HSPA6

Summary

HSPA6 (heat shock protein family A (Hsp70) member 6, HGNC:5239) is a protein-coding gene on chromosome 1q23.3, encoding Heat shock 70 kDa protein 6 (P17066). Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein comple….

Enables several functions, including ATP hydrolysis activity; heat shock protein binding activity; and unfolded protein binding activity. Involved in cellular response to heat and protein refolding. Located in COP9 signalosome; centriole; and cytosol.

Source: NCBI Gene 3310 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 113 total
• Druggable target: yes
• MANE Select transcript: NM_002155

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5239
Approved symbol	HSPA6
Name	heat shock protein family A (Hsp70) member 6
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Aliases	HSP70B'
Ensembl gene	ENSG00000173110
Ensembl biotype	protein_coding
OMIM	140555
Entrez	3310

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000309758

RefSeq mRNA: 1 — MANE Select: NM_002155 NM_002155

CCDS: CCDS1231

Canonical transcript exons

ENST00000309758 — 1 exons

Exon	Start	End
ENSE00001205191	161524540	161526894

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 97.77.

FANTOM5 (CAGE): breadth broad, TPM avg 11.7751 / max 6236.8834, expressed in 199 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6263	11.7751	199

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	97.77	gold quality
granulocyte	CL:0000094	94.72	gold quality
leukocyte	CL:0000738	91.24	gold quality
monocyte	CL:0000576	91.05	gold quality
spleen	UBERON:0002106	88.78	gold quality
omental fat pad	UBERON:0010414	84.60	gold quality
lower esophagus mucosa	UBERON:0035834	83.46	gold quality
upper lobe of left lung	UBERON:0008952	82.08	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	81.80	gold quality
placenta	UBERON:0001987	81.38	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.44	gold quality
adipose tissue	UBERON:0001013	79.59	gold quality
left adrenal gland cortex	UBERON:0035825	79.44	gold quality
right adrenal gland cortex	UBERON:0035827	78.90	gold quality
vermiform appendix	UBERON:0001154	78.73	gold quality
left adrenal gland	UBERON:0001234	78.08	gold quality
gall bladder	UBERON:0002110	77.90	gold quality
descending thoracic aorta	UBERON:0002345	77.78	gold quality
ascending aorta	UBERON:0001496	77.58	gold quality
lung	UBERON:0002048	77.54	gold quality
thoracic aorta	UBERON:0001515	77.41	gold quality
right atrium auricular region	UBERON:0006631	76.96	gold quality
right adrenal gland	UBERON:0001233	76.71	gold quality
apex of heart	UBERON:0002098	76.65	gold quality
right coronary artery	UBERON:0001625	76.37	gold quality
adenohypophysis	UBERON:0002196	76.24	gold quality
right lung	UBERON:0002167	75.91	gold quality
subcutaneous adipose tissue	UBERON:0002190	75.76	gold quality
mucosa of stomach	UBERON:0001199	75.59	gold quality
right lobe of liver	UBERON:0001114	75.56	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-CURD-95	yes	6443.27
E-MTAB-10137	yes	5522.51
E-CURD-88	yes	2838.19
E-CURD-10	yes	1002.00
E-MTAB-10290	yes	537.77
E-GEOD-135922	yes	13.53
E-MTAB-8498	yes	10.66
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HSF1, HSF2, SATB1

miRNA regulators (miRDB)

20 targeting HSPA6, 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-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-3908	98.75	67.31	1160
HSA-MIR-4731-3P	98.56	68.60	1860
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-6779-3P	97.51	65.82	789
HSA-MIR-1227-3P	97.36	66.94	834
HSA-MIR-6515-5P	97.08	65.48	1219
HSA-MIR-125B-2-3P	96.69	68.38	1210
HSA-MIR-6800-5P	94.59	64.80	525

Literature-anchored findings (GeneRIF, showing 26)

