DNAJB1

Summary

DNAJB1 (DnaJ heat shock protein family (Hsp40) member B1, HGNC:5270) is a protein-coding gene on chromosome 19p13.12, encoding DnaJ homolog subfamily B member 1 (P25685). Interacts with HSP70 and can stimulate its ATPase activity. It is a selective cancer dependency (DepMap: 10.0% of cell lines).

This gene encodes a member of the DnaJ or Hsp40 (heat shock protein 40 kD) family of proteins. DNAJ family members are characterized by a highly conserved amino acid stretch called the ‘J-domain’ and function as one of the two major classes of molecular chaperones involved in a wide range of cellular events, such as protein folding and oligomeric protein complex assembly. The encoded protein is a molecular chaperone that stimulates the ATPase activity of Hsp70 heat-shock proteins in order to promote protein folding and prevent misfolded protein aggregation. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 3337 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 66 total
• Cancer dependency (DepMap): dependent in 10.0% of screened cell lines
• MANE Select transcript: NM_006145

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5270
Approved symbol	DNAJB1
Name	DnaJ heat shock protein family (Hsp40) member B1
Location	19p13.12
Locus type	gene with protein product
Status	Approved
Aliases	Hsp40, Sis1, RSPH16B
Ensembl gene	ENSG00000132002
Ensembl biotype	protein_coding
OMIM	604572
Entrez	3337

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 20 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000254322, ENST00000396969, ENST00000594099, ENST00000595139, ENST00000595992, ENST00000596075, ENST00000596853, ENST00000598235, ENST00000598692, ENST00000601087, ENST00000601533, ENST00000676515, ENST00000676577, ENST00000676971, ENST00000676982, ENST00000677113, ENST00000677204, ENST00000677762, ENST00000677790, ENST00000677848, ENST00000678009, ENST00000678098, ENST00000678338, ENST00000678628, ENST00000679223

RefSeq mRNA: 3 — MANE Select: NM_006145 NM_001300914, NM_001313964, NM_006145

CCDS: CCDS12312, CCDS74295

Canonical transcript exons

ENST00000254322 — 3 exons

Exon	Start	End
ENSE00000902162	14514769	14516170
ENSE00000902164	14518139	14518397
ENSE00003638874	14516466	14517046

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 69.3060 / max 7601.5079, expressed in 1824 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179657	48.1786	1812
179658	15.8767	1808
179655	1.5385	1041
179659	1.0801	706
179661	1.0312	578
179652	0.5871	285
179654	0.5565	148
179653	0.4091	197
179664	0.0265	12
179663	0.0216	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.56	gold quality
gall bladder	UBERON:0002110	98.94	gold quality
pharyngeal mucosa	UBERON:0000355	98.92	gold quality
esophagus mucosa	UBERON:0002469	98.89	gold quality
left testis	UBERON:0004533	98.42	gold quality
ventricular zone	UBERON:0003053	98.28	gold quality
trachea	UBERON:0003126	98.24	gold quality
right testis	UBERON:0004534	98.24	gold quality
buccal mucosa cell	CL:0002336	98.16	gold quality
epithelium of esophagus	UBERON:0001976	97.68	gold quality
vagina	UBERON:0000996	97.65	gold quality
cardia of stomach	UBERON:0001162	97.64	gold quality
esophagus squamous epithelium	UBERON:0006920	97.59	gold quality
adrenal tissue	UBERON:0018303	97.48	gold quality
oral cavity	UBERON:0000167	97.43	gold quality
vena cava	UBERON:0004087	97.36	gold quality
peritoneum	UBERON:0002358	97.31	gold quality
omental fat pad	UBERON:0010414	97.31	gold quality
ganglionic eminence	UBERON:0004023	97.22	gold quality
body of tongue	UBERON:0011876	97.20	gold quality
esophagus	UBERON:0001043	97.19	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.10	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.07	gold quality
skin of abdomen	UBERON:0001416	97.05	gold quality
testis	UBERON:0000473	97.03	gold quality
right lobe of liver	UBERON:0001114	96.88	gold quality
right adrenal gland	UBERON:0001233	96.74	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.66	gold quality
islet of Langerhans	UBERON:0000006	96.65	gold quality
tongue squamous epithelium	UBERON:0006919	96.65	gold quality

