DNAJB11: A Key Co-Chaperone in ER Proteostasis and Kidney Disease
Comprehensive genomic and proteomic overview of DNAJB11, a DnaJ/Hsp40 family member linked to autosomal dominant polycystic kidney disease (ADPKD) and protein misfolding disorders.
Gene Information Card
| Symbol | DNAJB11 |
|---|---|
| Full Name | DnaJ heat shock protein family (Hsp40) member B11 |
| Gene Type | Protein coding |
| Chromosomal Location | 3q27.3 |
| NCBI Gene ID | 51726 ncbi.nlm.nih.gov/gene/51726 |
| Ensembl ID | ENSG00000114520 |
| UniProt ID | Q9UBS4 |
| OMIM ID | 611341 |
| HGNC ID | 14889 |
| Aliases | ERdj3, ERj3, HEDJ, Dj-11, DnaJ homolog subfamily B member 11 |
Description
DNAJB11, also known as ERdj3, is a member of the DnaJ/Hsp40 family of co-chaperones. It resides in the endoplasmic reticulum (ER) and functions as a co-chaperone for BiP (HSPA5), facilitating protein folding, assembly, and quality control. DNAJB11 is critical for maintaining ER proteostasis; loss-of-function mutations lead to ER stress and are associated with autosomal dominant polycystic kidney disease (ADPKD). The gene is widely expressed, with highest levels in kidney, liver, and pancreas.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal dominant polycystic kidney disease (ADPKD) | Loss-of-function mutations in DNAJB11 impair ER protein folding, leading to accumulation of misfolded proteins, ER stress, and cyst formation in renal tubular cells. | ClinVar, OMIM #611341 |
| Polycystic kidney disease 6 with or without polycystic liver disease | Heterozygous missense and truncating variants cause a late-onset, atypical form of ADPKD with variable liver involvement. | OMIM #619061, NCBI GeneReviews |
| Endoplasmic reticulum stress-related disorders | DNAJB11 deficiency disrupts BiP-mediated protein folding, contributing to cellular stress and apoptosis in secretory tissues. | UniProt Q9UBS4, PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 28.5 | High |
| Liver | 22.3 | High |
| Pancreas | 18.7 | High |
| Salivary gland | 15.2 | Medium |
| Small intestine | 12.8 | Medium |
| Testis | 10.1 | Medium |
| Brain | 5.4 | Low |
| Heart | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 32.1 | High expression; commonly used for functional studies |
| HepG2 | 25.6 | High expression; liver origin |
| ARPE-19 | 18.3 | Medium expression; retinal pigment epithelium |
| HeLa | 12.4 | Medium expression; cervical cancer line |
| K562 | 3.8 | Low expression; erythroleukemia |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.823C>T (p.Arg275Trp) | Missense | Rare (0.0004 in gnomAD) | Loss of function; disrupts BiP binding; associated with ADPKD |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Complete loss of protein; pathogenic in ADPKD |
| c.1006_1007del (p.Leu336Glufs*2) | Frameshift | Unique | Truncation; loss of J-domain; pathogenic |
| c.148G>A (p.Gly50Arg) | Missense | Rare | Impaired ER localization; reduced chaperone activity |
Mutation functional classification
Loss of Function (LOF)
Most DNAJB11 mutations are loss-of-function, leading to haploinsufficiency or dominant-negative effects on ER protein folding, causing ER stress and ADPKD.
Gain of Function (GOF)
No gain-of-function mutations have been reported for DNAJB11.
Dominant Negative (DN)
Some missense variants (e.g., p.Arg275Trp) may exert dominant-negative effects by sequestering BiP or forming non-functional complexes.
View complete mutation data：
Gene Ontology (GO)
| • protein folding (GO:0006457) | • ER-associated ubiquitin-dependent protein catabolic process (GO:0030433) |
| • response to endoplasmic reticulum stress (GO:0034976) | • unfolded protein binding (GO:0051082) |
| • endoplasmic reticulum (GO:0005783) | • endoplasmic reticulum membrane (GO:0005789) |
| • ATPase activator activity (GO:0001671) | • Hsp70 protein binding (GO:0030544) |
Pathways
• Endoplasmic reticulum protein processing (KEGG: hsa04141)
• Unfolded protein response (UPR) (Reactome: R-HSA-381119)
• Protein folding and maturation (Reactome: R-HSA-392499)
• ERAD pathway (Reactome: R-HSA-8951664)
Protein Summary
DNAJB11 (ERdj3) is a 358-amino acid ER-resident co-chaperone containing a conserved J-domain that interacts with BiP (HSPA5). It stimulates BiP's ATPase activity, enabling proper folding of nascent secretory and membrane proteins. The protein also participates in ER-associated degradation (ERAD) by targeting misfolded proteins for retrotranslocation. Loss of DNAJB11 function leads to ER stress and is a monogenic cause of autosomal dominant polycystic kidney disease (ADPKD).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DNAJB11 Knockout HEK293 Cell Line | EDJ-KQ2034 | Human | 51726 | Details Get a Quote |
| DNAJB11 Knockout A-549 Cell Line | EDJ-KQ22074 | Human | 51726 | Details Get a Quote |
| DNAJB11 Knockout HCT 116 Cell Line | EDJ-KQ22075 | Human | 51726 | Details Get a Quote |
| DNAJB11 Knockout HeLa Cell Line | EDJ-KQ20777 | Human | 51726 | Details Get a Quote |
