HSPA8

Summary

HSPA8 (heat shock protein family A (Hsp70) member 8, HGNC:5241) is a protein-coding gene on chromosome 11q24.1, encoding Heat shock cognate 71 kDa protein (P11142). Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, chaperone-mediated autophagy, activation of proteolysis of misfolded proteins, formation and dissoci…. It is a selective cancer dependency (DepMap: 56.5% of cell lines).

This gene encodes a member of the heat shock protein 70 family, which contains both heat-inducible and constitutively expressed members. This protein belongs to the latter group, which are also referred to as heat-shock cognate proteins. It functions as a chaperone, and binds to nascent polypeptides to facilitate correct folding. It also functions as an ATPase in the disassembly of clathrin-coated vesicles during transport of membrane components through the cell. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 3312 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 53 total
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 56.5% of screened cell lines
• MANE Select transcript: NM_006597

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5241
Approved symbol	HSPA8
Name	heat shock protein family A (Hsp70) member 8
Location	11q24.1
Locus type	gene with protein product
Status	Approved
Aliases	HSC71, HSC70, HSP73
Ensembl gene	ENSG00000109971
Ensembl biotype	protein_coding
OMIM	600816
Entrez	3312

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 30 protein_coding, 5 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000227378, ENST00000453788, ENST00000524552, ENST00000524590, ENST00000525463, ENST00000525624, ENST00000526110, ENST00000526686, ENST00000526862, ENST00000527387, ENST00000527983, ENST00000528292, ENST00000530391, ENST00000531063, ENST00000532091, ENST00000532167, ENST00000532182, ENST00000532636, ENST00000532780, ENST00000533238, ENST00000533540, ENST00000534319, ENST00000534567, ENST00000534624, ENST00000876974, ENST00000876975, ENST00000876976, ENST00000935611, ENST00000935612, ENST00000935613, ENST00000935614, ENST00000935615, ENST00000935616, ENST00000935617, ENST00000971745, ENST00000971746, ENST00000971747

RefSeq mRNA: 2 — MANE Select: NM_006597 NM_006597, NM_153201

CCDS: CCDS44754, CCDS8440

Canonical transcript exons

ENST00000534624 — 9 exons

Exon	Start	End
ENSE00000994832	123062064	123062136
ENSE00001101375	123058632	123058830
ENSE00001101382	123059059	123059261
ENSE00001101385	123058252	123058484
ENSE00002157784	123057489	123057919
ENSE00003473688	123061120	123061329
ENSE00003540604	123059473	123060028
ENSE00003560408	123060116	123060268
ENSE00003791394	123060593	123060798

Expression profiles

Bgee: expression breadth ubiquitous, 156 present calls, max score 99.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 802.3264 / max 10631.3983, expressed in 1828 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122888	795.4134	1828
122889	3.0649	1395
122879	1.4868	764
122886	1.0760	713
122885	1.0064	682
122890	0.2789	98

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	99.92	gold quality
superior frontal gyrus	UBERON:0002661	99.87	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.81	gold quality
prefrontal cortex	UBERON:0000451	99.80	gold quality
frontal cortex	UBERON:0001870	99.80	gold quality
frontal lobe	UBERON:0016525	99.80	gold quality
cerebellum	UBERON:0002037	99.79	gold quality
cerebellar cortex	UBERON:0002129	99.79	gold quality
right frontal lobe	UBERON:0002810	99.79	gold quality
cerebellar hemisphere	UBERON:0002245	99.78	gold quality
ventricular zone	UBERON:0003053	99.77	gold quality
cortical plate	UBERON:0005343	99.76	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.73	gold quality
embryo	UBERON:0000922	99.73	gold quality
ganglionic eminence	UBERON:0004023	99.73	gold quality
right testis	UBERON:0004534	99.73	gold quality
adrenal tissue	UBERON:0018303	99.73	gold quality
primary visual cortex	UBERON:0002436	99.71	gold quality
islet of Langerhans	UBERON:0000006	99.70	gold quality
cerebral cortex	UBERON:0000956	99.70	gold quality
left testis	UBERON:0004533	99.69	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.69	gold quality
adult mammalian kidney	UBERON:0000082	99.67	gold quality
anterior cingulate cortex	UBERON:0009835	99.67	gold quality
brain	UBERON:0000955	99.66	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.66	gold quality
granulocyte	CL:0000094	99.65	gold quality
stromal cell of endometrium	CL:0002255	99.65	gold quality
body of pancreas	UBERON:0001150	99.65	gold quality
pancreas	UBERON:0001264	99.65	gold quality

Single-cell (SCXA)

Detected in 23 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	13442.82
E-CURD-95	yes	4400.26
E-GEOD-149689	yes	836.60
E-HCAD-1	yes	91.50
E-CURD-122	yes	57.92
E-CURD-88	yes	46.35
E-GEOD-135922	yes	25.43
E-CURD-46	yes	21.83
E-MTAB-9543	yes	21.04
E-MTAB-10042	yes	9.69
E-CURD-112	yes	3.62
E-MTAB-7008	no	9244.27
E-MTAB-10137	no	4298.88
E-CURD-97	no	4138.72
E-MTAB-9689	no	1662.83

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): KLF4, MYC, SKIL, STAT5A, TP53

miRNA regulators (miRDB)

61 targeting HSPA8, 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-340-5P	100.00	72.50	4437
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-26A-5P	99.78	73.52	2303

