HSPA9

Summary

HSPA9 (heat shock protein family A (Hsp70) member 9, HGNC:5244) is a protein-coding gene on chromosome 5q31.2, encoding Stress-70 protein, mitochondrial (P38646). Mitochondrial chaperone that plays a key role in mitochondrial protein import, folding, and assembly. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

This gene encodes a member of the heat shock protein 70 gene family. The encoded protein is primarily localized to the mitochondria but is also found in the endoplasmic reticulum, plasma membrane and cytoplasmic vesicles. This protein is a heat-shock cognate protein. This protein plays a role in cell proliferation, stress response and maintenance of the mitochondria. A pseudogene of this gene is found on chromosome 2.

Source: NCBI Gene 3313 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal dominant sideroblastic anemia (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 129 total — 4 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 35
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_004134

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5244
Approved symbol	HSPA9
Name	heat shock protein family A (Hsp70) member 9
Location	5q31.2
Locus type	gene with protein product
Status	Approved
Aliases	GRP75, PBP74, mot-2, mthsp75
Ensembl gene	ENSG00000113013
Ensembl biotype	protein_coding
OMIM	600548
Entrez	3313

Gene structure

Transcript identifiers

Ensembl transcripts: 42 — 27 protein_coding, 8 nonsense_mediated_decay, 5 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000297185, ENST00000501917, ENST00000504902, ENST00000506477, ENST00000507097, ENST00000507115, ENST00000508003, ENST00000512328, ENST00000524109, ENST00000649578, ENST00000649692, ENST00000677064, ENST00000677066, ENST00000677425, ENST00000677527, ENST00000677553, ENST00000677693, ENST00000677988, ENST00000678051, ENST00000678300, ENST00000678384, ENST00000678551, ENST00000678794, ENST00000852878, ENST00000852879, ENST00000852880, ENST00000852881, ENST00000936335, ENST00000936337, ENST00000936338, ENST00000936339, ENST00000936340, ENST00000936341, ENST00000936342, ENST00000936343, ENST00000946842, ENST00000946843, ENST00000946844, ENST00000946845, ENST00000946846, ENST00000946847, ENST00000946848

RefSeq mRNA: 1 — MANE Select: NM_004134 NM_004134

CCDS: CCDS4208

Canonical transcript exons

ENST00000297185 — 17 exons

Exon	Start	End
ENSE00001038903	138556774	138556866
ENSE00001038910	138557869	138557986
ENSE00001038912	138557402	138557496
ENSE00003511613	138567001	138567163
ENSE00003533812	138558553	138558657
ENSE00003543459	138561580	138561789
ENSE00003548889	138575238	138575401
ENSE00003566941	138566626	138566718
ENSE00003591635	138574068	138574126
ENSE00003600777	138559864	138560091
ENSE00003604231	138556452	138556592
ENSE00003644877	138567455	138567561
ENSE00003654800	138567649	138567722
ENSE00003662198	138570960	138571141
ENSE00003669683	138568925	138569049
ENSE00003684112	138573763	138573850
ENSE00003841044	138553756	138556114

Expression profiles

Bgee: expression breadth ubiquitous, 303 present calls, max score 99.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 167.4763 / max 1418.2269, expressed in 1828 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63713	153.1947	1828
63712	8.3295	1686
63711	3.5509	1342
63707	1.2278	635
63715	0.9985	396
63714	0.1749	66

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	99.48	gold quality
right adrenal gland	UBERON:0001233	99.25	gold quality
right adrenal gland cortex	UBERON:0035827	99.22	gold quality
left adrenal gland	UBERON:0001234	99.18	gold quality
adrenal gland	UBERON:0002369	99.14	gold quality
adrenal cortex	UBERON:0001235	99.08	gold quality
left adrenal gland cortex	UBERON:0035825	99.07	gold quality
colonic epithelium	UBERON:0000397	98.99	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.74	gold quality
ventricular zone	UBERON:0003053	98.73	gold quality
calcaneal tendon	UBERON:0003701	98.65	gold quality
gastrocnemius	UBERON:0001388	98.45	gold quality
islet of Langerhans	UBERON:0000006	98.29	gold quality
rectum	UBERON:0001052	98.24	gold quality
muscle of leg	UBERON:0001383	98.24	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.23	gold quality
right atrium auricular region	UBERON:0006631	98.19	gold quality
heart right ventricle	UBERON:0002080	98.18	gold quality
cardiac ventricle	UBERON:0002082	98.17	gold quality
heart left ventricle	UBERON:0002084	98.17	gold quality
prefrontal cortex	UBERON:0000451	98.10	gold quality
liver	UBERON:0002107	98.07	gold quality
body of tongue	UBERON:0011876	98.07	gold quality
cortical plate	UBERON:0005343	98.04	gold quality
apex of heart	UBERON:0002098	97.92	gold quality
medial globus pallidus	UBERON:0002477	97.92	gold quality
ganglionic eminence	UBERON:0004023	97.90	gold quality
body of stomach	UBERON:0001161	97.89	gold quality
substantia nigra pars compacta	UBERON:0001965	97.89	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.89	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-98556	yes	1870.07
E-GEOD-93593	yes	8.77
E-CURD-135	no	750.54
E-MTAB-7303	no	474.05
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, BARX2, CEBPB, HSF1, MYC, NFATC1, NFATC2, NFIC, NKRF, NR4A1, POU1F1, PPARG, SFPQ, TP53

miRNA regulators (miRDB)

80 targeting HSPA9, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-3934-3P	99.76	65.51	1351

