DNAJB11

Summary

DNAJB11 (DnaJ heat shock protein family (Hsp40) member B11, HGNC:14889) is a protein-coding gene on chromosome 3q27.3, encoding DnaJ homolog subfamily B member 11 (Q9UBS4). As a co-chaperone for HSPA5 it is required for proper folding, trafficking or degradation of proteins. It is a selective cancer dependency (DepMap: 10.4% of cell lines).

This gene encodes a soluble glycoprotein of the endoplasmic reticulum (ER) lumen that functions as a co-chaperone of binding immunoglobulin protein, a 70 kilodalton heat shock protein chaperone required for the proper folding and assembly of proteins in the ER. The encoded protein contains a highly conserved J domain of about 70 amino acids with a characteristic His-Pro-Asp (HPD) motif and may regulate the activity of binding immunoglobulin protein by stimulating ATPase activity.

Source: NCBI Gene 51726 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal dominant polycystic kidney disease (Definitive, ClinGen) — +2 more curated relationships
• Clinical variants (ClinVar): 199 total — 15 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 31
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 10.4% of screened cell lines
• MANE Select transcript: NM_016306

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14889
Approved symbol	DNAJB11
Name	DnaJ heat shock protein family (Hsp40) member B11
Location	3q27.3
Locus type	gene with protein product
Status	Approved
Aliases	EDJ, HEDJ, ERdj3
Ensembl gene	ENSG00000090520
Ensembl biotype	protein_coding
OMIM	611341
Entrez	51726

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 5 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000265028, ENST00000439351, ENST00000464877, ENST00000495390, ENST00000679794, ENST00000680338, ENST00000681475, ENST00000681543, ENST00000871525, ENST00000938599, ENST00000956498

RefSeq mRNA: 2 — MANE Select: NM_016306 NM_001378451, NM_016306

CCDS: CCDS3277

Canonical transcript exons

ENST00000265028 — 10 exons

Exon	Start	End
ENSE00000781477	186577668	186577800
ENSE00000781478	186581371	186581513
ENSE00000871394	186585344	186585793
ENSE00001079629	186570720	186570965
ENSE00001079631	186572095	186572251
ENSE00003579448	186575840	186575937
ENSE00003793612	186581995	186582077
ENSE00003794249	186582716	186582773
ENSE00003794842	186584430	186584589
ENSE00003798676	186583865	186583976

Expression profiles

Bgee: expression breadth ubiquitous, 141 present calls, max score 96.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 65.4759 / max 602.0075, expressed in 1825 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
40268	65.2445	1825
40267	0.2314	112

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vermiform appendix	UBERON:0001154	96.33	gold quality
body of pancreas	UBERON:0001150	96.28	gold quality
bone marrow cell	CL:0002092	96.00	gold quality
placenta	UBERON:0001987	95.93	gold quality
islet of Langerhans	UBERON:0000006	95.90	gold quality
bone element	UBERON:0001474	95.87	gold quality
bone marrow	UBERON:0002371	95.87	gold quality
pancreas	UBERON:0001264	95.86	gold quality
endometrium	UBERON:0001295	95.30	gold quality
rectum	UBERON:0001052	95.15	gold quality
stromal cell of endometrium	CL:0002255	94.85	gold quality
right lobe of thyroid gland	UBERON:0001119	94.55	gold quality
left lobe of thyroid gland	UBERON:0001120	94.54	gold quality
lymph node	UBERON:0000029	94.41	gold quality
thyroid gland	UBERON:0002046	94.28	gold quality
mucosa of transverse colon	UBERON:0004991	94.18	gold quality
duodenum	UBERON:0002114	94.06	gold quality
monocyte	CL:0000576	94.01	gold quality
leukocyte	CL:0000738	93.80	gold quality
smooth muscle tissue	UBERON:0001135	93.58	gold quality
right lobe of liver	UBERON:0001114	93.21	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.09	gold quality
gall bladder	UBERON:0002110	93.00	gold quality
upper lobe of left lung	UBERON:0008952	92.99	gold quality
right atrium auricular region	UBERON:0006631	92.93	gold quality
spleen	UBERON:0002106	92.92	gold quality
left uterine tube	UBERON:0001303	92.84	gold quality
tonsil	UBERON:0002372	92.72	gold quality
body of stomach	UBERON:0001161	92.69	gold quality
calcaneal tendon	UBERON:0003701	92.58	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	91.50
E-MTAB-9467	yes	50.34
E-HCAD-1	yes	45.25
E-CURD-122	yes	38.74
E-MTAB-8410	yes	28.03
E-HCAD-9	yes	14.49
E-CURD-46	yes	12.02
E-MTAB-10553	yes	8.07
E-CURD-97	no	1064.28
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 10.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 22)