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 56.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Tumor-derived HSP70 peptide complexes have the immunogenic potential to instruct dendritic cells to cross-present endogenously expressed, nonmutated, and tumor antigenic peptides shared among tumors of the melanocytic lineage for T cell recognition. (PMID:12421917)
• Hsc70 may be involved in androgen action on dermal papilla cells. (PMID:12850307)
• no abnormal levels of hsc70 and hsp60 were detectable in pediatric c-ALL pre B-cells at diagnosis nor at relapse. In contrast, developmentally regulated levels of hsc70 and hsp60 expression during B-cell ontogenesis were observed (PMID:12890148)
• tau binds to Hsc70, and its phosphorylation is a recognition requirement for the addition of ubiquitin (PMID:14612456)
• a novel nuclear export and nuclear localization-related signals in human Hsp70 (PMID:14684748)
• a region of the TfR that can potentially interact with hsc70 (PMID:15086793)
• sequestered in discrete foci in the nucleus of the infected cell in herpes simplex virus type 1 infection. (PMID:15194794)
• Hsp105alpha is suggested to regulate the substrate binding cycle of Hsp70/Hsc70 by inhibiting the ATPase activity of Hsp70/Hsc70, thereby functioning as a negative regulator of the Hsp70/Hsc70 chaperone system. (PMID:15292236)
• Expressed in colon cancer cells [NIP71] (PMID:15336565)
• The head shock protein 70 kD (HSP-70i) has been shown to protect cells, tissues, and organs from harmful assaults in vivo and in vitro experimental models. (PMID:15625011)
• In this study, we discovered that the U-box ubiquitin ligase carboxyl-terminus of Hsc70 interacting protein (CHIP) ubiquitylated Epsin. (PMID:15694383)
• Present in cells as part of the dengue virus receptor. (PMID:15795242)
• CSP modulates G protein function by preferentially targeting the inactive GDP-bound form of G alpha(s) and promoting GDP/GTP exchange; the guanine nucleotide exchange activity of full-length CSP is regulated by Hsc70-SGT (PMID:15972823)
• This study identified heat shock protein 70 protein 8 as being expressed on the cell surface and downregulated upon differentiation. (PMID:16100000)
• Histidine 89 is an essential residue for Hsp70 in the phosphate transfer reaction. (PMID:16817320)
• Hsc70 is directly associated with Influenza virus matrix protein 1 and therefore is required for viral production (PMID:17022977)
• Our results suggest that the widespread accumulation of Hsc70 and Hsp70 may occur in brains with MSA, and that Hsc70 and Hsp70 may be associated with the pathogenesis of MSA. (PMID:17240362)
• Hsc70 plays a defined role in reovirus outer capsid disassembly, during or soon after membrane penetration, to prepare the entering particle for gene expression and replication (PMID:17284448)
• serum Hsp70 concentrations are decreased in normal human pregnancy (PMID:17296233)
• Following co-immunoprecipitation, a specific interaction between the head domain of K5 with Hsc70, a chaperone also involved in vesicle uncoating, was verified. (PMID:17397964)
• FKBP38 is a co-chaperone of HERG and contributes via the Hsc70/Hsp90 chaperone system to the trafficking of wild type and mutant HERG potassium channels (PMID:17569659)
• 70-kDa heat shock proteins as a AQP2 interactors and have shown for hsc70 that this interaction is involved in AQP2 trafficking. (PMID:17636261)
• Important functions of recently activated dendritic cells are thus critically modulated by the newly discovered HSPA8-EWI-2 interaction. (PMID:17785435)
• Amino acid domains 280-297 of VP6 and 531-554 of VP4 are implicated in heat shock cognate protein hsc70-mediated rotavirus infection. (PMID:17876681)
• an association between Hsc70 and ASIC2 that may underlie the increased retention of ASIC2 in the endoplasmic reticulum of glioma cells. (PMID:17878160)
• HSP70 was a useful indicator of stressed neurons in acute phase of epilepsy, but not associated with neuronal death (PMID:17929041)
• Our data show that a mutation in hsp70-Hom gene is associated with higher incidence of Postoperative atrial fibrillation. (PMID:17934269)
• BAG-1 associates with Tau protein in an Hsc70-dependent manner. (PMID:17954934)
• propose that one function of the Hsc70 nuclear foci may be to serve to facilitate the process of clearing stalled RNAP II complexes from viral genomes during times of highly active transcription (PMID:18231578)
• Association between endogenous LAP2alpha and Hsp70 in non-transfected cells was confirmed by co-immunoprecipitation. (PMID:18261988)
• Our results raise the possibility that HSP70 gene (i.e., haplotypes of rs2075799) might be implicated in the development of schizophrenia. (PMID:18299791)
• Cathepsin C propeptide interacts with intestinal alkaline phosphatase (IAP) and heat shock cognate protein 70. The propeptide of cathepsin C may stimulate the sorting to the lysosome contributing to the degradation of IAP in Caco-2 cells. (PMID:18307834)
• It was indicated that disruption of the HSC73-TAP association resulted in inhibition of TAP-dependent translocation of HSC73-bound peptides. (PMID:18380807)
• During the earliest stages of HSV-1 infection, the formation of Hsc70 foci adjacent to viral prereplicative sites occurs after PML bodies have been disrupted by ICP0. PML protein is not required for the formation of Hsc70 foci. (PMID:18434395)
• hsc70 binds tau at two sites that are involved in tau aggregation, one of which is regulated by alternative splicing; hsc70 binding might directly inhibit tau-tau interactions that precede tau oligomerization and aggregation. (PMID:18500754)
• The variant allele of THBS2 is a risk factor for TAA in hypertensive patients, whereas the variant alleles of HSPA8, GPX1, AGT, and TNF are protective against this condition (PMID:18600213)
• the hydrophobicity of the TA region dictates whether a precursor is delivered to the ER via the Hsp40/Hsc70 or Asna-1/TRC40-dependent route. (PMID:18667436)
• Bag1 NEF increased refolding by Hsc70 and DJA2, as did the newly characterized NEF Hsp110 (PMID:18684711)
• Simultaneously reducing the expression of both HSC70 and HSP72 induces proteasome-dependent degradation of HSP90 client proteins, G1 cell-cycle arrest, and extensive tumor-specific apoptosis in human tumor cell lines. (PMID:18772114)
• Cytosolic chaperone Hsc70 is required for the cytosolic reactivation of ricin A chain dislocated from the mammalian cell endoplasmic reticulum. (PMID:18988734)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
danio_rerio	hspa8b	ENSDARG00000037403
danio_rerio	hspa8	ENSDARG00000068992
mus_musculus	Hspa8	ENSMUSG00000015656
rattus_norvegicus	Hspa8-ps23	ENSRNOG00000030228
rattus_norvegicus	AABR07048992.1	ENSRNOG00000032585
rattus_norvegicus	Hspa8	ENSRNOG00000034066
rattus_norvegicus	Hsc70-ps1	ENSRNOG00000034093
rattus_norvegicus		ENSRNOG00000062985
drosophila_melanogaster	Hsp110	FBGN0026418
caenorhabditis_elegans	hsp-70	WBGENE00002026
caenorhabditis_elegans		WBGENE00009691
caenorhabditis_elegans		WBGENE00009692
caenorhabditis_elegans		WBGENE00016250

Paralogs (13): HSPA5 (ENSG00000044574), HSPA9 (ENSG00000113013), HSPH1 (ENSG00000120694), HSPA2 (ENSG00000126803), HYOU1 (ENSG00000149428), HSPA13 (ENSG00000155304), HSPA4L (ENSG00000164070), HSPA4 (ENSG00000170606), HSPA6 (ENSG00000173110), HSPA14 (ENSG00000187522), HSPA1B (ENSG00000204388), HSPA1A (ENSG00000204389), HSPA1L (ENSG00000204390)

Protein

Protein identifiers

Heat shock cognate 71 kDa protein — P11142 (reviewed: P11142)

Alternative names: Heat shock 70 kDa protein 8, Heat shock protein family A member 8, Lipopolysaccharide-associated protein 1

All UniProt accessions (15): P11142, A8K7Q2, E9PI65, E9PK54, E9PKE3, E9PLF4, E9PM13, E9PN25, E9PN89, E9PNE6, E9PPY6, E9PQK7, E9PQQ4, E9PS65, V9HW22

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, chaperone-mediated autophagy, activation of proteolysis of misfolded proteins, formation and dissociation of protein complexes, and antigen presentation. 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 of HSP70, 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 of HSP70 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. HSP70 goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The HSP70-associated co-chaperones are of three types: J-domain co-chaperones 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. Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70. Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex. Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes. Substrate recognition component in chaperone-mediated autophagy (CMA), a selective protein degradation process that mediates degradation of proteins with a -KFERQ motif: HSPA8/HSC70 specifically recognizes and binds cytosolic proteins bearing a -KFERQ motif and promotes their recruitment to the surface of the lysosome where they bind to lysosomal protein LAMP2. KFERQ motif-containing proteins are eventually transported into the lysosomal lumen where they are degraded. In conjunction with LAMP2, facilitates MHC class II presentation of cytoplasmic antigens by guiding antigens to the lysosomal membrane for interaction with LAMP2 which then elicits MHC class II presentation of peptides to the cell membrane. Participates in the ER-associated degradation (ERAD) quality control pathway in conjunction with J domain-containing co-chaperones and the E3 ligase STUB1. It is recruited to clathrin-coated vesicles through its interaction with DNAJC6 leading to activation of HSPA8/HSC70 ATPase activity and therefore uncoating of clathrin-coated vesicles.

