HSPA1A

Summary

HSPA1A (heat shock protein family A (Hsp70) member 1A, HGNC:5232) is a protein-coding gene on chromosome 6p21.33, encoding Heat shock 70 kDa protein 1A (P0DMV8). Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein comple….

This intronless gene encodes a 70kDa heat shock protein which is a member of the heat shock protein 70 family. In conjuction with other heat shock proteins, this protein stabilizes existing proteins against aggregation and mediates the folding of newly translated proteins in the cytosol and in organelles. It is also involved in the ubiquitin-proteasome pathway through interaction with the AU-rich element RNA-binding protein 1. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which encode similar proteins.

Source: NCBI Gene 3303 — RefSeq curated summary.

At a glance

• GWAS associations: 28
• Clinical variants (ClinVar): 35 total
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005345

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5232
Approved symbol	HSPA1A
Name	heat shock protein family A (Hsp70) member 1A
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Aliases	HSP70-1
Ensembl gene	ENSG00000204389
Ensembl biotype	protein_coding
OMIM	140550
Entrez	3303

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000375651, ENST00000608703

RefSeq mRNA: 1 — MANE Select: NM_005345 NM_005345

CCDS: CCDS34414

Canonical transcript exons

ENST00000375651 — 1 exons

Exon	Start	End
ENSE00001690505	31815543	31817942

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 99.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 305.7619 / max 42268.2990, expressed in 1756 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67046	303.8596	1751
67044	0.9511	279
67043	0.8584	310
67045	0.0927	33

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.81	gold quality
gall bladder	UBERON:0002110	99.47	gold quality
ventricular zone	UBERON:0003053	99.37	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.18	gold quality
right atrium auricular region	UBERON:0006631	99.01	gold quality
ganglionic eminence	UBERON:0004023	98.90	gold quality
blood	UBERON:0000178	98.89	gold quality
right lobe of liver	UBERON:0001114	98.86	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.83	gold quality
heart left ventricle	UBERON:0002084	98.80	gold quality
substantia nigra	UBERON:0002038	98.79	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.77	gold quality
lower esophagus	UBERON:0013473	98.74	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.74	gold quality
Ammon’s horn	UBERON:0001954	98.69	gold quality
caudate nucleus	UBERON:0001873	98.68	gold quality
temporal lobe	UBERON:0001871	98.62	gold quality
amygdala	UBERON:0001876	98.61	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.57	gold quality
mucosa of stomach	UBERON:0001199	98.54	gold quality
mucosa of transverse colon	UBERON:0004991	98.54	gold quality
heart	UBERON:0000948	98.52	gold quality
putamen	UBERON:0001874	98.52	gold quality
nucleus accumbens	UBERON:0001882	98.51	gold quality
hypothalamus	UBERON:0001898	98.50	gold quality
omental fat pad	UBERON:0010414	98.50	gold quality
body of uterus	UBERON:0009853	98.47	gold quality
fundus of stomach	UBERON:0001160	98.46	gold quality
apex of heart	UBERON:0002098	98.42	gold quality
ascending aorta	UBERON:0001496	98.40	gold quality

Single-cell (SCXA)

Detected in 34 experiment(s), a significant marker in 28.

Experiment	Marker?	Max mean expression
E-MTAB-10137	yes	13256.70
E-GEOD-180759	yes	6123.63
E-MTAB-9543	yes	5580.20
E-HCAD-25	yes	4824.87
E-CURD-97	yes	3512.14
E-GEOD-84465	yes	2097.36
E-HCAD-35	yes	2054.76
E-CURD-85	yes	2015.61
E-GEOD-130473	yes	1430.41
E-CURD-88	yes	1051.08
E-MTAB-8495	yes	717.44
E-HCAD-31	yes	704.88
E-GEOD-139324	yes	678.74
E-CURD-95	yes	608.33
E-MTAB-6701	yes	499.49

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
KCNH2	Activation

Upstream regulators (CollecTRI, top): AR, CREB1, DDIT3, FOS, FOXA1, FOXO3, GATA1, GLI3, HIF1A, HSF1, HSF2, HSPH1, KLF4, MTF1, MYBL2, MYC, NFAT5, NFKB1, NFKB, NFYA, NFYB, NFYC, PPARG, RELA, SP1, SRY, STAT3, TP53, XBP1

miRNA regulators (miRDB)

18 targeting HSPA1A, 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-4682	100.00	68.89	1258
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-888-3P	99.53	69.77	1057
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-4424	98.91	70.33	1145
HSA-MIR-412-3P	98.86	66.89	712
HSA-MIR-6754-3P	98.84	66.60	889
HSA-MIR-3928-5P	98.50	67.48	980
HSA-MIR-6806-3P	98.50	67.31	980
HSA-MIR-4662B	98.33	66.37	1163
HSA-MIR-4647	98.30	66.41	1139

Literature-anchored findings (GeneRIF, showing 40)