• This protein was identified as true homolog of yeast Scj1p. (PMID:15195998)
• ERdj3 is a stress-inducible endoplasmic reticulum DnaJ homologue which serves as a cofactor for BiP’s interactions with unfolded substrates (PMID:15525676)
• These data suggest that ERdj3 might have diverse roles in the ER, including that of the molecular cochaperone of BiP and an as yet unknown protective action against vero toxin.(ERDJ3) (PMID:15544163)
• These findings suggest that the Cys-rich region of HEDJ and its oxidation state are important in maintaining the substrate interaction domain in a binding-competent conformation. (PMID:17976514)
• Hsp40 ERdj3 requires its Hsp70 interaction and substrate-binding properties to complement various yeast Hsp40-dependent functions (PMID:19748898)
• The Salmonella type III secretion effector, salmonella leucine-rich repeat protein (SlrP), targets the human chaperone ERdj3. (PMID:20335166)
• Hsp90 and Hsp40/Erdj3 were essential for K1’s anti-apoptotic function. (PMID:20418907)
• In addition, BiP formed a complex with SV40 capsids in the endoplasmic reticulum in a DNAJB11-dependent fashion. (PMID:21673190)
• These data identify ERdj3 as a host protein involved with the cholera toxin intoxication process and provide new molecular details regarding cholera toxin A1-chaperone interactions. (PMID:21844235)
• ERdjs appear to play the dual roles of increasing BiP affinity for clients and regulating delivery of clients to BiP. (PMID:23378021)
• Depleting ERdj3 reduced the rate of mutant GCase degradation in patient-derived fibroblasts, while increasing folding, trafficking, and function by directing GCase to the profolding ER calnexin pathway. (PMID:25126989)
• ERdj3 mutant bound to unfolded endoplasmic reticulum proteins under steady state conditions in much greater amounts than wild-type. (PMID:25143379)
• regulated co-secretion of ERdj3 with misfolded clients directly links ER and extracellular proteostasis during conditions of ER stress. (PMID:25361606)
• BiP facilitates Sec61 channel closure (i.e. limits ER Ca(2+) leakage) via the Sec61 channel with the help of ERj3 and ERj6 (PMID:26085089)
• ZAAT ER clearance resulted from enhancing ERdj3-mediated ZAAT degradation by silencing ERdj3 while simultaneously enhancing autophagy. In this context, ERdj3 suppression may eliminate the toxic gain of function associated with polymerization of ZAAT (PMID:28419579)
• These results reveal ERdj3 tetramerization as an important structural framework for ERdj3 functions involved in coordinating endplasmic reticulum and extracellular proteostasis in the presence and absence of endplasmic reticulum stress. (PMID:28655754)
• strong positive expression of DNAJB11 was an independent prognostic factor for disease-free survival and overall survival in epithelial ovarian cancer (PMID:28752709)
• DNAJB11-associated disease is a phenotypic hybrid of Autosomal-dominant polycystic kidney disease and autosomal-dominant tubulointerstitial diseases. (PMID:29706351)
• ERdj3 expression is enhanced in hepatocellular carcinoma (HCC) tumors and is positively associated with more inferior survival outcomes. ERdj3 promotes intracellular Z mutant of alpha-1-antitrypsin (AATZ) accumulation in HCC cells via suppressing post-transcriptional AATZ degradation and promotes HCC cell proliferation, epithelial-mesenchymal transition, migratory ability and invasiveness in an AATZ-dependent manner. (PMID:29992839)
• These findings suggest that, under normal conditions, ERdj3 functions as an ER chaperone in complex with SDF2/SDF2L1 but is secreted into the extracellular space when it cannot form this complex. (PMID:31624144)
• Clinical spectrum, prognosis and estimated prevalence of DNAJB11-kidney disease. (PMID:32631624)
• DNAJB11 Mutation in ADPKD Patients: Clinical Characteristics in a Monocentric Cohort. (PMID:38275584)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnajb11	ENSDARG00000015088
mus_musculus	Dnajb11	ENSMUSG00000004460
rattus_norvegicus	Dnajb11	ENSRNOG00000001803
drosophila_melanogaster	shv	FBGN0031256
caenorhabditis_elegans		WBGENE00001038