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• Implication of PBP74/mortalin/GRP75 in the radio-adaptive response. (PMID:11869473)
• Cytoplasmic sequestration and inactivation of p53 by mot-2 occurs by its binding to the cytoplasmic sequestration domain;perturbation of mot-p53 interactions can be employed to abrogate cytoplasmic retention of wild-type p53 in tumors. (PMID:11900485)
• Results demonstrate that mot-2 and telomerase can cooperate in the immortalization process. (PMID:12729798)
• Unexpected extracellular location and characteristic biological function of Grp94 even at a late stage of type 1 diabetex. (PMID:12827241)
• Mortalin and HSP60 interact both in vivo and in vitro, and that the N-terminal region of mortalin is involved in these interactions. (PMID:15957980)
• attempted to disrupt mot-2-p53 interactions by overexpression of short p53 carboxyl-terminal peptides (PMID:16176931)
• Taken together, GRP78/75 and RHAMM complexes may stabilize microtubules in the interphase, associated with a downregulation of RHAMM. These results reveal a new biochemical activity of RHAMM. (PMID:16329989)
• Overexpression of mortalin was sufficient to increase the malignancy of breast carcinoma cells. This study demonstrates that upregulation of mortalin contributes significantly to tumorigenesis, and thus is a good candidate target for cancer therapy. (PMID:16425258)
• Findings not only identify mortalin as an upstream molecule of p53 but also provide evidence for the involvement of centrosomally localized p53 in the regulation of centrosome duplication. (PMID:16619038)
• We propose that the differential regulation of mortalin in AD and by the APOE genotype is a cellular defense mechanism responding to increases in oxidative stress. (PMID:17050040)
• review of mortalin involvement in cellular senescence from the perspective of its mitochondrial import, chaperone, and oxidative stress management functions [mortalin] (PMID:17460192)
• Mortalin binds to Mps1, and is phosphorylated by Mps1 on Thr62 and Ser65 (PMID:17573779)
• data suggest that mortalin is involved in the mediation of EPO signaling and plays an important role in stimulating the growth of erythroid progenitor cells (PMID:17635236)
• Mortalin (HSPA9) is associated with hepatocellular carcinoma metastasis and thus suggested as a tumor marker for predicting early recurrence. (PMID:17934217)
• mortalin, a mitochondrial protein, was decreased in the parkinson disease progression. (PMID:18219256)
• aptitude to impact on mitochondrial function and homeostasis; its interfacing energy metabolic functions with synaptic plasticity, and modulation of brain aging via the cellular senescence pathways (PMID:18770009)
• GRP75 has an essential role in the differentiation of neuroblastoma (PMID:18829503)
• cloned a splice variant of mortalin with a novel catecholamine binding function and that this chaperone-like protein may be neuroprotective in dopamine-related central nervous system disorders (PMID:19280369)
• Our study suggests that putative mutations in the mortalin, although rare, could contribute to the risk of developing Parkinson’s disease (PMID:19657588)
• Data show that mortalin supports cancer cell resistance to complement-dependent cytotoxicity and suggest consideration of mortalin as a novel target for cancer adjuvant immunotherapy. (PMID:19739077)
• Data show that Hsp70- and CHIP-dependent ubiquitination represents a molecular mechanism by which prolonged hypoxia selectively reduces the levels of HIF-1alpha but not HIF-2alpha protein. (PMID:19940151)
• Thus, the data suggest that human CRP40/mortalin is modulated by dopaminergic activity and may act to protect neurons from excess catecholamine activity in regions of the brain associated with psychosis. (PMID:20100649)
• Single turnover kinetic experiments of mortalin were performed and compared with another Hsp70 chaperone, Thermotogamaritima DnaK; with each exhibiting slow ATP turnover rates. (PMID:20152901)
• An additional previously unknown binding site for mortalin exists within the C-terminal domain of p53. (PMID:20153329)
• mot-2-Mediated cross talk between nuclear factor-B and p53 is involved in arsenite-induced tumorigenesis of human embryo lung fibroblast cells. (PMID:20199942)
• analysis of the functional interplay between mammalian mitochondrial Hsp70 chaperone machine components (PMID:20392697)
• Our genetic and functional studies of novel disease-associated variants in the mortalin gene define a loss of mortalin function, which causes impaired mitochondrial function and dynamics (PMID:20817635)
• Data show that mortalin can afford protection against Abeta(1-42)-induced neurotoxicity in SH-SY5Y cells. (PMID:20974113)
• the activating mechanism of mitochondrial outer membrane-bound m-calpain and the release of mitochondrial m-calpain (PMID:21145877)
• Targeting mortalin-p53 interaction with either mortalin small hairpin RNA or a chemical or peptide inhibitor could induce p53-mediated tumor cell-specific apoptosis in hepatocellular carcinoma; p53-null hepatoma or normal hepatocytes remain unaffected. (PMID:21233847)
• Cisplatin resistance of lung cancer cells is associated with overexpression of GRP75 gene (PMID:21496427)
• These findings implicate a conserved histidine as critical for DNLZ regulation of mitochondrial HSPA9 catalytic activity. (PMID:21530495)
• the relatively decreased mortalin expression level and its impaired interaction with Parkin could affect its roles in mitochondrial function. (PMID:21640711)
• Mortalin is up-regulated in liver tumors. (PMID:21714113)
• HSP70 as a critical regulator of ARF-mediated autophagy, and reinforce the importance of mitochondrial trafficking of ARF for its autophagy function (PMID:21738007)
• Cytoprotective efficacy of mortalin under Abeta-induced stress in SH-SY5Y cells is mediated, at least in part, by inhibition of mPTP opening. (PMID:22001761)
• Nef’s interaction with cellular mortalin is required for Nef secretion. (PMID:22013042)
• The present study further demonstrated that GRP75 translocates into the nucleus and physically interacts with retinoid receptors (RARalpha and RXRalpha) to augment retinoic acid-elicited neuronal differentiation. (PMID:22022577)
• DNLZ/HEP zinc-binding subdomain is critical for regulation of the mitochondrial chaperone HSPA9. (PMID:22162012)
• these data reveal the characteristic cytoplasmic sequestration of p53 by the heat shock protein mortalin in human colorectal adenocarcinoma cell lines, as is the case for other cancers, such as glioblastomas and hepatocellular carcinomas. (PMID:22683628)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	hspa9	ENSDARG00000003035
mus_musculus	Hspa9	ENSMUSG00000024359
rattus_norvegicus	Hspa9	ENSRNOG00000019525
drosophila_melanogaster	Hsc70-5	FBGN0001220
caenorhabditis_elegans		WBGENE00002010