• These findings are likely to be important in pathological conditions in which Hsp70B’ contributes to cell survival. (PMID:18229458)
• Hsp70B’ expressed on colon cells after proteasome inhibition was most closely related to Hsp72. They shared 100% AA identity in the peptide-binding region but differed in the lid and C-terminal domains.Hsp70B’ appeared to have diverged recently. (PMID:18347947)
• higher expression of HSPA6 & HSPA1A was exhibited in placental vascular disease (PVD)subjects compared to normal pregnancy; significant upregulation of HSP70 mRNA & protein in placental tissue & microvascular endothelial cells of PVD subjects was observed (PMID:18372927)
• Hsp70B’ and Hsp72 play cooperative roles in cell survival of proteotoxic stress. (PMID:18579131)
• Hsp70B’ also formed complexes with Hsp40 suggesting a common co-chaperone for HSP70 family members. (PMID:20084477)
• Heat shock protein 70B’ (HSP70B’) expression and release in response to human oxidized low density lipoprotein immune complexes in macrophages. (PMID:20348092)
• Following a brief period of thermal stress, YFP-tagged HSPA6 and HSPA1A rapidly appeared at centrioles in the cytoplasm of human neuronal cells. (PMID:24061851)
• Potential stress-sensitive sites were identified in differentiated human SH-SY5Y cells by the localization of HSPA6 (HSP70B’) and HSPA1A (HSP70-1) to nuclear components following heat shock (PMID:25319762)
• HSPA6 regulation by TNIP1 occurs in promoter regions lacking binding sites for known TNIP1-repressed transcription factors (PMID:25447897)
• High BCLC staging scores, advanced cirrhosis and the overexpression of HSPA12A and HSP90B1 might be associated with poor survival from HCC, whereas high levels of HSPA4, HSPA5 and HSPA6 might be associated with earlier recurrence of HCC (PMID:25798051)
• Data indicate that heat shock protein 90kD(HSP90) inhibition induces heat shock 70kD protein 6 (HSP70B’) expression. (PMID:25957766)
• endothelial nitric oxide synthase induces heat shock protein HSPA6 (HSP70B’) in human arterial smooth muscle cells (PMID:26656590)
• HSPA6 is a cigarette smoke-induced ulcerative colitis (UC)-susceptibility gene. The HSPA6 risk locus is associated with decreased HSPA6 expression. HSPA6 provides epithelial protection by stabilizing anti-apoptotic Bcl-XL, thereby contributing to the beneficial effect of cigarette smoking in UC. (PMID:26826017)
• measurable HSP70B’ was not associated with graft versus host disease following allogeneic hematopoietic cell transplantation (PMID:27020764)
• mRNA levels of HSP family members (HSP70B’, HSP72, HSP40/DNAJ, and HSP20/CRYAB) are upregulated by the intracellular MMP3 overload. (PMID:27206651)
• during recovery from neuronal stress, HSPA6 localized with perispeckles that have been characterized as transcription sites; the stress-induced association of HSPA6 with perispeckles displayed the greatest dynamism compared to the interaction of HSPA6 or HSPA1A with other stress-sensitive cytoplasmic and nuclear structures; this suggests involvement of HSPA6 in recovery of neurons from cellular stress (PMID:27527722)
• We found that HSF1 activation mediated by 1,4-NQ upregulated downstream genes, such as HSPA6. The results suggest that activation of the HSP90-HSF1 signal transduction pathway mediated by 1,4-NQ protects cells against 1,4-NQ and that per/polysulfides can diminish the reactivity of 1,4-NQ by forming sulfur adducts. (PMID:28049024)
• In vivo efficacy experiments with HSPA6 siRNA and MFH were performed using the A2780cp20 and HeyA8 ovarian cancer mouse models. A significantly reduction in tumor growth rate was observed with combination therapy. PES and MFH efficacy were also evaluated in the HeyA8 intraperitoneal tumor model, and resulted in robust antitumor effects. (PMID:28223424)
• that HSPA6 and HSPA1A contribute to protection of differentiated human neuronal cells from cellular stress (PMID:29090408)
• Increased systemic HSP70B levels in spinal muscular atrophy infants. (PMID:33991176)
• Re-sequencing of candidate genes FOXF1, HSPA6, HAAO, and KYNU in 522 individuals with VATER/VACTERL, VACTER/VACTERL-like association, and isolated anorectal malformation. (PMID:35362267)
• Alterations in Proteostasis System Components in Peripheral Blood Mononuclear Cells in Parkinson Disease: Focusing on the HSP70 and p62 Levels. (PMID:35454081)
• HSPA6 and its role in cancers and other diseases. (PMID:35666422)
• BARX1 promotes osteosarcoma cell proliferation and invasion by regulating HSPA6 expression. (PMID:36927457)
• PP4R1 accelerates the malignant progression of NSCLC via up-regulating HSPA6 expression and HSPA6-mediated ER stress. (PMID:37739270)
• ROR2 deficit may induce the tetralogy of Fallot via down-regulating of beta-catenin/SOX3/HSPA6 in vitro and in vivo. (PMID:37749917)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	Hsp110	FBGN0026418
caenorhabditis_elegans	hsp-70	WBGENE00002026
caenorhabditis_elegans		WBGENE00009691
caenorhabditis_elegans		WBGENE00009692
caenorhabditis_elegans		WBGENE00016250

