HSPB1

Summary

HSPB1 (heat shock protein family B (small) member 1, HGNC:5246) is a protein-coding gene on chromosome 7q11.23, encoding Heat shock protein beta-1 (P04792). Small heat shock protein which functions as a molecular chaperone probably maintaining denatured proteins in a folding-competent state. In precision oncology, HSPB1 EXPRESSION confers sensitivity to Gemcitabine in Pancreatic Ductal Adenocarcinoma (CIViC Level D).

This gene encodes a member of the small heat shock protein (HSP20) family of proteins. In response to environmental stress, the encoded protein translocates from the cytoplasm to the nucleus and functions as a molecular chaperone that promotes the correct folding of other proteins. This protein plays an important role in the differentiation of a wide variety of cell types. Expression of this gene is correlated with poor clinical outcome in multiple human cancers, and the encoded protein may promote cancer cell proliferation and metastasis, while protecting cancer cells from apoptosis. Mutations in this gene have been identified in human patients with Charcot-Marie-Tooth disease and distal hereditary motor neuropathy.

Source: NCBI Gene 3315 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Charcot-Marie-Tooth disease axonal type 2F (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 431 total — 17 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 36
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• MANE Select transcript: NM_001540

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5246
Approved symbol	HSPB1
Name	heat shock protein family B (small) member 1
Location	7q11.23
Locus type	gene with protein product
Status	Approved
Aliases	HSP27, HSP28, Hs.76067, Hsp25, CMT2F
Ensembl gene	ENSG00000106211
Ensembl biotype	protein_coding
OMIM	602195
Entrez	3315

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 10 protein_coding, 6 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000248553, ENST00000429938, ENST00000447574, ENST00000674547, ENST00000674560, ENST00000674638, ENST00000674650, ENST00000674965, ENST00000675134, ENST00000675226, ENST00000675417, ENST00000675488, ENST00000675538, ENST00000675624, ENST00000675733, ENST00000675906, ENST00000676195, ENST00000676231, ENST00000676398

RefSeq mRNA: 1 — MANE Select: NM_001540 NM_001540

CCDS: CCDS5583

Canonical transcript exons

ENST00000248553 — 3 exons

Exon	Start	End
ENSE00000876954	76302673	76303076
ENSE00003510935	76303802	76303865
ENSE00003584076	76303984	76304292

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 99.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1891.4412 / max 24538.0386, expressed in 1819 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
79157	1773.2789	1803
79163	54.6577	1780
79161	40.5401	1797
79164	8.4236	1359
79158	7.7391	1574
79160	2.3860	874
79159	2.2670	948
79162	1.4006	763
79165	0.7480	353

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.96	gold quality
ascending aorta	UBERON:0001496	99.94	gold quality
thoracic aorta	UBERON:0001515	99.94	gold quality
pharyngeal mucosa	UBERON:0000355	99.92	gold quality
aorta	UBERON:0000947	99.92	gold quality
right coronary artery	UBERON:0001625	99.92	gold quality
gingiva	UBERON:0001828	99.92	gold quality
descending thoracic aorta	UBERON:0002345	99.92	gold quality
gingival epithelium	UBERON:0001949	99.91	gold quality
popliteal artery	UBERON:0002250	99.91	gold quality
esophagus mucosa	UBERON:0002469	99.91	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.91	gold quality
tibial artery	UBERON:0007610	99.91	gold quality
vagina	UBERON:0000996	99.89	gold quality
esophagus	UBERON:0001043	99.89	gold quality
coronary artery	UBERON:0001621	99.89	gold quality
left coronary artery	UBERON:0001626	99.89	gold quality
mammalian vulva	UBERON:0000997	99.88	gold quality
apex of heart	UBERON:0002098	99.88	gold quality
decidua	UBERON:0002450	99.88	gold quality
blood vessel layer	UBERON:0004797	99.88	gold quality
lower esophagus	UBERON:0013473	99.88	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.88	gold quality
gluteal muscle	UBERON:0002000	99.87	gold quality
saphenous vein	UBERON:0007318	99.86	gold quality
oral cavity	UBERON:0000167	99.85	gold quality
penis	UBERON:0000989	99.85	gold quality
cardiac ventricle	UBERON:0002082	99.85	gold quality
heart left ventricle	UBERON:0002084	99.85	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.85	gold quality

Single-cell (SCXA)

Detected in 47 experiment(s), a significant marker in 36.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	10594.85
E-MTAB-10885	yes	9746.66
E-HCAD-1	yes	9558.15
E-CURD-79	yes	8977.98
E-MTAB-10287	yes	6553.79
E-MTAB-8495	yes	6145.08
E-MTAB-6653	yes	5445.59
E-CURD-88	yes	5225.31
E-CURD-95	yes	4691.55
E-GEOD-124472	yes	4562.86
E-HCAD-8	yes	4134.55
E-MTAB-6701	yes	3858.98
E-GEOD-124263	yes	3109.55
E-MTAB-6108	yes	2492.14
E-HCAD-23	yes	1864.44

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AR, ATF3, ATF5, CUX1, ESR1, GATA3, HSF1, HSF2, HSF4, JUN, NFKB2, PGS1, POU4F1, POU4F2, SP1, STAT1, STAT3, STAT5B, TCF23, TFCP2

miRNA regulators (miRDB)

6 targeting HSPB1, 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-539-5P	99.93	70.30	2855
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-552-3P	96.68	64.12	1026
HSA-MIR-541-3P	96.07	66.11	1271
HSA-MIR-654-5P	96.07	66.18	1280

Literature-anchored findings (GeneRIF, showing 40)