Subunit / interactions. Component of the chaperone-assisted selective autophagy (CASA) complex consisting of BAG3, HSPA8/HSC70, HSPB8 and STUB1/CHIP. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with PACRG. Interacts with HSPH1/HSP105. Interacts with IRAK1BP1 and BAG1. Interacts with DNAJC7. Interacts with DNAJB12 (via J domain). Interacts with DNAJB14 (via J domain). Interacts (via C-terminus) with the E3 ligase CHIP forming a 210 kDa complex of one CHIP and two HSPA8 molecules. Interacts with CITED1 (via N-terminus); the interaction suppresses the association of CITED1 to p300/CBP and Smad-mediated transcription transactivation. Component of the PRP19-CDC5L splicing complex composed of a core complex comprising a homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2, and at least three less stably associated proteins CTNNBL1, CWC15 and HSPA8. Interacts with TRIM5. Part of a complex composed at least of ASH2L, EMSY, HCFC1, HSPA8, CCAR2, MATR3, MKI67, RBBP5, TUBB2A, WDR5 and ZNF335; this complex may have a histone H3-specific methyltransferase activity. Interacts with METTL21A. Following LPS binding, may form a complex with CXCR4, GDF5 and HSP90AA1. Interacts with PRKN. Interacts with FOXP3. Interacts with DNAJC9 (via J domain). Interacts with MLLT11. Interacts with RNF207. Interacts with DNAJC21. Interacts with DNAJB2. Interacts with TTC1 (via TPR repeats). Interacts with SGTA (via TPR repeats). Interacts with HSF1 (via transactivation domain). Interacts with HOPX, HSP40 and HSP90. Component of the chaperone-assisted selective autophagy (CASA) complex consisting of BAG3, HSPA8/HSC70, HSPB8 and STUB1/CHIP. Interacts with STUB1. Interacts with BAG2. Interacts with BAG3. Interacts with DNAJC12. Interacts with ZMYND10. Interacts with HSPC138. Interacts with BCL2L1, GIMAP5 and MCL1; the interaction with BCL2L1 or MCL1 is impaired in the absence of GIMAP5. Interacts with NLPR12. Interacts with TTC4. Interacts with TOMM70; the interaction is required for preprotein mitochondrial import. May interact with DNJC9; the interaction seems to be histone-dependent. Interacts with BAG5 and JPH2; the interaction with JPH2 is increased in the presence of BAG5. Interacts with VGF-derived peptide TLQP-21. Interacts with molecular chaperone MIPEP155 (via N-terminal ATP-binding region); the interaction results in reduced ATPase activity of HSPA8, impaired interaction of HSPA8 with HSP90 and reduced lysosomal antigen trafficking. Interacts with CDKN1B; the interaction may be associated with susceptibility to ubiquitination. Interacts with HTN3 peptide Hst3; the interaction enhances HSPA8-CDKN1B complex formation. Interacts with DNAJC6 (via J domain) in an ATP-dependent manner; this interaction stimulates the HSPA8’s ATPase activity. Forms a complex composed of HSPA8, CLTC and DNAJC6. Interacts with HSPA8; this interaction modulates migratory and antigen-presenting capacities of dendritic cells. (Microbial infection) Interacts with SV40 VP1. (Microbial infection) Interacts with human herpes virus 1 (HHV-1) transcriptional regulator ICP22; this interaction recruits HSPA8/HSP40 to discrete nuclear foci.

Subcellular location. Cytoplasm. Melanosome. Nucleus. Nucleolus. Cell membrane. Lysosome membrane.

Tissue specificity. Ubiquitous.

Post-translational modifications. Acetylated. ISGylated. Trimethylation at Lys-561 reduces fibrillar SNCA binding.

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. Constitutively synthesized.

Similarity. Belongs to the heat shock protein 70 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P11142-1	1	yes
P11142-2	2, HSC54

RefSeq proteins (2): NP_006588, NP_694881 (=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

Enzyme classification (BRENDA):

• EC 7.4.2.3 — mitochondrial protein-transporting ATPase (BRENDA: 11 organisms, 48 substrates, 2 inhibitors, 0 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	—	0

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (91 total): helix 22, strand 21, modified residue 19, binding site 12, region of interest 4, turn 4, cross-link 2, sequence variant 2, initiator methionine 1, chain 1, splice variant 1, mutagenesis site 1, compositionally biased region 1

Structure

Experimental structures (PDB)

38 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5AQM	X-RAY DIFFRACTION	1.63
4H5R	X-RAY DIFFRACTION	1.64
5AQL	X-RAY DIFFRACTION	1.69
4H5V	X-RAY DIFFRACTION	1.75
5AQV	X-RAY DIFFRACTION	1.75
6B1N	X-RAY DIFFRACTION	1.8
3AGY	X-RAY DIFFRACTION	1.85
6ZYJ	X-RAY DIFFRACTION	1.85
4H5N	X-RAY DIFFRACTION	1.86
5AQF	X-RAY DIFFRACTION	1.88
3LDQ	X-RAY DIFFRACTION	1.9
4H5T	X-RAY DIFFRACTION	1.9
5AQT	X-RAY DIFFRACTION	1.9
6B1M	X-RAY DIFFRACTION	1.9
5AQR	X-RAY DIFFRACTION	1.91
5AQU	X-RAY DIFFRACTION	1.92
4H5W	X-RAY DIFFRACTION	1.94
5AQJ	X-RAY DIFFRACTION	1.96
5AQI	X-RAY DIFFRACTION	1.98
3FZH	X-RAY DIFFRACTION	2
5AQH	X-RAY DIFFRACTION	2
5AQS	X-RAY DIFFRACTION	2
3ESK	X-RAY DIFFRACTION	2.05
5AQP	X-RAY DIFFRACTION	2.08
5AQK	X-RAY DIFFRACTION	2.09
3FZK	X-RAY DIFFRACTION	2.1
3M3Z	X-RAY DIFFRACTION	2.1
5AQO	X-RAY DIFFRACTION	2.12
3FZF	X-RAY DIFFRACTION	2.2
3FZL	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11142-F1	89.01	0.65

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 (12): 71; 202–204; 202; 268–275; 268; 271; 275; 339–342; 339; 12–15; 14; 15

Post-translational modifications (21): 2, 108, 153, 246, 319, 319, 328, 329, 362, 469, 512, 512, 524, 541, 561, 561, 589, 597, 601, 512 …

Mutagenesis-validated functional residues (1):

Position	Phenotype
561	complete loss of in vitro methylation by mettl21a.

Function

Pathways and Gene Ontology

Reactome pathways

21 pathways

ID	Pathway
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-432720	Lysosome Vesicle Biogenesis
R-HSA-432722	Golgi Associated Vesicle Biogenesis
R-HSA-447041	CHL1 interactions
R-HSA-450408	AUF1 (hnRNP D0) binds and destabilizes mRNA
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-6798695	Neutrophil degranulation
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-8876725	Protein methylation
R-HSA-888590	GABA synthesis, release, reuptake and degradation
R-HSA-9613354	Lipophagy
R-HSA-9613829	Chaperone Mediated Autophagy
R-HSA-9615710	Late endosomal microautophagy
R-HSA-9828642	Respiratory syncytial virus genome transcription
R-HSA-9833482	PKR-mediated signaling
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-9918487	Dengue Virus Genome Translation and Replication

MSigDB gene sets: 560 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_LYSOSOMAL_TRANSPORT, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, MODULE_151, KEGG_MAPK_SIGNALING_PATHWAY, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN

GO Biological Process (47): mRNA splicing, via spliceosome (GO:0000398), protein folding (GO:0006457), response to unfolded protein (GO:0006986), cellular response to starvation (GO:0009267), positive regulation of cell migration (GO:0030335), regulation of protein stability (GO:0031647), protein refolding (GO:0042026), regulation of protein-containing complex assembly (GO:0043254), negative regulation of DNA-templated transcription (GO:0045892), ATP metabolic process (GO:0046034), membrane organization (GO:0061024), regulation of protein complex stability (GO:0061635), chaperone-mediated autophagy (GO:0061684), protein targeting to lysosome involved in chaperone-mediated autophagy (GO:0061740), cellular response to steroid hormone stimulus (GO:0071383), clathrin coat disassembly (GO:0072318), positive regulation of ferroptosis (GO:0160020), negative regulation of NLRP3 inflammasome complex assembly (GO:1900226), negative regulation of supramolecular fiber organization (GO:1902904), regulation of protein import (GO:1904589), chaperone-mediated autophagy translocation complex disassembly (GO:1904764), mRNA processing (GO:0006397), mRNA catabolic process (GO:0006402), autophagy (GO:0006914), response to stress (GO:0006950), signal transduction (GO:0007165), negative regulation of cell population proliferation (GO:0008285), RNA splicing (GO:0008380), negative regulation of signal transduction (GO:0009968), protein catabolic process (GO:0030163), negative regulation of cell growth (GO:0030308), negative regulation of protein ubiquitination (GO:0031397), positive regulation of interleukin-8 production (GO:0032757), cellular response to stress (GO:0033554), cellular response to oxidative stress (GO:0034599), regulation of cytoplasmic pattern recognition receptor signaling pathway (GO:0039531), positive regulation of erythrocyte differentiation (GO:0045648), protein stabilization (GO:0050821), negative regulation of cellular component organization (GO:0051129), cellular heat acclimation (GO:0070370)

GO Molecular Function (21): G protein-coupled receptor binding (GO:0001664), RNA binding (GO:0003723), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), enzyme binding (GO:0019899), MHC class II protein complex binding (GO:0023026), protein-macromolecule adaptor activity (GO:0030674), heat shock protein binding (GO:0031072), ubiquitin protein ligase binding (GO:0031625), protein folding chaperone (GO:0044183), cadherin binding (GO:0045296), receptor ligand activity (GO:0048018), obsolete unfolded protein binding (GO:0051082), protein-folding chaperone binding (GO:0051087), C3HC4-type RING finger domain binding (GO:0055131), ATP-dependent protein disaggregase activity (GO:0140545), ATP-dependent protein folding chaperone (GO:0140662), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787), histone deacetylase binding (GO:0042826)

GO Cellular Component (30): Prp19 complex (GO:0000974), extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), nucleolus (GO:0005730), cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), membrane (GO:0016020), secretory granule lumen (GO:0034774), melanosome (GO:0042470), lysosomal lumen (GO:0043202), clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane (GO:0061202), extracellular exosome (GO:0070062), blood microparticle (GO:0072562), lumenal side of lysosomal membrane (GO:0098575), protein folding chaperone complex (GO:0101031), ficolin-1-rich granule lumen (GO:1904813), ribonucleoprotein complex (GO:1990904), lysosome (GO:0005764), centrosome (GO:0005813), centriole (GO:0005814), endomembrane system (GO:0012505), aggresome (GO:0016235), nuclear speck (GO:0016607), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

Rollup of top-17 pathways:

Category	Pathways
Cellular response to heat stress	2
trans-Golgi Network Vesicle Budding	2
Autophagy	2
Cellular responses to stress	1
HSF1-dependent transactivation	1
L1CAM interactions	1
Regulation of mRNA stability by proteins that bind AU-rich elements	1
Signaling by Interleukins	1
Innate Immune System	1
mRNA Splicing	1
Membrane Trafficking	1
Post-translational protein modification	1
Neurotransmitter release cycle	1
Selective autophagy	1
Respiratory syncytial virus (RSV) genome replication, transcription and translation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
protein binding	5
signaling receptor binding	4
ATP-dependent activity	3
regulation of biological quality	2
protein folding	2
protein-folding chaperone binding	2
nuclear lumen	2
lysosome	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
cellular process	1
protein maturation	1
response to topologically incorrect protein	1
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
regulation of cellular component biogenesis	1
regulation of cellular component organization	1
protein-containing complex assembly	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
purine ribonucleotide metabolic process	1
purine ribonucleoside triphosphate metabolic process	1
cellular component organization	1
autophagy	1
protein catabolic process	1
protein carrier activity	1
protein targeting to lysosome	1
chaperone-mediated autophagy	1
protein targeting to vacuole involved in autophagy	1
cellular response to hormone stimulus	1
response to steroid hormone	1
cellular response to lipid	1
vesicle uncoating	1
clathrin-dependent endocytosis	1

Protein interactions and networks

STRING

8234 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HSPA8	DNAJB1	P25685	999
HSPA8	HSP90AA1	P07900	999
HSPA8	HSP90AB1	P08238	999
HSPA8	STUB1	Q9UNE7	998
HSPA8	BAG1	Q99933	998
HSPA8	BAG3	O95817	997
HSPA8	BAG2	O95816	997
HSPA8	DNAJC6	O75061	996
HSPA8	SGTA	O43765	994
HSPA8	ST13	P50502	992
HSPA8	HSPB8	Q9UJY1	992
HSPA8	HSPBP1	Q9NZL4	984
HSPA8	HSPA4	P34932	984
HSPA8	DNAJC5	Q9H3Z4	984
HSPA8	SNCA	P37840	962

IntAct

1146 interactions, top by confidence:

A	B	Type	Score
MAP2K1	RAF1	psi-mi:“MI:0914”(association)	0.960
HSPA8	HSPBP1	psi-mi:“MI:0915”(physical association)	0.930
HSPBP1	HSPA8	psi-mi:“MI:0915”(physical association)	0.930
HSPA8	STUB1	psi-mi:“MI:0915”(physical association)	0.870
STUB1	HSPA8	psi-mi:“MI:0915”(physical association)	0.870
HSPA8	BAG2	psi-mi:“MI:2364”(proximity)	0.860
BAG2	HSPA8	psi-mi:“MI:0915”(physical association)	0.860
HSPA8	HSPA4	psi-mi:“MI:0915”(physical association)	0.830
YWHAH	ABLIM1	psi-mi:“MI:0914”(association)	0.800
BAG1	HSPA8	psi-mi:“MI:0915”(physical association)	0.790
IFT70B	IFT56	psi-mi:“MI:0914”(association)	0.790
GMNN	MCIDAS	psi-mi:“MI:0914”(association)	0.770
HSPA8	GAK	psi-mi:“MI:0914”(association)	0.760
TTC4	HSP90AB1	psi-mi:“MI:0914”(association)	0.750
VSX1	USP12	psi-mi:“MI:0914”(association)	0.730
HSPA8	TRIM38	psi-mi:“MI:0915”(physical association)	0.720
TRIM38	HSPA8	psi-mi:“MI:0915”(physical association)	0.720
HSPA8	MAPT	psi-mi:“MI:0407”(direct interaction)	0.670
TRAF3IP1	HSPA8	psi-mi:“MI:0915”(physical association)	0.660

BioGRID (3478): HSPA8 (Biochemical Activity), HSPA8 (Affinity Capture-MS), HSPA8 (Two-hybrid), HSPA8 (Affinity Capture-MS), HSPA8 (Reconstituted Complex), STUB1 (Protein-peptide), HSPA8 (Two-hybrid), NMI (Two-hybrid), BAG3 (Two-hybrid), TRIM38 (Two-hybrid), HSPBP1 (Two-hybrid), HSPA8 (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), HSPA8 (Reconstituted Complex), HSPA8 (Two-hybrid)

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

13 interactions.