Paralogs (11): DNAJB6 (ENSG00000105993), DNAJB9 (ENSG00000128590), DNAJB1 (ENSG00000132002), DNAJB2 (ENSG00000135924), DNAJB5 (ENSG00000137094), DNAJB12 (ENSG00000148719), DNAJB4 (ENSG00000162616), DNAJB14 (ENSG00000164031), DNAJB7 (ENSG00000172404), DNAJB8 (ENSG00000179407), DNAJB13 (ENSG00000187726)

Protein

Protein identifiers

DnaJ homolog subfamily B member 11 — Q9UBS4 (reviewed: Q9UBS4)

Alternative names: APOBEC1-binding protein 2, DnaJ protein homolog 9, ER-associated DNAJ, ER-associated Hsp40 co-chaperone, Endoplasmic reticulum DNA J domain-containing protein 3, HEDJ, Human DnaJ protein 9, PWP1-interacting protein 4

All UniProt accessions (2): Q9UBS4, A0A7P0T9E8

UniProt curated annotations — full annotation on UniProt →

Function. As a co-chaperone for HSPA5 it is required for proper folding, trafficking or degradation of proteins. Binds directly to both unfolded proteins that are substrates for ERAD and nascent unfolded peptide chains, but dissociates from the HSPA5-unfolded protein complex before folding is completed. May help recruiting HSPA5 and other chaperones to the substrate. Stimulates HSPA5 ATPase activity. It is necessary for maturation and correct trafficking of PKD1.

Subunit / interactions. Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 and very small amounts of ERP29, but not, or at very low levels, CALR nor CANX. Binds to denatured substrates in an ATP-independent manner. Interacts via the J domain with HSPA5 in an ATP-dependent manner.

Subcellular location. Endoplasmic reticulum lumen.

Tissue specificity. Widely expressed.

Post-translational modifications. Contains high-mannose Endo H-sensitive carbohydrates. Cys-169, Cys-171, Cys-193 and Cys-196 form intramolecular disulfide bonds. The preferential partner for each Cys is not known. Thr-188 was reported to be phosphorylated upon DNA damage by ATM or ATR; however as this position has been shown to be in the ER lumen, the in vivo relevance is not proven.

Disease relevance. Polycystic kidney disease 6 with or without polycystic liver disease (PKD6) [MIM:618061] A form of polycystic kidney disease, a disorder characterized by progressive formation and enlargement of cysts in both kidneys, typically leading to end-stage renal disease in adult life. Cysts also occur in other organs, particularly the liver. PKD6 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Induction. By endoplasmic reticulum stress-inducing agents such as thapsigargin and tunicamycin.

RefSeq proteins (2): NP_001365380, NP_057390* (*=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
IPR051736	DnaJ-B11-like	Family

Pfam: PF00226, PF01556

UniProt features (15 total): mutagenesis site 5, sequence variant 4, signal peptide 1, chain 1, sequence conflict 1, domain 1, modified residue 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBS4-F1	84.34	0.56

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): 188

Glycosylation sites (1): 261

Mutagenesis-validated functional residues (5):

Position	Phenotype
169	drastic loss of interaction with denatured substrates.
171	drastic loss of interaction with denatured substrates.
193	drastic loss of interaction with denatured substrates.
196	drastic loss of interaction with denatured substrates.
53	loss of hspa5-binding, but no effect on interaction with denatured substrates.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-381038	XBP1(S) activates chaperone genes
R-HSA-9918432	Maturation of DENV proteins

MSigDB gene sets: 293 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, ATACCTC_MIR202, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_MRNA_MODIFICATION, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_PROTEIN_MATURATION, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, UEDA_PERIFERAL_CLOCK, GOBP_RNA_MODIFICATION

GO Biological Process (5): protein folding (GO:0006457), mRNA modification (GO:0016556), positive regulation of ATP-dependent activity (GO:0032781), negative regulation of neurogenesis (GO:0050768), protein maturation (GO:0051604)

GO Molecular Function (4): signaling receptor binding (GO:0005102), obsolete unfolded protein binding (GO:0051082), misfolded protein binding (GO:0051787), protein binding (GO:0005515)