• ThioredoxinT, a thioredoxin with testis-specific expression, has a clear association with the Y chromosome lampbrush loops ks-1 and kl-5 in primary spermatocytes (PMID:14579129)
• Drosophila thioredoxin can function as an anti-aging agent and as a suppressor of Parkin-associated endothelin receptor-like receptor - and poly-glutamine-induced neurotoxicity (PMID:17301052)
• Phosphatase inhibitors prevent HSP27 dephosphorylation, destruction of stress fibrils, and morphological changes in endothelial cells during ATP depletion (PMID:11740592)
• Characterization of proteins associated with heat shock protein hsp27 in the squamous cell carcinoma cell line A431 (PMID:11779227)
• HSP27 expression is cell differentiation and oral squamous cell carcinoma (PMID:11836590)
• in asthmatic subjects the basal epithelium cells express a high level of Hsp27 but no apoptotic morphology. (PMID:12482203)
• Expression of heat-shock protein 25 in dental pulp and enamel organ during odontogenesis in the rat molar. Hsp 25 is related to the formation and maintenance of the ruffled border of ruffle-ended ameloblasts and enamel-free-area cells. (PMID:12489163)
• Has specific actions in renal epithelia subjected to energy depletion, including interacting with actin to preserve architecture in specific intracellular domains. (PMID:12506142)
• Hsp27 has a role in regulating apoptosis through control of Akt activity (PMID:12740362)
• Maps to chromosome 7q11.23. Deletion may be resonsible for cognitive features of Williams syndrome. (PMID:12838549)
• Hsp27 is overexpressed in both dexamethasone resistant multiple myeloma cell lines and primary patient cells. (PMID:12855565)
• HSP27-dependent thermotolerance is suppressed by mumps virus infection through the destruction of STAT-1. (PMID:12917439)
• Taken together, our findings demonstrate that constitutively activated Stat3 up-regulates HSP27 and may facilitate phosphorylation of HSP27 at serine residue 78. (PMID:14715258)
• HSP27 expression was reduced in metaplasia and then significantly increased with neoplastic progresssion in Barrett esophagus. Gender-related differences were obnserved and HSP27 expression was higher in poorly-differentiated adenocarcinoma. (PMID:15013707)
• missense mutation in the gene encoding 27-kDa small heat-shock protein B1 (HSPB1, also called HSP27) that segregates in a family with Charcot-Marie-Tooth disease (PMID:15122254)
• HSP27 is involved in the UVC-resistance of human cells, at least those tested, possibly via functioning in nucleotide excision repair. (PMID:15265704)
• Hsp27 expression and cell survival are regulated by the POU transcription factor Brn3a (PMID:15272315)
• Results showed significant increases in expression and in HSP27 isoform numbers in renal cell carcinoma compared to normal kidney. (PMID:15274119)
• definition of the binding-competent oligomeric state of human Hsp27 (PMID:15542604)
• wild-type protein forms smaller oligomers than previously believed, define the roles played by various structural domains in Hsp27 oligomerization (PMID:15581903)
• Hsp27 protects against cytotoxic effects induced by oxidative stress in cultured mammalian cells (PMID:15649839)
• HSP27, an ERbeta-associated protein, shows attenuated expression with coronary atherosclerosis and modulates estrogen signaling. (PMID:15662019)
• Ser(82) in the human heat shock protein Hsp27 is a novel substrate for PKD (PMID:15728188)
• MEK6E activates p38 and results in phosphorylation of its downstream substrate, heat shock protein 27 (PMID:15790570)
• HSP25 downregulates PKCdelta, which is a key molecule for radiation-induced ROS generation and mitochondrial-mediated caspase-dependent apoptotic events. (PMID:15806174)
• particularly in conditions of enhanced oxidative stress, lymphomonocytes from liver disease patients present an increased expression of HSP27 (PMID:15969449)
• Taken together, our results indicated that expanded ataxin-7 that leads to neurodegeneration significantly impaired the expression of Hsp27 and Hsp70 protein. (PMID:16039988)
• One Hsp27 missense mutation, C379T, was detected in 4 autosomal dominant families with CMT disease type 2, and haplotype analysis indicated that the 4 families probably had a common founder. (PMID:16087758)
• Our results suggest that forms of stress that upregulate HSP27 and its phosphorylation may be useful as novel approaches to prevent adverse ocular effects arising from UV exposure in humans. (PMID:16114012)
• increased level of Hsp27 may reflect a dynamic process of the survived cells to unfold and remove mutant ataxin-3 (PMID:16126176)
• The first report of HSP27 gene mutation in Chinese patients with Charcot-Marie-Tooth disease , but it may be not common(0.90%). The C379T mutation in HSP27 gene also causes CMT2 except for distal hereditary motor neuropathy. (PMID:16215937)
• A tumor marker for hepatocellular hepatoma. (PMID:16240287)
• Hsp27 is an active participant in the (de)phosphorylation cascade controlling the activity of the splicing regulator SRp38. (PMID:16339078)
• findings provide a model system for the study of metastatic potential of tumors and are suggestive of an earlier unrecognized role for Hsp25 in tumor migration (PMID:16340246)
• A mutation in the small heat-shock protein HSPB1 leading to distal hereditary motor neuronopathy disrupts neurofilament assembly and the axonal transport of specific cellular cargoes. (PMID:16368711)
• Up-regulation of Hsp27 protein is associated with hepatocellular carcinoma (PMID:16400691)
• Both MAPKAPK2 and HSP27 are necessary for TGFbeta-mediated increases in MMP-2 and cell invasion in human prostate cancer. (PMID:16407830)
• Hsp27 can exploit a large number of oligomerization states (PMID:16436384)
• Heat-shock protein 27 of endothelial cells is modified by methylglyoxal, which may contribute to changes in endothelial cell function associated to diabetes.. (PMID:16487519)
• Can be degraded by enzymes released from atherosclerotic plaques. May reflect proteolytic imbalance. Downregulation decreases vascular smooth muscle cell resistance to proteolytically-induced apoptosis. Might play role in prevention of plaque rupture. (PMID:16574891)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	hspb1	ENSDARG00000041065
mus_musculus	Hspb1	ENSMUSG00000004951
rattus_norvegicus	Hspb1	ENSRNOG00000023546
drosophila_melanogaster	CG14207	FBGN0031037
caenorhabditis_elegans		WBGENE00002011
caenorhabditis_elegans		WBGENE00002015
caenorhabditis_elegans		WBGENE00002016
caenorhabditis_elegans		WBGENE00002017
caenorhabditis_elegans		WBGENE00002018
caenorhabditis_elegans		WBGENE00002019
caenorhabditis_elegans		WBGENE00002020
caenorhabditis_elegans		WBGENE00002023
caenorhabditis_elegans		WBGENE00008591
caenorhabditis_elegans		WBGENE00008592
caenorhabditis_elegans	hsp-12.1	WBGENE00011906

