DNAJB12 Gene - DnaJ Heat Shock Protein Family (Hsp40) Member B12
Functional insights into DNAJB12, a co-chaperone involved in protein folding, endoplasmic reticulum-associated degradation, and cellular stress response.
Gene Information Card
| Symbol | DNAJB12 |
|---|---|
| Full Name | DnaJ heat shock protein family (Hsp40) member B12 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q22.1 |
| NCBI Gene ID | 54788 ncbi.nlm.nih.gov/gene/54788 |
| Ensembl ID | ENSG00000148719 |
| UniProt ID | Q9NXW2 |
| OMIM ID | 611169 |
| HGNC ID | 20390 |
| Aliases | HSPF2, DJB12, ERdj5, JPD1 |
Description
DNAJB12 encodes a member of the DnaJ/Hsp40 family of co-chaperones. The protein contains a conserved J-domain that interacts with Hsp70 chaperones to facilitate protein folding, translocation, and degradation. DNAJB12 is localized to the endoplasmic reticulum (ER) membrane and plays a critical role in ER-associated degradation (ERAD) by recruiting Hsp70 to misfolded proteins for retrotranslocation and proteasomal degradation. It also participates in the unfolded protein response (UPR) and cellular stress adaptation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary spastic paraplegia (HSP) | Loss-of-function mutations in DNAJB12 impair ERAD of misfolded proteins, leading to axonal degeneration. | PMID: 25480986; OMIM 611169 |
| Cancer (multiple types) | Altered DNAJB12 expression affects protein homeostasis and apoptosis; overexpression linked to chemoresistance in breast and lung cancer. | COSMIC; PMID: 28431213 |
| Neurodegenerative disorders | Dysfunctional ERAD due to DNAJB12 variants may contribute to protein aggregation in Alzheimer's and Parkinson's disease. | PMID: 29100055 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Brain (cerebellum) | 8.2 | Medium |
| Liver | 6.7 | Low |
| Heart | 5.1 | Low |
| Kidney | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 9.8 | Embryonic kidney cells; high expression |
| HeLa | 7.4 | Cervical cancer cells; moderate expression |
| HepG2 | 5.6 | Hepatocellular carcinoma; low expression |
| SH-SY5Y | 6.2 | Neuroblastoma; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.284G>A (p.Arg95His) | Missense | 0.001% (gnomAD) | Reduced J-domain interaction with Hsp70, impaired ERAD |
| c.487C>T (p.Arg163*) | Nonsense | <0.001% | Loss of function; truncation of C-terminal domain |
| c.632_633insA (p.Gln211fs) | Frameshift | <0.001% | Premature stop; loss of ER membrane localization |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg163*, p.Gln211fs) lead to truncated or absent protein, disrupting ERAD and causing protein aggregation.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in DNAJB12.
Dominant Negative (DN)
Missense mutations (e.g., p.Arg95His) may act in a dominant-negative manner by sequestering Hsp70 without productive chaperone activity.
View complete mutation data：
Gene Ontology (GO)
| • protein folding (GO:0006457) | • ER-associated ubiquitin-dependent protein catabolic process (GO:0030433) |
| • unfolded protein binding (GO:0051082) | • endoplasmic reticulum (GO:0005783) |
| • ubiquitin protein ligase binding (GO:0031625) | • ATPase activator activity (GO:0001671) |
Pathways
• Endoplasmic reticulum-associated degradation (ERAD) pathway (Reactome: R-HSA-983168)
• Unfolded protein response (UPR) (Reactome: R-HSA-381119)
• Hsp70 chaperone cycle (Reactome: R-HSA-3371568)
Protein Summary
DNAJB12 is a 369-amino acid protein with an N-terminal J-domain (residues 1-70) that binds Hsp70, a glycine/phenylalanine-rich region, and a C-terminal domain that anchors the protein to the ER membrane. It functions as a co-chaperone to stimulate ATPase activity of Hsp70, facilitating substrate recognition and translocation. DNAJB12 is essential for ERAD of misfolded luminal and membrane proteins, and its loss leads to ER stress and accumulation of toxic protein aggregates.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DNAJB12 Knockout HEK293 Cell Line | EDJ-KQ13183 | Human | 54788 | Details Get a Quote |
| DNAJB12 Knockout A-549 Cell Line | EDJ-KQ42540 | Human | 54788 | Details Get a Quote |
| DNAJB12 Knockout HCT 116 Cell Line | EDJ-KQ42541 | Human | 54788 | Details Get a Quote |
| DNAJB12 Knockout HeLa Cell Line | EDJ-KQ42542 | Human | 54788 | Details Get a Quote |
