HSP90B1

Summary

HSP90B1 (heat shock protein 90 beta family member 1, HGNC:12028) is a protein-coding gene on chromosome 12q23.3, encoding Endoplasmin (P14625). ATP-dependent chaperone involved in the processing of proteins in the endoplasmic reticulum, regulating their transport. It is a selective cancer dependency (DepMap: 55.5% of cell lines).

This gene encodes a member of a family of adenosine triphosphate(ATP)-metabolizing molecular chaperones with roles in stabilizing and folding other proteins. The encoded protein is localized to melanosomes and the endoplasmic reticulum. Expression of this protein is associated with a variety of pathogenic states, including tumor formation. There is a microRNA gene located within the 5’ exon of this gene. There are pseudogenes for this gene on chromosomes 1 and 15.

Source: NCBI Gene 7184 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 121 total
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 55.5% of screened cell lines
• MANE Select transcript: NM_003299

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12028
Approved symbol	HSP90B1
Name	heat shock protein 90 beta family member 1
Location	12q23.3
Locus type	gene with protein product
Status	Approved
Aliases	GP96, GRP94
Ensembl gene	ENSG00000166598
Ensembl biotype	protein_coding
OMIM	191175
Entrez	7184

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 19 protein_coding, 17 retained_intron, 9 nonsense_mediated_decay

ENST00000299767, ENST00000540297, ENST00000548462, ENST00000548622, ENST00000549334, ENST00000550479, ENST00000550595, ENST00000551983, ENST00000552051, ENST00000614327, ENST00000640977, ENST00000679377, ENST00000679538, ENST00000679779, ENST00000679861, ENST00000680242, ENST00000680281, ENST00000680316, ENST00000680370, ENST00000680391, ENST00000680478, ENST00000680653, ENST00000680663, ENST00000680762, ENST00000680899, ENST00000680989, ENST00000681172, ENST00000681174, ENST00000681245, ENST00000681698, ENST00000681704, ENST00000681861, ENST00000681910, ENST00000681941, ENST00000681949, ENST00000863860, ENST00000863861, ENST00000863862, ENST00000863863, ENST00000863864, ENST00000925363, ENST00000925364, ENST00000925365, ENST00000925366, ENST00000949724

RefSeq mRNA: 1 — MANE Select: NM_003299 NM_003299

CCDS: CCDS9094

Canonical transcript exons

ENST00000299767 — 18 exons

Exon	Start	End
ENSE00001104601	103943074	103943319
ENSE00002286515	103930410	103930564
ENSE00002352857	103947633	103947926
ENSE00003466608	103941832	103941897
ENSE00003470186	103946618	103946696
ENSE00003500826	103938340	103938459
ENSE00003543028	103932826	103932942
ENSE00003584742	103942527	103942796
ENSE00003598676	103943738	103943874
ENSE00003601420	103932277	103932418
ENSE00003608721	103939509	103939625
ENSE00003623000	103941410	103941547
ENSE00003646047	103941629	103941706
ENSE00003648794	103947311	103947430
ENSE00003655353	103937695	103937806
ENSE00003659774	103946786	103946941
ENSE00003676011	103931521	103931623
ENSE00003689930	103933956	103934287

Expression profiles

Bgee: expression breadth ubiquitous, 305 present calls, max score 99.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 398.4874 / max 10409.5730, expressed in 1828 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127707	392.4801	1828
127708	4.7725	1474
127716	0.7660	405
127710	0.4688	79

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of thyroid gland	UBERON:0001119	99.83	gold quality
left lobe of thyroid gland	UBERON:0001120	99.81	gold quality
thyroid gland	UBERON:0002046	99.79	gold quality
corpus epididymis	UBERON:0004359	99.78	gold quality
pericardium	UBERON:0002407	99.73	gold quality
islet of Langerhans	UBERON:0000006	99.66	gold quality
adenohypophysis	UBERON:0002196	99.64	gold quality
pituitary gland	UBERON:0000007	99.63	gold quality
pylorus	UBERON:0001166	99.62	gold quality
calcaneal tendon	UBERON:0003701	99.62	gold quality
tendon of biceps brachii	UBERON:0008188	99.62	gold quality
endometrium	UBERON:0001295	99.60	gold quality
caput epididymis	UBERON:0004358	99.60	gold quality
ventricular zone	UBERON:0003053	99.59	gold quality
stromal cell of endometrium	CL:0002255	99.58	gold quality
left adrenal gland cortex	UBERON:0035825	99.57	gold quality
body of pancreas	UBERON:0001150	99.56	gold quality
left adrenal gland	UBERON:0001234	99.55	gold quality
adrenal cortex	UBERON:0001235	99.55	gold quality
smooth muscle tissue	UBERON:0001135	99.54	gold quality
right adrenal gland	UBERON:0001233	99.54	gold quality
rectum	UBERON:0001052	99.53	gold quality
right lobe of liver	UBERON:0001114	99.53	gold quality
ascending aorta	UBERON:0001496	99.53	gold quality
right adrenal gland cortex	UBERON:0035827	99.53	gold quality
thoracic aorta	UBERON:0001515	99.52	gold quality
right coronary artery	UBERON:0001625	99.52	gold quality
vermiform appendix	UBERON:0001154	99.51	gold quality
caecum	UBERON:0001153	99.50	gold quality
cardia of stomach	UBERON:0001162	99.50	gold quality

Single-cell (SCXA)

Detected in 31 experiment(s), a significant marker in 26.