Paralogs (8): HSPB6 (ENSG00000004776), CRYAB (ENSG00000109846), HSPB8 (ENSG00000152137), CRYAA (ENSG00000160202), HSPB3 (ENSG00000169271), HSPB2 (ENSG00000170276), HSPB7 (ENSG00000173641), HSPB9 (ENSG00000260325)

Protein

Protein identifiers

Heat shock protein beta-1 — P04792 (reviewed: P04792)

Alternative names: 28 kDa heat shock protein, Estrogen-regulated 24 kDa protein, Heat shock 27 kDa protein, Heat shock protein family B member 1, Stress-responsive protein 27

All UniProt accessions (11): P04792, A0A6Q8PF43, A0A6Q8PFE7, A0A6Q8PFK8, A0A6Q8PGK1, A0A6Q8PGY2, A0A6Q8PH65, A0A6Q8PHA6, A0A6Q8PHJ6, C9J3N8, V9HW43

UniProt curated annotations — full annotation on UniProt →

Function. Small heat shock protein which functions as a molecular chaperone probably maintaining denatured proteins in a folding-competent state. Plays a role in stress resistance and actin organization. Through its molecular chaperone activity may regulate numerous biological processes including the phosphorylation and the axonal transport of neurofilament proteins.

Subunit / interactions. Homooligomer. Homodimer; becomes monomeric upon activation. Heterooligomer; with HSPB6. Associates with alpha- and beta-tubulin. Interacts with TGFB1I1. Interacts with CRYAB. Interacts with HSPB8. Interacts with HSPBAP1.

Subcellular location. Cytoplasm. Nucleus. Cytoskeleton. Spindle.

Tissue specificity. Detected in all tissues tested: skeletal muscle, heart, aorta, large intestine, small intestine, stomach, esophagus, bladder, adrenal gland, thyroid, pancreas, testis, adipose tissue, kidney, liver, spleen, cerebral cortex, blood serum and cerebrospinal fluid. Highest levels are found in the heart and in tissues composed of striated and smooth muscle.

Post-translational modifications. Phosphorylated upon exposure to protein kinase C activators and heat shock. Phosphorylation by MAPKAPK2 and MAPKAPK3 in response to stress dissociates HSPB1 from large small heat-shock protein (sHsps) oligomers and impairs its chaperone activity and ability to protect against oxidative stress effectively. Phosphorylation by MAPKAPK5 in response to PKA stimulation induces F-actin rearrangement.

Disease relevance. Charcot-Marie-Tooth disease, axonal, type 2F (CMT2F) [MIM:606595] A dominant axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. Onset of Charcot-Marie-Tooth disease type 2F is between 15 and 25 years with muscle weakness and atrophy usually beginning in feet and legs (peroneal distribution). Upper limb involvement occurs later. The disease is caused by variants affecting the gene represented in this entry. Neuronopathy, distal hereditary motor, autosomal dominant 3 (HMND3) [MIM:608634] A form of distal hereditary motor neuronopathy, a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. The disease is caused by variants affecting the gene represented in this entry.

Induction. Up-regulated in response to environmental stresses such as heat shock. Up-regulated by estrogen stimulation. (Microbial infection) Up-regulated in response to enterovirus 71 (EV71) infection (at protein level).

Similarity. Belongs to the small heat shock protein (HSP20) family.

RefSeq proteins (1): NP_001531* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001436	Alpha-crystallin/sHSP_animal	Family
IPR002068	A-crystallin/Hsp20_dom	Domain
IPR008978	HSP20-like_chaperone	Homologous_superfamily
IPR037876	ACD_HspB1	Domain

Pfam: PF00011

UniProt features (56 total): sequence variant 23, modified residue 13, strand 7, sequence conflict 4, mutagenesis site 3, turn 2, chain 1, domain 1, region of interest 1, helix 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
3Q9P	X-RAY DIFFRACTION	2
6GJH	X-RAY DIFFRACTION	2.1
3Q9Q	X-RAY DIFFRACTION	2.2
4MJH	X-RAY DIFFRACTION	2.6
6DV5	X-RAY DIFFRACTION	3.58
2N3J	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P04792-F1	68.82	0.32

Functional residue map

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

Post-translational modifications (13): 86, 98, 123, 174, 176, 199, 12, 15, 26, 65, 78, 82, 83

Mutagenesis-validated functional residues (3):

Position	Phenotype
15	mimicks phosphorylation state, leading to dreased ability to act as molecular chaperones; when associated with d-78 and
78	mimicks phosphorylation state, leading to dreased ability to act as molecular chaperones; when associated with d-15 and
82	mimicks phosphorylation state, leading to dreased ability to act as molecular chaperones; when associated with d-15 and

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-4420097	VEGFA-VEGFR2 Pathway
R-HSA-450408	AUF1 (hnRNP D0) binds and destabilizes mRNA
R-HSA-5687128	MAPK6/MAPK4 signaling
R-HSA-9009391	Extra-nuclear estrogen signaling
R-HSA-3371453	Regulation of HSF1-mediated heat shock response
R-HSA-3371511	HSF1 activation
R-HSA-3371568	Attenuation phase
R-HSA-3371571	HSF1-dependent transactivation

MSigDB gene sets: 523 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_DIGESTION, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_AXO_DENDRITIC_TRANSPORT, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_POSITIVE_REGULATION_OF_ENDOTHELIAL_CELL_CHEMOTAXIS, GOBP_CELL_CHEMOTAXIS, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, PEREZ_TP63_TARGETS, ENK_UV_RESPONSE_KERATINOCYTE_UP, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_PLATELET_ACTIVATION