Single-cell (SCXA)

Detected in 28 experiment(s), a significant marker in 20.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	17491.55
E-CURD-89	yes	17401.86
E-CURD-122	yes	5843.36
E-CURD-88	yes	5739.11
E-HCAD-36	yes	4874.35
E-MTAB-4850	yes	3067.39
E-ENAD-20	yes	2925.85
E-MTAB-9841	yes	2777.58
E-MTAB-9221	yes	2512.79
E-GEOD-114530	yes	2162.49
E-MTAB-10287	yes	2145.22
E-GEOD-180759	yes	1818.14
E-GEOD-134144	yes	1289.53
E-MTAB-6379	yes	1160.14
E-CURD-98	yes	903.14

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HSF1, MYC, ZNF699

miRNA regulators (miRDB)

70 targeting DNAJB1, 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-12118	100.00	65.88	1270
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-4696	99.48	67.48	1040

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 10.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Altered expression of HSPF1 was found in brains and lymphoblastoid cells from patients with bipolar disorder. (PMID:14743183)
• sequestered in discrete foci in the nucleus of the infected cell in herpes simplex virus type 1 infection (PMID:15194794)
• It is confirmed an increased expression of HSPF1 in the lymphoblastoid cell lines from patients with bipolar I disorder, bipolar II disorder, and schizophrenia. (PMID:15362566)
• Hsp40 is crucial for Nef-mediated enhancement of viral gene expression and replication (PMID:16179353)
• hepatitis B virus X protein is the major target of Hdj1 in the inhibition of hepatitis B virus replication (PMID:16842747)
• These results demonstrate a role for Hsp40/DnaJB6 in the regulation of HIV-2 PIC nuclear transport. (PMID:18032501)
• The 2.7A structure reveals that Hdj1 forms a homodimer in the crystal by a crystallographic two-fold axis. (PMID:18211704)
• 5-fluorouracil & carboplatin specifically induce expression of Hsp40 in hepatoma cells. siRNA knockdown of Hsp40 diminishes survival of drug-exposed cells. (PMID:19901540)
• Data show that GM significantly suppressed refolding of firefly luciferase in the presence of HSP70 and HSP40. (PMID:20026329)
• Hsp70B’ also formed complexes with Hsp40 suggesting a common co-chaperone for HSP70 family members. (PMID:20084477)
• Data show that HSP70, GRP78/BiP and HSP40/DnaJ each independently suppressed hA misfolding. (PMID:20735358)
• Determined are crystal structures of the C-terminal peptide-binding domain of human Hsp40 Hdj1 (CTD) and of its complex with the C-terminal octapeptide of human Hsp70, (634’)GPTIEEVD(641’). (PMID:20809635)
• The crystal structure of full-length Hdj1 was diffracted to 3.90A resolution. (PMID:21139202)
• The antiviral activity of overexpressed DNAJC14 occurs in a time- and dose-dependent manner. (PMID:21249176)
• HSF1 and major HSP’s are expressed strongly in classical Hodgkin lymphoma. (PMID:21480956)
• Chaperone activity of proteins Hsp70 and Hdj1 in human leukemia u-937 cells were increased after heat shock. (PMID:21639839)
• Cellular localization studies showed that NP and Hsp40 co-localize primarily in the nucleus. During IAV infection in mammalian cells, expression of NP coincided with the dissociation of P58(IPK) from Hsp40 and decrease PKR phosphorylation (PMID:21698289)
• Differential expression of Hsp40 and Hsp70 reciprocally regulates viral gene expression and replication in HIV-1 infection. (PMID:21763498)
• Mammalian Hsp110 (Apg-2), Hsp70 (Hsc70 or Hsp70) and Hsp40 (Hdj1) were necessary and sufficient to slowly dissolve large disordered aggregates and recover natively folded protein (PMID:22022600)
• Hsp40 regulates the amount of keratin proteins via ubiquitin-proteasome pathway. (PMID:22075554)
• methionine deprivation results in an antioxidant response that includes an increase in the levels of HSPA1A and DNAJB1 mRNA (PMID:23395854)
• There was a positive correlation between DnaJB1 and severity of pulmonary arterial hypertension in peripheral blood mononuclear cells from patients with limited cutaneous systemic sclerosis. (PMID:23400395)