Experiment	Marker?	Max mean expression
E-GEOD-150728	yes	11857.87
E-MTAB-6386	yes	5805.67
E-MTAB-9154	yes	5750.48
E-MTAB-9467	yes	5192.71
E-MTAB-9543	yes	4899.97
E-CURD-122	yes	4707.52
E-HCAD-32	yes	3379.11
E-CURD-55	yes	3292.98
E-CURD-77	yes	2886.58
E-GEOD-149689	yes	2766.56
E-CURD-88	yes	2618.22
E-HCAD-1	yes	2215.49
E-CURD-46	yes	1962.07
E-HCAD-9	yes	1831.64
E-HCAD-4	yes	1169.33

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF6, DDIT3, ESR1, HIF1A, NCK1, NCK2, NFKB, TP53, XBP1

miRNA regulators (miRDB)

67 targeting HSP90B1, 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-4262	100.00	73.26	3931
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 55.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• associated with HBV polymerase in human liver cell HepG2 (PMID:11958450)
• OmpA of E. coli K1 interacts with a gp96-like molecule on HBMECs for invasion (Ecgp: 96-kDa human brain microvascular endothelial cell (HBMEC) glycoprotein) (PMID:12654781)
• Heat shock protein 96 purified from melanoma or liver metastases of colon carcinoma cells contains immunogenic peptides that can be presented to CD8+ T cells and can activate them both in vitro and in vivo. (PMID:14500642)
• Orientia tsutsugamushi down-regulated gp96 an endothelial cell line, HMEC-1. (PMID:15107540)
• Expression of GRP94 suppressed A23187-induced apoptosis and stabilized calcium homeostasis. (PMID:15192333)
• In patients with cholangiocellular carcinoma, the presence of cells expresing Grp94 is related to CD83-positive dendritic cells. (PMID:15257553)
• The glucose-regulated protein (GRP94) is upregulated in human endothelial cells in response to hypoxia by HIF-1. (PMID:15620698)
• HSP70 and grp94 express differently in cell plasma and nuclei. The expression intensity of HSP70 is related to the differentiation of esophageal carcinoma. (PMID:15637761)
• Results strongly argue against a regular role for gp96 as a peptide chaperone in antigen processing. (PMID:15728573)
• GRP94 is highly expressed in human gastric carcinoma BGC-823 cells through the whole cell cycle. (PMID:15962384)
• Gp96 is exploited by Listeria monocytogenes as a receptor for cell invasion or signalling events that may interfere with the host immune response in the course of Listeria infection. (PMID:16015374)
• Heat shock protein 90beta (Hsp90beta)-bound activated tyrosine kinase Ack1 and treatment of cells with geldanamycin, a Hsp90 inhibitor, inhibited Ack1 kinase activity and suppressed prostate tumorigenesis. (PMID:16288044)
• These results suggest that CYP2E1 mediated oxidative stress downregulates the expression of GRP proteins in HepG2 cells and oxidative stress is an important mechanism in causing ER dysfunction in these cells. (PMID:16497268)
• It was found that in vitro these proteins were capable of maturating human monocyte-derived dendritic cells (MDDC) isolated from healthy donors as well as from HBV-positive, hepatocellular carcinoma (HCC) patients. (PMID:16630554)
• TLR2 and TLR4 ligand interaction with the N-terminal domain of Gp96 amplifies innate and adaptive immune response (PMID:16754684)
• TLR4 signaling to lipopolysaccharide can be positively enforced by expressing gp96 on cell surfaces through the chaperone function of, but not the direct signaling by, transgenic gp96. (PMID:17082602)
• ICMT inhibition induces endothelial cell apoptosis through GRP94 (PMID:17347446)
• Retention of amyloidogenic mutant TTRs induced the unfolded protein response and upegulated the expression of GRP94. (PMID:17431395)
• NTN4, TRA1, and STC2 have roles in progression of breast cancer (PMID:17545519)
• These results suggest that a novel mechanism other than endoplasmic reticulum(ER) stress element-dependent mRNA transcription is required for induction of GRP94 and phosphorylation of PKR contributes to the induction of GRP94 under ER stress. (PMID:17612505)
• Immunohistochemical analysis showed highly expressed Grp94 in primary OSCCs (oral squamous cell carcinoma). Grp94 may have potential clinical application as a novel diagnosis and prognostic biomarker for human OSCCs. (PMID:17726464)
• HSP90B1 may have a pathophysiological role in bipolar disorder in the Japanese population. (PMID:17805476)
• results indicate a significant correlation between the immunopositivity of HSP72 and gp96 and the progression of colonic carcinomas (PMID:18155754)
• Heat shock protein 90beta1 is essential for polyunsaturated fatty acid-induced mitochondrial Ca2+ efflux (PMID:18178560)
• We found higher expression of gp96 protein in breast carcinoma cells and low or no expression in normal breast cells. (PMID:18190237)
• OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERAD (PMID:18264092)
• These data indicate that HCV E2 blocks apoptosis induced by HCV infection and the host immune system through overproduction of GRP94, and that HCV E2 plays an important role in persistent HCV infection. (PMID:18273841)
• We could demonstrate an association of GRP78 and GRP94 mRNA and protein expression with tumor stage and behaviour in esophageal adenocarcinomas. (PMID:18331622)
• the novel involvement of GRP94 suppression in prostate cancer metastasis. (PMID:18340425)
• We conclude that human colonocyte gp96 serves as a plasma membrane binding protein that enhances cellular entry of Clostridium difficile toxin A (TxA), participates in cellular signaling events in the inflammatory cascade, and facilitates cytotoxicity. (PMID:18411291)
• Up-regulated expression of GRP78 and GRP94 was possibly involved in pathogenesis, growth, invasion, and metastasis of gastric carcinomas. (PMID:18482745)
• Grp94 with IgG promoted the angiogenic differentiation in HUVECs. (PMID:18554719)
• Data show that Stat3 activation and its interaction with Ec-gp96, which in turn interacts with E. coli outer membrane protein A, are critical for E. coli invasion. (PMID:18662321)
• Interaction of gp96 with CD91 is a productive event that directly and specifically triggers functional responses in plasmacytoid dendritic cells. (PMID:18941243)
• Upregulation of GRP78 and GRP94 can significantly confer the chemoresistance to VP-16 in human lung cancer cell line SK-MES-1. (PMID:19212831)
• Construction of the glycan tree is a key to identification of the necessary and sufficient elements in the structure-function activity of HSP96. (PMID:19578160)
• Silencing of GRP94 expression promotes apoptosis in pancreatic cancer cells. (PMID:19724918)
• For multiple antigens and viral systems, GRP94 is dispensable for the generation of both peptide class I complexes in cultured cells and immunogens in donor cells with cross-priming activity. (PMID:19752220)
• These data identify for the first time the cellular chaperones associated with secretion of an ADAMTS protease and suggest a role for gp96 in modulating pro-ADAMTS9 processing. (PMID:19875450)
• HSPgp96 may play acontributive role on the pathogenesis and development in human osteosarcoma. (PMID:19895174)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	hsp90b1	ENSDARG00000003570
mus_musculus	Hsp90b1	ENSMUSG00000020048
rattus_norvegicus	Hsp90b1	ENSRNOG00000026963
drosophila_melanogaster	Gp93	FBGN0039562
caenorhabditis_elegans		WBGENE00011480