• No variation in Hsp70 mRNA level during cardiac surgery in pediatric patients evaluated by semiquantitative RT-PCR (PMID:11798084)
• Interaction of the molecular chaperone Hsp70 with human NAD(P)H:quinone oxidoreductase 1 (PMID:11821413)
• Effect of hyaluronan oligosaccharides on the expression of heat shock protein 72. (PMID:11864979)
• These data strongly suggest that in TNF-induced apoptosis, Hsp72 specifically interferes with the Bid-dependent apoptotic pathway via inhibition of JNK. (PMID:11971973)
• IL-6 activates HSP72 gene expression in human skeletal muscle. (PMID:12207910)
• These observations suggest that heat shock protein 72 functions as an endogenous inhibitor of ASK1. (PMID:12391142)
• Increase in arterial HSP72 was accounted for, at least in part, by release from the hepatosplanchnic viscera with values increasing (P < 0.05) from undetectable levels at rest to 5.2 +/- 0.2 pg min(-1) after 120 min. (PMID:12411538)
• HSP72 may protect intestinal epithelial cells from Clostridium difficile toxin A-mediated damage through actin stabilization, mitochondrial protection, and inhibition of apoptosis activation, but not by prevention of RhoA glucosylation. (PMID:12490434)
• lipid rafts are part of a mechanism ensuring the correct functions of Hsp70 (PMID:12682040)
• in very low birth weight neonates carrying HSP72 (1267)GG genetic variation, which is associated with low inducibility of HSP72, the risk of of acute renal failure was increased (PMID:12840151)
• Basal expression of both HSP72 and HO-1 mRNA were lower (P < 0.05) by 33 and 55%, respectively, when comparing diabetic patients with age-matched and young control subjects (PMID:12941774)
• cytoplasmic localization of Hsp72 might be correlated with the development of thermotolerance (PMID:14981913)
• HSP-72 gene expression at the time of engraftment does not play a role in graft protection. (PMID:15280693)
• These data demonstrate that the human brain is able to release Hsp72 in vivo in response to a physical stressor such as exercise. (PMID:15544165)
• the mesothelial stress response confers cytoprotection in experimental peritoneal dialysis, mediated by the induction of HSP-72 (PMID:15569319)
• Ability of Hsp72 to inhibit Fas-mediated apoptosis is limited to type II cells where involvement of the intrinsic pathway is required for efficient effector caspase activation. (PMID:15632129)
• results show hsp70i bookmarking is mediated by HSF2 which binds this promoter in mitotic cells, recruits protein phosphatase 2A & interacts with the CAP-G subunit of condensin to promote dephosphorylation & inactivation of condensin complexes (PMID:15662014)
• downregulation of Hsp72 leads to severe suppression of the major survival pathways, ERK and NF-kappaB, which may be responsible for enhanced sensitivity of prostate carcinoma cells to a variety of anticancer treatments (PMID:15735699)
• Acute trauma can lead to a marked elevation of HSP72. (PMID:15877962)
• L-glutamine potentiation of Hsp72 is associated with increased epithelial resistance to apoptotic injury. (PMID:16012946)
• EndoG forms complexes with AIF and FEN-1 but not with PCNA. Heat shock proteins 70 interact with EndoG and are involved in the regulation of its activity. (PMID:16133872)
• Hsp70 blocks heat-induced apoptosis primarily by inhibiting Bax activation and thereby preventing the release of proapoptotic factors from mitochondria (PMID:16172114)
• Our results indicate that pro-apoptotic activity of quercetin may be correlated not only with the inhibition of Hsp72 expression but also with suppression of its migration to the nucleus. (PMID:16201310)
• Up-regulation of HSP70 Heat Shock Protein is associated with hepatocellular carcinoma (PMID:16400691)
• These result suggest that overexpression of HSP70 plays an important role in protecting gastric cells against NH(2)Cl-induced injury. (PMID:16492383)
• HSP25 and HSP70i activate HSF1 and have roles in inhibition of ERK1/2 phosphorylation (PMID:16624816)
• During exercise, with and without carbohydrate ingestion, plasma HSP72 increased 5-fold. The concentrations of HSP72 in CSF did not change with exercise and was below the corresponding plasma level. (PMID:16647242)
• eHsp72 was present in plasma and pulmonary edema (PE)fluid of ALI patients and it was significantly higher in PE fluid from patients with preserved alveolar epithelial fluid clearance. eHsp72 may serve as a marker of SPR activation of ALI patients. (PMID:16679378)
• K562 cells transfected with the vector exhibited slower proliferation, increased apoptosis and increased G(0)/G(1) arrest. (PMID:16806014)
• applied a genetic-demographic approach to a dataset relevant to two genes, APOE and HSP70.1, previously shown to be related to longevity by the gene-frequency method (PMID:16896546)
• Knockdown of Hsp701A gene by siRNA enhances sensitivity to chemotherapeutic drug in HepG2 cells. (PMID:16948906)
• Upon heat shock, the Hsp70.1 promoter-bound PARP-1 is released to activate transcription through ADP-ribosylation of other Hsp70.1 promoter-bound proteins. (PMID:17158748)
• This data indicates a tumor-specific expression of hsp70, but does not support its relevance in the DC cross-presentation of TAs. (PMID:17235439)
• EDTA-treated blood was significantly higher in Hsp72 concentration than all other treatments (P < or = 0.001), whilst heparin plasma (LH) was significantly higher than serum derived on ice (SI) and at room temperature (SR) . (PMID:17278879)
• Hsp72 provides a selective advantage to cancer cells by suppressing default senescence via p53-dependent and p53-independent pathways. (PMID:17332370)
• identification of the most common polymorphisms in HSPA1A & HSPA1B in asthmatics & controls from 3 ethnic groups; study indicates most of the HSPA1A and HSPA1B polymorphisms identified in dbSNP are rare or were derived during post transcriptional events (PMID:17364813)
• HSPA1A is an important regulator of the stability and function of ZNF198 and its oncogenic derivative, ZNF198-FGFr1. (PMID:17471537)
• Polymorphism of HSP70-1 gene could contribute to the higher risk of ischemic stroke. (PMID:17555092)
• HSP70-1+190G/C may affect susceptibility to ischemic stroke (IS) and smoking along with HSP70-1+190G/C may increase the risk of IS. (PMID:17582394)
• Acetylglucosamine (GlcNAc) level and Hsp70-GlcNAc-binding activity (HGBA) behaviour after exposure of HeLa and HepG(2) cells to a wide variety of stresses, was investigated. (PMID:17645866)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
mus_musculus	Hspa1b	ENSMUSG00000090877
mus_musculus	Hspa1a	ENSMUSG00000091971
rattus_norvegicus	Hspa1b	ENSRNOG00000045654
drosophila_melanogaster	Hsp110	FBGN0026418
caenorhabditis_elegans	hsp-70	WBGENE00002026
caenorhabditis_elegans		WBGENE00009691
caenorhabditis_elegans		WBGENE00009692
caenorhabditis_elegans		WBGENE00016250

Paralogs (13): HSPA5 (ENSG00000044574), HSPA8 (ENSG00000109971), HSPA9 (ENSG00000113013), HSPH1 (ENSG00000120694), HSPA2 (ENSG00000126803), HYOU1 (ENSG00000149428), HSPA13 (ENSG00000155304), HSPA4L (ENSG00000164070), HSPA4 (ENSG00000170606), HSPA6 (ENSG00000173110), HSPA14 (ENSG00000187522), HSPA1B (ENSG00000204388), HSPA1L (ENSG00000204390)

Protein

Protein identifiers

Heat shock 70 kDa protein 1A — P0DMV8 (reviewed: P0DMV8)

Alternative names: Heat shock 70 kDa protein 1, Heat shock protein family A member 1A