Paralogs (13): HSPA5 (ENSG00000044574), HSPA8 (ENSG00000109971), 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

Stress-70 protein, mitochondrial — P38646 (reviewed: P38646)

Alternative names: 75 kDa glucose-regulated protein, Heat shock 70 kDa protein 9, Heat shock protein family A member 9, Mortalin, Peptide-binding protein 74

All UniProt accessions (14): P38646, A0A384P5G6, A0A3B3ITI4, A0A7I2V2G2, A0A7I2V2K6, A0A7I2V2S7, A0A7I2V3D9, A0A7I2V3F7, A0A7I2V4A9, A0A7I2YQB2, A0A7I2YQQ5, D6RCD7, H0Y8K0, H0Y8S0

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial chaperone that plays a key role in mitochondrial protein import, folding, and assembly. Plays an essential role in the protein quality control system, the correct folding of proteins, the re-folding of misfolded proteins, and the targeting of proteins for subsequent degradation. These processes are achieved through cycles of ATP binding, ATP hydrolysis, and ADP release, mediated by co-chaperones. In mitochondria, it associates with the TIM (translocase of the inner membrane) protein complex to assist in the import and folding of mitochondrial proteins. Plays an important role in mitochondrial iron-sulfur cluster (ISC) biogenesis, interacts with and stabilizes ISC cluster assembly proteins FXN, NFU1, NFS1 and ISCU. Regulates erythropoiesis via stabilization of ISC assembly. Regulates mitochondrial calcium-dependent apoptosis by coupling two calcium channels, ITPR1 and VDAC1, at the mitochondria-associated endoplasmic reticulum (ER) membrane to facilitate calcium transport from the ER lumen to the mitochondria intermembrane space, providing calcium for the downstream calcium channel MCU, which releases it into the mitochondrial matrix. Although primarily located in the mitochondria, it is also found in other cellular compartments. In the cytosol, it associates with proteins involved in signaling, apoptosis, or senescence. It may play a role in cell cycle regulation via its interaction with and promotion of degradation of TP53. May play a role in the control of cell proliferation and cellular aging. Protects against reactive oxygen species (ROS). Extracellular HSPA9 plays a cytoprotective role by preventing cell lysis following immune attack by the membrane attack complex by disrupting formation of the complex.

Subunit / interactions. Interacts strongly with the intermediate form of FXN and weakly with its mature form. Interacts with HSCB. Associates with the mitochondrial contact site and cristae organizing system (MICOS) complex, composed of at least MICOS10/MIC10, CHCHD3/MIC19, CHCHD6/MIC25, APOOL/MIC27, IMMT/MIC60, APOO/MIC23/MIC26 and QIL1/MIC13. This complex was also known under the names MINOS or MitOS complex. The MICOS complex associates with mitochondrial outer membrane proteins SAMM50, MTX1, MTX2 and DNAJC11, mitochondrial inner membrane protein TMEM11 and with HSPA9. Interacts with DNLZ, the interaction is required to prevent self-aggregation. Interacts with TESPA1. Interacts with PDPN. Interacts with NFU1, NFS1 and ISCU. Interacts with TP53; the interaction promotes TP53 degradation. Interacts (via SBD domain) with UBXN2A; the interaction with UBXN2A inhibits HSPA9 interaction with and degradation of TP53, thereby promotes TP53 translocation to the nucleus. Interacts with ITPR1 AND VDAC1; this interaction couples ITPR1 to VDAC1. Component of the TIM23 mitochondrial inner membrane pre-sequence translocase complex.

Subcellular location. Mitochondrion. Nucleus. Nucleolus. Cytoplasm. Mitochondrion matrix.

Disease relevance. Anemia, sideroblastic, 4 (SIDBA4) [MIM:182170] A form of sideroblastic anemia, a bone marrow disorder defined by the presence of pathologic iron deposits in erythroblast mitochondria. Sideroblastic anemia is characterized by anemia of varying severity, hypochromic peripheral erythrocytes, systemic iron overload secondary to chronic ineffective erythropoiesis, and the presence of bone marrow ringed sideroblasts. Sideroblasts are characterized by iron-loaded mitochondria clustered around the nucleus. SIDBA4 has been reported to be inherited as an autosomal recessive disease, with a pseudodominant pattern of inheritance in some families. The disease is caused by variants affecting the gene represented in this entry. Even-plus syndrome (EVPLS) [MIM:616854] An autosomal recessive syndrome characterized by epiphyseal and vertebral dysplasia, prenatal-onset short stature, a distinct craniofacial phenotype with microtia, a flat facial profile with flat nose and triangular nares, cardiac malformations, and additional findings such as anal atresia, hypodontia, aplasia cutis, and others. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. The chaperone activity is regulated by ATP-induced allosteric coupling of the nucleotide-binding (NBD) and substrate-binding (SBD) domains. ATP binding in the NBD leads to a conformational change in the NBD, which is transferred through the interdomain linker (IDL) to the substrate-binding domain (SBD). This elicits a reduced substrate affinity and a faster substrate exchange rate. Upon hydrolysis of ATP to ADP, the protein undergoes a conformational change that increases its affinity for substrate proteins. It cycles through repeated phases of ATP hydrolysis and nucleotide exchange, facilitating repeated cycles of substrate binding and release. Functions in collaboration with co-chaperones. Functions with the co-chaperone, DNLZ, to maintain solubility and regulate ATP hydrolysis. Nucleotide exchange factors, GRPEL1 and GRPEL2, accelerate nucleotide exchange.