• Results show that TDP-43 is constitutively bound to members of the Hsp40/Hsp70 family, and that heat shock-induced TDP-43 aggregation is mediated by the availability of these chaperones interacting with the inherently disordered C-terminal prion domain. (PMID:23962724)
• HSP40 and HSP110 function together in protein homeostasis control. (PMID:24091676)
• Httex1 overstretches the protein quality control resources and that the defects can be partly rescued by overexpression of hsp40 and hsp70. (PMID:24196953)
• Studies with specific phosphoantibodies indicate that MK5 phosphorylates Hsp40/DnaJB1 in vivo at Ser-149 or/and Ser-151 and Ser-171 in the C-terminal domain of Hsp40/DnaJB1. (PMID:24309468)
• we combined the Hsp70-NEF pairs with cochaperones of the J protein family (DnaJA1, DnaJA2, DnaJB1, and DnaJB4) to generate 16 permutations. (PMID:24318877)
• we discovered a new MDM2 interacting protein, DNAJB1, and provided evidence to support its p53-dependent tumor suppressor function. (PMID:24361594)
• Evidence supporting the presence of the DNAJB1-PRKACA chimeric transcript in 100% of the FL-HCCs examined (15/15) suggests that this genetic alteration contributes to tumor pathogenesis. (PMID:24578576)
• HSP40 interacts with pyruvate kinase M2 and regulates glycolysis and cell proliferation in tumor cells. (PMID:24658033)
• We also found that, despite an initial report to the contrary, the human homolog of Sis1, Hdj1, is capable of [PSI+] prion propagation in place of Sis1 (PMID:25058638)
• Whole exome sequencing followed by immunohistochemistry of fibrolamellar hepatocellular carcinoma cell lines and tumors showed two structural variants resulting in fusion transcripts: DNAJB1-PRKCA and CLPTM1L-GLIS3. (PMID:25122662)
• Authors identified DNAJB1 as a negative regulator of PDCD5-mediated apoptosis and found that the apoptosis network of PDCD5 regulates cancer cell death. (PMID:25444898)
• In this cohort of fibrolamellar hepatocellular carcinoma, almost 80% contained the DNAJB1-PRKACA fusion transcript. (PMID:25557953)
• study provides a new molecular mechanism to regulate EGFR signaling through modulation of MIG6 by DNAJB1 as a negative regulator. (PMID:26239118)
• siRNA experiments confirmed that a reduction in Hsp27 or Hsp40 rescued CFTR in the DeltaF508 mutant, but the rescue was not additive or synergistic with C4 + 18 treatment, indicating these correctors shared a common pathway for rescue (PMID:26336106)
• DNAJB1-PRKACA was evaluated as a key driver of fibrolamellar carcinoma and as a candidate therapeutic target (PMID:26505878)
• These studies demonstrate an important role for cellular chaperone Hsp40/DnaJB1 in influenza A virus life cycle by assisting nuclear trafficking of viral ribonucleoproteins. (PMID:26750153)
• These results indicate that Mixed fibrolamellar hepatocellular carcinoma (mFL-HCC) is similar to pure FL-HCC at the genomic level and the DNAJB1:PRKACA fusion can be used as a diagnostic tool for both pure and mFL-HCC (PMID:27029710)
• Data show that DnaJ (Hsp40) homolog, subfamily B, member 1 (DNAJB1) is a transcriptional target of forkhead box protein E3 (FOXE3) in a pathway that is crucial for the development of the anterior segment of the eye. (PMID:27218149)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnajb6b	ENSDARG00000020953
danio_rerio	dnajb1b	ENSDARG00000041394
danio_rerio	dnajc18	ENSDARG00000056005
danio_rerio	dnajb1a	ENSDARG00000099383
mus_musculus	Dnajb1	ENSMUSG00000005483
rattus_norvegicus	Dnajb1	ENSRNOG00000021824
drosophila_melanogaster	CG2887	FBGN0030207
drosophila_melanogaster	CG5001	FBGN0031322
drosophila_melanogaster	CG3061	FBGN0038195
drosophila_melanogaster	CG30156	FBGN0050156
drosophila_melanogaster	DnaJ-1	FBGN0263106
caenorhabditis_elegans		WBGENE00001019
caenorhabditis_elegans		WBGENE00001031
caenorhabditis_elegans		WBGENE00001044