A	Effect	B	Mechanism
GRPEL1	“down-regulates activity”	HSPA8	binding
DNAJB12	“up-regulates activity”	HSPA8	binding
HSPA8	“down-regulates quantity”	CFTR	binding
HSPA8	“up-regulates activity”	RNF5	binding
HSPA8	“form complex”	PRP19-CDC5L	binding
KLF4	“up-regulates quantity by expression”	HSPA8	“transcriptional regulation”
BAG1	“up-regulates activity”	HSPA8	binding
BAG3	“up-regulates activity”	HSPA8	binding
HSPA8	“up-regulates activity”	“Chaperone-mediated autophagy”
HSPA8	“down-regulates quantity by destabilization”	“AP-2/clathrin vescicle”	binding
DNAJC6	“up-regulates activity”	HSPA8	relocalization
STUB1	“down-regulates quantity by destabilization”	HSPA8	polyubiquitination
BAG1	“down-regulates quantity by destabilization”	HSPA8	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 229 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
Signaling by RAS mutants	5	13.3×	3e-03
Attenuation phase	5	12.8×	3e-03
Signaling by high-kinase activity BRAF mutants	6	12.0×	3e-03
HSF1 activation	5	12.0×	3e-03
MAP2K and MAPK activation	6	10.8×	3e-03
Signaling by RAF1 mutants	6	10.5×	3e-03
HSF1-dependent transactivation	5	10.0×	7e-03
Signaling by moderate kinase activity BRAF mutants	6	9.6×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of protein ubiquitination	5	21.9×	2e-03
intrinsic apoptotic signaling pathway	6	10.7×	5e-03
cellular response to heat	6	10.2×	6e-03
response to unfolded protein	6	8.9×	8e-03
G1/S transition of mitotic cell cycle	8	8.0×	3e-03
protein folding	14	7.2×	2e-05
negative regulation of apoptotic process	19	3.3×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	1
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

834 predictions. Top by Δscore:

Variant	Effect	Δscore
11:123057915:GCAGT:G	acceptor_gain	1.0000
11:123057916:CAGT:C	acceptor_gain	1.0000
11:123057916:CAGTC:C	acceptor_gain	1.0000
11:123057917:AGT:A	acceptor_gain	1.0000
11:123057918:GT:G	acceptor_gain	1.0000
11:123057919:TCTGA:T	acceptor_loss	1.0000
11:123057920:C:CC	acceptor_gain	1.0000
11:123057920:CTG:C	acceptor_loss	1.0000
11:123058249:AACCT:A	donor_loss	1.0000
11:123058250:ACCTG:A	donor_loss	1.0000
11:123058251:C:G	donor_loss	1.0000
11:123058262:T:C	donor_gain	1.0000
11:123058286:CA:C	donor_gain	1.0000
11:123058480:ACGGC:A	acceptor_gain	1.0000
11:123058481:CGGC:C	acceptor_gain	1.0000
11:123058481:CGGCC:C	acceptor_gain	1.0000
11:123058482:GGC:G	acceptor_gain	1.0000
11:123058483:GC:G	acceptor_gain	1.0000
11:123058484:CC:C	acceptor_gain	1.0000
11:123058484:CCTA:C	acceptor_loss	1.0000
11:123058485:C:CC	acceptor_gain	1.0000
11:123058485:CTAGG:C	acceptor_loss	1.0000
11:123058486:T:C	acceptor_loss	1.0000
11:123058630:AC:A	donor_gain	1.0000
11:123058631:CC:C	donor_gain	1.0000
11:123058830:CC:C	acceptor_loss	1.0000
11:123058830:CCT:C	acceptor_gain	1.0000
11:123058831:C:CC	acceptor_gain	1.0000
11:123058832:T:C	acceptor_gain	1.0000
11:123058832:T:TC	acceptor_gain	1.0000

AlphaMissense

4270 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:123057879:A:G	L599P	1.000
11:123058265:A:G	L581P	1.000
11:123058370:G:T	A546D	1.000
11:123058382:A:G	L542P	1.000
11:123058422:C:G	D529H	1.000
11:123058443:C:G	A522P	1.000
11:123058646:A:T	I503N	1.000
11:123058685:G:T	A490D	1.000
11:123058691:A:T	V488D	1.000
11:123058703:C:T	G484D	1.000
11:123058704:C:G	G484R	1.000
11:123058745:C:T	G470D	1.000
11:123058746:C:G	G470R	1.000
11:123058772:A:G	L461P	1.000
11:123058814:C:G	R447P	1.000
11:123058820:C:A	G445V	1.000
11:123058820:C:T	G445D	1.000
11:123058821:C:G	G445R	1.000
11:123059098:G:C	F428L	1.000
11:123059098:G:T	F428L	1.000
11:123059099:A:G	F428S	1.000
11:123059100:A:G	F428L	1.000
11:123059120:G:T	P421H	1.000
11:123059177:C:A	G402V	1.000
11:123059177:C:T	G402D	1.000
11:123059178:C:G	G402R	1.000
11:123059186:A:G	L399P	1.000
11:123059198:T:A	D395V	1.000
11:123059199:C:G	D395H	1.000
11:123059204:A:G	L393P	1.000

dbSNP variants (sampled 300 via entrez): RS1000333769 (11:123059644 C>T), RS1000893027 (11:123062137 A>C,G), RS1000900919 (11:123064291 T>C), RS1001112689 (11:123058554 G>A,C,T), RS1001113413 (11:123061368 T>C), RS1001617610 (11:123062527 G>A,C), RS1002008807 (11:123063274 T>A,C), RS1002068462 (11:123062646 G>A), RS1002888953 (11:123061053 G>A), RS1002909624 (11:123057432 C>T), RS1003257093 (11:123059809 G>A), RS1003446976 (11:123064354 A>G), RS1004903529 (11:123062680 G>A), RS1005343071 (11:123057659 C>A,T), RS1005371957 (11:123062048 TGAGCA>T)

Disease associations

OMIM: gene MIM:600816 | disease phenotypes: MIM:606369

GenCC curated gene-disease

Mondo (1): Lennox-Gastaut syndrome (MONDO:0016532)

Orphanet (1): Lennox-Gastaut syndrome (Orphanet:2382)

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST005992_33	Mean corpuscular hemoglobin concentration	5.000000e-23
GCST007979_4	Postoperative acute renal failure after cardiac surgery	9.000000e-06
GCST012020_171	Serum metabolite levels	2.000000e-11
GCST012021_52	Serum metabolite levels	2.000000e-11
GCST90002390_43	Mean corpuscular hemoglobin	5.000000e-21
GCST90002391_204	Mean corpuscular hemoglobin concentration	1.000000e-16
GCST90002404_129	Red cell distribution width	5.000000e-31

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0009951	response to surgery
EFO:0009955	post-operative acute kidney injury
EFO:0004527	mean corpuscular hemoglobin
EFO:0009188	Red cell distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065768	Lennox Gastaut Syndrome	C10.228.140.490.493.750; C16.320.495

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1275223 (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)

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — Heat shock proteins

Binding affinities (BindingDB)