Domain organisation. The N-terminal nucleotide binding domain (NBD) is responsible for binding and hydrolyzing ATP. The C-terminal substrate-binding domain (SBD) 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.

Similarity. Belongs to the heat shock protein 70 family.

RefSeq proteins (1): NP_004125* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012725	Chaperone_DnaK	Family
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 3.6.4.10 — non-chaperonin molecular chaperone ATPase (BRENDA: 16 organisms, 6 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (121 total): strand 27, modified residue 26, helix 20, sequence variant 14, binding site 7, sequence conflict 7, turn 6, region of interest 6, mutagenesis site 5, transit peptide 1, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
6P2U	X-RAY DIFFRACTION	2
6PMT	X-RAY DIFFRACTION	2.3
6NHK	X-RAY DIFFRACTION	2.78
3N8E	X-RAY DIFFRACTION	2.8
4KBO	X-RAY DIFFRACTION	2.8
9BLS	ELECTRON MICROSCOPY	2.96
9BLT	ELECTRON MICROSCOPY	3.38
9BLU	ELECTRON MICROSCOPY	3.38

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P38646-F1	86.10	0.60

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 (7): 64; 313; 316; 320; 388; 391; 63

Post-translational modifications (26): 76, 87, 135, 135, 138, 138, 143, 206, 206, 206, 234, 288, 300, 300, 368, 394, 408, 513, 567, 567 …

Mutagenesis-validated functional residues (5):

Position	Phenotype
441	no effect on interaction with ubxn2a.
442	abolishes interaction with ubxn2a.
489	significant loss of interaction with fxn and iscu. significant increase in interaction with nfs1.
555	reduces interaction with ubxn2a.
558	abolishes interaction with ubxn2a.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-1268020	Mitochondrial protein import
R-HSA-3371453	Regulation of HSF1-mediated heat shock response
R-HSA-6799198	Complex I biogenesis
R-HSA-8949613	Cristae formation
R-HSA-8950505	Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
R-HSA-9837999	Mitochondrial protein degradation
R-HSA-9841251	Mitochondrial unfolded protein response (UPRmt)
R-HSA-9865881	Complex III assembly

MSigDB gene sets: 479 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, AP1_01, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, TSENG_IRS1_TARGETS_UP, GOBP_MYELOID_CELL_HOMEOSTASIS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, BASSO_B_LYMPHOCYTE_NETWORK, RORA1_01, GCANCTGNY_MYOD_Q6, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_NEGATIVE_REGULATION_OF_STEM_CELL_DIFFERENTIATION

GO Biological Process (14): protein export from nucleus (GO:0006611), intracellular protein transport (GO:0006886), inner mitochondrial membrane organization (GO:0007007), iron-sulfur cluster assembly (GO:0016226), erythrocyte differentiation (GO:0030218), calcium import into the mitochondrion (GO:0036444), protein refolding (GO:0042026), positive regulation of apoptotic process (GO:0043065), negative regulation of apoptotic process (GO:0043066), regulation of erythrocyte differentiation (GO:0045646), negative regulation of erythrocyte differentiation (GO:0045647), negative regulation of hematopoietic stem cell differentiation (GO:1902037), negative regulation of hemopoiesis (GO:1903707), protein folding (GO:0006457)

GO Molecular Function (12): RNA binding (GO:0003723), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), heat shock protein binding (GO:0031072), ubiquitin protein ligase binding (GO:0031625), protein folding chaperone (GO:0044183), 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), enzyme binding (GO:0019899)

GO Cellular Component (12): SAM complex (GO:0001401), nucleolus (GO:0005730), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), TIM23 mitochondrial import inner membrane translocase complex (GO:0005744), mitochondrial matrix (GO:0005759), focal adhesion (GO:0005925), mitochondrial nucleoid (GO:0042645), extracellular exosome (GO:0070062), MIB complex (GO:0140275), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Respiratory electron transport	2
Protein localization	1
Cellular response to heat stress	1
Mitochondrial biogenesis	1
Interleukin-12 signaling	1
Metabolism of proteins	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein folding	2
apoptotic process	2
regulation of apoptotic process	2
erythrocyte differentiation	2
ATP-dependent activity	2
protein binding	2
intracellular membraneless organelle	2
intracellular membrane-bounded organelle	2
inner mitochondrial membrane protein complex	2
mitochondrion	2
intracellular protein transport	1
nuclear export	1
intracellular protein localization	1
protein transport	1
intracellular transport	1
mitochondrial membrane organization	1
metallo-sulfur cluster assembly	1
myeloid cell differentiation	1
erythrocyte homeostasis	1
mitochondrial calcium ion transmembrane transport	1
intercellular transport	1
positive regulation of programmed cell death	1
negative regulation of programmed cell death	1
regulation of myeloid cell differentiation	1
negative regulation of myeloid cell differentiation	1
regulation of erythrocyte differentiation	1
hematopoietic stem cell differentiation	1
negative regulation of hematopoietic progenitor cell differentiation	1
regulation of hematopoietic stem cell differentiation	1
negative regulation of stem cell differentiation	1
negative regulation of immune system process	1
negative regulation of cell development	1
hemopoiesis	1
negative regulation of multicellular organismal process	1
regulation of hemopoiesis	1
cellular process	1
protein maturation	1
nucleic acid binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