Paralogs (11): DNAJB11 (ENSG00000090520), DNAJB6 (ENSG00000105993), DNAJB9 (ENSG00000128590), DNAJB2 (ENSG00000135924), DNAJB5 (ENSG00000137094), DNAJB12 (ENSG00000148719), DNAJB4 (ENSG00000162616), DNAJB14 (ENSG00000164031), DNAJB7 (ENSG00000172404), DNAJB8 (ENSG00000179407), DNAJB13 (ENSG00000187726)

Protein

Protein identifiers

DnaJ homolog subfamily B member 1 — P25685 (reviewed: P25685)

Alternative names: DnaJ protein homolog 1, Heat shock 40 kDa protein 1, Human DnaJ protein 1

All UniProt accessions (11): A0A1B0GX60, A0A7I2V3K7, A0A7I2YQW1, P25685, M0QXK0, M0QYT3, M0QZD0, M0R080, M0R128, M0R1D6, Q6FHS4

UniProt curated annotations — full annotation on UniProt →

Function. Interacts with HSP70 and can stimulate its ATPase activity. Acts also with TTC1 as a chaperone adapter that regulates HSP70-dependent folding process by interacting with the HSP70 amino terminal region. Stimulates the association between HSC70 and HIP. Negatively regulates heat shock-induced HSF1 transcriptional activity during the attenuation and recovery phase period of the heat shock response. Stimulates ATP hydrolysis and the folding of unfolded proteins mediated by HSPA1A/B (in vitro).

Subunit / interactions. Interacts with DNAJC3. Interacts with HSF1 (via transactivation domain); this interaction results in the inhibition of heat shock- and HSF1-induced transcriptional activity during the attenuation and recovery phase period of the heat shock response. Interacts with BAG3. Interacts with TTC1 and HSP70/HSPA1A.

Subcellular location. Cytoplasm. Nucleus. Nucleolus.

Induction. By heat shock.

Isoforms (2)

UniProt ID	Names	Canonical?
P25685-1	1	yes
P25685-2	2

RefSeq proteins (3): NP_001287843, NP_001300893, NP_006136* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001623	DnaJ_domain	Domain
IPR002939	DnaJ_C	Domain
IPR008971	HSP40/DnaJ_pept-bd	Homologous_superfamily
IPR018253	DnaJ_domain_CS	Conserved_site
IPR036869	J_dom_sf	Homologous_superfamily
IPR051339	DnaJ_subfamily_B	Family

Pfam: PF00226, PF01556

UniProt features (34 total): strand 14, helix 8, sequence conflict 4, turn 3, initiator methionine 1, chain 1, domain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
3AGX	X-RAY DIFFRACTION	1.85
3AGY	X-RAY DIFFRACTION	1.85
4WB7	X-RAY DIFFRACTION	1.9
8FE2	X-RAY DIFFRACTION	2.34
9NFS	X-RAY DIFFRACTION	2.45
3AGZ	X-RAY DIFFRACTION	2.51
8FE5	X-RAY DIFFRACTION	2.51
7NDX	X-RAY DIFFRACTION	2.54
2QLD	X-RAY DIFFRACTION	2.7
8FEC	X-RAY DIFFRACTION	2.7
6BYR	X-RAY DIFFRACTION	3.66
6WJG	ELECTRON MICROSCOPY	6.2
6WJF	ELECTRON MICROSCOPY	7.5
1HDJ	SOLUTION NMR
6Z5N	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P25685-F1	83.71	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.