19 measured of 40 human assays (53 total across all organisms); most potent 19 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
HEXACHLOROPHENE	IC50	98.3 nM
(ADP)[5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl trihydrogen diphosphate	IC50	280 nM
3-(3,4,5-trihydroxy-6-keto-xanthen-9-yl)propionic acid	IC50	578 nM
7-methyl-2-(3,4,5-trihydroxy-6-keto-xanthen-9-yl)bicyclo[2.2.1]hept-5-ene-3-carboxylic acid	IC50	634 nM
ATP(4-)	IC50	3370 nM
(4-methoxy-1,3-benzothiazol-2-yl)-[5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl]amine	IC50	5160 nM
MLS000521411	IC50	6900 nM
1-Cyclopropyl-3-(2,3-di-furan-2-yl-quinoxalin-6-yl)-urea	EC50	9260 nM
2-(3,4,5-trihydroxy-6-oxo-6H-xanthen-9-yl)cyclohexanecarboxylic acid	IC50	9850 nM
(5Z)-5-(5-bromo-2-methoxybenzylidene)-2-(2-furyl)[1,3]thiazolo[3,2-b][1,2,4]triazol-6(5H)-one	IC50	12800 nM
8-carbethoxy-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-4-carboxylic acid	IC50	15800 nM
(9Z)-9-(3,3-dihydroxyprop-2-enylidene)-5,6-dihydroxy-xanthene-3,4-quinone	IC50	15800 nM
3-[(4Z)-4-[(E)-3-(2-furanyl)prop-2-enylidene]-3-methyl-5-oxo-1-pyrazolyl]benzoic acid	IC50	17400 nM
6-methyl-8-nitro-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-4-carboxylic acid	IC50	24300 nM
MLS000050353	EC50	33300 nM
6,7-dimethyl-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-4-carboxylic acid	IC50	40400 nM
6-iodanyl-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-4-carboxylic acid	IC50	47800 nM
3-(2,5-dimethyl-1-pyrrolyl)benzoic acid	EC50	49500 nM
2-[4-[3,9-bis(oxidanylidene)-2-(oxolan-2-ylmethyl)-1H-chromeno[2,3-c]pyrrol-1-yl]phenoxy]ethanamide	IC50	50000 nM

ChEMBL bioactivities

52 potent at pChembl≥5 of 82 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.25	Kd	56	nM	MOLIBRESIB
6.95	Kd	111.1	nM	CHEMBL3752910
6.92	ED50	121.1	nM	CHEMBL3752910
6.89	IC50	130	nM	MOLIBRESIB
6.58	Kd	260	nM	ADENOSINE DIPHOSPHATE
6.55	Kd	281.8	nM	CHEMBL3427682
6.55	Kd	280	nM	CHEMBL3427682
6.55	IC50	280	nM	ADENOSINE DIPHOSPHATE
6.53	Kd	295.1	nM	CHEMBL3427679
6.52	Kd	300	nM	CHEMBL3427679
6.50	Kd	320	nM	ADENOSINE DIPHOSPHATE
6.49	Kd	323.6	nM	ADENOSINE DIPHOSPHATE
6.40	Kd	400	nM	CHEMBL3091929
6.34	Kd	457.1	nM	CHEMBL3822603
6.34	Kd	460	nM	CHEMBL3822603
6.20	Kd	625	nM	CHEMBL5639838
6.18	Kd	660	nM	CHEMBL4168736
6.14	Kd	724.4	nM	CHEMBL515570
6.14	Kd	720	nM	CHEMBL515570
6.05	Kd	900	nM	CHEMBL3091928
6.00	Kd	1000	nM	CHEMBL3091931
5.85	Kd	1400	nM	CHEMBL473365
5.84	Kd	1445	nM	CHEMBL473365
5.82	Kd	1500	nM	CHEMBL3091944
5.79	Kd	1613	nM	CHEMBL5653589
5.77	Kd	1700	nM	CHEMBL3091926
5.75	ED50	1759	nM	CHEMBL5653589
5.72	Kd	1900	nM	CHEMBL3091726
5.70	Kd	2000	nM	CHEMBL3091941
5.64	Kd	2300	nM	CHEMBL3091943
5.62	Kd	2400	nM	CHEMBL3091725
5.62	Kd	2380	nM	CHEMBL4168736
5.58	Kd	2600	nM	CHEMBL3091927
5.56	Kd	2754	nM	CHEMBL3822829
5.56	IC50	2730	nM	CHEMBL502775
5.55	Kd	2800	nM	CHEMBL3822829
5.49	Kd	3236	nM	SANGIVAMYCIN
5.48	Kd	3300	nM	CHEMBL3823700
5.48	Kd	3300	nM	SANGIVAMYCIN
5.47	Kd	3388	nM	CHEMBL3823700
5.46	Kd	3500	nM	CHEMBL516357
5.45	Kd	3548	nM	CHEMBL516357
5.40	Kd	4000	nM	CHEMBL3091728
5.40	IC50	3980	nM	CHEMBL1481974
5.27	Kd	5400	nM	CHEMBL3091930
5.26	Kd	5540	nM	CHEMBL4168736
5.25	IC50	5580	nM	CHEMBL471004
5.16	Kd	6918	nM	CHEMBL516197
5.16	Kd	7000	nM	CHEMBL516197
5.11	Kd	7700	nM	CHEMBL3091727