489 interactions, top by confidence:

A	B	Type	Score
SDHB	SDHA	psi-mi:“MI:0914”(association)	0.820
HSCB	SDHB	psi-mi:“MI:0914”(association)	0.820
HSCB	SDHB	psi-mi:“MI:0915”(physical association)	0.820
SDHAF1	SDHB	psi-mi:“MI:0914”(association)	0.790
SDHB	SDHAF1	psi-mi:“MI:0914”(association)	0.790
HSCB	SDHAF1	psi-mi:“MI:0914”(association)	0.750
HSCB	HSPA9	psi-mi:“MI:0914”(association)	0.740
HSCB	HSPA9	psi-mi:“MI:0915”(physical association)	0.740
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
LYRM2	NDUFAB1	psi-mi:“MI:0914”(association)	0.730
TPT1	XRCC6	psi-mi:“MI:0914”(association)	0.710
HSCB	EPRS1	psi-mi:“MI:0914”(association)	0.670
GRPEL1	HSPA9	psi-mi:“MI:0915”(physical association)	0.670
COQ8A	COQ9	psi-mi:“MI:0914”(association)	0.670
SDHB	HSPA9	psi-mi:“MI:0914”(association)	0.660
HSPA9	SDHB	psi-mi:“MI:0915”(physical association)	0.660
SDHAF3	NDUFAB1	psi-mi:“MI:0914”(association)	0.640
TPT1	HSPA9	psi-mi:“MI:0915”(physical association)	0.570

BioGRID (935): HSPA9 (Affinity Capture-MS), HSPA9 (Affinity Capture-MS), CDKN2A (Affinity Capture-Western), HSPA9 (Affinity Capture-MS), HSPA9 (Affinity Capture-MS), YKT6 (Two-hybrid), HSPA9 (Affinity Capture-RNA), HSPA9 (Affinity Capture-RNA), HSPA9 (Affinity Capture-RNA), HSPA9 (Affinity Capture-RNA), HSPA9 (Affinity Capture-MS), HSPA9 (Affinity Capture-MS), HSPA9 (Affinity Capture-MS), HSPA9 (Affinity Capture-MS), HSPA9 (Affinity Capture-MS)

ESM2 similar proteins: A0A0D1CD96, G0SCU5, G3I8R9, G4NAY4, O24581, O35501, P07823, P11021, P16474, P19208, P20029, P20163, P22010, P24067, P27420, P29844, P29845, P36604, P38646, P38647, P48721, P49118, P59769, P78695, P83616, P83617, P86233, Q03684, Q03685, Q08276, Q0VCX2, Q16956, Q24798, Q24895, Q39043, Q3S4T7, Q42434, Q5R4P0, Q5R511, Q6BZH1

Diamond homologs: A0L4Z2, A1B4E9, A1K4C5, A1UUC3, A3PNM1, A4WW89, A5FZ19, A5V5P9, A6UEY0, A7HZ39, A7IC65, A8GMF9, A8GR22, A8IPT1, A9HEA3, A9ILH7, A9W6R7, B0BWH1, B0T138, B0UR84, B1LZ51, B1ZGR1, B2IBR4, B3CNB5, B3E7W9, B3PXH3, B3Q972, B5YH59, B5ZWQ2, B6IVA4, B6JCI3, B7KSZ4, B8EIP9, B8FGS3, B8IHL3, B9JZ87, C0QGP6, C0R3W7, C3PMM7, C4K110

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
TTK	up-regulates	HSPA9	phosphorylation
HSPA9	“up-regulates activity”	“iron-sulfur cluster”	relocalization
HSPA9	“down-regulates activity”	MVD	binding
HSPA9	“form complex”	“TIM23 complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 171 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
Maturation of TCA enzymes and regulation of TCA cycle	8	38.1×	8e-09
Citric acid cycle (TCA cycle)	8	28.2×	5e-08
Mitochondrial protein import	11	15.4×	3e-08
DNA Damage Recognition in GG-NER	5	11.9×	4e-03
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	6	9.7×	2e-03
Aerobic respiration and respiratory electron transport	13	9.6×	1e-07
Respiratory electron transport	12	9.5×	4e-07
Complex I biogenesis	6	8.3×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
ubiquinone biosynthetic process	6	38.5×	3e-06
protein neddylation	5	24.1×	4e-04
tricarboxylic acid cycle	5	17.5×	1e-03
intrinsic apoptotic signaling pathway	6	14.7×	6e-04
proton motive force-driven mitochondrial ATP synthesis	7	12.6×	4e-04
mitochondrial electron transport, NADH to ubiquinone	5	12.3×	5e-03
G1/S transition of mitotic cell cycle	7	9.6×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	2
Uncertain significance	75
Likely benign	22
Benign	5

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
224069	NM_004134.7(HSPA9):c.409_410del (p.Asp136_Ile137insTer)	Pathogenic
224328	NM_004134.7(HSPA9):c.376C>T (p.Arg126Trp)	Pathogenic
224329	NM_004134.7(HSPA9):c.383A>G (p.Tyr128Cys)	Pathogenic
870216	NM_004134.7(HSPA9):c.818T>G (p.Leu273Ter)	Pathogenic
1324551	NM_004134.7(HSPA9):c.1728+2T>G	Likely pathogenic
870215	NM_004134.7(HSPA9):c.955C>T (p.Leu319Phe)	Likely pathogenic