GO Biological Process (24): regulation of protein phosphorylation (GO:0001932), regulation of translational initiation (GO:0006446), protein folding (GO:0006457), response to unfolded protein (GO:0006986), response to heat (GO:0009408), response to virus (GO:0009615), regulation of autophagy (GO:0010506), positive regulation of interleukin-1 beta production (GO:0032731), positive regulation of tumor necrosis factor production (GO:0032760), intracellular signal transduction (GO:0035556), cellular response to vascular endothelial growth factor stimulus (GO:0035924), protein refolding (GO:0042026), negative regulation of apoptotic process (GO:0043066), regulation of canonical NF-kappaB signal transduction (GO:0043122), positive regulation of blood vessel endothelial cell migration (GO:0043536), positive regulation of angiogenesis (GO:0045766), vascular endothelial growth factor receptor signaling pathway (GO:0048010), intestinal epithelial structure maintenance (GO:0060729), platelet aggregation (GO:0070527), negative regulation of protein kinase C signaling (GO:0090038), anterograde axonal protein transport (GO:0099641), negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway (GO:1902176), positive regulation of endothelial cell chemotaxis (GO:2001028), negative regulation of apoptotic signaling pathway (GO:2001234)

GO Molecular Function (11): RNA binding (GO:0003723), protein kinase C binding (GO:0005080), protein kinase C inhibitor activity (GO:0008426), protein kinase binding (GO:0019901), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), ubiquitin binding (GO:0043130), protein folding chaperone (GO:0044183), obsolete unfolded protein binding (GO:0051082), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), protein binding (GO:0005515)

GO Cellular Component (14): proteasome complex (GO:0000502), cornified envelope (GO:0001533), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), cytoplasm (GO:0005737), spindle (GO:0005819), cytosol (GO:0005829), cytoskeleton (GO:0005856), focal adhesion (GO:0005925), Z disc (GO:0030018), extracellular exosome (GO:0070062), axon cytoplasm (GO:1904115), plasma membrane (GO:0005886), contractile muscle fiber (GO:0043292)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Cellular response to heat stress	3
Signaling by VEGF	1
Regulation of mRNA stability by proteins that bind AU-rich elements	1
MAPK family signaling cascades	1
ESR-mediated signaling	1
HSF1-dependent transactivation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular membraneless organelle	3
intracellular anatomical structure	2
protein folding	2
cytoplasm	2
protein phosphorylation	1
regulation of protein modification process	1
regulation of phosphorylation	1
translational initiation	1
regulation of translation	1
cellular process	1
protein maturation	1
response to topologically incorrect protein	1
response to stress	1
response to temperature stimulus	1
response to other organism	1
autophagy	1
regulation of catabolic process	1
interleukin-1 beta production	1
regulation of interleukin-1 beta production	1
positive regulation of interleukin-1 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
signal transduction	1
cellular response to growth factor stimulus	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
canonical NF-kappaB signal transduction	1
regulation of intracellular signal transduction	1
positive regulation of endothelial cell migration	1
blood vessel endothelial cell migration	1
regulation of blood vessel endothelial cell migration	1
angiogenesis	1
regulation of angiogenesis	1
positive regulation of vasculature development	1
cell surface receptor protein tyrosine kinase signaling pathway	1
maintenance of gastrointestinal epithelium	1
platelet activation	1

Protein interactions and networks

STRING

3282 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HSPB1	CYCS	P00001	991
HSPB1	HSPA4	P34932	989
HSPB1	AKT1	P31749	964
HSPB1	PLEC	Q15149	963
HSPB1	EIF4G1	Q04637	942
HSPB1	HSP90AB1	P08238	929
HSPB1	HSP90AA1	P07900	924
HSPB1	HSPA8	P11142	923
HSPB1	MAPKAPK2	P49137	915
HSPB1	HSPA1A	P08107	913
HSPB1	BAG3	O95817	882
HSPB1	HSPBAP1	Q96EW2	873
HSPB1	DNAJB1	P25685	860
HSPB1	HSPH1	Q92598	850
HSPB1	MAPKAPK5	Q8IW41	841

IntAct

1237 interactions, top by confidence:

A	B	Type	Score
CRYAB	HSPB1	psi-mi:“MI:0915”(physical association)	0.910
HSPB1	HSPB1	psi-mi:“MI:0915”(physical association)	0.830
HSPB1	HSPB1	psi-mi:“MI:0407”(direct interaction)	0.830
CRYAA	HSPB1	psi-mi:“MI:0915”(physical association)	0.810
JADE1	KAT7	psi-mi:“MI:0914”(association)	0.720
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
RPSA	HSPB1	psi-mi:“MI:0915”(physical association)	0.670
SH3KBP1	USP27X	psi-mi:“MI:0914”(association)	0.640
MAPK7	PFDN6	psi-mi:“MI:0914”(association)	0.640
RAF1	CALU	psi-mi:“MI:0914”(association)	0.640
DAXX	HSPB1	psi-mi:“MI:0915”(physical association)	0.620
HSPB1	DAXX	psi-mi:“MI:0915”(physical association)	0.620
ANXA8	HSPB1	psi-mi:“MI:0915”(physical association)	0.560
ANXA5	HSPB1	psi-mi:“MI:0915”(physical association)	0.560
AQP8	HSPB1	psi-mi:“MI:0915”(physical association)	0.560
TRIM23	HSPB1	psi-mi:“MI:0915”(physical association)	0.560
ATP6V1B1	HSPB1	psi-mi:“MI:0915”(physical association)	0.560
HSPB1	BAK1	psi-mi:“MI:0915”(physical association)	0.560
TEN1	HSPB1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (972): HSPB1 (Two-hybrid), HSPB1 (Affinity Capture-Western), HSPB1 (Reconstituted Complex), AKT1 (Reconstituted Complex), HSPB1 (Biochemical Activity), HSPB1 (Affinity Capture-MS), HSPB1 (Affinity Capture-MS), HSPB1 (Affinity Capture-MS), HSPB1 (Affinity Capture-MS), HSPB1 (Affinity Capture-MS), HSPB1 (Affinity Capture-MS), HSPB1 (Affinity Capture-MS), HSPB1 (Affinity Capture-MS), HSPB1 (Affinity Capture-MS), HSPB1 (Affinity Capture-MS)

ESM2 similar proteins: A5JV83, O93591, P02487, P02497, P02500, P02506, P02507, P02508, P02509, P02510, P02511, P02512, P04792, P05811, P06904, P09887, P14602, P15990, P15991, P23927, P23928, P24622, P24623, P30218, P30219, P35385, P41316, P42929, P42930, P42931, Q00649, Q05557, Q05713, Q3T149, Q5EAC9, Q5ENY9, Q5R9K0, Q5RAB0, Q5S1U1, Q60HG8

Diamond homologs: A5JV83, O14558, P02487, P02488, P02489, P02507, P02510, P02511, P02512, P04120, P04792, P05811, P06581, P06582, P14602, P15991, P23927, P23928, P30218, P30219, P34696, P35385, P41316, P42929, P42930, P42931, P82147, P97541, Q00649, Q04757, Q05557, Q05713, Q148F8, Q1RI96, Q3T149, Q5EAC9, Q5ENY9, Q5R9K0, Q5RAB0, Q5S1U1

SIGNOR signaling

26 interactions.