Paralogs (3): HSP90AA1 (ENSG00000080824), HSP90AB1 (ENSG00000096384), TRAP1 (ENSG00000126602)

Protein

Protein identifiers

Endoplasmin — P14625 (reviewed: P14625)

Alternative names: 94 kDa glucose-regulated protein, Heat shock protein 90 kDa beta member 1, Heat shock protein family C member 4, Tumor rejection antigen 1, gp96 homolog

All UniProt accessions (18): A0A087WT78, A0A7P0T823, A0A7P0T885, A0A7P0T8C8, A0A7P0T8R3, A0A7P0T917, A0A7P0TAC2, A0A7P0TAE1, A0A7P0TAG4, A0A7P0TAT8, P14625, A0A7P0TAY2, A0A7P0TBC2, A0A7P0Z405, A0A7P0Z4B4, F8W026, H0YIV0, V9HWP2

UniProt curated annotations — full annotation on UniProt →

Function. ATP-dependent chaperone involved in the processing of proteins in the endoplasmic reticulum, regulating their transport. Together with MESD, acts as a modulator of the Wnt pathway by promoting the folding of LRP6, a coreceptor of the canonical Wnt pathway. When associated with CNPY3, required for proper folding of Toll-like receptors. Promotes folding and trafficking of TLR4 to the cell surface. May participate in the unfolding of cytosolic leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1 to facilitate their translocation into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and secretion; the translocation process is mediated by the cargo receptor TMED10.

Subunit / interactions. Homodimer; disulfide-linked. Component of an EIF2 complex at least composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5. Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 and very small amounts of ERP29, but not, or at very low levels, CALR nor CANX. Interacts with AIMP1; regulates its retention in the endoplasmic reticulum. Hyperglycosylated form interacts with OS9; promoting its degradation by the endoplasmic reticulum associated degradation (ERAD). Interacts with CNPY3. This interaction is disrupted in the presence of ATP. Interacts with TLR4 and TLR9, but not with TLR3. Interacts with MZB1 in a calcium-dependent manner. Interacts with METTL23. Interacts with IL1B; the interaction facilitates cargo translocation into the ERGIC. Interacts with EIF2AK3.

Subcellular location. Endoplasmic reticulum lumen. Sarcoplasmic reticulum lumen. Melanosome.

Post-translational modifications. Phosphorylated by CK2. N-glycosylated cotranslationally at Asn-217 by STT3A-containing OST-A complex: this glycosylation is constitutive. In response to various stress, 5 additional facultative sites (Asn-62, Asn-107, Asn-445, Asn-481 and Asn-502) can be glycosylated post-translationally by STT3B-containing OST-B complex, leading to a hyperglycosylated form that is degraded by the ER-associated degradation (ERAD) pathway. In normal conditions, the OST-A complex together with CCDC134 prevent glycosylation at facultative sites during protein folding, thereby preventing hyperglycosylation. Mechanistically, nascent HSP90B1 is tethered during translation to a specialized CCDC134-containing translocon that forms a microenvironment for its folding, in which STT3A associates with the SRT pseudosubstrate motif, and prevents access to facultative glycosylation sites until folding is completed, rendering its facultative sites inaccessible to the OST-B complex.

Domain organisation. The SRT pseudosubstrate motif associates with STT3A during translation in normal conditions, preventing glycosylation of facultative sites until HSP90B1 folding is completed.

Similarity. Belongs to the heat shock protein 90 family.

RefSeq proteins (1): NP_003290* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001404	Hsp90_fam	Family
IPR003594	HATPase_dom	Domain
IPR019805	Heat_shock_protein_90_CS	Conserved_site
IPR020568	Ribosomal_Su5_D2-typ_SF	Homologous_superfamily
IPR020575	Hsp90_N	Domain
IPR036890	HATPase_C_sf	Homologous_superfamily
IPR037196	HSP90_C	Homologous_superfamily

Pfam: PF00183, PF13589

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (60 total): modified residue 10, mutagenesis site 8, helix 8, strand 8, glycosylation site 6, binding site 4, sequence conflict 3, compositionally biased region 3, region of interest 2, short sequence motif 2, turn 2, signal peptide 1, chain 1, site 1, disulfide bond 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7ULL	X-RAY DIFFRACTION	2.31
4NH9	X-RAY DIFFRACTION	2.77
9N9J	ELECTRON MICROSCOPY	3.2
9YGY	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P14625-F1	82.57	0.53

Functional residue map

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

Catalytic / active sites (1): 448 (important for atp hydrolysis)

Ligand- & substrate-binding residues (4): 149; 162; 199; 107

Post-translational modifications (10): 64, 168, 172, 306, 403, 404, 447, 479, 633, 786

Disulfide bonds (1): 138

Glycosylation sites (6): 62, 107, 217, 445, 481, 502

Mutagenesis-validated functional residues (8):

Position	Phenotype
44	hyperglycosylation and subsequent degradation following destruction of the srt pseudosubstrate motif.
64	in 5n mutant; prevents hyperglycosylation and subsequent degradation; when associated with a-109, a-447, i-483 and i-504
109	in 5n mutant; prevents hyperglycosylation and subsequent degradation; when associated with a-64, a-447, i-483 and i-504.
217	does not promote or impair hyperglycosylation.
219	in 1n mutant; abolished glycosylation by stt3a.
447	in 5n mutant; prevents hyperglycosylation and subsequent degradation; when associated with a-64, a-109, i-483 and i-504.
483	in 5n mutant; prevents hyperglycosylation and subsequent degradation; when associated with a-64, a-109, a-447 and i-504.
504	in 5n mutant; prevents hyperglycosylation and subsequent degradation; when associated with a-64, a-109, a-447 and i-483.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-1679131	Trafficking and processing of endosomal TLR
R-HSA-3000480	Scavenging by Class A Receptors
R-HSA-381183	ATF6 (ATF6-alpha) activates chaperone genes
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-8957275	Post-translational protein phosphorylation

MSigDB gene sets: 430 (showing top): GOBP_ENDOPLASMIC_RETICULUM_TO_CYTOSOL_TRANSPORT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, AREB6_03, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, RACCACAR_AML_Q6, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GGGTGGRR_PAX4_03, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY

GO Biological Process (15): response to hypoxia (GO:0001666), protein folding (GO:0006457), protein transport (GO:0015031), positive regulation of Wnt signaling pathway (GO:0030177), retrograde protein transport, ER to cytosol (GO:0030970), actin rod assembly (GO:0031247), positive regulation of toll-like receptor signaling pathway (GO:0034123), protein folding in endoplasmic reticulum (GO:0034975), response to endoplasmic reticulum stress (GO:0034976), ERAD pathway (GO:0036503), negative regulation of apoptotic process (GO:0043066), obsolete sequestering of calcium ion (GO:0051208), cellular response to manganese ion (GO:0071287), cellular response to ATP (GO:0071318), protein localization to plasma membrane (GO:0072659)

GO Molecular Function (13): RNA binding (GO:0003723), protein phosphatase inhibitor activity (GO:0004864), calcium ion binding (GO:0005509), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), protein phosphatase binding (GO:0019903), protein folding chaperone (GO:0044183), low-density lipoprotein particle receptor binding (GO:0050750), obsolete unfolded protein binding (GO:0051082), ATP-dependent protein folding chaperone (GO:0140662), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (19): extracellular region (GO:0005576), nucleus (GO:0005634), endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788), endoplasmic reticulum membrane (GO:0005789), smooth endoplasmic reticulum (GO:0005790), cytosol (GO:0005829), focal adhesion (GO:0005925), membrane (GO:0016020), midbody (GO:0030496), protein-containing complex (GO:0032991), sarcoplasmic reticulum lumen (GO:0033018), endoplasmic reticulum chaperone complex (GO:0034663), melanosome (GO:0042470), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), endocytic vesicle lumen (GO:0071682), sperm plasma membrane (GO:0097524), sarcoplasmic reticulum (GO:0016529)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Toll-like Receptor Cascades	1
Binding and Uptake of Ligands by Scavenger Receptors	1
ATF6 (ATF6-alpha) activates chaperones	1
Metabolism of proteins	1
Signaling by Interleukins	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	3
endoplasmic reticulum	3
protein folding	2
ATP-dependent activity	2
intracellular membrane-bounded organelle	2
intracellular organelle lumen	2
response to stress	1
response to decreased oxygen levels	1
cellular process	1
protein maturation	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
positive regulation of signal transduction	1
Wnt signaling pathway	1
regulation of Wnt signaling pathway	1
protein exit from endoplasmic reticulum	1
ERAD pathway	1
endoplasmic reticulum to cytosol transport	1
actin filament bundle assembly	1
toll-like receptor signaling pathway	1
regulation of toll-like receptor signaling pathway	1
positive regulation of pattern recognition receptor signaling pathway	1
cellular response to stress	1
proteasomal protein catabolic process	1
response to endoplasmic reticulum stress	1
response to chemical	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
response to manganese ion	1
cellular response to metal ion	1
response to ATP	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
protein localization to membrane	1
protein localization to cell periphery	1
nucleic acid binding	1
phosphoprotein phosphatase activity	1

Protein interactions and networks

STRING

6417 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HSP90B1	HSPA5	P11021	997
HSP90B1	LRP1	Q07954	996
HSP90B1	PDIA4	P13667	995
HSP90B1	HYOU1	Q9Y4L1	995
HSP90B1	DNAJB11	Q9UBS4	989
HSP90B1	TLR4	O00206	988
HSP90B1	HSPA4	P34932	982
HSP90B1	OS9	Q13438	980
HSP90B1	TLR2	O60603	976
HSP90B1	CALR	P27797	976
HSP90B1	PPIB	P23284	975
HSP90B1	UGGT1	Q9NYU2	941
HSP90B1	HSPA9	P30036	938
HSP90B1	CANX	P27824	936
HSP90B1	ATF6	P18850	926

IntAct

357 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
OS9	HSP90B1	psi-mi:“MI:0914”(association)	0.640
FANCC	HSP90B1	psi-mi:“MI:0915”(physical association)	0.580
COL1A1	CRTAP	psi-mi:“MI:0915”(physical association)	0.580
HSP90B1	HSPA5	psi-mi:“MI:0915”(physical association)	0.560
APP	HSP90B1	psi-mi:“MI:0915”(physical association)	0.560
EGFR	HSP90B1	psi-mi:“MI:0915”(physical association)	0.550
COL1A1	GOLIM4	psi-mi:“MI:0914”(association)	0.500
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
HSP90B1	EIF2AK3	psi-mi:“MI:0915”(physical association)	0.400
ERBB2	HSP90B1	psi-mi:“MI:0915”(physical association)	0.400
HSP90B2P	HSP90B1	psi-mi:“MI:0915”(physical association)	0.400
ASPM	HSP90B1	psi-mi:“MI:0915”(physical association)	0.400
RAB8A	HSP90B1	psi-mi:“MI:0915”(physical association)	0.400
STXBP2	HSP90B1	psi-mi:“MI:0915”(physical association)	0.400
PPP1R12A	HSP90B1	psi-mi:“MI:0915”(physical association)	0.400
XRRA1	HSP90B1	psi-mi:“MI:0915”(physical association)	0.400
EVI5	HSP90B1	psi-mi:“MI:0915”(physical association)	0.400
ANXA8L1	HSP90B1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (940): HSP90B1 (Affinity Capture-MS), HSP90B1 (Affinity Capture-MS), HSP90B1 (Affinity Capture-MS), BIRC2 (Affinity Capture-Western), BIRC2 (FRET), HSP90B1 (Affinity Capture-MS), HSP90B1 (Affinity Capture-MS), HSP90B1 (Affinity Capture-MS), HSP90B1 (Affinity Capture-MS), HSP90B1 (Affinity Capture-MS), HSP90B1 (Affinity Capture-MS), HSP90B1 (Affinity Capture-MS), HSP90B1 (Affinity Capture-MS), HSP90B1 (Affinity Capture-MS), HSP90B1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0D1C6P2, A8XA40, D4AVD4, E2RA18, J9VLH0, O04151, O04153, O14967, O18750, O81919, O82709, P08110, P11012, P14625, P24643, P27798, P27824, P29402, P29413, P34652, P35564, P35565, P36581, P41148, P52194, P83003, P93508, Q06814, Q23858, Q29092, Q2TBR8, Q38798, Q38858, Q39817, Q39994, Q3SYT6, Q40401, Q4R520, Q5R440, Q5R6F7