Post-translational modifications (1): 307

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-3371453	Regulation of HSF1-mediated heat shock response
R-HSA-3371497	HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand
R-HSA-3371568	Attenuation phase
R-HSA-3371571	HSF1-dependent transactivation
R-HSA-5687128	MAPK6/MAPK4 signaling
R-HSA-3371511	HSF1 activation

MSigDB gene sets: 399 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, AAGCAAT_MIR137, BROWNE_HCMV_INFECTION_8HR_UP, CMYB_01, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, TACAATC_MIR508, NAGASHIMA_NRG1_SIGNALING_UP, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_HEAT, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A5, YORDY_RECIPROCAL_REGULATION_BY_ETS1_AND_SP100_DN

GO Biological Process (8): negative regulation of transcription by RNA polymerase II (GO:0000122), protein folding (GO:0006457), response to unfolded protein (GO:0006986), forebrain development (GO:0030900), cellular response to heat (GO:0034605), negative regulation of inclusion body assembly (GO:0090084), regulation of cellular response to heat (GO:1900034), positive regulation of protein folding (GO:1903334)

GO Molecular Function (10): ATPase activator activity (GO:0001671), transcription corepressor activity (GO:0003714), Hsp70 protein binding (GO:0030544), protein folding chaperone (GO:0044183), cadherin binding (GO:0045296), obsolete unfolded protein binding (GO:0051082), protein-folding chaperone binding (GO:0051087), ATPase binding (GO:0051117), transcription regulator inhibitor activity (GO:0140416), protein binding (GO:0005515)

GO Cellular Component (12): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), postsynaptic density (GO:0014069), neuronal cell body (GO:0043025), dendritic spine (GO:0043197), sperm head (GO:0061827), extracellular exosome (GO:0070062), glutamatergic synapse (GO:0098978), postsynapse (GO:0098794)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Cellular response to heat stress	3
Cellular responses to stress	1
HSF1-dependent transactivation	1
MAPK family signaling cascades	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
negative regulation of DNA-templated transcription	2
protein folding	2
nuclear lumen	2
synapse	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
cellular process	1
protein maturation	1
response to topologically incorrect protein	1
brain development	1
anatomical structure development	1
response to heat	1
cellular response to stress	1
negative regulation of cellular component organization	1
inclusion body assembly	1
regulation of inclusion body assembly	1
cellular response to heat	1
regulation of cellular response to stress	1
positive regulation of cellular process	1
regulation of protein folding	1
ATP-dependent activity	1
molecular function activator activity	1
transcription coregulator activity	1
heat shock protein binding	1
protein-folding chaperone binding	1
molecular_function	1
cell adhesion molecule binding	1
protein binding	1
enzyme binding	1
regulation of gene expression	1
transcription regulator activity	1
molecular function inhibitor activity	1
binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cytoplasm	1
asymmetric synapse	1
postsynaptic specialization	1

Protein interactions and networks

STRING

4321 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAJB1	HSP90AA1	P07900	999
DNAJB1	HSP90AB1	P08238	999
DNAJB1	HSPA8	P11142	999
DNAJB1	HSPA4	P34932	999
DNAJB1	BAG1	Q99933	988
DNAJB1	STIP1	P31948	986
DNAJB1	STUB1	Q9UNE7	971
DNAJB1	HSPA1A	P08107	959
DNAJB1	FKBP4	Q02790	949
DNAJB1	ST13	P50502	942
DNAJB1	HSPBP1	Q9NZL4	942
DNAJB1	FKBP5	Q13451	928
DNAJB1	CDC37	Q16543	900
DNAJB1	HTT	P42858	896
DNAJB1	GRPEL1	Q9HAV7	892

IntAct

243 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
DNAJB1	TTLL12	psi-mi:“MI:0915”(physical association)	0.800
TELO2	TTI1	psi-mi:“MI:0914”(association)	0.760
DNAJB4	DNAJB5	psi-mi:“MI:0914”(association)	0.730
CFTR	XPO1	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
DNAJB1	CDC37	psi-mi:“MI:0915”(physical association)	0.660
NUDC	DNAJB1	psi-mi:“MI:0914”(association)	0.640
DNAJB1	DNAJB5	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
DNAJC8	SF3B1	psi-mi:“MI:0914”(association)	0.640
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
GABPB1	DNAJB1	psi-mi:“MI:0915”(physical association)	0.560
DNAJB1	TBL1X	psi-mi:“MI:0915”(physical association)	0.560
DNAJB1	TFF2	psi-mi:“MI:0915”(physical association)	0.560
DNAJB1	UNG	psi-mi:“MI:0915”(physical association)	0.560
WT1	DNAJB1	psi-mi:“MI:0915”(physical association)	0.560
PABIR3	DNAJB1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (451): DNAJB1 (Affinity Capture-MS), DNAJB1 (Two-hybrid), DNAJB1 (Affinity Capture-Western), DNAJB1 (Affinity Capture-Western), DNAJB1 (Affinity Capture-MS), DNAJB1 (Affinity Capture-MS), DNAJB1 (Affinity Capture-MS), DNAJB1 (Affinity Capture-MS), DNAJB1 (Affinity Capture-MS), DAG1 (Co-fractionation), DNAJB1 (Co-fractionation), DNAJB1 (Co-fractionation), DNAJB1 (Co-fractionation), DNAJB1 (Co-fractionation), DNAJB1 (Co-fractionation)