A	Effect	B	Mechanism
HSPB1	down-regulates	DIABLO
MAPKAPK2	down-regulates	HSPB1	phosphorylation
AKT	down-regulates	HSPB1	phosphorylation
AKT2	down-regulates	HSPB1	phosphorylation
AKT3	down-regulates	HSPB1	phosphorylation
PRKG1	down-regulates	HSPB1	phosphorylation
PRKG2	down-regulates	HSPB1	phosphorylation
RPS6KB1	down-regulates	HSPB1	phosphorylation
HSPB1	“up-regulates quantity by stabilization”	GCH1	binding
AKT1	down-regulates	HSPB1	phosphorylation
PRKCD	“down-regulates activity”	HSPB1	phosphorylation
HSPB1	down-regulates	CASP3
MAPKAPK3	unknown	HSPB1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 202 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 CSF3 (G-CSF)	6	21.8×	1e-05
Negative regulation of MAPK pathway	9	15.2×	1e-06
SHC1 events in ERBB2 signaling	5	15.2×	3e-04
RAF activation	7	15.0×	2e-05
Signaling by SCF-KIT	9	14.2×	1e-06
Signaling by high-kinase activity BRAF mutants	7	14.1×	2e-05
Signaling by RAS mutants	5	13.5×	6e-04
VEGFR2 mediated vascular permeability	5	13.0×	6e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of peptidyl-serine phosphorylation	6	25.4×	2e-05
insulin-like growth factor receptor signaling pathway	8	21.9×	8e-07
Fc-gamma receptor signaling pathway involved in phagocytosis	5	19.4×	8e-04
response to interleukin-1	5	14.1×	2e-03
response to hydrogen peroxide	5	12.9×	3e-03
positive regulation of substrate adhesion-dependent cell spreading	6	12.4×	1e-03
response to heat	5	11.6×	4e-03
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	5	11.3×	5e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	11
Uncertain significance	226
Likely benign	100
Benign	9

Top pathogenic / likely-pathogenic (28)

Variant ID	HGVS	Classification
1455479	NC_000007.13:g.(?75933099)(75933490_?)del	Pathogenic
1930599	NM_001540.5(HSPB1):c.245_246insT (p.Ser83fs)	Pathogenic
2035012	NM_001540.5(HSPB1):c.472del (p.Ser158fs)	Pathogenic
410713	NM_001540.5(HSPB1):c.522_523delinsCT (p.Gln175Ter)	Pathogenic
533813	NM_001540.5(HSPB1):c.404C>A (p.Ser135Tyr)	Pathogenic
533814	NM_001540.5(HSPB1):c.116C>T (p.Pro39Leu)	Pathogenic
584236	NC_000007.14:g.(?76303802)(76304173_?)del	Pathogenic
637505	NM_001540.5(HSPB1):c.171_172insGCGCCCT (p.Leu58fs)	Pathogenic
7478	NM_001540.5(HSPB1):c.404C>T (p.Ser135Phe)	Pathogenic
7479	NM_001540.5(HSPB1):c.379C>T (p.Arg127Trp)	Pathogenic
7481	NM_001540.5(HSPB1):c.545C>T (p.Pro182Leu)	Pathogenic
7482	NM_001540.5(HSPB1):c.406C>T (p.Arg136Trp)	Pathogenic
7484	NM_001540.5(HSPB1):c.418C>G (p.Arg140Gly)	Pathogenic
7485	NM_001540.5(HSPB1):c.295C>A (p.Leu99Met)	Pathogenic
831819	NC_000007.14:g.(?76303789)(76304183_?)del	Pathogenic
946496	NM_001540.5(HSPB1):c.544C>G (p.Pro182Ala)	Pathogenic
986844	NM_001540.5(HSPB1):c.126G>A (p.Trp42Ter)	Pathogenic
2440796	NM_001540.5(HSPB1):c.504dup (p.Met169fs)	Likely pathogenic
2497721	NM_001540.5(HSPB1):c.433C>T (p.Pro145Ser)	Likely pathogenic
2884503	NM_001540.5(HSPB1):c.116C>G (p.Pro39Arg)	Likely pathogenic
3026735	NM_001540.5(HSPB1):c.504del (p.Met169fs)	Likely pathogenic
3338066	NM_001540.5(HSPB1):c.610dup (p.Ala204fs)	Likely pathogenic
3896881	NM_001540.5(HSPB1):c.109dup (p.Arg37fs)	Likely pathogenic
465276	NM_001540.5(HSPB1):c.532G>T (p.Glu178Ter)	Likely pathogenic
533819	NC_000007.14:g.(?76303782)(76304193_?)del	Likely pathogenic
565333	NM_001540.5(HSPB1):c.403T>G (p.Ser135Ala)	Likely pathogenic
637259	NM_001540.5(HSPB1):c.505del (p.Met169fs)	Likely pathogenic
871116	NM_001540.5(HSPB1):c.287del (p.Arg96fs)	Likely pathogenic

SpliceAI

240 predictions. Top by Δscore:

Variant	Effect	Δscore
7:76303055:G:GT	donor_gain	1.0000
7:76303077:G:GG	donor_gain	1.0000
7:76303077:GTGA:G	donor_loss	1.0000
7:76303078:T:A	donor_loss	1.0000
7:76303798:A:AG	acceptor_gain	1.0000
7:76303798:AAAG:A	acceptor_gain	1.0000
7:76303799:AAGG:A	acceptor_loss	1.0000
7:76303800:A:C	acceptor_loss	1.0000
7:76303800:A:G	acceptor_gain	1.0000
7:76303801:G:GG	acceptor_gain	1.0000
7:76303801:GGCAA:G	acceptor_gain	1.0000
7:76303861:TACAC:T	donor_gain	1.0000
7:76303862:ACAC:A	donor_gain	1.0000
7:76303863:CAC:C	donor_gain	1.0000
7:76303864:AC:A	donor_gain	1.0000
7:76303865:CG:C	donor_loss	1.0000
7:76303866:G:GG	donor_gain	1.0000
7:76303973:T:TA	acceptor_gain	1.0000
7:76303976:A:AG	acceptor_gain	1.0000
7:76303976:AC:A	acceptor_gain	1.0000
7:76303977:C:CA	acceptor_gain	1.0000
7:76303977:C:G	acceptor_gain	1.0000
7:76303980:CCAG:C	acceptor_loss	1.0000
7:76303982:A:AG	acceptor_gain	1.0000
7:76303982:A:AT	acceptor_loss	1.0000
7:76303982:AG:A	acceptor_gain	1.0000
7:76303982:AGGCT:A	acceptor_gain	1.0000
7:76303983:G:GA	acceptor_gain	1.0000
7:76303983:GG:G	acceptor_gain	1.0000
7:76303983:GGC:G	acceptor_gain	1.0000

AlphaMissense

1313 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:76302995:T:A	W95R	1.000
7:76302995:T:C	W95R	1.000
7:76303022:T:C	F104L	1.000
7:76303023:T:C	F104S	1.000
7:76303023:T:G	F104C	1.000
7:76303024:C:A	F104L	1.000
7:76303024:C:G	F104L	1.000
7:76303044:T:A	V111D	1.000
7:76303071:T:A	I120N	1.000
7:76303071:T:C	I120T	1.000
7:76303071:T:G	I120S	1.000
7:76303802:G:A	G122D	1.000
7:76303840:T:C	S135P	1.000
7:76303849:T:C	F138L	1.000
7:76303850:T:C	F138S	1.000
7:76303850:T:G	F138C	1.000
7:76303851:C:A	F138L	1.000
7:76303851:C:G	F138L	1.000
7:76303861:T:C	Y142H	1.000
7:76304043:T:C	L163P	1.000
7:76302996:G:C	W95S	0.999
7:76302997:G:C	W95C	0.999
7:76302997:G:T	W95C	0.999
7:76303008:T:C	L99P	0.999
7:76303014:T:A	V101D	0.999
7:76303022:T:A	F104I	0.999
7:76303022:T:G	F104V	0.999
7:76303038:T:A	L109Q	0.999
7:76303038:T:C	L109P	0.999
7:76303076:G:C	G122R	0.999

dbSNP variants (sampled 300 via entrez): RS1000061797 (7:76304219 C>G,T), RS1000151523 (7:76303262 T>C), RS1000484222 (7:76303412 A>G,T), RS1000666283 (7:76303371 CCCCGCG>C), RS1001604174 (7:76302280 T>C), RS1001668001 (7:76302465 G>A,T), RS1002587710 (7:76302264 T>A), RS1002606976 (7:76301014 T>C), RS1003066231 (7:76301988 C>A,T), RS1003586748 (7:76304665 TGTG>T), RS1004054928 (7:76304623 A>G), RS1004519769 (7:76303614 A>C,G), RS1004998334 (7:76303749 G>A), RS1005472547 (7:76300684 G>A), RS1006067529 (7:76301942 C>G,T)

Disease associations

OMIM: gene MIM:602195 | disease phenotypes: MIM:606595, MIM:608634, MIM:118220, MIM:608323

GenCC curated gene-disease

Disease	Classification	Inheritance
Charcot-Marie-Tooth disease axonal type 2F	Definitive	Autosomal dominant
neuronopathy, distal hereditary motor, type 2B	Moderate	Autosomal dominant
distal hereditary motor neuropathy type 2	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Charcot-Marie-Tooth disease axonal type 2F	Definitive	AD

Mondo (8): Charcot-Marie-Tooth disease axonal type 2F (MONDO:0011687), neuronopathy, distal hereditary motor, type 2B (MONDO:0012080), Charcot-Marie-Tooth disease (MONDO:0015626), distal hereditary motor neuropathy type 2 (MONDO:0015352), distal hereditary motor neuropathy (MONDO:0018894), hereditary peripheral neuropathy (MONDO:0020127), Charcot-Marie-Tooth disease type 4 (MONDO:0018995), Charcot-Marie-Tooth disease dominant intermediate C (MONDO:0012012)

Orphanet (7): Distal hereditary motor neuropathy type 2 (Orphanet:139525), Autosomal dominant Charcot-Marie-Tooth disease type 2F (Orphanet:99940), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166), Distal hereditary motor neuropathy (Orphanet:53739), Genetic peripheral neuropathy (Orphanet:98497), Charcot-Marie-Tooth disease type 4 (Orphanet:64749), Autosomal dominant intermediate Charcot-Marie-Tooth disease type C (Orphanet:100045)

HPO phenotypes

36 total (30 of 36 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001178	Ulnar claw
HP:0001288	Gait disturbance
HP:0001315	Reduced tendon reflexes
HP:0001761	Pes cavus
HP:0001762	Talipes equinovarus
HP:0002380	Fasciculations
HP:0002460	Distal muscle weakness
HP:0002522	Areflexia of lower limbs
HP:0002600	Hyporeflexia of lower limbs
HP:0002601	Paresis of extensor muscles of the big toe
HP:0002936	Distal sensory impairment
HP:0003376	Steppage gait
HP:0003394	Muscle spasm
HP:0003431	Decreased motor nerve conduction velocity
HP:0003444	EMG: chronic denervation signs
HP:0003445	EMG: neuropathic changes
HP:0003470	Paralysis
HP:0003477	Peripheral axonal neuropathy
HP:0003581	Adult onset
HP:0003584	Late onset
HP:0003596	Middle age onset
HP:0003677	Slowly progressive
HP:0007267	Chronic axonal neuropathy
HP:0007289	Limb fasciculations
HP:0007328	Impaired pain sensation
HP:0007340	Lower limb muscle weakness
HP:0008944	Distal lower limb amyotrophy
HP:0009027	Foot dorsiflexor weakness
HP:0009053	Distal lower limb muscle weakness