GO Cellular Component (8): obsolete extracellular space (GO:0005615), nucleus (GO:0005634), endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788), membrane (GO:0016020), endoplasmic reticulum chaperone complex (GO:0034663), protein folding chaperone complex (GO:0101031), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
IRE1alpha activates chaperones	1
Dengue Virus Genome Translation and Replication	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
cellular process	1
protein maturation	1
RNA modification	1
mRNA metabolic process	1
regulation of ATP-dependent activity	1
positive regulation of molecular function	1
ATP-dependent activity	1
negative regulation of cell development	1
neurogenesis	1
regulation of neurogenesis	1
negative regulation of nervous system development	1
gene expression	1
protein metabolic process	1
binding	1
cytoplasm	1
endomembrane system	1
endoplasmic reticulum	1
intracellular organelle lumen	1
endoplasmic reticulum protein-containing complex	1
intracellular protein-containing complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2693 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAJB11	HSP90B1	P14625	989
DNAJB11	PDIA4	P13667	960
DNAJB11	PPIB	P23284	895
DNAJB11	HYOU1	Q9Y4L1	890
DNAJB11	HSPA5	P11021	881
DNAJB11	SDF2L1	Q9HCN8	853
DNAJB11	GANAB	Q14697	768
DNAJB11	ST8SIA2	Q92186	759
DNAJB11	PDIA6	Q15084	737
DNAJB11	SEC61A1	P38378	720
DNAJB11	SDF2	Q99470	712
DNAJB11	PDIA2	Q13087	695
DNAJB11	PDIA3	P30101	686
DNAJB11	HSPA4	P34932	680
DNAJB11	ERP44	Q9BS26	649

IntAct

196 interactions, top by confidence:

A	B	Type	Score
DNAJB11	HSPA5	psi-mi:“MI:0407”(direct interaction)	0.830
DNAJB11	HSPA5	psi-mi:“MI:0914”(association)	0.830
HSPA5	DNAJB11	psi-mi:“MI:0407”(direct interaction)	0.830
ERBB3	PIK3R2	psi-mi:“MI:0914”(association)	0.700
DNAJB11	SIMC1	psi-mi:“MI:0915”(physical association)	0.660
SDF2L1	OLFM2	psi-mi:“MI:0914”(association)	0.640
DNAJB11	slrP	psi-mi:“MI:0915”(physical association)	0.600
DNAJB11	slrP	psi-mi:“MI:0403”(colocalization)	0.600
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
HTN3	DNAJB11	psi-mi:“MI:0915”(physical association)	0.560
COL1A1	PDIA4	psi-mi:“MI:0914”(association)	0.560
SNX5	SNX2	psi-mi:“MI:0914”(association)	0.550
DNAJB11	PTN	psi-mi:“MI:0915”(physical association)	0.550
SNX5	DNAJB11	psi-mi:“MI:0915”(physical association)	0.550
UBR1	DNAJB11	psi-mi:“MI:0915”(physical association)	0.550
ILK	HAX1	psi-mi:“MI:0914”(association)	0.530
SDF2L1	CLIC1	psi-mi:“MI:0914”(association)	0.530
EGFR	NDUFA4	psi-mi:“MI:0914”(association)	0.530
SDF2	ALS2	psi-mi:“MI:0914”(association)	0.530
COL1A1	GOLIM4	psi-mi:“MI:0914”(association)	0.500
COL1A1	GOLIM4	psi-mi:“MI:0915”(physical association)	0.500
DNAJB11	E7	psi-mi:“MI:0915”(physical association)	0.490
env	PSMD11	psi-mi:“MI:0914”(association)	0.460

BioGRID (498): DNAJB11 (Affinity Capture-MS), DNAJB11 (Affinity Capture-MS), DNAJB11 (Affinity Capture-MS), DNAJB11 (Affinity Capture-MS), HSPA5 (Reconstituted Complex), DNAJB11 (Affinity Capture-MS), DNAJB11 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), ROCK2 (Affinity Capture-MS), NUBPL (Affinity Capture-MS), SLC25A30 (Affinity Capture-MS), SDF2 (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), TUBA1A (Affinity Capture-MS), TUBB8 (Affinity Capture-MS)

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: A0LJ41, A1KR91, A3DF24, A4XKA5, A5EYE5, A5ITA7, A6LRN5, A6Q486, A6QHC2, A6U251, A6UEY1, A7X2Y0, A8Z4B8, A9IGC5, A9KG87, A9LZV9, A9N8H1, B0SHT0, B0SRF0, B2IBR5, B2TLZ8, B2V2I6, B3CP03, B6IZJ1, B6J7U6, B8I304, B9FHF3, B9JZ89, B9MJZ0, C0R562, C3MC05, O27352, O35824, O60884, O66921, O74752, O75953, O89114, P25491, P31689