Paralogs (13): HSPA5 (ENSG00000044574), HSPA8 (ENSG00000109971), HSPA9 (ENSG00000113013), HSPH1 (ENSG00000120694), HSPA2 (ENSG00000126803), HYOU1 (ENSG00000149428), HSPA13 (ENSG00000155304), HSPA4L (ENSG00000164070), HSPA4 (ENSG00000170606), HSPA14 (ENSG00000187522), HSPA1B (ENSG00000204388), HSPA1A (ENSG00000204389), HSPA1L (ENSG00000204390)

Protein

Protein identifiers

Heat shock 70 kDa protein 6 — P17066 (reviewed: P17066)

Alternative names: Heat shock 70 kDa protein B’, Heat shock protein family A member 6

All UniProt accessions (2): P17066, A0A384NKX5

UniProt curated annotations — full annotation on UniProt →

Function. Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release.

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

Induction. Only at higher temperatures, and no basal expression.

Similarity. Belongs to the heat shock protein 70 family.

RefSeq proteins (1): NP_002146* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00012

UniProt features (73 total): sequence variant 22, strand 17, helix 15, turn 6, binding site 5, region of interest 3, sequence conflict 2, chain 1, mutagenesis site 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3FE1	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17066-F1	89.02	0.67

Functional residue map

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

Ligand- & substrate-binding residues (5): 14–17; 73; 204–206; 270–277; 341–344

Post-translational modifications (1): 563

Mutagenesis-validated functional residues (1):

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

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-3371453	Regulation of HSF1-mediated heat shock response
R-HSA-6798695	Neutrophil degranulation
R-HSA-3371511	HSF1 activation
R-HSA-3371568	Attenuation phase
R-HSA-3371571	HSF1-dependent transactivation

MSigDB gene sets: 221 (showing top): TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, REACTOME_INNATE_IMMUNE_SYSTEM, BENPORATH_ES_WITH_H3K27ME3, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOCC_SECRETORY_GRANULE, PEREZ_TP63_TARGETS, KEGG_MAPK_SIGNALING_PATHWAY, MODULE_45, RIZKI_TUMOR_INVASIVENESS_3D_DN, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_PROTEIN_MATURATION, LU_TUMOR_VASCULATURE_UP, DAUER_STAT3_TARGETS_DN, GOBP_PROTEIN_FOLDING

GO Biological Process (3): response to unfolded protein (GO:0006986), cellular response to heat (GO:0034605), protein refolding (GO:0042026)

GO Molecular Function (9): ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), enzyme binding (GO:0019899), heat shock protein binding (GO:0031072), 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)