All UniProt accessions (3): A8K5I0, P0DMV8, V9GZ37

UniProt curated annotations — full annotation on UniProt →

Function. Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The co-chaperones have been shown to not only regulate different steps of the ATPase cycle, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The co-chaperones are of three types: J-domain co-chaperones such as HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1. Maintains protein homeostasis during cellular stress through two opposing mechanisms: protein refolding and degradation. Its acetylation/deacetylation state determines whether it functions in protein refolding or protein degradation by controlling the competitive binding of co-chaperones HOPX and STUB1. During the early stress response, the acetylated form binds to HOPX which assists in chaperone-mediated protein refolding, thereafter, it is deacetylated and binds to ubiquitin ligase STUB1 that promotes ubiquitin-mediated protein degradation. Regulates centrosome integrity during mitosis, and is required for the maintenance of a functional mitotic centrosome that supports the assembly of a bipolar mitotic spindle. Enhances STUB1-mediated SMAD3 ubiquitination and degradation and facilitates STUB1-mediated inhibition of TGF-beta signaling. Essential for STUB1-mediated ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg) during inflammation. Required as a co-chaperone for optimal STUB1/CHIP ubiquitination of NFATC3. Negatively regulates heat shock-induced HSF1 transcriptional activity during the attenuation and recovery phase period of the heat shock response. Involved in the clearance of misfolded PRDM1/Blimp-1 proteins. Sequesters them in the cytoplasm and promotes their association with SYNV1/HRD1, leading to proteasomal degradation. (Microbial infection) In case of rotavirus A infection, serves as a post-attachment receptor for the virus to facilitate entry into the cell.

Subunit / interactions. Component of the CatSper complex. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with CHCHD3, DNAJC7, IRAK1BP1, PPP5C and TSC2. Interacts with TERT; the interaction occurs in the absence of the RNA component, TERC, and dissociates once the TERT complex has formed. Interacts with TRIM5 (via B30.2/SPRY domain). Interacts with METTL21A. Interacts with DNAAF2. Interacts with PRKN. Interacts with FOXP3. Interacts with NOD2; the interaction enhances NOD2 stability. Interacts with DNAJC9 (via J domain). Interacts with ATF5; the interaction protects ATF5 from degradation via proteasome-dependent and caspase-dependent processes. Interacts with RNF207 (via the C-terminus); this interaction additively increases KCNH2 expression. Interacts with HSF1 (via transactivation domain); this interaction results in the inhibition of heat shock- and HSF1-induced transcriptional activity during the attenuation and recovery phase period of the heat shock response. Interacts with NAA10, HSP40, HSP90 and HDAC4. Interacts (via C-terminus) with STUB1 (via TPR repeats). The acetylated form and the non-acetylated form interact with HOPX and STUB1 respectively. Interacts with NEDD1. Interacts (via NBD) with BAG1, BAG2, BAG3 and HSPH1/HSP105. Interacts with SMAD3. Interacts with DNAJC8. Interacts with NLRP12. Interacts with PGLYRP. Forms a ternary complex with BAG3 and HSPB8. Interacts with TTC1 and HSP40/DNAJB1; these interactions prevent the negative role of HSPBP1 on HSP70 folding.

Subcellular location. Cytoplasm. Nucleus. Cytoskeleton. Microtubule organizing center. Centrosome. Secreted.

Post-translational modifications. In response to cellular stress, acetylated at Lys-77 by NA110 and then gradually deacetylated by HDAC4 at later stages. Acetylation enhances its chaperone activity and also determines whether it will function as a chaperone for protein refolding or degradation by controlling its binding to co-chaperones HOPX and STUB1. The acetylated form and the non-acetylated form bind to HOPX and STUB1 respectively. Acetylation also protects cells against various types of cellular stress.

Disease relevance. In certain aggressive cases of activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL), plays a role in the cytoplasmic sequestration of misfolded N-terminal mutated PRDM1 proteins, promotes their association with SYNV1/HRD1 and degradation through the SYNV1-proteasome pathway. HSPA1A inhibition restores PRDM1 nuclear localization and transcriptional activity in lymphoma cell lines and suppresses growth in xenografts.

Domain organisation. The N-terminal nucleotide binding domain (NBD) (also known as the ATPase domain) is responsible for binding and hydrolyzing ATP. The C-terminal substrate-binding domain (SBD) (also known as peptide-binding domain) binds to the client/substrate proteins. The two domains are allosterically coupled so that, when ATP is bound to the NBD, the SBD binds relatively weakly to clients. When ADP is bound in the NBD, a conformational change enhances the affinity of the SBD for client proteins.

Induction. By heat shock.

Similarity. Belongs to the heat shock protein 70 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P0DMV8-1	1	yes
P0DMV8-2	2

RefSeq proteins (1): NP_005336* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013126	Hsp_70_fam	Family
IPR018181	Heat_shock_70_CS	Conserved_site
IPR029047	HSP70_peptide-bd_sf	Homologous_superfamily
IPR029048	HSP70_C_sf	Homologous_superfamily
IPR043129	ATPase_NBD	Homologous_superfamily

Pfam: PF00012

UniProt features (102 total): strand 31, helix 30, modified residue 11, turn 7, binding site 5, mutagenesis site 5, sequence conflict 5, region of interest 3, initiator methionine 1, chain 1, splice variant 1, sequence variant 1, compositionally biased region 1

Structure

Experimental structures (PDB)

75 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5BN8	X-RAY DIFFRACTION	1.34
6K39	X-RAY DIFFRACTION	1.4
6G3R	X-RAY DIFFRACTION	1.4
6ZYI	X-RAY DIFFRACTION	1.52
5AQW	X-RAY DIFFRACTION	1.53
3Q49	X-RAY DIFFRACTION	1.54
5AQY	X-RAY DIFFRACTION	1.56
3ATV	X-RAY DIFFRACTION	1.58
3ATU	X-RAY DIFFRACTION	1.65
5AQZ	X-RAY DIFFRACTION	1.65
6FHK	X-RAY DIFFRACTION	1.66
5BN9	X-RAY DIFFRACTION	1.69
3AY9	X-RAY DIFFRACTION	1.75
2E8A	X-RAY DIFFRACTION	1.77
7Q4R	X-RAY DIFFRACTION	1.79
2E88	X-RAY DIFFRACTION	1.8
5BPM	X-RAY DIFFRACTION	1.83
1S3X	X-RAY DIFFRACTION	1.84
5MKR	X-RAY DIFFRACTION	1.87
9DYA	X-RAY DIFFRACTION	1.89
5AR0	X-RAY DIFFRACTION	1.9
7GY4	X-RAY DIFFRACTION	1.92
7GY5	X-RAY DIFFRACTION	1.92
7GY6	X-RAY DIFFRACTION	1.92
7GY7	X-RAY DIFFRACTION	1.92
7GY8	X-RAY DIFFRACTION	1.92
7GY9	X-RAY DIFFRACTION	1.92
7GYA	X-RAY DIFFRACTION	1.92
7GYB	X-RAY DIFFRACTION	1.92
7GYC	X-RAY DIFFRACTION	1.92