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 200 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 ALK	5	20.5×	6e-04
EPHA-mediated growth cone collapse	5	13.7×	3e-03
Dengue Virus Attachment and Entry	6	11.2×	2e-03
Constitutive Signaling by Aberrant PI3K in Cancer	10	9.1×	6e-05
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	11	7.7×	6e-05
PIP3 activates AKT signaling	13	6.2×	6e-05
RAF/MAP kinase cascade	12	5.3×	6e-04
Signaling by Interleukins	10	4.6×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
cell surface receptor protein tyrosine kinase signaling pathway	18	17.8×	1e-14
phosphatidylinositol 3-kinase/protein kinase B signal transduction	10	12.0×	8e-06
peptidyl-tyrosine phosphorylation	5	12.0×	7e-03
positive regulation of fibroblast proliferation	6	10.1×	4e-03
memory	9	9.4×	2e-04
insulin receptor signaling pathway	7	8.8×	2e-03
epidermal growth factor receptor signaling pathway	6	8.4×	8e-03
ERAD pathway	8	8.2×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	15
Likely pathogenic	11
Uncertain significance	69
Likely benign	56
Benign	32

Top pathogenic / likely-pathogenic (26)

Variant ID	HGVS	Classification
1172653	NM_016306.6(DNAJB11):c.70C>T (p.Arg24Ter)	Pathogenic
1805387	NM_016306.6(DNAJB11):c.151C>T (p.Gln51Ter)	Pathogenic
2053433	NM_016306.6(DNAJB11):c.100C>T (p.Arg34Ter)	Pathogenic
2281222	NM_016306.6(DNAJB11):c.724C>T (p.Arg242Ter)	Pathogenic
3342272	NM_016306.6(DNAJB11):c.258C>G (p.Tyr86Ter)	Pathogenic
3377507	NM_016306.6(DNAJB11):c.537_543del (p.Gln179fs)	Pathogenic
3662262	NM_016306.6(DNAJB11):c.781_782del (p.Asn261fs)	Pathogenic
3899993	NM_016306.6(DNAJB11):c.532del (p.Thr178fs)	Pathogenic
4818743	NM_016306.6(DNAJB11):c.831_849dup (p.Lys284fs)	Pathogenic
4818745	NM_016306.6(DNAJB11):c.730A>T (p.Lys244Ter)	Pathogenic
4818746	NM_016306.6(DNAJB11):c.425T>A (p.Leu142Ter)	Pathogenic
4818747	NM_016306.4:c.70_85del	Pathogenic
549848	NM_016306.6(DNAJB11):c.166_167insTT (p.Arg56fs)	Pathogenic
549849	NM_016306.6(DNAJB11):c.479del (p.Ala160fs)	Pathogenic
549851	NM_016306.6(DNAJB11):c.616C>T (p.Arg206Ter)	Pathogenic
1328423	NM_016306.6(DNAJB11):c.600-2A>C	Likely pathogenic
3233356	NM_016306.6(DNAJB11):c.266dup (p.Tyr89Ter)	Likely pathogenic
3236224	NM_016306.6(DNAJB11):c.635_636del (p.Ile212fs)	Likely pathogenic
3237351	NM_016306.6(DNAJB11):c.544_550del (p.Pro182fs)	Likely pathogenic
3342267	NM_016306.6(DNAJB11):c.763_767del (p.Arg254_Gly255insTer)	Likely pathogenic
3366872	NM_016306.6(DNAJB11):c.324-1G>T	Likely pathogenic
3721381	NM_016306.6(DNAJB11):c.456+2T>A	Likely pathogenic
3907695	NM_016306.6(DNAJB11):c.926_927del (p.Asn308_Phe309insTer)	Likely pathogenic
4532219	NM_016306.6(DNAJB11):c.537del (p.Gln179fs)	Likely pathogenic
549847	NM_016306.6(DNAJB11):c.161C>G (p.Pro54Arg)	Likely pathogenic
549850	NM_016306.6(DNAJB11):c.230T>C (p.Leu77Pro)	Likely pathogenic

SpliceAI

1621 predictions. Top by Δscore:

Variant	Effect	Δscore
3:186572086:A:AG	acceptor_gain	1.0000
3:186572093:A:AG	acceptor_gain	1.0000
3:186572093:AGAC:A	acceptor_gain	1.0000
3:186572094:G:GT	acceptor_gain	1.0000
3:186572094:GAC:G	acceptor_gain	1.0000
3:186572094:GACG:G	acceptor_gain	1.0000
3:186572094:GACGA:G	acceptor_gain	1.0000
3:186572249:GAG:G	donor_gain	1.0000
3:186572251:GGTG:G	donor_loss	1.0000
3:186572252:G:GA	donor_loss	1.0000
3:186572252:G:GG	donor_gain	1.0000
3:186572253:T:G	donor_loss	1.0000
3:186575822:ACT:A	acceptor_gain	1.0000
3:186575822:ACTG:A	acceptor_gain	1.0000
3:186575824:T:A	acceptor_gain	1.0000
3:186575836:CCA:C	acceptor_loss	1.0000
3:186575837:CAG:C	acceptor_loss	1.0000
3:186575838:A:AG	acceptor_gain	1.0000
3:186575838:AG:A	acceptor_gain	1.0000
3:186575838:AGGT:A	acceptor_loss	1.0000
3:186575839:G:GG	acceptor_gain	1.0000
3:186575839:GG:G	acceptor_gain	1.0000
3:186575839:GGTT:G	acceptor_gain	1.0000
3:186575839:GGTTC:G	acceptor_gain	1.0000
3:186575933:TCACA:T	donor_gain	1.0000
3:186575934:CACA:C	donor_gain	1.0000
3:186575935:ACA:A	donor_gain	1.0000
3:186575936:CA:C	donor_gain	1.0000
3:186575936:CAG:C	donor_loss	1.0000
3:186575937:AGT:A	donor_loss	1.0000

AlphaMissense

2346 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:186572183:C:G	H53D	1.000
3:186572185:T:A	H53Q	1.000
3:186572185:T:G	H53Q	1.000
3:186572225:T:C	F67L	1.000
3:186572227:C:A	F67L	1.000
3:186572227:C:G	F67L	1.000
3:186581500:T:A	C196S	1.000
3:186581500:T:C	C196R	1.000
3:186581501:G:C	C196S	1.000
3:186572152:A:C	K42N	0.999
3:186572152:A:T	K42N	0.999
3:186572163:G:C	R46T	0.999
3:186572163:G:T	R46M	0.999
3:186572164:G:C	R46S	0.999
3:186572164:G:T	R46S	0.999
3:186572172:C:A	A49D	0.999
3:186572183:C:A	H53N	0.999
3:186572184:A:G	H53R	0.999
3:186572226:T:C	F67S	0.999
3:186572226:T:G	F67C	0.999
3:186572235:T:C	L70P	0.999
3:186572244:C:A	A73D	0.999
3:186575844:T:A	L77Q	0.999
3:186575844:T:C	L77P	0.999
3:186575862:G:C	R83P	0.999
3:186581419:T:A	C169S	0.999
3:186581419:T:C	C169R	0.999
3:186581420:G:C	C169S	0.999
3:186581425:T:C	C171R	0.999
3:186581467:T:C	F185L	0.999

dbSNP variants (sampled 300 via entrez): RS1000067910 (3:186571568 G>C), RS1000314712 (3:186582562 C>G), RS1000448123 (3:186575293 G>A), RS1001056698 (3:186576439 T>C), RS1001332263 (3:186581590 A>G), RS1001448127 (3:186582093 T>A), RS1001474032 (3:186584896 G>GAGGT), RS1002062422 (3:186570170 G>A,T), RS1002223003 (3:186576184 T>A), RS1002328132 (3:186583257 G>A), RS1002444132 (3:186583599 C>T), RS1003412590 (3:186569049 C>T), RS1003718175 (3:186575576 G>A), RS1003741623 (3:186568829 G>A), RS1003768721 (3:186582868 AC>A)

Disease associations

OMIM: gene MIM:611341 | disease phenotypes: MIM:618061, MIM:173900

GenCC curated gene-disease

Disease	Classification	Inheritance
polycystic kidney disease 6 with or without polycystic liver disease	Strong	Autosomal dominant
autosomal dominant polycystic kidney disease	Supportive	Autosomal dominant
ciliopathy	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
ciliopathy	Limited	AR
autosomal dominant polycystic kidney disease	Definitive	AD

Mondo (5): polycystic kidney disease 6 with or without polycystic liver disease (MONDO:0054842), cystic kidney disease (MONDO:0002473), autosomal dominant polycystic kidney disease (MONDO:0004691), polycystic kidney disease (MONDO:0020642), ciliopathy (MONDO:0005308)

