	2179.98
E-MTAB-9689	no	2147.79
E-MTAB-9388	no	1232.98

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

21 targeting HSPE1, 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-4795-3P	100.00	74.62	4024
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-5583-3P	99.06	65.68	1018
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-4764-5P	98.88	65.53	894
HSA-MIR-3074-3P	97.83	67.26	922
HSA-MIR-101-5P	96.84	65.66	649

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 37)

• Hereditary spastic paraplegia SPG13 is associated with a mutation in the gene encoding the mitochondrial chaperonin Hsp60. (PMID:11898127)
• The low stability of the monomeric unit suggests that folding and assembly reactions for cpn10 are coupled. (PMID:12220543)
• The genome structure of this gene has been established. (PMID:12483302)
• Cpn10 and placental lactogen are capable of stimulating the synthesis of type I collagen by human osteoblasts in culture (PMID:12703979)
• Identification of amino acids important for the assembly of the cpn10 heptamer. (PMID:14525625)
• complex mechanisms are involved in the protection by hsp10 against simulated ischemia and reoxygenation-induced myocyte death (PMID:15059967)
• Hsp10 exerts anti-inflammatory activity by inhibiting Toll-like receptor signaling possibly by interacting with extracellular Hsp60 (PMID:15546885)
• The HSP10 plays a role in bone marrow cell differentiation other than being a mitochondrial co-chaperonin. (PMID:15590416)
• Chaperonin 10 and calgranulin A are identified as markers for diagnosis and screening of endometrial carcinoma. (PMID:15816004)
• the cpn10 interfaces can adapt to structural alterations without loss of either subunit-subunit affinity or heptamer specificity (PMID:15978542)
• biophysical analysis of dissociation equilibrium for the heptameric co-chaperonin proteins 10 from Aquifex aeolicus and human mitochondria (PMID:16100270)
• HSP60 and HSP10 are expressed in large bowel carcinomas with lymph node metastases (PMID:16253146)
• proteomic analysis of possible role of heat shock protein 10 in colorectal cancer (PMID:16502466)
• Results describe the time-resolved folding and assembly mechanism of the heptameric co-chaperonin protein 10 (cpn10) in vitro. (PMID:16979655)
• Investigation of single-nucleotide variations in the Hsp10 gene and their disease-causing potential. (PMID:17072495)
• In this review, we revise the involvement of Hsp10 in signal transduction pathways and its possible role in cancer etiology. (PMID:17278877)
• Data show that Hhsp10 formed fibrils from only the acidic unfolded state and Core peptide regions of these protein fibrils were determined by proteolysis followed by a combination of Edman degradation and mass spectroscopy analyses. (PMID:18329043)
• The effects of cpn 10 on cells of the oligodendrocyte lineage, were assessed. (PMID:18465204)
• In patients with serous ovarian carcinomas, gene expression analysis coupled with immunohistochemistry allowed the identification of HSP10 as an independent factor of progression-free survival. (PMID:18500265)
• the GroEL-GroES chamber behaves as a passive “Anfinsen cage” whose primary role is to prevent multimolecular association during folding. (PMID:18987317)
• Results describe a novel function of chaperonin 10 as a general differentiation factor, not limited to erythroid cells, and show how this biological effect is mediated by GSK-3alpha/beta. (PMID:19142874)
• HSP10 was identified as a new autoantigen in both autoimmune pancreatitis and fulminant type 1 diabetes. (PMID:19520060)
• HSP10 protein was detected only in oocytes from human preantral follicles, whereas in antral follicles, it was localised in oocytes, granulosa cells, theca cells and stroma cells. (PMID:19903031)
• Data show that that in presence of 300 mg/mL Ficoll the thermodynamic stability of each cpn10 monomer increases by over 30%, whereas the interfaces are stabilized by less than 10%. (PMID:21375247)
• Hsp10 and Hsp90 may be involved in large bowel carcinogenesis. (PMID:25075042)
• Hsp10 has a role in nuclear localization and lung cells response to cigarette smoke (PMID:25355063)
• Cpn10 has a role in the spatial regulation of NPAT signaling (PMID:26429916)
• Data indicate that on addition of the heat-shock proteins GroEL-GroES molecular chaperone system, the folding of the nascent chemokine receptor type 5 (CCR5) was significantly enhanced. (PMID:26585937)
• Hsp10 and Hsp60 may be implicated in carcinogenesis from its very early steps in colorectal cancer. (PMID:27491302)
• EPF induces the differentiation of regulatory T cells and increases their immunosuppressive activities. (PMID:27840373)
• High expression of HSP10 is negatively associated with estrogen receptor/progesterone receptor status and might be a novel independent biomarker for poor prognosis in invasive ductal breast carcinoma. (PMID:27993580)
• miR-146a, miR-146b, and miR-155 are exerting anti-inflammatory properties by down-regulating IL-6 and IL-8, and influencing the expression of HSP10 in the activated endothelium (PMID:28662100)
• elevated expression of HSP10 protein inhibits apoptosis and associates with poor prognosis of astrocytoma (PMID:29028811)
• An inventory of interactors of the human HSP60/HSP10 chaperonin in the mitochondrial matrix space. (PMID:32060690)
• structural basis for active single- and double-ring complexes coexisting in the mHsp60-mHsp10 chaperonin reaction cycle (PMID:32317635)
• Overexpression of HSP10 correlates with HSP60 and Mcl-1 levels and predicts poor prognosis in non-small cell lung cancer patients. (PMID:32986659)
• Structural basis for the structural dynamics of human mitochondrial chaperonin mHsp60. (PMID:34285302)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	hspe1	ENSDARG00000056167
mus_musculus	Hspe1	ENSMUSG00000073676
mus_musculus	Hspe1-rs1	ENSMUSG00000117621
rattus_norvegicus	Hspd1l2	ENSRNOG00000056007
drosophila_melanogaster	CG11267	FBGN0036334
drosophila_melanogaster	CG9920	FBGN0038200
caenorhabditis_elegans		WBGENE00021248