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DMV8-F1	89.50	0.69

Functional residue map

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

Ligand- & substrate-binding residues (5): 339–342; 12–15; 71; 202–204; 268–275

Post-translational modifications (11): 2, 77, 108, 246, 348, 469, 561, 561, 631, 633, 636

Mutagenesis-validated functional residues (5):

Position	Phenotype
10	reduces affinity for adp.
77	no loss of acetylation and atpase activity. exhibits normal protein refolding activity during the early phase but exhibi
77	significant loss of acetylation and atpase activity. decreased binding to hopx and hsp90 and increased binding to stub1
199	reduces affinity for adp.
561	complete loss of in vitro methylation by mettl21a.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-168330	Viral RNP Complexes in the Host Cell Nucleus
R-HSA-3371453	Regulation of HSF1-mediated heat shock response
R-HSA-3371497	HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand
R-HSA-3371568	Attenuation phase
R-HSA-3371571	HSF1-dependent transactivation
R-HSA-450408	AUF1 (hnRNP D0) binds and destabilizes mRNA
R-HSA-6798695	Neutrophil degranulation
R-HSA-9833482	PKR-mediated signaling
R-HSA-9841251	Mitochondrial unfolded protein response (UPRmt)
R-HSA-9918487	Dengue Virus Genome Translation and Replication
R-HSA-3371511	HSF1 activation

MSigDB gene sets: 669 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GOBP_MYELOID_CELL_DIFFERENTIATION, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_CHROMOSOME_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, BENPORATH_ES_WITH_H3K27ME3, GOBP_POSITIVE_REGULATION_OF_ERYTHROCYTE_DIFFERENTIATION, GOBP_LYSOSOMAL_TRANSPORT, GOBP_MYELOID_CELL_HOMEOSTASIS, YAGI_AML_WITH_INV_16_TRANSLOCATION

GO Biological Process (43): negative regulation of transcription by RNA polymerase II (GO:0000122), mRNA catabolic process (GO:0006402), response to unfolded protein (GO:0006986), lysosomal transport (GO:0007041), negative regulation of cell population proliferation (GO:0008285), positive regulation of gene expression (GO:0010628), negative regulation of cell growth (GO:0030308), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), endoplasmic reticulum unfolded protein response (GO:0030968), regulation of protein ubiquitination (GO:0031396), negative regulation of protein ubiquitination (GO:0031397), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), positive regulation of interleukin-8 production (GO:0032757), positive regulation of RNA splicing (GO:0033120), cellular response to oxidative stress (GO:0034599), cellular response to heat (GO:0034605), cellular response to unfolded protein (GO:0034620), protein refolding (GO:0042026), negative regulation of apoptotic process (GO:0043066), positive regulation of erythrocyte differentiation (GO:0045648), ATP metabolic process (GO:0046034), protein stabilization (GO:0050821), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), chaperone-mediated protein complex assembly (GO:0051131), cellular heat acclimation (GO:0070370), positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070434), cellular response to steroid hormone stimulus (GO:0071383), positive regulation of microtubule nucleation (GO:0090063), negative regulation of inclusion body assembly (GO:0090084), negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway (GO:1901029), regulation of mitotic spindle assembly (GO:1901673), negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway (GO:1902236), positive regulation of tumor necrosis factor-mediated signaling pathway (GO:1903265), negative regulation of extrinsic apoptotic signaling pathway in absence of ligand (GO:2001240), protein folding (GO:0006457), negative regulation of signal transduction (GO:0009968), regulation of protein stability (GO:0031647), cellular response to stress (GO:0033554), regulation of cytoplasmic pattern recognition receptor signaling pathway (GO:0039531), regulation of protein-containing complex assembly (GO:0043254)

GO Molecular Function (25): virus receptor activity (GO:0001618), G protein-coupled receptor binding (GO:0001664), transcription corepressor activity (GO:0003714), RNA binding (GO:0003723), signaling receptor binding (GO:0005102), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), enzyme binding (GO:0019899), heat shock protein binding (GO:0031072), obsolete denatured protein binding (GO:0031249), ubiquitin protein ligase binding (GO:0031625), histone deacetylase binding (GO:0042826), protein folding chaperone (GO:0044183), cadherin binding (GO:0045296), receptor ligand activity (GO:0048018), obsolete unfolded protein binding (GO:0051082), misfolded protein binding (GO:0051787), C3HC4-type RING finger domain binding (GO:0055131), disordered domain specific binding (GO:0097718), transcription regulator inhibitor activity (GO:0140416), ATP-dependent protein disaggregase activity (GO:0140545), ATP-dependent protein folding chaperone (GO:0140662), nucleotide binding (GO:0000166), protein binding (GO:0005515), death receptor agonist activity (GO:0038177)

GO Cellular Component (24): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), inclusion body (GO:0016234), aggresome (GO:0016235), nuclear speck (GO:0016607), vesicle (GO:0031982), protein-containing complex (GO:0032991), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), blood microparticle (GO:0072562), ficolin-1-rich granule lumen (GO:1904813), ribonucleoprotein complex (GO:1990904), cytoskeleton (GO:0005856), COP9 signalosome (GO:0008180)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Cellular response to heat stress	3
Cellular responses to stress	2
Export of Viral Ribonucleoproteins from Nucleus	1
HSF1-dependent transactivation	1
Regulation of mRNA stability by proteins that bind AU-rich elements	1
Innate Immune System	1
Antimicrobial mechanism of IFN-stimulated genes	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
protein binding	4
cytoplasm	4
intracellular membrane-bounded organelle	3
negative regulation of DNA-templated transcription	2
negative regulation of cellular process	2
regulation of gene expression	2
protein ubiquitination	2
protein folding	2
signaling receptor binding	2
protein domain specific binding	2
intracellular anatomical structure	2
microtubule organizing center	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
RNA catabolic process	1
negative regulation of gene expression	1
mRNA metabolic process	1
response to topologically incorrect protein	1
vacuolar transport	1
cell population proliferation	1
regulation of cell population proliferation	1
gene expression	1
positive regulation of macromolecule biosynthetic process	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
cellular response to unfolded protein	1
response to endoplasmic reticulum stress	1
intracellular signal transduction	1
regulation of protein modification by small protein conjugation or removal	1
regulation of protein ubiquitination	1
negative regulation of protein modification by small protein conjugation or removal	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
positive regulation of proteasomal protein catabolic process	1
positive regulation of ubiquitin-dependent protein catabolic process	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