SpliceAI

1825 predictions. Top by Δscore:

Variant	Effect	Δscore
5:138556588:TTGCA:T	acceptor_gain	1.0000
5:138556589:TGCA:T	acceptor_gain	1.0000
5:138556590:GCA:G	acceptor_gain	1.0000
5:138556590:GCAC:G	acceptor_loss	1.0000
5:138556591:CA:C	acceptor_gain	1.0000
5:138556591:CAC:C	acceptor_gain	1.0000
5:138556594:T:TC	acceptor_gain	1.0000
5:138556769:CTCA:C	donor_loss	1.0000
5:138556770:TCACC:T	donor_loss	1.0000
5:138556771:CAC:C	donor_loss	1.0000
5:138556772:A:AC	donor_gain	1.0000
5:138556772:AC:A	donor_gain	1.0000
5:138556772:ACCT:A	donor_gain	1.0000
5:138556773:C:CC	donor_gain	1.0000
5:138556773:CC:C	donor_gain	1.0000
5:138556773:CCT:C	donor_gain	1.0000
5:138556773:CCTC:C	donor_gain	1.0000
5:138556773:CCTCA:C	donor_gain	1.0000
5:138556863:GTTC:G	acceptor_loss	1.0000
5:138556864:TTCC:T	acceptor_loss	1.0000
5:138556865:TCC:T	acceptor_loss	1.0000
5:138556866:CCT:C	acceptor_gain	1.0000
5:138556867:C:CC	acceptor_gain	1.0000
5:138556868:T:C	acceptor_gain	1.0000
5:138556868:T:TC	acceptor_gain	1.0000
5:138556877:T:C	acceptor_gain	1.0000
5:138556877:T:TC	acceptor_gain	1.0000
5:138557397:ATCAC:A	donor_loss	1.0000
5:138557398:TCACC:T	donor_loss	1.0000
5:138557399:CA:C	donor_loss	1.0000

AlphaMissense

4455 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:138556470:G:C	F648L	1.000
5:138556470:G:T	F648L	1.000
5:138556472:A:G	F648L	1.000
5:138556842:C:G	A585P	1.000
5:138557437:C:G	A565P	1.000
5:138557901:G:T	A534D	1.000
5:138557907:A:T	V532D	1.000
5:138557920:C:A	G528W	1.000
5:138557943:A:T	V520D	1.000
5:138558603:C:G	G489R	1.000
5:138558652:G:C	F472L	1.000
5:138558652:G:T	F472L	1.000
5:138558654:A:G	F472L	1.000
5:138559937:C:T	G446D	1.000
5:138559938:C:G	G446R	1.000
5:138559946:A:G	L443P	1.000
5:138559958:T:A	D439V	1.000
5:138559959:C:G	D439H	1.000
5:138559961:A:G	L438P	1.000
5:138559964:A:G	L437P	1.000
5:138559964:A:T	L437H	1.000
5:138559967:A:G	L436P	1.000
5:138560000:C:T	G425E	1.000
5:138560009:G:T	A422D	1.000
5:138560010:C:G	A422P	1.000
5:138560012:G:T	A421D	1.000
5:138560015:C:A	G420V	1.000
5:138560015:C:T	G420E	1.000
5:138560016:C:G	G420R	1.000
5:138560016:C:T	G420R	1.000

dbSNP variants (sampled 300 via entrez): RS1000072039 (5:138564400 G>A), RS1000134715 (5:138570784 A>G), RS1000333433 (5:138575769 A>C,G), RS1000338184 (5:138569768 T>C), RS1000440229 (5:138575081 A>T), RS1000522964 (5:138559805 A>G), RS1000709602 (5:138553619 A>G), RS1000828694 (5:138573735 TA>T), RS1000842358 (5:138571747 A>G), RS1000956830 (5:138576872 C>A,T), RS1001118593 (5:138572159 G>A,C), RS1001349793 (5:138570190 G>A), RS1001389468 (5:138576733 G>A,T), RS1001463203 (5:138565868 C>G), RS1001558976 (5:138553268 G>A)

Disease associations

OMIM: gene MIM:600548 | disease phenotypes: MIM:616854, MIM:182170

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal dominant sideroblastic anemia	Strong	Autosomal dominant
even-plus syndrome	Strong	Autosomal recessive
autosomal recessive sideroblastic anemia	Supportive	Autosomal recessive

Mondo (3): even-plus syndrome (MONDO:0014801), autosomal dominant sideroblastic anemia (MONDO:0008422), autosomal recessive sideroblastic anemia (MONDO:0016828)

Orphanet (2): EVEN-plus syndrome (Orphanet:496751), Autosomal recessive sideroblastic anemia (Orphanet:260305)

HPO phenotypes

35 total (30 of 35 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000076	Vesicoureteral reflux
HP:0000089	Renal hypoplasia
HP:0000218	High palate
HP:0000248	Brachycephaly
HP:0000456	Bifid nasal tip
HP:0000457	Depressed nasal ridge
HP:0000470	Short neck
HP:0000518	Cataract
HP:0000664	Synophrys
HP:0000668	Hypodontia
HP:0001047	Atopic dermatitis
HP:0001057	Aplasia cutis congenita
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum
HP:0001562	Oligohydramnios
HP:0001631	Atrial septal defect
HP:0001655	Patent foramen ovale
HP:0001877	Abnormal erythrocyte morphology
HP:0001924	Sideroblastic anemia
HP:0002023	Anal atresia
HP:0002553	Highly arched eyebrow
HP:0002656	Epiphyseal dysplasia
HP:0003196	Short nose
HP:0003417	Coronal cleft vertebrae
HP:0003510	Severe short stature
HP:0004828	Refractory anemia with ringed sideroblasts
HP:0006989	Dysplastic corpus callosum