ESM2 similar proteins: A6QBG7, B9FHF3, O35824, O60884, O74752, O75953, O89114, O94625, O94657, P25294, P25303, P25491, P25685, P42824, P42825, P43644, P59910, P78004, P81999, Q03363, Q04960, Q09912, Q0JB88, Q24133, Q2HJ94, Q2KIT4, Q3AQP5, Q3MI00, Q3ZBA6, Q54ED3, Q5BIP8, Q5R8J8, Q5RAJ6, Q626I7, Q6MNG0, Q6TUG0, Q8A8C3, Q8GWW8, Q8MPX3, Q8TA83

Diamond homologs: A1V9Q3, A3MA88, A4G8D1, A4XYF5, A5FZ18, A5N6M3, A6Q486, A6QBG7, A6T225, A6VCL7, A9IGC5, B0VA24, B0VQ00, B2I2G6, B2TLZ8, B2V2I6, B3EE31, B3QPW8, B4S9D0, B7GV08, B7I2B2, B7V1H2, B8F7S3, B9FHF3, C1DD87, C1DFM2, D2H417, D3ZD82, F1RTY8, O42196, O75190, O75953, O89114, P0CW06, P0CW07, P25685, P30725, P43735, P56101, P60904

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
MAPKAPK5	up-regulates	DNAJB1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 211 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
Activation of BAD and translocation to mitochondria	5	26.6×	1e-04
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	23.5×	1e-04
Activation of BH3-only proteins	5	17.4×	5e-04
HCMV Infection	5	11.4×	2e-03
Translocation of SLC2A4 (GLUT4) to the plasma membrane	10	10.8×	8e-06
Intrinsic Pathway for Apoptosis	5	10.2×	4e-03
SARS-CoV-1-host interactions	8	9.8×	1e-04
SARS-CoV-2-host interactions	10	8.3×	6e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1067 predictions. Top by Δscore:

Variant	Effect	Δscore
19:14516170:CCT:C	acceptor_gain	1.0000
19:14516172:T:C	acceptor_gain	1.0000
19:14516172:T:TC	acceptor_gain	1.0000
19:14516460:CCTTA:C	donor_loss	1.0000
19:14516461:CTTA:C	donor_loss	1.0000
19:14516462:TTA:T	donor_loss	1.0000
19:14516463:TA:T	donor_loss	1.0000
19:14517045:GCC:G	acceptor_loss	1.0000
19:14517047:C:CC	acceptor_gain	1.0000
19:14517047:CTGAA:C	acceptor_loss	1.0000
19:14518134:CACA:C	donor_loss	1.0000
19:14518135:ACAC:A	donor_loss	1.0000
19:14518138:C:A	donor_loss	1.0000
19:14518141:T:TA	donor_gain	1.0000
19:14529710:AGGT:A	donor_loss	1.0000
19:14529711:GGTA:G	donor_loss	1.0000
19:14529712:GTAAG:G	donor_loss	1.0000
19:14529713:T:G	donor_loss	1.0000
19:14516167:GAGC:G	acceptor_gain	0.9900
19:14516168:AGCCT:A	acceptor_loss	0.9900
19:14516169:GC:G	acceptor_gain	0.9900
19:14516169:GCCTT:G	acceptor_loss	0.9900
19:14516171:C:CC	acceptor_gain	0.9900
19:14516172:T:A	acceptor_loss	0.9900
19:14516464:ACCT:A	donor_gain	0.9900
19:14516464:ACCTC:A	donor_gain	0.9900
19:14516465:CCT:C	donor_gain	0.9900
19:14516465:CCTC:C	donor_gain	0.9900
19:14516465:CCTCC:C	donor_gain	0.9900
19:14516467:T:TA	donor_gain	0.9900