115 interactions, top by confidence:

A	B	Type	Score
	TOMM70	psi-mi:“MI:0914”(association)	0.980
CDK8	MED19	psi-mi:“MI:0914”(association)	0.850
PSMB2	PSMD11	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CEP170	KIF2A	psi-mi:“MI:2364”(proximity)	0.650
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
MAP1LC3B	HSPA1A	psi-mi:“MI:0915”(physical association)	0.560
PRKN	HSPA1A	psi-mi:“MI:0915”(physical association)	0.560
S100B	HSPA1A	psi-mi:“MI:0915”(physical association)	0.560
SYK	HSPA1A	psi-mi:“MI:0915”(physical association)	0.560
SQSTM1	HSPA1A	psi-mi:“MI:0915”(physical association)	0.560
HSPA1A	HTT	psi-mi:“MI:0915”(physical association)	0.560
HSPA1A	ATXN1	psi-mi:“MI:0915”(physical association)	0.560

ESM2 similar proteins: A2Q0Z1, O59855, O65719, O73885, P02827, P08106, P08108, P08418, P09446, P0DMV8, P0DMV9, P0DMW0, P0DMW1, P11142, P11147, P14659, P17156, P19120, P19378, P22953, P27541, P34930, P34933, P36415, P41753, P47773, P53421, P53623, P54652, P63017, P63018, Q01233, Q01877, Q05944, Q06248, Q10265, Q27965, Q27975, Q4U0F3, Q557E0

Diamond homologs: A0A0D1CD96, A0A509AJG0, A2Q0Z1, A5A8V7, F5HB71, G3I8R9, J9VZ70, O24581, O59855, O73885, O93866, P02827, P06761, P07823, P08108, P08418, P09189, P0CB32, P0DMV8, P0DMV9, P10591, P10592, P11021, P11142, P14659, P16474, P17156, P17879, P19120, P19208, P19378, P20029, P20163, P22010, P22202, P24067, P26413, P27420, P29844, P34933

SIGNOR signaling

15 interactions.

A	Effect	B	Mechanism
HSPA1A	down-regulates	MAPK8
HSPA1A	down-regulates	NR3C1	binding
HSPA1A	“up-regulates quantity”	ENPP1	“post transcriptional regulation”
HSPA1A	“up-regulates quantity by stabilization”	NOD2	binding
FOXA1	“up-regulates quantity by expression”	HSPA1A	“transcriptional regulation”
STAT3	“up-regulates quantity by expression”	HSPA1A	“transcriptional regulation”
HSPH1	“up-regulates quantity by expression”	HSPA1A	“transcriptional regulation”
HSPA1A	“up-regulates quantity by stabilization”	FLCN	binding
BAG5	“down-regulates activity”	HSPA1A	binding
HSPA1A	down-regulates	APAF1	binding
TOMM70	“up-regulates activity”	HSPA1A	binding
HSPA1A	“up-regulates activity”	GSTA4	relocalization
HSPA1A	“down-regulates quantity by destabilization”	ACOT4	binding
HSPA1A	“up-regulates quantity by stabilization”	PACRG	binding
NEK6	“up-regulates activity”	HSPA1A	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 108 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
ER to Golgi Anterograde Transport	6	10.3×	3e-03
KEAP1-NFE2L2 pathway	6	9.4×	3e-03
Transport to the Golgi and subsequent modification	6	8.0×	6e-03
Clathrin-mediated endocytosis	7	7.8×	3e-03
Signaling by Interleukins	8	6.7×	3e-03
Cytokine Signaling in Immune system	11	5.8×	2e-03
Membrane Trafficking	11	5.3×	2e-03
Vesicle-mediated transport	11	5.0×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3 predictions. Top by Δscore:

Variant	Effect	Δscore
6:31817820:C:CA	acceptor_gain	0.4400
6:31817563:T:A	donor_gain	0.2600
6:31817829:C:G	acceptor_gain	0.2200

AlphaMissense

4221 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1001162238 (6:31814530 A>C), RS1002327850 (6:31814201 G>A), RS1003842291 (6:31815399 A>C), RS1004422815 (6:31818412 A>C), RS1005023338 (6:31814394 T>A,C), RS1005521886 (6:31814175 G>A), RS1005572569 (6:31813964 G>A), RS1006327808 (6:31818072 A>G), RS1007485619 (6:31813812 G>T), RS1008186205 (6:31815153 G>A,T), RS1008438 (6:31815431 A>C,T), RS1008488145 (6:31814920 A>T), RS1009600159 (6:31813639 G>A), RS1009695632 (6:31814870 C>T), RS1011470352 (6:31814561 A>G,T)

Disease associations

OMIM: gene MIM:140550 | disease phenotypes: MIM:606963

GenCC curated gene-disease

Mondo (1): chronic obstructive pulmonary disease (MONDO:0005002)

Orphanet (0):

HPO phenotypes

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

GWAS associations

28 associations (top):