Orphanet (1): Autosomal dominant polycystic kidney disease (Orphanet:730)

HPO phenotypes

31 total (30 of 31 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000083	Renal insufficiency
HP:0000105	Enlarged kidney
HP:0000107	Renal cyst
HP:0000113	Polycystic kidney dysplasia
HP:0000790	Hematuria
HP:0000791	Uric acid nephrolithiasis
HP:0000822	Hypertension
HP:0001407	Hepatic cysts
HP:0001634	Mitral valve prolapse
HP:0001737	Pancreatic cysts
HP:0001997	Gout
HP:0002616	Aortic root aneurysm
HP:0003259	Elevated circulating creatinine concentration
HP:0003581	Adult onset
HP:0003676	Progressive
HP:0003774	Stage 5 chronic kidney disease
HP:0004944	Dilatation of the cerebral artery
HP:0006557	Polycystic liver disease
HP:0008672	Calcium oxalate nephrolithiasis
HP:0011004	Abnormal systemic arterial morphology
HP:0011760	Pituitary growth hormone cell adenoma
HP:0012207	Reduced sperm motility
HP:0012213	Decreased glomerular filtration rate
HP:0012330	Pyelonephritis
HP:0012591	Abnormal urinary electrolyte concentration
HP:0012592	Albuminuria
HP:0012622	Chronic kidney disease
HP:0030157	Flank pain