Diamond homologs: A0KL53, A1ANS1, A1WXE4, A2YWQ1, A3QF50, A4SLY0, A5A6K9, A5GER7, B0TP05, F4JFN3, O02192, O02705, O03986, O18750, O43109, O44001, O57521, O61998, P02828, P02829, P04809, P04810, P04811, P06660, P07900, P07901, P08110, P08113, P08238, P11499, P11501, P12861, P14625, P15108, P24724, P27323, P27741, P27890, P30946, P30947

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
S	“up-regulates quantity by expression”	HSP90B1	“transcriptional regulation”

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	77
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2603 predictions. Top by Δscore:

Variant	Effect	Δscore
12:103931610:G:GT	donor_gain	1.0000
12:103931621:GAG:G	donor_gain	1.0000
12:103932275:A:AG	acceptor_gain	1.0000
12:103932276:G:GG	acceptor_gain	1.0000
12:103932276:GA:G	acceptor_gain	1.0000
12:103932276:GAGA:G	acceptor_gain	1.0000
12:103932416:GAG:G	donor_gain	1.0000
12:103932419:G:GC	donor_loss	1.0000
12:103933950:A:AG	acceptor_gain	1.0000
12:103933951:T:G	acceptor_gain	1.0000
12:103933951:TTTAG:T	acceptor_loss	1.0000
12:103933954:A:AG	acceptor_gain	1.0000
12:103933954:AGT:A	acceptor_gain	1.0000
12:103933954:AGTGT:A	acceptor_gain	1.0000
12:103933955:G:GG	acceptor_gain	1.0000
12:103933955:GT:G	acceptor_gain	1.0000
12:103933955:GTG:G	acceptor_gain	1.0000
12:103933955:GTGT:G	acceptor_gain	1.0000
12:103933955:GTGTG:G	acceptor_gain	1.0000
12:103934283:ATTAC:A	donor_gain	1.0000
12:103934284:TTAC:T	donor_gain	1.0000
12:103934285:TAC:T	donor_gain	1.0000
12:103934285:TACG:T	donor_loss	1.0000
12:103934286:AC:A	donor_gain	1.0000
12:103934287:CGTG:C	donor_loss	1.0000
12:103934288:G:GG	donor_gain	1.0000
12:103934289:T:G	donor_loss	1.0000
12:103934291:AG:A	donor_loss	1.0000
12:103938330:A:AG	acceptor_gain	1.0000
12:103938331:T:G	acceptor_gain	1.0000

AlphaMissense

5347 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:103932356:T:C	F78L	1.000
12:103932358:C:A	F78L	1.000
12:103932358:C:G	F78L	1.000
12:103932387:T:A	L88H	1.000
12:103932387:T:C	L88P	1.000
12:103932398:T:C	S92P	1.000
12:103932402:T:C	L93S	1.000
12:103932836:G:C	R102T	1.000
12:103932836:G:T	R102I	1.000
12:103932837:A:C	R102S	1.000
12:103932837:A:T	R102S	1.000
12:103932838:G:A	E103K	1.000
12:103932839:A:C	E103A	1.000
12:103932839:A:T	E103V	1.000
12:103932840:A:C	E103D	1.000
12:103932840:A:T	E103D	1.000
12:103932842:T:C	L104P	1.000
12:103932847:T:C	S106P	1.000
12:103932852:T:A	N107K	1.000
12:103932852:T:G	N107K	1.000
12:103932859:G:C	D110H	1.000
12:103933989:G:C	D149H	1.000
12:103933996:G:A	G151D	1.000
12:103934035:G:A	G164D	1.000
12:103934044:C:A	A167D	1.000
12:103934119:T:A	I192N	1.000
12:103934121:G:C	G193R	1.000
12:103934121:G:T	G193C	1.000
12:103934122:G:A	G193D	1.000
12:103934127:T:C	F195L	1.000

dbSNP variants (sampled 300 via entrez): RS1000165009 (12:103936990 A>G), RS1000189589 (12:103931779 TGTCCCTAGGA>T), RS1000214071 (12:103944264 A>G), RS1000576236 (12:103931416 C>A,T), RS1000651564 (12:103931165 G>C), RS1000851766 (12:103945813 A>G), RS1000920225 (12:103935393 AG>A), RS1001439979 (12:103948308 A>T), RS1002159758 (12:103942280 TAG>T), RS1002322946 (12:103941939 T>C), RS1002485135 (12:103940566 G>C), RS1003043937 (12:103947352 A>G), RS1003168251 (12:103930915 A>C,G), RS1003531003 (12:103929669 A>G), RS1003605760 (12:103936681 C>T)

Disease associations

OMIM: gene MIM:191175 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008196_2	Soluble VCAM-1 levels	3.000000e-14
GCST009391_1391	Metabolite levels	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010368	lysophosphatidylethanolamine 18:1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1075323 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 8,118 (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
CHEMBL2103879	GANETESPIB	3	2,075
CHEMBL1214827	ONALESPIB	2	878
CHEMBL1232461	MOLIBRESIB	2	1,538
CHEMBL200102	PU-H71	2	221
CHEMBL252164	LUMINESPIB	2	1,800
CHEMBL467399	BIIB021	2	1,606

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — Heat shock proteins

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
Grp94 inhibitor 54	Inhibition	8.7	pIC50
semapimod	Inhibition	6.7	pIC50
compound 18c [PMID: 25901531]	Inhibition	6.66	pIC50

Binding affinities (BindingDB)

5 measured of 165 human assays (165 total across all organisms); most potent 5 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL4748119	KD	4200 nM
[5-acetyloxy-2-[3-(ethylcarbamoyl)-4-[4-(morpholin-4-ylmethyl)phenyl]-1,2-oxazol-5-yl]-4-propan-2-ylphenyl] acetate	IC50	78000 nM	US-9718793: Isoxazole compounds as inhibitors of heat shock proteins
[5-(dimethylcarbamoyloxy)-2-[3-(ethylcarbamoyl)-4-[4-(morpholin-4-ylmethyl)phenyl]-1,2-oxazol-5-yl]-4-propan-2-ylphenyl] N,N-dimethylcarbamate	IC50	78000 nM	US-9718793: Isoxazole compounds as inhibitors of heat shock proteins
[2-[3-(ethylcarbamoyl)-4-[4-(morpholin-4-ylmethyl)phenyl]-1,2-oxazol-5-yl]-5-(ethylcarbamoyloxy)-4-propan-2-ylphenyl] N-ethylcarbamate	IC50	78000 nM	US-9718793: Isoxazole compounds as inhibitors of heat shock proteins
US10413550, Example 78g	IC50	78000 nM	US-10413550: Isoxazole compounds as inhibitors of heat shock proteins