GO Cellular Component (11): extracellular region (GO:0005576), nucleus (GO:0005634), cytoplasm (GO:0005737), centriole (GO:0005814), cytosol (GO:0005829), plasma membrane (GO:0005886), secretory granule lumen (GO:0034774), extracellular exosome (GO:0070062), blood microparticle (GO:0072562), ficolin-1-rich granule lumen (GO:1904813), COP9 signalosome (GO:0008180)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cellular response to heat stress	3
Innate Immune System	1
HSF1-dependent transactivation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein folding	2
ATP-dependent activity	2
protein binding	2
response to topologically incorrect protein	1
response to heat	1
cellular response to stress	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
molecular_function	1
protein folding chaperone	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
microtubule organizing center	1
intracellular membraneless organelle	1
cytoplasm	1
membrane	1
cell periphery	1
secretory granule	1
cytoplasmic vesicle lumen	1
extracellular vesicle	1
extracellular region	1
intracellular organelle lumen	1
ficolin-1-rich granule	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

4769 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HSPA6	HSP90AB1	P08238	755
HSPA6	DNAJB4	Q9UDY4	722
HSPA6	DNAJB1	P25685	688
HSPA6	HSPB1	P04792	683
HSPA6	PGM1	P36871	672
HSPA6	HSP90AA1	P07900	633
HSPA6	HSPB2	Q16082	629
HSPA6	HSPB3	Q12988	623
HSPA6	HSPA12A	O43301	557
HSPA6	DNAJA1	P31689	527
HSPA6	HSPA12B	Q96MM6	525
HSPA6	FOSB	P53539	520
HSPA6	FOXC1	Q12948	505
HSPA6	DNAJA4	Q8WW22	502
HSPA6	BAG3	O95817	500

IntAct

241 interactions, top by confidence:

A	B	Type	Score
MAP3K14	CHUK	psi-mi:“MI:0914”(association)	0.950
PPP5C	HSP90AA1	psi-mi:“MI:0914”(association)	0.870
IFT70B	IFT56	psi-mi:“MI:0914”(association)	0.790
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
IFT27	IFT56	psi-mi:“MI:0914”(association)	0.690
BRAF	KRAS	psi-mi:“MI:0914”(association)	0.680
RAF1	CALU	psi-mi:“MI:0914”(association)	0.640
BAG4	HSPA6	psi-mi:“MI:0915”(physical association)	0.560
HSPA6	COMMD6	psi-mi:“MI:0915”(physical association)	0.560
HSPA6	LGALS7	psi-mi:“MI:0915”(physical association)	0.560
HSPA6	KRT222	psi-mi:“MI:0915”(physical association)	0.560
HSPA6	C22orf15	psi-mi:“MI:0915”(physical association)	0.560
AHCYL1	HSPA6	psi-mi:“MI:0915”(physical association)	0.560
HSPA6	RPA1	psi-mi:“MI:0915”(physical association)	0.560
HSPA6	PPIB	psi-mi:“MI:0915”(physical association)	0.560
HSPA6	PRAP1	psi-mi:“MI:0915”(physical association)	0.560
HSPA6	FLNA	psi-mi:“MI:0915”(physical association)	0.560
TUBB3	POTEF	psi-mi:“MI:0914”(association)	0.530
KLHL34	BAG3	psi-mi:“MI:0914”(association)	0.530
ILK	HSPA8	psi-mi:“MI:0914”(association)	0.530
ABHD15	HSPA8	psi-mi:“MI:0914”(association)	0.530
PRKCZ	IPO5	psi-mi:“MI:0914”(association)	0.530
RPS6KA1	HSP90AA1	psi-mi:“MI:0914”(association)	0.530
TRABD	FCN1	psi-mi:“MI:0914”(association)	0.530
GNB2	PFDN6	psi-mi:“MI:0914”(association)	0.530
RFFL	TUSC2	psi-mi:“MI:0914”(association)	0.530

BioGRID (485): HSPA6 (Affinity Capture-MS), DNAJA1 (Affinity Capture-Western), DNAJA2 (Affinity Capture-Western), DNAJA4 (Affinity Capture-Western), DNAJB1 (Affinity Capture-Western), DNAJB4 (Affinity Capture-Western), DNAJB5 (Affinity Capture-Western), DNAJB6 (Affinity Capture-Western), DNAJB7 (Affinity Capture-Western), DNAJB8 (Affinity Capture-Western), HSPA6 (Affinity Capture-MS), HSPA6 (Affinity Capture-MS), HSPA6 (Affinity Capture-MS), HSPA6 (Affinity Capture-MS), HSPA6 (Affinity Capture-MS)