Protein

Protein identifiers

10 kDa heat shock protein, mitochondrial — P61604 (reviewed: P61604)

Alternative names: 10 kDa chaperonin, Chaperonin 10, Early-pregnancy factor, Heat shock protein family E member 1

All UniProt accessions (4): P61604, A0A384N6A4, B8ZZ54, B8ZZL8

UniProt curated annotations — full annotation on UniProt →

Function. Co-chaperonin implicated in mitochondrial protein import and macromolecular assembly. Together with Hsp60, 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. 2 heptameric Hsp10 rings interact with a Hsp60 tetradecamer in the structure of a back-to-back double heptameric ring to form the symmetrical football complex.

Subcellular location. Mitochondrion matrix.

Induction. By stress.

Similarity. Belongs to the GroES chaperonin family.

RefSeq proteins (1): NP_002148* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011032	GroES-like_sf	Homologous_superfamily
IPR018369	Chaprnonin_Cpn10_CS	Conserved_site
IPR020818	Chaperonin_GroES	Family
IPR037124	Chaperonin_GroES_sf	Homologous_superfamily

Pfam: PF00166

UniProt features (34 total): modified residue 21, strand 9, turn 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
9SHG	ELECTRON MICROSCOPY	1.91
9SHH	ELECTRON MICROSCOPY	2.11
9SHI	ELECTRON MICROSCOPY	2.19
9ES0	ELECTRON MICROSCOPY	2.58
8G7N	ELECTRON MICROSCOPY	2.7
9ES4	ELECTRON MICROSCOPY	2.91
9ES1	ELECTRON MICROSCOPY	2.95
9H5S	ELECTRON MICROSCOPY	2.98
6MRC	ELECTRON MICROSCOPY	3.08
4PJ1	X-RAY DIFFRACTION	3.15
8G7O	ELECTRON MICROSCOPY	3.4
9H5T	ELECTRON MICROSCOPY	3.44
9ES5	ELECTRON MICROSCOPY	3.5
6HT7	X-RAY DIFFRACTION	3.7
6MRD	ELECTRON MICROSCOPY	3.82
9L8P	ELECTRON MICROSCOPY	7.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P61604-F1	87.94	0.62