Study	Trait	p-value
GCST004131_25	Inflammatory bowel disease	2.000000e-31
GCST004133_79	Ulcerative colitis	5.000000e-65
GCST004521_114	Autism spectrum disorder or schizophrenia	3.000000e-17
GCST004521_117	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_118	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_126	Autism spectrum disorder or schizophrenia	2.000000e-10
GCST004521_154	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST004521_17	Autism spectrum disorder or schizophrenia	2.000000e-12
GCST004521_173	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_209	Autism spectrum disorder or schizophrenia	5.000000e-16
GCST004521_211	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_213	Autism spectrum disorder or schizophrenia	5.000000e-13
GCST004521_224	Autism spectrum disorder or schizophrenia	5.000000e-10
GCST004521_227	Autism spectrum disorder or schizophrenia	4.000000e-12
GCST004521_265	Autism spectrum disorder or schizophrenia	7.000000e-14
GCST004521_281	Autism spectrum disorder or schizophrenia	5.000000e-09
GCST004521_296	Autism spectrum disorder or schizophrenia	6.000000e-18
GCST004521_45	Autism spectrum disorder or schizophrenia	2.000000e-16
GCST004521_70	Autism spectrum disorder or schizophrenia	8.000000e-20
GCST004521_81	Autism spectrum disorder or schizophrenia	1.000000e-14
GCST007201_371	Schizophrenia	5.000000e-20
GCST008916_30	Asthma	1.000000e-09
GCST008917_2	Asthma (childhood onset)	4.000000e-07
GCST008921_1	Asthma and major depressive disorder	2.000000e-16
GCST011426_16	Systemic lupus erythematosus	6.000000e-06
GCST012228_223	Waist-hip index	2.000000e-09
GCST90020025_511	Waist-to-hip ratio adjusted for BMI	2.000000e-10
GCST90020027_833	Waist-hip index	4.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D029424	Pulmonary Disease, Chronic Obstructive	C08.381.495.389; C23.550.291.500.875

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3885585 (PROTEIN FAMILY), CHEMBL5460 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 338,203 (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
CHEMBL496	HEXACHLOROPHENE	4	26,164
CHEMBL1232461	MOLIBRESIB	2	1,538
CHEMBL14249	ADENOSINE TRIPHOSPHATE	2	287,353
CHEMBL6246	ELLAGIC ACID	2	23,148

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1043620	Toxicity	3	carbamazepine

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs506770	HSPA1A, HSPA1L		0.00	0
rs1043620	HSPA1A, HSPA1L	3	2.00	1	carbamazepine
rs2227956	HSPA1A, HSPA1L, LSM2	3	2.25	1	carbamazepine

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — Heat shock proteins

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

Ligand	Action	Affinity	Parameter
XL888	Binding	7.62	pIC50

Binding affinities (BindingDB)

5 measured of 20 human assays (23 total across all organisms); most potent 5 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
adenosine-derived inhibitor, 16	IC50	600 nM
adenosine-derived inhibitor, 13	IC50	1300 nM
adenosine-derived inhibitor, 14	IC50	1700 nM
adenosine-derived inhibitor, 8	IC50	4900 nM
adenosine-derived inhibitor, 6	IC50	10000 nM

ChEMBL bioactivities

26 potent at pChembl≥5 of 59 total, top 26 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.15	Kd	71	nM	MOLIBRESIB
6.82	IC50	150	nM	MOLIBRESIB
6.79	Kd	162.6	nM	CHEMBL3752910
6.74	ED50	181.1	nM	CHEMBL3752910
6.48	IC50	332	nM	CHEMBL502775
6.24	IC50	578	nM	CHEMBL1481974
6.20	IC50	634	nM	CHEMBL471004
6.12	IC50	760	nM	ELLAGIC ACID
5.84	Kd	1449	nM	CHEMBL5653589
5.79	Kd	1630	nM	CHEMBL5639838
5.79	ED50	1614	nM	CHEMBL5653589
5.71	IC50	1970	nM	CHEMBL1409373
5.62	IC50	2420	nM	CHEMBL244695
5.50	IC50	3130	nM	CHEMBL1363132
5.49	IC50	3240	nM	CHEMBL201289
5.47	IC50	3370	nM	ADENOSINE TRIPHOSPHATE
5.32	IC50	4770	nM	CHEMBL1376870
5.25	IC50	5560	nM	CHEMBL1334633
5.22	IC50	6060	nM	CHEMBL1570401
5.20	IC50	6260	nM	CHEMBL1528814
5.15	IC50	7140	nM	CHEMBL492894
5.14	IC50	7180	nM	CHEMBL1447034
5.08	IC50	8320	nM	CHEMBL1539325
5.08	IC50	8360	nM	CHEMBL1333555
5.01	IC50	9870	nM	CHEMBL1527520
5.01	IC50	9850	nM	CHEMBL487046