ESM2 similar proteins: A5D6R3, A7YW45, D4A1R8, H1UBN0, O14744, O35920, O75131, O95741, P10688, P10895, P17066, P23475, P31254, P51178, P59108, Q04967, Q08DB4, Q0VE82, Q1RLL3, Q28HC6, Q298L5, Q2KHY1, Q32NH8, Q4QR99, Q4R5M3, Q5BJS7, Q5R4W6, Q5R698, Q5RAE1, Q5RET0, Q5XQC7, Q6NUA1, Q86YQ8, Q8BLR2, Q8BT60, Q8C166, Q8CIG8, Q8GWT4, Q8IMX7, Q8IYJ1

Diamond homologs: A0A509AJG0, A2Q0Z1, A5A8V7, G3I8R9, O24581, O59855, O73885, P02827, P06761, P07823, P08106, P08108, P08418, P09189, P0CB32, P0DMV8, P0DMV9, P0DMW0, P0DMW1, P10591, P10592, P11021, P11142, P11147, P14659, P16474, P16627, P17066, P17156, P17879, P19120, P19208, P19378, P20029, P20163, P22202, P22954, P24067, P26413, P27420

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
HSF1	“up-regulates quantity by expression”	HSPA6	“transcriptional regulation”
HSF2	“up-regulates quantity by expression”	HSPA6	“transcriptional regulation”
SATB1	“down-regulates quantity by repression”	HSPA6	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 212 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
MAP3K8 (TPL2)-dependent MAPK1/3 activation	5	22.9×	7e-05
CD209 (DC-SIGN) signaling	5	16.6×	3e-04
activated TAK1 mediates p38 MAPK activation	5	15.9×	4e-04
TRAF6 mediated NF-kB activation	5	14.6×	5e-04
Dengue Virus Genome Translation and Replication	7	14.2×	5e-05
MAP kinase activation	7	13.8×	5e-05
Constitutive Signaling by AKT1 E17K in Cancer	5	13.6×	6e-04
TAK1-dependent IKK and NF-kappa-B activation	7	13.5×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
non-canonical NF-kappaB signal transduction	7	31.0×	6e-07
TORC1 signaling	5	21.1×	3e-04
protein refolding	6	19.7×	8e-05
canonical NF-kappaB signal transduction	9	17.4×	6e-07
insulin-like growth factor receptor signaling pathway	6	15.7×	3e-04
extrinsic apoptotic signaling pathway via death domain receptors	7	14.8×	8e-05
response to unfolded protein	7	11.1×	3e-04
response to heat	5	11.1×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	107
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

4 predictions. Top by Δscore:

Variant	Effect	Δscore
1:161525316:G:GC	acceptor_gain	0.5100
1:161524784:C:G	donor_gain	0.2300
1:161524647:G:GT	donor_gain	0.2100
1:161524913:GC:G	donor_gain	0.2000

AlphaMissense

4221 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:161525188:A:T	E177V	1.000
1:161525260:A:T	D201V	1.000
1:161525477:G:C	K273N	1.000
1:161525477:G:T	K273N	1.000
1:161525676:G:A	G340R	1.000
1:161525676:G:C	G340R	1.000
1:161525676:G:T	G340W	1.000
1:161525677:G:A	G340E	1.000
1:161525677:G:T	G340V	1.000
1:161525680:G:A	G341D	1.000
1:161524782:A:C	S42R	0.999
1:161524784:C:A	S42R	0.999
1:161524784:C:G	S42R	0.999
1:161524877:G:C	K73N	0.999
1:161524877:G:T	K73N	0.999
1:161525104:C:A	P149H	0.999
1:161525104:C:G	P149R	0.999
1:161525112:T:C	F152L	0.999
1:161525114:C:A	F152L	0.999
1:161525114:C:G	F152L	0.999
1:161525127:C:A	R157S	0.999
1:161525128:G:C	R157P	0.999
1:161525187:G:A	E177K	0.999
1:161525188:A:C	E177A	0.999
1:161525189:G:C	E177D	0.999
1:161525189:G:T	E177D	0.999
1:161525200:C:A	A181D	0.999
1:161525260:A:C	D201A	0.999
1:161525261:C:A	D201E	0.999
1:161525261:C:G	D201E	0.999