Functional residue map

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

Post-translational modifications (21): 56, 56, 56, 66, 66, 70, 70, 79, 80, 80, 2, 86, 86, 99, 8, 28, 40, 40, 40, 54 …

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9013408	RHOG GTPase cycle
R-HSA-9841251	Mitochondrial unfolded protein response (UPRmt)

MSigDB gene sets: 304 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, BASSO_B_LYMPHOCYTE_NETWORK, RORA1_01, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MORF_RRM1, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_OSTEOBLAST_DIFFERENTIATION, TGACCTY_ERR1_Q2, MORF_HDAC2, USF_C, PUJANA_CHEK2_PCC_NETWORK, SCHUHMACHER_MYC_TARGETS_UP, MUELLER_PLURINET

GO Biological Process (4): osteoblast differentiation (GO:0001649), protein folding (GO:0006457), response to unfolded protein (GO:0006986), intrinsic apoptotic signaling pathway (GO:0097193)

GO Molecular Function (7): RNA binding (GO:0003723), ATP binding (GO:0005524), protein folding chaperone (GO:0044183), metal ion binding (GO:0046872), obsolete unfolded protein binding (GO:0051082), protein-folding chaperone binding (GO:0051087), protein binding (GO:0005515)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), membrane (GO:0016020), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RHO GTPase cycle	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ossification	1
cell differentiation	1
cellular process	1
protein maturation	1
response to topologically incorrect protein	1
intracellular signal transduction	1
apoptotic signaling pathway	1
nucleic acid binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
molecular_function	1
protein folding	1
cation binding	1
protein binding	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

4471 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HSPE1	HSPD1	P10809	999
HSPE1	GRPEL1	Q9HAV7	967
HSPE1	CLPB	Q9H078	873
HSPE1	HSPA9	P30036	857
HSPE1	HSPA4	P34932	843
HSPE1	CLPP	Q16740	816
HSPE1	TST	Q16762	789
HSPE1	SPG7	Q9UQ90	783
HSPE1	CLPX	O76031	770
HSPE1	HSP90AA1	P07900	763
HSPE1	HSP90AB1	P08238	761
HSPE1	DNAJB1	P25685	746
HSPE1	CUTA	O60888	727
HSPE1	HSPA1A	P08107	716
HSPE1	LONP1	P36776	714

IntAct

169 interactions, top by confidence:

A	B	Type	Score
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
HSPE1	SELENOM	psi-mi:“MI:0915”(physical association)	0.560
HSPE1	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
VCAM1	PSMD11	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
AIFM1	SEC16A	psi-mi:“MI:2364”(proximity)	0.420
SYNC	HSPE1	psi-mi:“MI:0915”(physical association)	0.400
MCF2L	HSPE1	psi-mi:“MI:0915”(physical association)	0.400
CS	HSPE1	psi-mi:“MI:0915”(physical association)	0.400
RTP5	HSPE1	psi-mi:“MI:0915”(physical association)	0.400
IRF8	HSPE1	psi-mi:“MI:0915”(physical association)	0.400
GABRE	HSPE1	psi-mi:“MI:0915”(physical association)	0.400
PDPR	HSPE1	psi-mi:“MI:0915”(physical association)	0.400
LINC02693	HSPE1	psi-mi:“MI:0915”(physical association)	0.400
ERBB4	HSPE1	psi-mi:“MI:0915”(physical association)	0.400
TTN	HSPE1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (379): HSPE1 (Affinity Capture-MS), HSPE1 (Affinity Capture-MS), HSPE1 (Affinity Capture-RNA), AKR1B1 (Co-fractionation), CAT (Co-fractionation), CCT3 (Co-fractionation), CCT5 (Co-fractionation), ESD (Co-fractionation), GRHPR (Co-fractionation), HSPA4 (Co-fractionation), HSPA4L (Co-fractionation), HSPE1 (Co-fractionation), HSPE1 (Co-fractionation), HSPE1 (Co-fractionation), HSPE1 (Co-fractionation)