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006585_1383	Blood protein levels	2.000000e-16
GCST007205_5	Schizophrenia	3.000000e-07
GCST009731_74	Blood protein levels in cardiovascular risk	2.000000e-25

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010595	heat shock protein beta-1 measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D002607	Charcot-Marie-Tooth Disease	C10.500.300.200; C10.574.500.495.200; C10.668.829.800.300.200; C16.131.666.300.200; C16.320.400.375.200
C564257	Charcot-Marie-Tooth Disease, Dominant Intermediate C (supp.)
C535413	Charcot-Marie-Tooth disease, Type 2F (supp.)
C580044	Distal Hereditary Motor Neuropathy, Type II (supp.)
C567084	Neuronopathy, Distal Hereditary Motor, Type IIB (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5976 (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: 1,681 (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
CHEMBL103667	DORAMAPIMOD	2	1,681

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
HSPB1 EXPRESSION	Gemcitabine	Pancreatic Ductal Adenocarcinoma	Sensitivity/Response	CIViC D	EID939

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

ChEMBL bioactivities

10 potent at pChembl≥5 of 20 total, top 10 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.22	IC50	6	nM	CHEMBL476141
7.96	Kd	10.94	nM	CHEMBL5653589
7.96	ED50	10.94	nM	CHEMBL5653589
7.60	IC50	25	nM	Skepinone-L
7.57	IC50	27	nM	GW775608X
7.28	IC50	53	nM	CHEMBL478649
7.24	IC50	58	nM	DORAMAPIMOD
7.06	IC50	88	nM	GW743024X
6.80	IC50	160	nM	SB-242235
6.70	IC50	200	nM	CHEMBL1935538

PubChem BioAssay actives

8 with measured affinity, of 185 total; 8 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
N-[3-[4-(cyclopropylmethylcarbamoyl)phenyl]-4-methylphenyl]-2-piperidin-1-ylpyridine-4-carboxamide	341051: Inhibition of HSP27 phosphorylation in IL-1-alpha-stimulated HLF cells	ic50	0.0060	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148557: Binding affinity to human HSPB1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0109	uM
N-[3-[4-(cyclopropylmethylcarbamoyl)phenyl]-4-methylphenyl]-2-morpholin-4-ylpyridine-4-carboxamide	341051: Inhibition of HSP27 phosphorylation in IL-1-alpha-stimulated HLF cells	ic50	0.0270	uM
N-cyclopropyl-3-[4-(cyclopropylmethylcarbamoyl)phenyl]-4-methylbenzamide	341051: Inhibition of HSP27 phosphorylation in IL-1-alpha-stimulated HLF cells	ic50	0.0530	uM
1-[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	341051: Inhibition of HSP27 phosphorylation in IL-1-alpha-stimulated HLF cells	ic50	0.0580	uM
N-[3-[4-(cyclopropylmethylcarbamoyl)phenyl]-4-methylphenyl]furan-3-carboxamide	341051: Inhibition of HSP27 phosphorylation in IL-1-alpha-stimulated HLF cells	ic50	0.0880	uM
4-[5-(4-fluorophenyl)-3-piperidin-4-ylimidazol-4-yl]-2-methoxypyrimidine	341051: Inhibition of HSP27 phosphorylation in IL-1-alpha-stimulated HLF cells	ic50	0.1600	uM
N-[3-[(2,5-dimethylphenyl)methoxy]-4-[methyl(methylsulfonyl)amino]phenyl]-1,3-benzodioxole-5-carboxamide	1231949: Inhibition of HSP27 (unknown origin) by insulin aggregation assay	ic50	0.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases expression, decreases expression, increases abundance, increases phosphorylation	16
Particulate Matter	decreases expression, increases abundance, increases expression, affects cotreatment, affects expression (+2 more)	7
Arsenic Trioxide	decreases expression, increases expression	6
Resveratrol	affects cotreatment, decreases expression, increases response to substance, increases expression, increases phosphorylation	5
bisphenol A	increases expression	4
Benzo(a)pyrene	decreases expression, increases expression	4
Doxorubicin	increases expression, affects response to substance, decreases response to substance, increases reaction, decreases expression (+1 more)	4
Estradiol	increases expression, decreases expression, affects binding, increases activity, increases reaction (+1 more)	4
Quercetin	increases response to substance, affects cotreatment, increases expression, affects expression, decreases reaction (+2 more)	4
Tobacco Smoke Pollution	affects expression, increases expression	4
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, affects expression, increases expression	4
SB 203580	decreases phosphorylation, decreases reaction, increases phosphorylation, increases expression	3
Air Pollutants	increases abundance, increases expression, decreases expression	3
Cisplatin	affects response to substance, affects cotreatment, increases expression, increases reaction	3
Tretinoin	affects cotreatment, increases expression, decreases expression	3
thiodipropionic acid	increases expression	2
cobaltous chloride	increases expression	2
ochratoxin A	decreases expression	2
Vorinostat	affects cotreatment, affects expression, decreases expression	2
Caffeine	decreases expression, decreases phosphorylation	2
Cannabidiol	affects cotreatment, increases expression	2
Copper	affects binding, affects expression, decreases expression	2
Fluorouracil	affects cotreatment, affects response to substance, decreases response to substance	2
Glucose	increases secretion, decreases reaction, increases phosphorylation	2
Hydrogen Peroxide	increases expression, increases phosphorylation, decreases phosphorylation	2
Oxygen	increases reaction, increases expression, decreases reaction, affects expression	2
Plant Extracts	affects expression, affects cotreatment, decreases expression	2
Polycyclic Aromatic Hydrocarbons	increases abundance, increases expression, affects cotreatment	2
Silver	increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2

ChEMBL screening assays

70 unique, capped per target: 70 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2060020	Binding	Binding affinity to Hsp27 in human SKBR3 cell lysate at 25 uM after 30 mins by mass spectrometric analysis	Identification of a class of novel tubulin inhibitors. — J Med Chem