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002539_60	Schizophrenia	5.000000e-09
GCST004521_139	Autism spectrum disorder or schizophrenia	2.000000e-09
GCST006803_68	Schizophrenia	7.000000e-10
GCST006990_3	Cerebrospinal AB1-42 levels in Alzheimer’s disease dementia	7.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004670	beta-amyloid 1-42 measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567160	Anemia, Sideroblastic, Autosomal Dominant (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295757 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (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
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

31 potent at pChembl≥5 of 35 total, top 31 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.52	Kd	30.45	nM	CHEMBL5653589
7.51	ED50	30.83	nM	CHEMBL5653589
7.51	Kd	31.05	nM	CHEMBL3752910
7.50	ED50	31.43	nM	CHEMBL3752910
7.07	Kd	85	nM	MOLIBRESIB
6.70	IC50	200	nM	MOLIBRESIB
6.52	Kd	300	nM	CHEMBL4649247
6.30	Kd	500	nM	CHEMBL4646130
6.22	Kd	600	nM	SHETA-2
6.16	Kd	700	nM	CHEMBL4639280
6.16	Kd	700	nM	CHEMBL4648396
5.96	Kd	1100	nM	CHEMBL4636754
5.96	Kd	1100	nM	CHEMBL4634383
5.96	Kd	1100	nM	CHEMBL4634892
5.96	Kd	1100	nM	CHEMBL4635630
5.82	Kd	1500	nM	CHEMBL4634635
5.80	Kd	1600	nM	CHEMBL4641260
5.80	Kd	1600	nM	CHEMBL4646109
5.80	Kd	1600	nM	CHEMBL4635080
5.75	Kd	1800	nM	CHEMBL4647600
5.64	Kd	2300	nM	CHEMBL4648147
5.64	Kd	2300	nM	CHEMBL4643228
5.62	Kd	2400	nM	CHEMBL4649123
5.54	Kd	2900	nM	CHEMBL4642813
5.48	Kd	3300	nM	CHEMBL4636437
5.39	Kd	4070	nM	CHEMBL5592860
5.37	IC50	4300	nM	CHEMBL5414287
5.27	Kd	5400	nM	CHEMBL4643799
5.16	Kd	6980	nM	CHEMBL5595359
5.13	Kd	7481	nM	CHEMBL5431926
5.00	IC50	1.01e+04	nM	CHEMBL5424525