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D052177	Kidney Diseases, Cystic	C12.050.351.968.419.403; C12.200.777.419.403; C12.950.419.403
D007690	Polycystic Kidney Diseases	C12.050.351.968.419.403.875; C12.200.777.419.403.875; C12.950.419.403.875; C16.131.077.717; C16.320.184.625
D016891	Polycystic Kidney, Autosomal Dominant	C12.050.351.968.419.403.875.500; C12.200.777.419.403.875.500; C12.950.419.403.875.500; C16.131.077.717.500; C16.320.184.625.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067236 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	affects cotreatment, affects expression, increases expression	6
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression, affects expression (+1 more)	5
Valproic Acid	affects expression, decreases methylation, increases expression	4
Thapsigargin	increases response to substance, increases expression, decreases expression, increases reaction, decreases transport	4
bisphenol A	affects expression, increases expression	3
Nickel	increases expression	2
Tunicamycin	increases expression	2
FR900359	increases phosphorylation	1
sodium arsenate	decreases expression	1
titanium dioxide	decreases expression	1
trichostatin A	affects expression	1
tetrahydropalmatine	decreases expression	1
bufalin	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
caffeic acid	decreases expression, increases reaction	1
nefazodone	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-methoxycinnamate methyl ester	decreases expression, increases reaction	1
obeticholic acid	increases expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
ICG 001	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Vorinostat	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Vehicle Emissions	affects expression, increases reaction	1
Benztropine	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651292	Binding	Binding affinity to human DNAJB11 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00414440	PHASE4	COMPLETED	Efficacy, Safety and Tolerability of Everolimus in Preventing End-stage Renal Disease in Patients With Autosomal Dominant Polycystic Kidney Disease
NCT03273413	PHASE4	ACTIVE_NOT_RECRUITING	Statin Therapy in Patients With Early Stage ADPKD
NCT03949894	PHASE4	COMPLETED	Evaluating the Safety and effectivenesS in Adult KorEaN Patients Treated With Tolvaptan for Management of Autosomal domInAnt poLycystic Kidney Disease
NCT00309283	PHASE3	COMPLETED	Somatostatin in Polycystic Kidney: a Long-term Three Year Follow up Study
NCT00346918	PHASE3	COMPLETED	Sirolimus (Rapamune®) for Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT00428948	PHASE3	COMPLETED	Tolvaptan Phase 3 Efficacy and Safety Study in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT01022424	PHASE3	COMPLETED	A Long-term Administration Study of OPC-41061 in Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD) (2) [Extension of Study 156-05-002]
NCT01214421	PHASE3	COMPLETED	Tolvaptan Extension Study in Participants With ADPKD
NCT01377246	PHASE3	COMPLETED	Somatostatin In Patients With Autosomal Dominant Polycystic Kidney Disease And Moderate To Severe Renal Insufficiency
NCT01616927	PHASE3	UNKNOWN	Study of Lanreotide to Treat Polycystic Kidney Disease
NCT01853553	PHASE3	COMPLETED	Mineralocorticoid Antagonism and Endothelial Dysfunction in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT02115659	PHASE3	UNKNOWN	Triptolide-Containing Formulation as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT02134899	PHASE3	COMPLETED	The Efficacy of Everolimus in Reducing Total Native Kidney Volume in Polycystic Kidney Disease Transplanted Recipients
NCT02160145	PHASE3	COMPLETED	Efficacy and Safety of Tolvaptan in Subjects With Chronic Kidney Disease Between Late Stage 2 to Early Stage 4 Due to Autosomal Dominant Polycystic Kidney Disease
NCT02964273	PHASE3	COMPLETED	Safety, Pharmacokinetics, Tolerability and Efficacy of Tolvaptan in Children and Adolescents With ADPKD (Autosomal Dominant Polycystic Kidney Disease)
NCT03764605	PHASE3	UNKNOWN	Metformin vs Tolvaptan for Treatment of Autosomal Dominant Polycystic Kidney Disease
NCT03918447	PHASE3	TERMINATED	A Trial of Bardoxolone Methyl in Patients With ADPKD - FALCON
NCT04064346	PHASE3	TERMINATED	Efficacy and Safety of Lixivaptan in the Treatment of Autosomal Dominant Polycystic Kidney Disease
NCT04152837	PHASE3	TERMINATED	Safety of Lixivaptan in Subjects Previously Treated With Tolvaptan for Autosomal Dominant Polycystic Kidney Disease
NCT04939935	PHASE3	RECRUITING	Implementation of Metformin theraPy to Ease Decline of Kidney Function in Polycystic Kidney Disease (IMPEDE-PKD)
NCT05373264	PHASE3	RECRUITING	HYDROchlorothiazide to PROTECT Polycystic Kidney Disease Patients and Improve Their Quality of Life
NCT04705051	PHASE3	TERMINATED	Long-term Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) With Venglustat
NCT00841568	PHASE2	COMPLETED	A Long-term Administration Study of OPC-41061 in Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD) [Extension of Study 156-04-001]
NCT01210560	PHASE2	COMPLETED	Dose-finding Study of New Tolvaptan Formulation in Subjects With ADPKD
NCT01336972	PHASE2	COMPLETED	Short-term Renal Hemodynamic Effects of Tolvaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT01451827	PHASE2	COMPLETED	8-Week Study of Tolvaptan Dose Forms in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT01670110	PHASE2	COMPLETED	Pasireotide LAR in Severe Polycystic Liver Disease
NCT01932450	PHASE2	UNKNOWN	Radiofrequency Ablation for ADPKD Blood Pressure and Disease Progression Control
NCT02527863	PHASE2	COMPLETED	Effect of the Aquaretic Tolvaptan on Nitric Oxide System
NCT02616055	PHASE2	TERMINATED	Long-Term Treatment and Follow up of Subjects Completing 24 Months of Treatment With Tesevatinib on Study KD019-101
NCT03203642	PHASE2	COMPLETED	Study of the Efficacy and Safety of Tesevatinib in Subjects With ADPKD
NCT03487913	PHASE2	COMPLETED	The ELiSA Study - Evaluation of Lixivaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease
NCT03541447	PHASE2	COMPLETED	Tolvaptan-Octreotide LAR Combination in ADPKD
NCT04284657	PHASE2	COMPLETED	Pravastatin and Alkali Therapy in Patients With Autosomal Dominant Polycystic Kidney Disease
NCT04578548	PHASE2	TERMINATED	A Study to Evaluate the Effects of GLPG2737 in Participants With Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT05190744	PHASE2	COMPLETED	Probenecid (PB) to Treat Hereditary Nephrogenic Diabetes Insipidus (NDI), ADPKD Treated With Tolvaptan, and Severely Polyuric Patients With Previous Lithium Administration
NCT05870007	PHASE2	ENROLLING_BY_INVITATION	Atorvastatin and Alkali Therapy in Patients With Autosomal Dominant Polycystic Kidney Disease
NCT06100133	PHASE2	UNKNOWN	Treat Autosomal Dominant Polycystic Kidney Disease With Oral Ketone Ester?
NCT06289998	PHASE2	ACTIVE_NOT_RECRUITING	Study of Tamibarotene in Patients With ADPKD
NCT06435858	PHASE2	RECRUITING	Short-term Effects of an SGLT2 Inhibitor on Divalent Ions in Autosomal Dominant Polycystic Kidney Disease