PubChem BioAssay actives

46 with measured affinity, of 152 total; 30 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179134: Binding affinity against HSPA8 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0560	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148555: Binding affinity to human HSPA8 incubated for 45 mins by Kinobead based pull down assay	kd	0.1111	uM
[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate	527455: Binding affinity to human Hsc70 by isothermal calorimetry assay	kd	0.2600	uM
(2R,3R,4S,5R)-2-[6-amino-8-[(4-chlorophenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1310291: Binding affinity to human truncated HSC70 NBD (1 to 381 residues) by SPR analysis	kd	0.2800	uM
(2R,3R,4S,5R)-2-[6-amino-8-[(4-methylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1310291: Binding affinity to human truncated HSC70 NBD (1 to 381 residues) by SPR analysis	kd	0.2951	uM
5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[6-[2-[(Z)-[(5E)-5-[5-(1,1-difluoroethyl)-3-methyl-1,3-benzothiazol-2-ylidene]-3-ethyl-4-oxo-1,3-thiazolidin-2-ylidene]methyl]pyridin-1-ium-1-yl]hexyl]pentanamide chloride	1056234: Binding affinity to human HSC70 after 3 hrs by ELISA	kd	0.4000	uM
(2R,3R,4S,5R)-2-[6-amino-8-[(4-fluorophenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1310291: Binding affinity to human truncated HSC70 NBD (1 to 381 residues) by SPR analysis	kd	0.4571	uM
177372351	2141349: Binding affinity to human recombinant full length HSPA8 (42 to 401 residues) expressed in Escherichia coli BL21 (DE3) cells assessed as dissociation constant	kd	0.6250	uM
(2Z,5E)-5-(6-bromo-3-methyl-1,3-benzothiazol-2-ylidene)-3-ethyl-2-[[3-[[5-(trifluoromethyl)furan-2-yl]methyl]-1,3-thiazol-3-ium-2-yl]methylidene]-1,3-thiazolidin-4-one chloride	1505723: Binding affinity to human HSC70 after 2 hrs by fluorescence shift assay	kd	0.6600	uM
(2R,3R,4S,5R)-2-[6-amino-8-(quinolin-6-ylmethylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1310291: Binding affinity to human truncated HSC70 NBD (1 to 381 residues) by SPR analysis	kd	0.7200	uM
5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[6-[2-[(Z)-[(5E)-3-ethyl-5-(5-methoxy-3-methyl-1,3-benzothiazol-2-ylidene)-4-oxo-1,3-thiazolidin-2-ylidene]methyl]pyridin-1-ium-1-yl]hexyl]pentanamide chloride	1056234: Binding affinity to human HSC70 after 3 hrs by ELISA	kd	0.9000	uM
5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[6-[2-[(Z)-[(5E)-3-ethyl-5-[3-methyl-6-(trifluoromethyl)-1,3-benzothiazol-2-ylidene]-4-oxo-1,3-thiazolidin-2-ylidene]methyl]pyridin-1-ium-1-yl]hexyl]pentanamide chloride	1056234: Binding affinity to human HSC70 after 3 hrs by ELISA	kd	1.0000	uM
(2R,3R,4S,5R)-2-[6-amino-8-(benzylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1310291: Binding affinity to human truncated HSC70 NBD (1 to 381 residues) by SPR analysis	kd	1.4000	uM
5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[6-[2-[(Z)-[(5E)-3-ethyl-5-(6-fluoro-3-methyl-1,3-benzothiazol-2-ylidene)-4-oxo-1,3-thiazolidin-2-ylidene]methyl]pyridin-1-ium-1-yl]hexyl]pentanamide chloride	1056234: Binding affinity to human HSC70 after 3 hrs by ELISA	kd	1.5000	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148555: Binding affinity to human HSPA8 incubated for 45 mins by Kinobead based pull down assay	kd	1.6133	uM
5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[6-[2-[(Z)-[(5E)-5-(6-chloro-3-methyl-1,3-benzothiazol-2-ylidene)-3-ethyl-4-oxo-1,3-thiazolidin-2-ylidene]methyl]pyridin-1-ium-1-yl]hexyl]pentanamide chloride	1056234: Binding affinity to human HSC70 after 3 hrs by ELISA	kd	1.7000	uM
5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[6-[2-[(Z)-[(5E)-3-ethyl-5-(7-fluoro-3-methyl-1,3-benzothiazol-2-ylidene)-4-oxo-1,3-thiazolidin-2-ylidene]methyl]pyridin-1-ium-1-yl]hexyl]pentanamide chloride	1056234: Binding affinity to human HSC70 after 3 hrs by ELISA	kd	1.9000	uM
5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[6-[2-[(Z)-[(5E)-3-ethyl-5-(3-methyl-1,3-benzothiazol-2-ylidene)-4-oxo-1,3-thiazolidin-2-ylidene]methyl]pyridin-1-ium-1-yl]hexyl]pentanamide chloride	1056234: Binding affinity to human HSC70 after 3 hrs by ELISA	kd	2.0000	uM
5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[6-[2-[(Z)-[(5E)-3-ethyl-5-(5-fluoro-3-methyl-1,3-benzothiazol-2-ylidene)-4-oxo-1,3-thiazolidin-2-ylidene]methyl]pyridin-1-ium-1-yl]hexyl]pentanamide chloride	1056234: Binding affinity to human HSC70 after 3 hrs by ELISA	kd	2.3000	uM
5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[[4-[[2-[(Z)-[(5E)-3-ethyl-5-(4-fluoro-3-methyl-1,3-benzothiazol-2-ylidene)-4-oxo-1,3-thiazolidin-2-ylidene]methyl]-1,3-thiazol-3-ium-3-yl]methyl]phenyl]methyl]pentanamide chloride	1056234: Binding affinity to human HSC70 after 3 hrs by ELISA	kd	2.4000	uM
5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[6-[2-[(Z)-[(5E)-5-(7-chloro-3-methyl-1,3-benzothiazol-2-ylidene)-3-ethyl-4-oxo-1,3-thiazolidin-2-ylidene]methyl]pyridin-1-ium-1-yl]hexyl]pentanamide chloride	1056234: Binding affinity to human HSC70 after 3 hrs by ELISA	kd	2.6000	uM
4-amino-6-(benzylamino)-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrrolo[2,3-d]pyrimidine-5-carbonitrile	1310291: Binding affinity to human truncated HSC70 NBD (1 to 381 residues) by SPR analysis	kd	2.7542	uM
4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrrolo[2,3-d]pyrimidine-5-carboxamide	1310291: Binding affinity to human truncated HSC70 NBD (1 to 381 residues) by SPR analysis	kd	3.2359	uM
4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-(methylamino)pyrrolo[2,3-d]pyrimidine-5-carbonitrile	1310291: Binding affinity to human truncated HSC70 NBD (1 to 381 residues) by SPR analysis	kd	3.3000	uM
(2R,3R,4S,5R)-2-[6-amino-8-[(3,4-dichlorophenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1310291: Binding affinity to human truncated HSC70 NBD (1 to 381 residues) by SPR analysis	kd	3.5000	uM
5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[6-[2-[(Z)-[(5E)-5-(5-chloro-3-methyl-1,3-benzothiazol-2-ylidene)-3-ethyl-4-oxo-1,3-thiazolidin-2-ylidene]methyl]pyridin-1-ium-1-yl]hexyl]pentanamide chloride	1056234: Binding affinity to human HSC70 after 3 hrs by ELISA	kd	4.0000	uM
5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[6-[2-[(Z)-[(5E)-3-ethyl-5-(6-methoxy-3-methyl-1,3-benzothiazol-2-ylidene)-4-oxo-1,3-thiazolidin-2-ylidene]methyl]pyridin-1-ium-1-yl]hexyl]pentanamide chloride	1056234: Binding affinity to human HSC70 after 3 hrs by ELISA	kd	5.4000	uM
(2R,3R,4S,5R)-2-(6,8-diaminopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol	1310291: Binding affinity to human truncated HSC70 NBD (1 to 381 residues) by SPR analysis	kd	6.9183	uM
5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[6-[2-[(Z)-[(5E)-5-(4-chloro-3-methyl-1,3-benzothiazol-2-ylidene)-3-ethyl-4-oxo-1,3-thiazolidin-2-ylidene]methyl]pyridin-1-ium-1-yl]hexyl]pentanamide chloride	1056234: Binding affinity to human HSC70 after 3 hrs by ELISA	kd	7.7000	uM
N-[(2S,3R)-1-[(4,5-dimethyl-1,3-thiazol-2-yl)amino]-3-methyl-1-oxopentan-2-yl]-1H-indole-2-carboxamide	1968964: Inhibition of HspA8 (unknown origin) by FP assay	ic50	9.8000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, increases secretion, affects expression	7
bisphenol A	affects expression, decreases expression, increases expression	6
Tobacco Smoke Pollution	increases metabolic processing, affects expression, decreases expression, increases expression	6
Particulate Matter	increases reaction, increases abundance, increases expression, affects cotreatment, decreases expression (+1 more)	6
Cadmium	increases secretion, increases abundance, increases expression	5
Copper	affects binding, decreases expression, increases expression	5
Cadmium Chloride	affects expression, increases abundance, increases expression, increases secretion	5
Cisplatin	affects cotreatment, increases expression, decreases expression, increases secretion	4
Estradiol	affects expression, increases expression	4
Vehicle Emissions	increases abundance, increases expression, affects expression, increases reaction	3
Benzo(a)pyrene	decreases reaction, increases expression, increases reaction, affects reaction	3
Rotenone	affects expression, decreases expression	3
arsenite	affects binding, increases reaction, increases oxidation	2
nickel chloride	decreases expression, increases expression	2
nickel acetate	increases expression, affects expression	2
Decitabine	increases expression, affects methylation	2
Acetaminophen	decreases expression, increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases expression	2
Cannabidiol	affects cotreatment, decreases expression, increases expression	2
Dinitrochlorobenzene	affects binding, increases metabolic processing	2
Doxorubicin	affects cotreatment, increases expression	2
Ibuprofen	affects localization	2
Indomethacin	affects localization	2
Ivermectin	affects cotreatment, increases expression, decreases expression	2
Silver	increases expression	2
Dronabinol	decreases expression	2
Valproic Acid	affects cotreatment, increases expression	2
Cyclosporine	increases expression, increases secretion	2
Copper Sulfate	affects expression, decreases expression, increases expression	2
spautin-1	affects cotreatment, affects localization, increases transport	1