dbSNP variants (sampled 300 via entrez): RS1000837579 (1:161523429 T>G), RS1002108704 (1:161523889 C>A,T), RS1003814009 (1:161524128 C>T), RS1006012126 (1:161523811 G>A,C), RS1006686826 (1:161524603 A>T), RS1009898626 (1:161523544 G>C), RS1009927780 (1:161523231 T>C,G), RS1010530923 (1:161524320 C>T), RS1011062918 (1:161524154 T>C), RS1012032638 (1:161523892 G>A,C,T), RS1013958839 (1:161526732 A>C,G), RS1014468660 (1:161523146 C>G), RS1014878748 (1:161523631 C>CA), RS1015254375 (1:161526189 C>T), RS1015743543 (1:161522876 C>T)

Disease associations

OMIM: gene MIM:140555 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000964_2	Ulcerative colitis	2.000000e-20
GCST001725_37	Inflammatory bowel disease	2.000000e-38
GCST002014_2	Helicobacter pylori serologic status	2.000000e-08
GCST002188_2	Functional impairment in major depressive disorder, bipolar disorder and schizophrenia	3.000000e-06
GCST004131_77	Inflammatory bowel disease	9.000000e-14
GCST004133_13	Ulcerative colitis	2.000000e-18
GCST005537_144	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	8.000000e-07
GCST008362_143	Birth weight	4.000000e-10
GCST008362_93	Birth weight	4.000000e-11
GCST008363_18	Offspring birth weight	8.000000e-09
GCST90011898_29	Alanine aminotransferase levels	8.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005412	functional impairment measurement
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3232688 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — Heat shock proteins

PubChem BioAssay actives

1 with measured affinity, of 74 total; 1 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-[(2S,3R)-1-[(4,5-dimethyl-1,3-thiazol-2-yl)amino]-3-methyl-1-oxopentan-2-yl]-1H-indole-2-carboxamide	1968963: Inhibition of HspA6 (unknown origin) by FP assay	ic50	0.5000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	7
Cadmium	increases abundance, increases expression	7
Silicon Dioxide	increases expression	5
Tobacco Smoke Pollution	increases expression	5
Cadmium Chloride	decreases expression, increases abundance, increases expression	5
Arsenic Trioxide	increases expression, increases reaction, decreases reaction	4
methylmercuric chloride	affects reaction, increases expression	3
Bortezomib	increases expression	3
Cisplatin	affects cotreatment, increases expression	3
Copper	affects binding, decreases expression, increases expression	3
Estradiol	decreases expression, increases expression, affects cotreatment	3
Silver	increases expression	3
Cyclosporine	increases expression	3
Particulate Matter	affects cotreatment, increases abundance, increases expression	3
bisphenol A	decreases expression	2
pyrithione zinc	increases expression	2
2-butenal	affects cotreatment, increases expression	2
arsenite	increases reaction, increases expression, affects binding	2
perfluorooctanoic acid	increases expression	2
cupric oxide	increases expression	2
Troglitazone	increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Dinitrochlorobenzene	increases expression	2
Formaldehyde	increases expression	2
Nickel	increases expression	2
Tetradecanoylphorbol Acetate	affects cotreatment, increases expression, decreases expression	2
Thiram	increases expression	2
Zinc	increases expression, affects cotreatment	2
Asbestos, Crocidolite	increases expression	2
Copper Sulfate	increases expression	2

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3242437	Binding	Induction of HSP90B’ (unknown origin)-mediated heat shock response expressed in human 293T cells coexpressing GFP assessed as heat shock index after overnight incubation by luciferase reporter gene assay relative to control	Structure-activity relationships for withanolides as inducers of the cellular heat-shock response. — J Med Chem

Clinical trials (associated diseases)

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