Cellosaurus cell lines

7 cell lines: 7 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1U0	Abcam HeLa HSPB1 KO	Cancer cell line	Female
CVCL_D8MM	Ubigene HCT 116 HSPB1 KO	Cancer cell line	Male
CVCL_E0EI	Ubigene HeLa HSPB1 KO	Cancer cell line	Female
CVCL_SR77	HAP1 HSPB1 (-) 1	Cancer cell line	Male
CVCL_SR78	HAP1 HSPB1 (-) 2	Cancer cell line	Male
CVCL_SR79	HAP1 HSPB1 (-) 3	Cancer cell line	Male
CVCL_SR80	HAP1 HSPB1 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04762758	PHASE3	UNKNOWN	Phase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients
NCT00271635	PHASE2	COMPLETED	Ascorbic Acid Treatment in CMT1A Trial (AATIC)
NCT01401257	PHASE2	COMPLETED	Phase II, Randomized, Placebo-controlled Trial in Patients With Charcot-marie-tooth Disease Type 1A
NCT02561702	PHASE2	COMPLETED	Mexiletine for Muscle Cramps in Charcot Marie Tooth Disease
NCT02967679	PHASE2	COMPLETED	SERENDEM : MD1003 in Patients Suffering From Demyelinating Neuropathies, an Open Label Pilot Study
NCT03124459	PHASE2	TERMINATED	Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease
NCT03254199	PHASE2	TERMINATED	A Study to Assess the Safety and Effectiveness of FLX-787 in Subjects With Charcot-Marie-Tooth Disease Experiencing Muscle Cramps.
NCT03943290	PHASE2	TERMINATED	Extension Study to Evaluate the Long-Term Effects of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD) and Charcot-Marie Tooth (CMT) Disease Types 1 and X (CMT1 and CMTX)
NCT05777226	PHASE2	UNKNOWN	Research of SORD-CMT Natural History and Epalrestat Treatment
NCT06482437	PHASE2	COMPLETED	Safety and Efficacy of NMD670 in Adult Patients With Type 1 and Type 2 Charcot-Marie-Tooth Disease
NCT01289704	PHASE2/PHASE3	UNKNOWN	Treadmill, Stretching and Proprioceptive Exercise (TreSPE) Rehabilitation Program for Charcot-Marie-Tooth Neuropathy Type 1A (CMT1A)
NCT00541164	PHASE1/PHASE2	COMPLETED	Effects of Coenzyme Q10 on Charcot-Marie-Tooth Disease
NCT05361031	PHASE1/PHASE2	COMPLETED	The Safety and Tolerability of Engensis (VM202) in Patients With Charcot-Marie-Tooth Disease Subtype 1A (CMT1A)
NCT07223632	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Treatment of Charcot-Marie-Tooth Disease, Axonal, Type 2S (CMT2S) in an Individual Patient
NCT00149045	Not specified	COMPLETED	Follow up and Observation of Charcot Marie Tooth Disease in Families
NCT01193075	Not specified	RECRUITING	Natural History Evaluation of Charcot Marie Tooth Disease (CMT) Types CMT1B, CMT2A, CMT4A, CMT4C, and Others
NCT01203085	Not specified	COMPLETED	Development of Charcot Marie Tooth Disease (CMT) Pediatric Scale for Children With CMT
NCT01455623	Not specified	COMPLETED	Development and Validation of a Disability Severity Index for CMT
NCT01918826	Not specified	UNKNOWN	Evaluation of the Analgesic Efficiency of the Transcutaneous Neurostimulation in the Charcot Syndrome Marie Tooth on the Pains of Lower Limbs
NCT02001038	Not specified	COMPLETED	Survey of Current Management of Orthopaedic Complications in CMT Patients
NCT02011204	Not specified	COMPLETED	Study of Electrical Impedance Myography (EIM) in ALS
NCT02194010	Not specified	COMPLETED	Disability Severity Scale (DSI) and Hereditary Motor and Sensory Neuropathy Overall Disability Scale (HMSN-R-ODS)
NCT02429947	Not specified	COMPLETED	An Analysis of the Symptomatic Domains Most Relevant to Charcot Marie Tooth Neuropathy (CMT) Patients
NCT02532244	Not specified	COMPLETED	Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT02788734	Not specified	COMPLETED	Patient Reported Outcomes Measures (PROM) in Carpal Tunnel Therapies in Patients With Inherited Neuropathies
NCT02979145	Not specified	UNKNOWN	Charcot-Marie-Tooth Disease (CMT) Infant Scale (INC-6611)
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project
NCT03460951	Not specified	COMPLETED	Diffusion Tensor Imaging in Chronic Inflammatory Demyelinating Polyneuropathy (PIDC)
NCT03715283	Not specified	COMPLETED	Change in MUNIX in Patients With CMT1A Undergoing a Home Ankle Strengthening Program Versus Standard of Care
NCT03782883	Not specified	COMPLETED	The Impact of Charcot-Marie-Tooth Disease in the Real World
NCT03810508	Not specified	TERMINATED	A Natural History Study of Charcot-Marie-Tooth 4J (CMT4J)
NCT03966287	Not specified	COMPLETED	Analysis of Pain and Quality of Life in Patients With Charcot-Marie-Tooth Neuropathy (CMT)
NCT04010188	Not specified	RECRUITING	A Registered Cohort Study on Charcot-Marie-Tooth Disease
NCT04283175	Not specified	COMPLETED	Validation Study of Posturology Platforms for Evaluating Postural Control of Hemiparetic and Neuro-muscular Patients
NCT04461613	Not specified	UNKNOWN	Physical Activity in Persons With Charcot-Marie-Tooth: Developing a Measurement Instrument
NCT04786522	Not specified	COMPLETED	Irisin Levels in Patients With Charcot-Marie-Tooth (CMT) Disease
NCT04967716	Not specified	UNKNOWN	Genetics of Charcot-Marie-Tooth Dystrophy and Related Diseases
NCT04980807	Not specified	COMPLETED	Observational Study of Neuromuscular Function in CMT Type 1&2 and Healthy Controls
NCT05011006	Not specified	NOT_YET_RECRUITING	NT-3 Levels and Function in Individuals With CMT