PubChem BioAssay actives

81 with measured affinity, of 262 total; 25 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-[[(2R,3S,4R,5R)-5-[6-amino-8-(quinolin-6-ylmethylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxymethyl]benzonitrile	1799196: HSP70 Biacore Direct Binding Assay from Article 10.1021/jm801627a: “Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design.”	kd	0.0500	uM
(2R,3R,4S,5R)-2-[6-amino-8-(quinolin-6-ylmethylamino)purin-9-yl]-5-[[4-(trifluoromethyl)phenyl]methoxymethyl]oxolane-3,4-diol	1799196: HSP70 Biacore Direct Binding Assay from Article 10.1021/jm801627a: “Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design.”	kd	0.0600	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179196: Binding affinity against HSPA1A (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0710	uM
[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] hydrogen phosphate	1799593: Fluorescence-Polarization (FP) Binding Assay from Article 10.1021/jm101625x: “Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.”	ki	0.1100	uM
4-[[(2R,3S,4R,5R)-5-[6-amino-8-[(3,4-dichlorophenyl)methylamino]purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxymethyl]benzonitrile	1799593: Fluorescence-Polarization (FP) Binding Assay from Article 10.1021/jm101625x: “Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.”	ki	0.1200	uM
(2R,3R,4S,5R)-2-[6-amino-8-(quinolin-6-ylmethylamino)purin-9-yl]-5-[(3,4,5-trifluorophenyl)methoxymethyl]oxolane-3,4-diol	1799196: HSP70 Biacore Direct Binding Assay from Article 10.1021/jm801627a: “Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design.”	kd	0.1200	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148550: Binding affinity to human HSPA1B/HSPA1A incubated for 45 mins by Kinobead based pull down assay	kd	0.1626	uM
4-[[(2R,3S,4R,5R)-5-[6-amino-8-(benzylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxymethyl]benzonitrile	1799196: HSP70 Biacore Direct Binding Assay from Article 10.1021/jm801627a: “Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design.”	kd	0.2000	uM
(2R,3R,4S,5R)-2-[6-amino-8-(methylamino)purin-9-yl]-5-(pyridin-3-ylmethoxymethyl)oxolane-3,4-diol	1799593: Fluorescence-Polarization (FP) Binding Assay from Article 10.1021/jm101625x: “Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.”	ki	0.4500	uM
[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	1799195: HSP70 Fluorescence Polarization Assay from Article 10.1021/jm801627a: “Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design.”	ic50	0.5000	uM
[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate	1799195: HSP70 Fluorescence Polarization Assay from Article 10.1021/jm801627a: “Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design.”	ic50	0.5000	uM
(2R,3R,4S,5R)-2-[6-amino-8-[(3,4-dichlorophenyl)methylamino]purin-9-yl]-5-(phenylmethoxymethyl)oxolane-3,4-diol	1799593: Fluorescence-Polarization (FP) Binding Assay from Article 10.1021/jm101625x: “Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.”	ki	1.0500	uM
(2R,3R,4S,5R)-2-[6-amino-8-(methylamino)purin-9-yl]-5-(phenylmethoxymethyl)oxolane-3,4-diol	1799593: Fluorescence-Polarization (FP) Binding Assay from Article 10.1021/jm101625x: “Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.”	ki	1.1000	uM
(2R,3R,4S,5R)-2-[6-amino-8-(quinolin-6-ylmethylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1799593: Fluorescence-Polarization (FP) Binding Assay from Article 10.1021/jm101625x: “Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.”	ki	1.2900	uM
(2R,3R,4S,5R)-2-[6-amino-8-[(3,4-dichlorophenyl)methylamino]purin-9-yl]-5-(methoxymethyl)oxolane-3,4-diol	1799593: Fluorescence-Polarization (FP) Binding Assay from Article 10.1021/jm101625x: “Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.”	ki	1.4400	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148550: Binding affinity to human HSPA1B/HSPA1A incubated for 45 mins by Kinobead based pull down assay	kd	1.4489	uM
177372351	2141350: Binding affinity to HSPA1A (unknown origin) assessed as dissociation constant	kd	1.6300	uM
(2R,3R,4S,5R)-2-[6-amino-8-[(3,4-dichlorophenyl)methylamino]purin-9-yl]-5-[(3,4,5-trifluorophenyl)methoxymethyl]oxolane-3,4-diol	1799195: HSP70 Fluorescence Polarization Assay from Article 10.1021/jm801627a: “Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design.”	ic50	1.7000	uM
2-[[(2R,3S,4R,5R)-5-[6-amino-8-(methylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxy]acetamide	1799593: Fluorescence-Polarization (FP) Binding Assay from Article 10.1021/jm101625x: “Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.”	ki	1.8500	uM
(2R,3R,4S,5R)-2-[6-amino-8-(methylamino)purin-9-yl]-5-(cyclohexylmethoxymethyl)oxolane-3,4-diol	1799593: Fluorescence-Polarization (FP) Binding Assay from Article 10.1021/jm101625x: “Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.”	ki	4.0700	uM
(2R,3R,4S,5R)-2-[6-amino-8-[(3,4-dichlorophenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1799593: Fluorescence-Polarization (FP) Binding Assay from Article 10.1021/jm101625x: “Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.”	ki	4.3100	uM
(2R,3R,4S,5R)-2-[6-amino-8-(quinolin-2-ylmethylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1799593: Fluorescence-Polarization (FP) Binding Assay from Article 10.1021/jm101625x: “Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.”	ki	4.3200	uM
(2R,3R,4S,5R)-2-(6,8-diaminopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol	1799593: Fluorescence-Polarization (FP) Binding Assay from Article 10.1021/jm101625x: “Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.”	ki	4.4600	uM
(2R,3R,4S,5R)-2-[6-amino-8-(1,3-benzodioxol-5-ylmethylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1799195: HSP70 Fluorescence Polarization Assay from Article 10.1021/jm801627a: “Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design.”	ic50	4.9000	uM
(2R,3R,4S,5R)-2-[6-amino-8-(methylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1799593: Fluorescence-Polarization (FP) Binding Assay from Article 10.1021/jm101625x: “Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.”	ki	8.3000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases reaction, increases response to substance, decreases reaction (+2 more)	20
Cadmium Chloride	decreases expression, increases abundance, increases expression, affects expression	11
Cadmium	increases abundance, increases expression, affects binding, increases reaction	10
Arsenic Trioxide	increases phosphorylation, increases reaction, decreases reaction, increases expression, affects expression (+2 more)	9
Tobacco Smoke Pollution	affects expression, increases expression, increases methylation	9
Benzo(a)pyrene	increases response to substance, increases expression, increases methylation, increases abundance	7
Silver	increases reaction, increases expression, affects binding	7
Formaldehyde	affects cotreatment, decreases reaction, increases phosphorylation, decreases expression, increases expression	5
Hydrogen Peroxide	increases reaction, increases expression, affects expression, affects binding	5
Quercetin	increases expression, decreases expression, increases response to substance, affects cotreatment	5
Copper	increases expression, affects binding, decreases expression	4
Silicon Dioxide	affects secretion, increases expression	4
Zinc	affects cotreatment, increases expression, affects binding, increases reaction	4
Copper Sulfate	increases expression	4
bisphenol A	affects expression, decreases methylation, affects cotreatment, increases expression	3
lead acetate	affects cotreatment, increases abundance, increases expression	3
cobaltous chloride	increases expression	3
ochratoxin A	decreases expression	3
cadmium sulfate	affects binding, increases reaction, increases expression	3
Acetylcysteine	decreases reaction, increases expression	3
Cisplatin	affects reaction, decreases expression, affects cotreatment, increases expression	3
Oxygen	affects cotreatment, increases expression, decreases reaction, decreases expression	3
Silver Nitrate	affects binding, increases reaction, increases expression	3
Valproic Acid	increases expression	3
Zinc Sulfate	affects localization, affects binding, increases reaction, increases expression	3
Particulate Matter	increases abundance, affects expression, increases reaction, increases secretion, decreases expression	3
geldanamycin	increases expression	2
tungsten carbide	affects cotreatment, increases expression	2
sodium arsenate	decreases reaction, increases expression, increases abundance	2
pyrithione zinc	increases expression	2