ESM2 similar proteins: A2BT11, A2BYG2, A2C4I3, A3PES5, A4QBT9, A4TEN7, A5GNB0, A8G6T7, A9BCC5, B0JUI1, B1W3U3, B1WWG9, B1XK80, B2IT70, B7KCB8, B8HQ34, C0ZW96, C1B075, C5BZX2, P07889, P0A347, P0A348, P22880, P26772, P38910, P61603, P61604, Q00769, Q05971, Q0I7U2, Q0S3C0, Q10WQ5, Q2JL42, Q2JUN8, Q318V5, Q37761, Q3AHM3, Q3AZK4, Q46J69, Q5DC69

Diamond homologs: A0PME8, A0Q2T2, A1A040, A1AST2, A1R8M2, A1TKQ6, A1VCP9, A1VJZ9, A1W3W9, A1WL04, A2BT11, A2BYG2, A2C4I3, A2SCV0, A4G836, A4IJV2, A4SZV5, A5G9I1, A5GNB0, A6T1E4, A8ZU47, A9BCC5, A9I682, B1XRX2, B1XXY8, B1ZMQ8, B2A5V2, B2HD09, B2IT70, B2SCZ5, B3E8F9, B5E9Y1, B6IU97, B7GFR5, B8DJC3, B8DVZ4, B8FM87, B8HQ34, B9DMM3, B9LZ36

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

653 predictions. Top by Δscore:

Variant	Effect	Δscore
2:197501071:CA:C	acceptor_loss	1.0000
2:197501072:A:AC	acceptor_loss	1.0000
2:197501073:G:A	acceptor_loss	1.0000
2:197501073:GGCA:G	acceptor_gain	1.0000
2:197501186:G:GT	donor_gain	1.0000
2:197501187:A:T	donor_gain	1.0000
2:197501235:A:T	donor_gain	1.0000
2:197501236:AAGG:A	donor_loss	1.0000
2:197501238:GGTA:G	donor_loss	1.0000
2:197501239:G:GC	donor_loss	1.0000
2:197503034:TTAA:T	acceptor_loss	1.0000
2:197503035:TAAG:T	acceptor_loss	1.0000
2:197503036:A:AG	acceptor_gain	1.0000
2:197503036:AAG:A	acceptor_gain	1.0000
2:197503036:AAGG:A	acceptor_gain	1.0000
2:197503037:A:AG	acceptor_loss	1.0000
2:197503037:A:G	acceptor_gain	1.0000
2:197503037:AG:A	acceptor_gain	1.0000
2:197503038:G:GA	acceptor_loss	1.0000
2:197503038:GG:G	acceptor_gain	1.0000
2:197503038:GGGT:G	acceptor_gain	1.0000
2:197503112:T:TA	donor_gain	1.0000
2:197503113:A:AA	donor_gain	1.0000
2:197503125:CAAGG:C	donor_loss	1.0000
2:197503126:AAGGT:A	donor_loss	1.0000
2:197503127:AGG:A	donor_loss	1.0000
2:197503127:AGGTG:A	donor_loss	1.0000
2:197503128:GGTG:G	donor_loss	1.0000
2:197503129:G:A	donor_loss	1.0000
2:197503129:GTGT:G	donor_loss	1.0000