PubChem BioAssay actives

28 with measured affinity, of 89 total; 27 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148556: Binding affinity to human HSPA9 incubated for 45 mins by Kinobead based pull down assay	kd	0.0305	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148556: Binding affinity to human HSPA9 incubated for 45 mins by Kinobead based pull down assay	kd	0.0311	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179140: Binding affinity against HSPA9 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0850	uM
1-(4-nitrophenyl)-3-(1,2,2,4,4-pentamethyl-3-oxoquinolin-6-yl)urea	1650539: Binding affinity to mortalin substrate binding domain (unknown origin)	kd	0.3000	uM
1-(4-nitrophenyl)-3-(1,2,2,4,4-pentamethyl-3H-quinolin-6-yl)thiourea	1650539: Binding affinity to mortalin substrate binding domain (unknown origin)	kd	0.5000	uM
1-(4-nitrophenyl)-3-(2,2,4,4-tetramethyl-3H-thiochromen-6-yl)thiourea	1650539: Binding affinity to mortalin substrate binding domain (unknown origin)	kd	0.6000	uM
1-(4-nitrophenyl)-3-(1,1,4,4-tetramethyl-2,3-dihydroquinolin-1-ium-6-yl)urea iodide	1650539: Binding affinity to mortalin substrate binding domain (unknown origin)	kd	0.7000	uM
1-(3-hydroxy-1,2,2,4,4-pentamethyl-3H-quinolin-6-yl)-3-[4-(trifluoromethyl)phenyl]urea	1650539: Binding affinity to mortalin substrate binding domain (unknown origin)	kd	0.7000	uM
1-(3-hydroxy-1,2,2,4,4-pentamethyl-3H-quinolin-6-yl)-3-[4-(trifluoromethoxy)phenyl]urea	1650539: Binding affinity to mortalin substrate binding domain (unknown origin)	kd	1.1000	uM
1-(4-nitrophenyl)-3-(1,2,2,4,4-pentamethyl-3-oxoquinolin-6-yl)thiourea	1650539: Binding affinity to mortalin substrate binding domain (unknown origin)	kd	1.1000	uM
1-(4,4-dimethyl-2,3-dihydro-1H-quinolin-6-yl)-3-(4-nitrophenyl)urea	1650539: Binding affinity to mortalin substrate binding domain (unknown origin)	kd	1.1000	uM
1-(4-aminophenyl)-3-(1,2,2,4,4-pentamethyl-3-oxoquinolin-6-yl)urea	1650539: Binding affinity to mortalin substrate binding domain (unknown origin)	kd	1.1000	uM
1-(1,2,2,4,4-pentamethyl-3-oxoquinolin-6-yl)-3-[4-(trifluoromethyl)phenyl]urea	1650539: Binding affinity to mortalin substrate binding domain (unknown origin)	kd	1.5000	uM
1-(4,4-dimethyl-2,3-dihydro-1H-quinolin-6-yl)-3-(4-nitrophenyl)thiourea	1650539: Binding affinity to mortalin substrate binding domain (unknown origin)	kd	1.6000	uM
1-(3-hydroxy-1,2,2,4,4-pentamethyl-3H-quinolin-6-yl)-3-(4-nitrophenyl)urea	1650539: Binding affinity to mortalin substrate binding domain (unknown origin)	kd	1.6000	uM
1-(1,2,2,4,4-pentamethyl-3-oxoquinolin-6-yl)-3-[4-(trifluoromethyl)phenyl]thiourea	1650539: Binding affinity to mortalin substrate binding domain (unknown origin)	kd	1.6000	uM
1-(1,2,2,4,4-pentamethyl-3-oxoquinolin-6-yl)-3-[4-(trifluoromethoxy)phenyl]urea	1650539: Binding affinity to mortalin substrate binding domain (unknown origin)	kd	1.8000	uM
1-(3-hydroxy-1,2,2,4,4-pentamethyl-3H-quinolin-6-yl)-3-[4-(trifluoromethyl)phenyl]thiourea	1650539: Binding affinity to mortalin substrate binding domain (unknown origin)	kd	2.3000	uM
1-(3-hydroxy-1,2,2,4,4-pentamethyl-3H-quinolin-6-yl)-3-(4-nitrophenyl)thiourea	1650539: Binding affinity to mortalin substrate binding domain (unknown origin)	kd	2.3000	uM
1-(1,2,2,4,4-pentamethyl-3-oxoquinolin-6-yl)-3-[4-(trifluoromethoxy)phenyl]thiourea	1650539: Binding affinity to mortalin substrate binding domain (unknown origin)	kd	2.4000	uM
1-(3-hydroxy-1,2,2,4,4-pentamethyl-3H-quinolin-6-yl)-3-[4-(trifluoromethoxy)phenyl]thiourea	1650539: Binding affinity to mortalin substrate binding domain (unknown origin)	kd	2.9000	uM
1-(4,4-dimethyl-2,3-dihydro-1H-quinolin-6-yl)-3-[4-(trifluoromethyl)phenyl]thiourea	1650539: Binding affinity to mortalin substrate binding domain (unknown origin)	kd	3.3000	uM
8-methoxy-10-[5-(9-methyl-3,9-diazaspiro[5.5]undecan-3-yl)pentyl]pyrido[3,2-b][1,4]benzothiazine	2113572: Binding affinity to recombinant His-tagged GRP75 (unknown origin) by MST assay	kd	4.0700	uM
N-[(2S)-3-methyl-1-oxo-1-(1,3-thiazol-2-ylamino)butan-2-yl]-1H-indole-2-carboxamide	1968965: Inhibition of HspA9 (unknown origin) by FP assay	ic50	4.3000	uM
1-(4,4-dimethyl-2,3-dihydro-1H-quinolin-6-yl)-3-[4-(trifluoromethoxy)phenyl]thiourea	1650539: Binding affinity to mortalin substrate binding domain (unknown origin)	kd	5.4000	uM
8-chloro-10-[5-(4-methylpiperazin-1-yl)pentyl]pyrido[3,2-b][1,4]benzothiazine;dihydrochloride	2113572: Binding affinity to recombinant His-tagged GRP75 (unknown origin) by MST assay	kd	6.9800	uM
2-(3-amino-6-imino-8a,9-dihydroxanthen-9-yl)-5-[2-[2-[2-[2-[3-[[3-[5-[2-[[(2S)-3-methyl-1-oxo-1-(1,3-thiazol-2-ylamino)butan-2-yl]carbamoyl]-1H-indol-5-yl]-3,4,5,13-tetrazatetracyclo[13.4.0.02,6.07,12]nonadeca-1(19),2(6),3,7,9,11,15,17-octaen-13-yl]-3-oxopropyl]amino]-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethylcarbamoyl]benzoic acid	1968972: Binding affinity to HspA9 (unknown origin) assessed as dissociation constant by FP assay	kd	7.4810	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases phosphorylation, affects cotreatment, increases reaction, increases abundance, decreases reaction (+4 more)	8
bisphenol A	affects cotreatment, affects expression, decreases expression, increases expression	5
Valproic Acid	affects cotreatment, increases expression, affects expression	5
Cyclosporine	affects expression, increases expression, affects cotreatment	4
Arsenic	affects expression, increases expression, affects cotreatment, increases abundance	3
Cadmium Chloride	affects expression, decreases expression, increases abundance, increases expression	3
withaferin A	decreases expression, affects binding, decreases reaction, affects localization, increases activity (+1 more)	2
ochratoxin A	affects reaction, decreases expression, increases expression	2
U 0126	affects expression, affects reaction, decreases reaction, increases expression	2
entinostat	increases expression, affects cotreatment	2
3-(4-methylphenylsulfonyl)-2-propenenitrile	increases reaction, decreases reaction, increases expression, affects binding	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
withanone	decreases reaction, affects localization, increases activity, affects cotreatment, decreases expression (+1 more)	2
Resveratrol	affects cotreatment, increases expression, decreases reaction	2
Decitabine	increases expression, increases reaction, increases response to substance	2
Air Pollutants	affects cotreatment, increases abundance, increases expression	2
Doxorubicin	increases expression	2
Ivermectin	decreases expression, increases expression	2
Tetrachlorodibenzodioxin	affects expression, decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
1-Methyl-4-phenylpyridinium	increases expression, affects expression, affects reaction	2
Thapsigargin	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	increases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
decabromobiphenyl ether	increases expression	1

ChEMBL screening assays

17 unique, capped per target: 17 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4270850	Binding	Binding affinity to stress-70 protein in human Hela cells lysates assessed as protein enrichment by measuring normalized heavy/light ratio at by nano-LC-ESIMS/MS analysis	Determination of Gymnemic Acid I as a Protein Biosynthesis Inhibitor Using Chemical Proteomics. — J Nat Prod

Clinical trials (associated diseases)

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