ChEMBL screening assays

25 unique, capped per target: 23 binding, 1 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3803750	Binding	Binding affinity to HSPA1A/HSPA1B in HEK293 proteomes assessed as spectral count ratio at 20 uM incubated for 16 hrs by TAMRA biotin-azide dye based LC-MS/MS analysis relative to control	Characterizing the Covalent Targets of a Small Molecule Inhibitor of the Lysine Acetyltransferase P300. — ACS Med Chem Lett
CHEMBL1613765	Functional	PUBCHEM_BIOASSAY: Dose response cell-based high-throughput screening assay to identify transcriptional activators of heat shock protein 70 (Hsp70). (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL4137439	ADMET	Induction of heat shock response in human MCF7 cells assessed as increase in HSP72 levels up to 10 uM after 24 hrs by Western blot analysis	Exploration of Benzothiazole Rhodacyanines as Allosteric Inhibitors of Protein-Protein Interactions with Heat Shock Protein 70 (Hsp70). — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00120978	PHASE4	UNKNOWN	Can Advair and Flovent Reduce Systemic Inflammation Related to Chronic Obstructive Pulmonary Disease (COPD)? A Multi-Center Randomized Controlled Trial
NCT00134979	PHASE4	COMPLETED	Formoterol Certihaler, Tiotropium HandiHaler and Tiotropium HandiHaler in Combination With Formoterol Certihaler in Patients With Stable Chronic Obstructive Pulmonary Disease
NCT00158847	PHASE4	TERMINATED	Modification Of Disease Outcome In COPD
NCT00170222	PHASE4	COMPLETED	Placebo Versus Antibiotics in Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD)
NCT00175565	PHASE4	COMPLETED	Inhaled Steroid Reduces Systemic Inflammation in COPD
NCT00181207	PHASE4	COMPLETED	Airway Clearance for Prevention of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
NCT00186706	PHASE4	COMPLETED	Selenium Supplementation in Chronic Obstructive Pulmonary Disease (COPD) Patients
NCT00190437	PHASE4	COMPLETED	ANTEAB: a Study of Early Antibiotherapy in the ICU Management of Acute Exacerbations of COPD
NCT00202176	PHASE4	COMPLETED	Effects of Bronchodilators in Mild Chronic Obstructive Pulmonary Disease (COPD)
NCT00202189	PHASE4	COMPLETED	Effects of Inhaled Corticosteroids in Chronic Obstructive Pulmonary Disease (COPD)
NCT00232674	PHASE4	COMPLETED	Efficacy Study of the Effect of Budesonide on Emphysema
NCT00288548	PHASE4	UNKNOWN	Metoprolol and Formoterol in Chronic Obstructive Pulmonary Disease (COPD)
NCT00291408	PHASE4	WITHDRAWN	Effect of Symbicort on HAT and HDAC in Sputum Macrophages of COPD
NCT00291460	PHASE4	UNKNOWN	Inspiratory Muscle Training in Hypercapnic COPD
NCT00292838	PHASE4	COMPLETED	Relative Potency of Inhaled Corticosteroids
NCT00311961	PHASE4	COMPLETED	Intravenous Versus Oral Administration of Prednisolone in Exacerbations of Chronic Obstructive Pulmonary Disease (COPD)
NCT00316992	PHASE4	COMPLETED	Safety of Ramelteon in Subjects With Chronic Obstructive Pulmonary Disease
NCT00331656	PHASE4	UNKNOWN	Comparative Study of Non-Invasive Mask Ventilation vs Cuirass Ventilation in Patients With Acute Respiratory Failure.
NCT00335621	PHASE4	WITHDRAWN	Replacement of Nebulised Ipratropium With Inhaled Tiotropium in Stable Chronic Obstructive Pulmonary Disease (COPD)
NCT00354354	PHASE4	COMPLETED	Bronchodilators and Oxygen Kinetics With Exercise in Chronic Obstructive Pulmonary Disease (COPD) Patients
NCT00379028	PHASE4	COMPLETED	Airway Clearance Study
NCT00405236	PHASE4	COMPLETED	Effect of Tiotropium on Inflammation and Exacerbations in COPD
NCT00412204	PHASE4	COMPLETED	Study to Evaluate the Effects of Tiotropium Bromide on Chronic Obstructive Pulmonary Disease (COPD) During Exercise
NCT00424528	PHASE4	COMPLETED	Efficacy Safety Study of Arformoterol/Tiotropium Combination Versus Either Therapy Alone in Chronic Obstructive Pulmonary Disease (COPD)
NCT00440245	PHASE4	COMPLETED	Bronchoprotection of Salbutamol in Asthma and Chronic Obstructive Pulmonary Disease
NCT00440687	PHASE4	COMPLETED	Withdrawal of Inhaled Corticosteroids in Patients With COPD in Primary Care
NCT00489853	PHASE4	COMPLETED	Evaluation of Efficacy on Exercise Tolerance of Symbicort (Budesonide/Formoterol) Compared to Placebo and Oxis in Patients With Severe COPD
NCT00491803	PHASE4	COMPLETED	Sildenafil Effects on Pulmonary Haemodynamics and Gas Exchange in Chronic Obstructive Pulmonary Disease (COPD)
NCT00495586	PHASE4	COMPLETED	Effectiveness of Antibiotic Therapy for Exacerbations of Chronic Obstructive Pulmonary Disease
NCT00525564	PHASE4	COMPLETED	Effects of Salmeterol on Walking Capacity in Patients With COPD
NCT00532584	PHASE4	WITHDRAWN	Effect of Steroids on Gene Expression in the Healthy Smokers Lungs
NCT00542880	PHASE4	COMPLETED	Evaluation of Onset of Effect in Patients With Severe Chronic Obstructive Pulmonary Disease (COPD) Treated With Symbicort® Compared to Seretide®
NCT00561886	PHASE4	COMPLETED	Change of Inspiratory Peak Flow in COPD
NCT00569270	PHASE4	COMPLETED	Dynamic Hyperinflation and Tiotropium
NCT00571428	PHASE4	COMPLETED	Efficacy Safety Study of Arformoterol QD Dosing Versus BID Dosing in COPD
NCT00578968	PHASE4	COMPLETED	Cardiac Limitations in Chronic Obstructive Pulmonary Disease: Benefits of Bronchodilation
NCT00592033	PHASE4	COMPLETED	Effect of Oxygen in Normoxaemic COPD Patients Who Desaturate During Exercise
NCT00628225	PHASE4	COMPLETED	Smoking Cessation in Patients With COPD (SMOCC) in General Practice
NCT00633776	PHASE4	WITHDRAWN	Perforomist Versus Foradil Evaluated by Inspiratory Capacity and High Resolution Computed Tomography (HRCT)
NCT00639236	PHASE4	COMPLETED	Effectiveness and Safety of Inhaling Hypertonic Saline in Patients With Chronic Obstructive Pulmonary Disease