AlphaMissense

2255 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:14516170:C:G	A265P	1.000
19:14516548:A:G	F237S	1.000
19:14516587:C:T	G224E	1.000
19:14516598:G:C	F220L	1.000
19:14516598:G:T	F220L	1.000
19:14516600:A:G	F220L	1.000
19:14516624:A:G	W212R	1.000
19:14516624:A:T	W212R	1.000
19:14516626:C:T	G211E	1.000
19:14516627:C:G	G211R	1.000
19:14516627:C:T	G211R	1.000
19:14516715:C:A	K181N	1.000
19:14516715:C:G	K181N	1.000
19:14516952:A:C	F102L	1.000
19:14516952:A:T	F102L	1.000
19:14516954:A:G	F102L	1.000
19:14518186:A:G	L55P	1.000
19:14518186:A:T	L55H	1.000
19:14518199:C:G	A51P	1.000
19:14518215:G:C	F45L	1.000
19:14518215:G:T	F45L	1.000
19:14518217:A:G	F45L	1.000
19:14518254:G:C	H32Q	1.000
19:14518254:G:T	H32Q	1.000
19:14518256:G:C	H32D	1.000
19:14516022:A:G	L314P	0.999
19:14516061:C:T	G301D	0.999
19:14516062:C:G	G301R	0.999
19:14516166:A:G	L266P	0.999
19:14516511:T:A	R249S	0.999

dbSNP variants (sampled 300 via entrez): RS1000000469 (19:14538647 C>T), RS1000239745 (19:14523143 T>C), RS1000277920 (19:14525491 A>G,T), RS1000378030 (19:14543847 T>G), RS1000579116 (19:14555127 T>G), RS1000646195 (19:14548886 C>T), RS1000700558 (19:14529351 G>A), RS1000770669 (19:14553434 T>C), RS1000816249 (19:14534415 T>G), RS1000823536 (19:14553676 A>C), RS1000881421 (19:14526977 G>C), RS1000893626 (19:14549977 GC>G), RS1000932868 (19:14520542 C>T), RS1000956889 (19:14558280 G>A), RS1000997449 (19:14548724 C>T)

Disease associations

OMIM: gene MIM:604572 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007324_158	Adventurousness	4.000000e-12
GCST007325_132	General risk tolerance (MTAG)	7.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008579	risk-taking behaviour

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases expression, increases abundance, decreases expression	8
Cadmium	increases abundance, increases expression	7
Tobacco Smoke Pollution	affects expression, increases expression	7
Arsenic Trioxide	increases expression, decreases reaction	4
Copper	affects cotreatment, increases abundance, increases expression, affects binding, decreases expression	4
Cadmium Chloride	decreases expression, increases abundance, increases expression	4
cobaltous chloride	increases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	3
Acetaminophen	increases expression	3
Cyclosporine	affects cotreatment, increases expression	3
methylmercuric chloride	increases expression	2
diethyl maleate	increases expression	2
arsenite	affects binding, increases reaction, increases expression, decreases expression, increases abundance	2
LDN 193189	affects cotreatment, increases expression	2
(+)-JQ1 compound	decreases expression, increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression	2
Arsenic	affects cotreatment, increases abundance, increases expression	2
Cannabidiol	increases expression	2
Diazinon	increases expression, increases methylation	2
Ivermectin	affects cotreatment, increases expression, decreases expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
Silver	increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Dronabinol	decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	decreases expression	1

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2VZ	Abcam HEK293T DNAJB1 KO	Transformed cell line	Female
CVCL_B8ER	Abcam HCT 116 DNAJB1 KO	Cancer cell line	Male
CVCL_B8UV	Abcam MCF-7 DNAJB1 KO	Cancer cell line	Female
CVCL_B9H0	Abcam A-549 DNAJB1 KO	Cancer cell line	Male
CVCL_E1CH	Ubigene SW620 DNAJB1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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