AlphaMissense

649 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:197501212:G:C	A48P	0.999
2:197503082:T:A	V71D	0.999
2:197503243:G:A	G98E	0.999
2:197501123:T:A	V18D	0.998
2:197501200:G:C	A44P	0.998
2:197501207:T:A	V46E	0.998
2:197501219:G:A	G50E	0.998
2:197503100:G:A	G77E	0.998
2:197501102:C:A	P11Q	0.997
2:197501114:G:C	R15P	0.997
2:197501201:C:A	A44E	0.997
2:197503085:T:C	L72P	0.997
2:197503088:T:A	L73H	0.997
2:197503103:G:A	G78D	0.997
2:197503242:G:A	G98R	0.997
2:197503242:G:C	G98R	0.997
2:197501117:T:A	V16E	0.996
2:197501120:T:C	L17S	0.996
2:197501162:T:C	I31T	0.996
2:197501218:G:A	G50R	0.996
2:197501218:G:C	G50R	0.996
2:197501219:G:T	G50V	0.996
2:197503222:T:C	F91S	0.996
2:197501101:C:T	P11S	0.995
2:197501130:G:C	R20S	0.995
2:197501130:G:T	R20S	0.995
2:197501162:T:A	I31N	0.995
2:197501162:T:G	I31S	0.995
2:197501168:T:A	L33H	0.995
2:197503102:G:C	G78R	0.995

dbSNP variants (sampled 300 via entrez): RS1000014618 (2:197500984 A>G), RS1000170100 (2:197498572 C>G,T), RS1000285822 (2:197503948 A>G), RS1000721409 (2:197502009 A>G), RS1001857571 (2:197499666 CGCGGTGCGGA>C), RS1001857591 (2:197500559 C>T), RS1001926320 (2:197501487 G>A,T), RS1002436934 (2:197499708 C>G), RS1002980024 (2:197501627 G>C), RS1003192914 (2:197500344 T>C,G), RS1003634727 (2:197500500 C>T), RS1004507373 (2:197502319 G>A), RS1004572645 (2:197498436 T>C), RS1004788644 (2:197502573 G>C), RS1005196440 (2:197500214 G>A,C,T)

Disease associations

OMIM: gene MIM:600141 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3808268 (SINGLE PROTEIN), CHEMBL4106131 (PROTEIN COMPLEX)

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

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

pChembl	Type	Value	Unit	Molecule
7.12	Kd	76.53	nM	CHEMBL5653589
7.12	ED50	76.53	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
5.13	IC50	7400	nM	CHEMBL1713063
5.13	IC50	7400	nM	CHEMBL5314343

PubChem BioAssay actives

59 with measured affinity, of 369 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148559: Binding affinity to human HSPE1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0765	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
4-nonylphenol	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	9.5000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Tobacco Smoke Pollution	affects expression, increases expression	4
Particulate Matter	decreases expression, increases abundance, affects expression, increases reaction	4
bisphenol A	increases expression, decreases reaction, increases abundance, affects expression	3
Rotenone	affects reaction, increases expression	3
Tretinoin	decreases expression	3
Leflunomide	decreases expression	2
Acetaminophen	decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Cisplatin	decreases reaction, increases expression, decreases response to substance	2
Hydrogen Peroxide	affects expression	2
Ivermectin	affects cotreatment, increases expression, decreases expression	2
Dronabinol	increases expression, decreases expression	2
Cyclosporine	increases expression, decreases expression	2
Thapsigargin	decreases expression, increases expression, increases reaction	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression, affects cotreatment	1
ginger extract	decreases reaction, increases abundance, increases expression	1
pyrithione zinc	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
cupric oxide	decreases expression	1
caffeic acid	increases expression, increases reaction	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	decreases expression	1
phenethyl isothiocyanate	affects binding	1
raltitrexed	increases expression	1
1,4-phenylenebis(methylene)selenocyanate	affects expression	1
4-methoxycinnamate methyl ester	increases expression, increases reaction	1

ChEMBL screening assays

11 unique, capped per target: 9 binding, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5338464	Binding	Binding affinity to Hspe1 (unknown origin) assessed as fold change in protein upregulation at 200 uM preincubated for 2 hrs followed by pronase addition and measured after 30 mins by coomassie blue staining based SDS-PAGE gel analysis	Structurally Diverse Alkaloids with Anti-Renal-Fibrosis Activity from the Centipede Scolopendra subspinipes mutilans. — J Nat Prod
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

Clinical trials (associated diseases)

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