ChEMBL bioactivities

276 potent at pChembl≥5 of 302 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.40	Ki	4	nM	LUMINESPIB
8.30	Ki	5	nM	CHEMBL3104859
7.66	IC50	22	nM	ONALESPIB
7.58	IC50	26	nM	PU-H71
7.52	Kd	30	nM	PU-H71
7.52	IC50	30	nM	ONALESPIB
7.52	Kd	30	nM	ONALESPIB
7.50	IC50	32	nM	CHEMBL3426787
7.42	IC50	37.7	nM	GANETESPIB
7.31	IC50	49.42	nM	CHEMBL4647894
7.30	IC50	50	nM	CHEMBL4744238
7.27	IC50	54.1	nM	CHEMBL4647171
7.25	Kd	55.92	nM	CHEMBL5653589
7.25	ED50	55.92	nM	CHEMBL5653589
7.21	Ki	61	nM	CHEMBL1230584
7.11	IC50	78.01	nM	CHEMBL4641526
7.11	IC50	77.96	nM	CHEMBL4635982
7.07	IC50	85	nM	LUMINESPIB
7.05	Kd	90	nM	CHEMBL3805415
7.05	IC50	88.98	nM	CHEMBL4639163
7.02	IC50	96.2	nM	CHEMBL4635778
7.00	IC50	101	nM	CHEMBL3426784
7.00	IC50	100.5	nM	CHEMBL4648197
6.96	Ki	110	nM	NECA
6.92	IC50	120	nM	CHEMBL365118
6.92	Kd	120	nM	CHEMBL6164477
6.89	Ki	130	nM	CHEMBL519809
6.88	IC50	132	nM	PU-H71
6.77	IC50	170	nM	CHEMBL192480
6.76	IC50	174.8	nM	CHEMBL4648091
6.75	Ki	176	nM	BIIB021
6.72	IC50	190.2	nM	CHEMBL4638275
6.72	IC50	192.1	nM	CHEMBL4641450
6.71	IC50	197.1	nM	CHEMBL4636983
6.71	IC50	196	nM	CHEMBL4782374
6.71	IC50	195	nM	CHEMBL4779990
6.71	IC50	194	nM	CHEMBL4869481
6.70	Kd	200	nM	CHEMBL3805249
6.70	IC50	198	nM	CHEMBL4797602
6.70	Kd	200	nM	CHEMBL5073759
6.70	IC50	200	nM	CHEMBL3805249
6.69	IC50	203	nM	CHEMBL6168361
6.68	IC50	209.3	nM	CHEMBL4649532
6.67	IC50	216	nM	CHEMBL4753741
6.66	IC50	220	nM	CHEMBL3426781
6.66	IC50	217	nM	CHEMBL4777147
6.66	Kd	220	nM	CHEMBL3426781
6.63	IC50	232	nM	CHEMBL4753836
6.62	IC50	240	nM	CHEMBL3426734
6.62	Ki	240	nM	CHEMBL261482