ChEMBL screening assays

44 unique, capped per target: 44 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1176173	Binding	Binding affinity to HSC70 EEVD domain by mass spectroscopy	Heat shock protein 70 (hsp70) as an emerging drug target. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1TZ	Abcam HeLa HSPA8 KO	Cancer cell line	Female
CVCL_E0EH	Ubigene HeLa HSPA8 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01370486	PHASE4	WITHDRAWN	Melatonin Versus Placebo in the Lennox-Gastaut Syndrome: Neurophysiological and Neuropsychological Effects
NCT02731300	PHASE4	COMPLETED	Transcranial Direct Current Stimulation, Treatment of Childhood Drug-Resistant Lennox-Gastaut Syndrome, A Pilot Study
NCT04133480	PHASE4	WITHDRAWN	Investigation of Cognitive Outcomes With Cannabidiol Oral Solution
NCT05044819	PHASE4	ACTIVE_NOT_RECRUITING	Assessment of Potential for Chronic Liver Injury in Participants Treated With Epidiolex (Cannabidiol) Oral Solution
NCT06924827	PHASE4	NOT_YET_RECRUITING	A Study to Investigate the Transition of Children From ‘Artisanal Cannabidiol (CBD) to Epidiolex
NCT00004776	PHASE3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Oral Topiramate for Lennox-Gastaut Syndrome
NCT01146951	PHASE3	COMPLETED	A Placebo-Controlled, Double-Blind Comparative Study of E2080 in Lennox-Gastaut Syndrome Patients (Study E2080-J081-304)
NCT01151540	PHASE3	COMPLETED	A Long Term Extension Study of E2080 in Lennox-Gastaut Patients
NCT01160770	PHASE3	COMPLETED	Safety and Effectiveness of Open-Label Clobazam in Subjects With Lennox-Gastaut Syndrome
NCT01405053	PHASE3	COMPLETED	Study of Rufinamide in Pediatric Subjects 1 to Less Than 4 Years of Age With Lennox-Gastaut Syndrome Inadequately Controlled With Other Anti-epileptic Drugs
NCT02224560	PHASE3	COMPLETED	Efficacy and Safety of GWP42003-P for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults
NCT02224573	PHASE3	COMPLETED	An Open Label Extension Study of Cannabidiol (GWP42003-P) in Children and Adults With Dravet or Lennox-Gastaut Syndromes
NCT02224690	PHASE3	COMPLETED	A Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P; CBD) as Adjunctive Treatment for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults
NCT02318537	PHASE3	WITHDRAWN	Cannabidiol Oral Solution as an Adjunctive Therapy for Treatment of Participants With Inadequately Controlled Lennox-Gastaut Syndrome
NCT02834793	PHASE3	TERMINATED	Study of Perampanel as Adjunctive Treatment for Inadequately Controlled Seizures Associated With Lennox-Gastaut Syndrome
NCT03355209	PHASE3	COMPLETED	A Study to Investigate the Efficacy and Safety of ZX008 (Fenfluramine Hydrochloride) as an Adjunctive Therapy in Children and Adults With Lennox-Gastaut Syndrome
NCT03936777	PHASE3	COMPLETED	A Study to Investigate the Long-Term Safety of ZX008 (Fenfluramine Hydrochloride) Oral Solution in Children and Adults With Epileptic Encephalopathy Including Dravet Syndrome and Lennox-Gastaut Syndrome
NCT04611438	PHASE3	UNKNOWN	Research on Cognitive Effect of Cannabidiol on Dravet Syndrome and Lennox-Gastaut SyndromeGastaut Syndrome
NCT04938427	PHASE3	COMPLETED	A Study of Soticlestat as an Add-on Therapy in Children, Teenagers, and Adults With Lennox-Gastaut Syndrome
NCT05066217	PHASE3	RECRUITING	An Efficacy and Safety Study of Clemizole HCl in Patients With Lennox-Gastaut Syndrome
NCT05163314	PHASE3	TERMINATED	A Study of Soticlestat as an Add-on Therapy in Children and Adults With Dravet Syndrome or Lennox-Gastaut Syndrome
NCT05219617	PHASE3	RECRUITING	Investigate Efficacy and Safety of Carisbamate as Adjunctive Treatment for Seizures Associated With LGS in Children and Adults
NCT06422377	PHASE3	TERMINATED	A Study Evaluating Soticlestat in Participants With Dravet Syndrome or Lennox-Gastaut Syndrome Who Have Been Exposed to Fenfluramine
NCT02655198	PHASE2	UNKNOWN	Add-on Therapy With Low Dose Fenfluramine in Lennox Gastaut Epilepsy
NCT03635073	PHASE2	TERMINATED	A Study of Soticlestat in Adults and Children With Rare Epilepsies
NCT03650452	PHASE2	COMPLETED	A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of TAK-935 (OV935) as an Adjunctive Therapy in Pediatric Participants With Developmental and/or Epileptic Encephalopathies
NCT05339126	PHASE2	ACTIVE_NOT_RECRUITING	RNS System LGS Feasibility Study
NCT05626634	PHASE2	COMPLETED	Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy
NCT06401538	PHASE2	RECRUITING	BMB-101 in Absence Epilepsy and DEE
NCT03467113	PHASE1	COMPLETED	A Study to Assess the Safety and Tolerability of ZX008 in Children and Young Adults With Dravet Syndrome or Lennox Gastaut Syndrome Currently Taking Cannabidiol
NCT03731715	PHASE1	COMPLETED	Carisbamate in Adult & Pediatric Subjects With Lennox-Gastaut Syndrome
NCT04062981	PHASE1	COMPLETED	Carisbamate Safety Study in Adult and Pediatric Subjects With Lennox-Gastaut Syndrome
NCT02815540	PHASE1/PHASE2	TERMINATED	The Effects of Cannabidiol (CBD) on Electrical and Autonomic Cardiac Function in Children With Severe Epilepsy
NCT05364021	PHASE1/PHASE2	COMPLETED	Study to Investigate LP352 in Subjects With Developmental and Epileptic Encephalopathies
NCT06738732	PHASE1/PHASE2	NOT_YET_RECRUITING	CBD Delivery with the A-Synaptic GT4 Transdermal Delivery System in with Dravet Syndrome And/or Lennox-Gastaut Syndrome
NCT02632149	EARLY_PHASE1	UNKNOWN	Trial to Assess Vagus Nerve Stimulation Therapy in Children With Lennox-Gastaut Syndrome
NCT00004729	Not specified	COMPLETED	Ketogenic Diet for Child Epilepsy and Seizure Control
NCT00552045	Not specified	COMPLETED	Epilepsy Phenome/Genome Project
NCT01991041	Not specified	COMPLETED	European Registry of Anti-Epileptic Drug Use in Patients With Lennox-Gastaut Syndrome (LGS)
NCT02175173	Not specified	COMPLETED	Post-marketing Surveillance of Long-term Administration of Inovelon Tablets in Patients With Lennox-Gastaut Syndrome