PubChem BioAssay actives

272 with measured affinity, of 594 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-(2,4-dihydroxy-5-propan-2-ylphenyl)-N-ethyl-4-[4-(morpholin-4-ylmethyl)phenyl]-1,2-oxazole-3-carboxamide	1063123: Binding affinity to human N-terminal polyHis-tagged GRP94 (L69 to N337) expressed in Escherichia coli BL21(DE3) after 3 hrs by fluorescence polarization assay	ki	0.0040	uM
[(4E,6Z,8R,9S,10E,12S,13R,14S,16R)-19-[2-(dimethylamino)ethylamino]-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl] carbamate	1063123: Binding affinity to human N-terminal polyHis-tagged GRP94 (L69 to N337) expressed in Escherichia coli BL21(DE3) after 3 hrs by fluorescence polarization assay	ki	0.0050	uM
(2,4-dihydroxy-5-propan-2-ylphenyl)-[5-[(4-methylpiperazin-1-yl)methyl]-1,3-dihydroisoindol-2-yl]methanone	1701879: Displacement of FITC-geldanamycin from N-terminal GRP94 (unknown origin) after 30 mins by fluorescence polarization competitive binding assay	ic50	0.0220	uM
8-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine	1206606: Displacement of Cy3B-GM from recombinant Grp94 (unknown origin) after 24 hrs by fluorescence polarization assay	ic50	0.0260	uM
methyl 2-[2-(1-benzylimidazol-2-yl)ethyl]-3-chloro-4,6-dihydroxybenzoate	1249614: Inhibition of GRP94 (unknown origin) expressed in HEK293 cells assessed as reduction of Toll-like receptor trafficking to cell membrane treated for 24 hrs prior to testing by DAPI staining-based epifluorescence microscopic analysis	ic50	0.0320	uM
3-(2,4-dihydroxy-5-propan-2-ylphenyl)-4-(1-methylindol-5-yl)-1H-1,2,4-triazol-5-one	1653908: Inhibition of GRP94 (unknown origin)	ic50	0.0377	uM
methyl 2-[4-(2,4-dihydroxy-5-propan-2-ylphenyl)-5-[4-(piperidin-1-ylmethyl)phenyl]triazol-1-yl]acetate	1653908: Inhibition of GRP94 (unknown origin)	ic50	0.0494	uM
(2,4-dihydroxy-5-propan-2-ylphenyl)-(2-methyl-5,7-dihydropyrrolo[3,4-d]pyrimidin-6-yl)methanone	1701879: Displacement of FITC-geldanamycin from N-terminal GRP94 (unknown origin) after 30 mins by fluorescence polarization competitive binding assay	ic50	0.0500	uM
methyl 2-[4-(2,4-dihydroxy-5-propan-2-ylphenyl)-5-(3-methylsulfonylphenyl)triazol-1-yl]acetate	1653908: Inhibition of GRP94 (unknown origin)	ic50	0.0541	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148549: Binding affinity to human HSP90B1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0559	uM
5-[2-amino-4-chloro-7-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]pyrrolo[2,3-d]pyrimidin-5-yl]-2-methylpent-4-yn-2-ol	716074: Binding affinity at Grp94 incubated for 16 hrs by fluorescence polarization competition assay	ki	0.0610	uM
methyl 2-[5-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-(2,4-dihydroxy-5-propan-2-ylphenyl)triazol-1-yl]acetate	1653908: Inhibition of GRP94 (unknown origin)	ic50	0.0780	uM
4-[1-benzyl-5-(4-methylsulfonylphenyl)triazol-4-yl]-6-propan-2-ylbenzene-1,3-diol	1653908: Inhibition of GRP94 (unknown origin)	ic50	0.0780	uM
methyl 2-[4-(2,4-dihydroxy-5-propan-2-ylphenyl)-5-(4-methylsulfonylphenyl)triazol-1-yl]acetate	1653908: Inhibition of GRP94 (unknown origin)	ic50	0.0890	uM
methyl 3-chloro-4,6-dihydroxy-2-[2-[1-[(2-propan-2-yloxyphenyl)methyl]imidazol-2-yl]ethyl]benzoate	1300338: Apparent binding affinity to Grp94 (unknown origin) after 24 hrs by fluorescence polarization assay using FITC-GDA as tracer	kd	0.0900	uM
ethyl 2-[4-(2,4-dihydroxy-5-propan-2-ylphenyl)-5-(3-methylsulfonylphenyl)triazol-1-yl]acetate	1653908: Inhibition of GRP94 (unknown origin)	ic50	0.0962	uM
ethyl 2-[4-(2,4-dihydroxy-5-propan-2-ylphenyl)-5-(4-methylsulfonylphenyl)triazol-1-yl]acetate	1653908: Inhibition of GRP94 (unknown origin)	ic50	0.1005	uM
2-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]-1-[3-(propan-2-ylamino)propyl]imidazo[4,5-c]pyridin-4-amine	1206606: Displacement of Cy3B-GM from recombinant Grp94 (unknown origin) after 24 hrs by fluorescence polarization assay	ic50	0.1010	uM
(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-N-ethyl-3,4-dihydroxyoxolane-2-carboxamide	1694546: Displacement of FITC-geldanamycin from GRP94 (unknown origin) after 24 hrs by fluorescence polarization assay	ki	0.1100	uM
8-(2,4-dichlorophenyl)sulfanyl-9-pent-4-ynylpurin-6-amine	1206606: Displacement of Cy3B-GM from recombinant Grp94 (unknown origin) after 24 hrs by fluorescence polarization assay	ic50	0.1200	uM
(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxy-N-methyloxolane-2-carboxamide	1694546: Displacement of FITC-geldanamycin from GRP94 (unknown origin) after 24 hrs by fluorescence polarization assay	ki	0.1300	uM
9-pent-4-ynyl-8-(2,4,5-trichlorophenyl)sulfanylpurin-6-amine	1206606: Displacement of Cy3B-GM from recombinant Grp94 (unknown origin) after 24 hrs by fluorescence polarization assay	ic50	0.1700	uM
methyl 2-[4-(2,4-dihydroxy-5-propan-2-ylphenyl)-5-[4-[2-(dimethylamino)ethoxy]phenyl]triazol-1-yl]acetate	1653908: Inhibition of GRP94 (unknown origin)	ic50	0.1748	uM
6-chloro-9-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]purin-2-amine	1063123: Binding affinity to human N-terminal polyHis-tagged GRP94 (L69 to N337) expressed in Escherichia coli BL21(DE3) after 3 hrs by fluorescence polarization assay	ki	0.1760	uM
methyl 2-[4-(2,4-dihydroxy-5-propan-2-ylphenyl)-5-[3-(methanesulfonamido)phenyl]triazol-1-yl]acetate	1653908: Inhibition of GRP94 (unknown origin)	ic50	0.1902	uM
ethyl 2-[5-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-(2,4-dihydroxy-5-propan-2-ylphenyl)triazol-1-yl]acetate	1653908: Inhibition of GRP94 (unknown origin)	ic50	0.1921	uM
2-amino-9-[(6-bromo-1,3-benzodioxol-5-yl)methyl]-6-chloro-7H-purin-8-one	1765852: Inhibition of PU-H71-FITC3 binding to recombinant N-terminal Grp94 (unknown origin) incubated for 2 hrs by fluorescence polarization assay	ic50	0.1940	uM
(2,4-dihydroxy-5-propan-2-ylphenyl)-[4-(dimethylamino)-2-(2-methoxyethoxy)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]methanone	1701879: Displacement of FITC-geldanamycin from N-terminal GRP94 (unknown origin) after 30 mins by fluorescence polarization competitive binding assay	ic50	0.1950	uM
(2,4-dihydroxy-5-propan-2-ylphenyl)-[2-(2-methoxyethoxy)-4-(methylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]methanone	1701879: Displacement of FITC-geldanamycin from N-terminal GRP94 (unknown origin) after 30 mins by fluorescence polarization competitive binding assay	ic50	0.1960	uM
methyl 2-[4-(2,4-dihydroxy-5-propan-2-ylphenyl)-5-[4-(morpholin-4-ylmethyl)phenyl]triazol-1-yl]acetate	1653908: Inhibition of GRP94 (unknown origin)	ic50	0.1971	uM
(2,4-dihydroxy-5-propan-2-ylphenyl)-[2-(2-methoxyethoxy)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]methanone	1701879: Displacement of FITC-geldanamycin from N-terminal GRP94 (unknown origin) after 30 mins by fluorescence polarization competitive binding assay	ic50	0.1980	uM
methyl 3-chloro-2-[2-[1-[(2-ethoxyphenyl)methyl]imidazol-2-yl]ethyl]-4,6-dihydroxybenzoate	1300338: Apparent binding affinity to Grp94 (unknown origin) after 24 hrs by fluorescence polarization assay using FITC-GDA as tracer	kd	0.2000	uM
ethyl (2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolane-2-carboxylate	1832103: Binding affinity to Grp94 (unknown origin) by fluorescent polarization assay	kd	0.2000	uM
ethyl 2-[4-(2,4-dihydroxy-5-propan-2-ylphenyl)-5-[3-(methanesulfonamido)phenyl]triazol-1-yl]acetate	1653908: Inhibition of GRP94 (unknown origin)	ic50	0.2093	uM
[4-(cyclopropylamino)-2-(2-methoxyethoxy)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]-(2,4-dihydroxy-5-propan-2-ylphenyl)methanone	1701879: Displacement of FITC-geldanamycin from N-terminal GRP94 (unknown origin) after 30 mins by fluorescence polarization competitive binding assay	ic50	0.2160	uM
[2-[2-(diethylamino)ethoxy]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]-(2,4-dihydroxy-5-propan-2-ylphenyl)methanone	1701879: Displacement of FITC-geldanamycin from N-terminal GRP94 (unknown origin) after 30 mins by fluorescence polarization competitive binding assay	ic50	0.2170	uM
8-(3,5-dichlorophenyl)sulfanyl-9-[3-(propan-2-ylamino)propyl]purin-6-amine	1206606: Displacement of Cy3B-GM from recombinant Grp94 (unknown origin) after 24 hrs by fluorescence polarization assay	ic50	0.2200	uM
(2,4-dihydroxy-5-propan-2-ylphenyl)-[4-methoxy-2-(2-methoxyethoxy)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]methanone	1701879: Displacement of FITC-geldanamycin from N-terminal GRP94 (unknown origin) after 30 mins by fluorescence polarization competitive binding assay	ic50	0.2320	uM
(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-N-cyclopropyl-3,4-dihydroxyoxolane-2-carboxamide	1694546: Displacement of FITC-geldanamycin from GRP94 (unknown origin) after 24 hrs by fluorescence polarization assay	ki	0.2400	uM
8-(3-bromo-5-chlorophenyl)sulfanyl-9-pent-4-ynylpurin-6-amine	1206606: Displacement of Cy3B-GM from recombinant Grp94 (unknown origin) after 24 hrs by fluorescence polarization assay	ic50	0.2400	uM
(2,4-dihydroxy-5-propan-2-ylphenyl)-(2-methyl-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl)methanone	1701879: Displacement of FITC-geldanamycin from N-terminal GRP94 (unknown origin) after 30 mins by fluorescence polarization competitive binding assay	ic50	0.2450	uM
methyl 3-chloro-4,6-dihydroxy-2-[2-[1-[(2-propoxyphenyl)methyl]imidazol-2-yl]ethyl]benzoate	1300338: Apparent binding affinity to Grp94 (unknown origin) after 24 hrs by fluorescence polarization assay using FITC-GDA as tracer	kd	0.2500	uM
8-(3,5-dichlorophenyl)sulfanyl-9-pent-4-ynylpurin-6-amine	1206606: Displacement of Cy3B-GM from recombinant Grp94 (unknown origin) after 24 hrs by fluorescence polarization assay	ic50	0.2600	uM
8-[[6-(dimethylamino)-1,3-benzodioxol-5-yl]sulfanyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine	1206606: Displacement of Cy3B-GM from recombinant Grp94 (unknown origin) after 24 hrs by fluorescence polarization assay	ic50	0.2650	uM
9-but-3-ynyl-8-(3,5-dichlorophenyl)sulfanylpurin-6-amine	1206606: Displacement of Cy3B-GM from recombinant Grp94 (unknown origin) after 24 hrs by fluorescence polarization assay	ic50	0.2870	uM
8-(3,5-dibromophenyl)sulfanyl-9-pent-4-ynylpurin-6-amine	1206606: Displacement of Cy3B-GM from recombinant Grp94 (unknown origin) after 24 hrs by fluorescence polarization assay	ic50	0.2900	uM
(2,4-dihydroxy-5-propan-2-ylphenyl)-[2-[2-(dimethylamino)ethoxy]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]methanone	1701879: Displacement of FITC-geldanamycin from N-terminal GRP94 (unknown origin) after 30 mins by fluorescence polarization competitive binding assay	ic50	0.2900	uM
2-amino-6-chloro-9-[(2-fluoro-4-methylphenyl)methyl]-7H-purin-8-one	1765852: Inhibition of PU-H71-FITC3 binding to recombinant N-terminal Grp94 (unknown origin) incubated for 2 hrs by fluorescence polarization assay	ic50	0.3180	uM
1,3-dihydroisoindol-2-yl-(2,4-dihydroxy-5-indol-1-ylphenyl)methanone	2135532: Binding affinity to GRP94 (unknown origin) assessed as dissociation constant incubated for 24 hrs by fluorescence polarization assay	kd	0.3200	uM
(6-amino-9-pent-4-ynylpurin-8-yl)-(2,4-dichlorophenyl)methanone	1206606: Displacement of Cy3B-GM from recombinant Grp94 (unknown origin) after 24 hrs by fluorescence polarization assay	ic50	0.3400	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tunicamycin	increases expression	8
Cadmium Chloride	increases abundance, increases expression, increases methylation, affects expression, decreases expression	6
Thapsigargin	increases expression, decreases expression, increases reaction	6
bisphenol A	increases expression, decreases expression, affects expression, affects cotreatment	4
Cadmium	increases abundance, increases expression, decreases expression	4
sodium arsenite	decreases expression	3
Copper	affects binding, affects expression, affects cotreatment, decreases expression, increases abundance	3
Estradiol	affects cotreatment, increases expression	3
1-Methyl-4-phenylpyridinium	decreases expression, increases expression, affects expression, affects reaction	3
Cyclosporine	increases expression	3
Arsenic Trioxide	decreases expression, increases expression	2
Acetaminophen	decreases expression	2
Cannabidiol	increases expression	2
Drugs, Chinese Herbal	decreases expression, increases reaction	2
Rotenone	decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Copper Sulfate	decreases expression, increases expression	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
geldanamycin	affects binding, decreases reaction	1
beta-N-methylamino-L-alanine	increases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	increases expression	1
dienochlor	decreases expression	1
methylselenic acid	increases expression, decreases reaction	1
surfactin peptide	increases expression	1
titanium dioxide	increases expression	1
mequinol	affects cotreatment, increases expression	1

ChEMBL screening assays

64 unique, capped per target: 64 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1100284	Binding	Inhibition of Grp94	Heat shock protein 90: inhibitors in clinical trials. — J Med Chem

Cellosaurus cell lines

3 cell lines: 2 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2Z7	Abcam HEK293T HSP90B1 KO	Transformed cell line	Female
CVCL_D9GF	Ubigene HEK293 HSP90B1 KO	Transformed cell line	Female
CVCL_E0EF	Ubigene HeLa HSP90B1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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