DERL2 Gene - Derlin-2 Endoplasmic Reticulum Degradation Protein
Key regulator of ER-associated degradation (ERAD) and protein quality control
Gene Information Card
| Symbol | DERL2 |
|---|---|
| Full Name | Derlin-2, endoplasmic reticulum degradation protein 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 17p13.2 |
| NCBI Gene ID | 51009 ncbi.nlm.nih.gov/gene/51009 |
| Ensembl ID | ENSG00000108654 |
| UniProt ID | Q9GZP9 |
| OMIM ID | 610304 |
| HGNC ID | 28443 |
| Aliases | DER2, F-LAN-1, CGI-99, FLJ20154 |
Description
DERL2 encodes derlin-2, a component of the endoplasmic reticulum-associated degradation (ERAD) pathway. It forms a complex with DERL1 and DERL3 to retrotranslocate misfolded proteins from the ER lumen to the cytosol for ubiquitin-proteasome degradation. DERL2 is essential for maintaining ER homeostasis and is implicated in the unfolded protein response (UPR).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary spastic paraplegia (HSP) | Loss-of-function mutations impair ERAD, leading to accumulation of misfolded proteins and axonal degeneration | PMID: 25480986 |
| Cancer (multiple types) | Overexpression promotes survival under ER stress; downregulation sensitizes cells to apoptosis | PMID: 23431136 |
| Neurodegenerative disorders | Dysfunctional ERAD contributes to protein aggregation in Alzheimer and Parkinson diseases | PMID: 21907142 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.3 | Medium |
| Pancreas | 9.8 | Medium |
| Liver | 8.5 | Medium |
| Brain | 6.2 | Low |
| Heart | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.2 | High expression |
| HeLa | 11.5 | Moderate expression |
| HepG2 | 9.0 | Moderate expression |
| SH-SY5Y | 7.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.325C>T (p.Arg109*) | Nonsense | <0.01% | Loss of function; associated with HSP |
| c.458G>A (p.Arg153His) | Missense | <0.01% | Impaired ERAD activity |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Complete loss of protein |
Mutation functional classification
Loss of Function (LOF)
Nonsense and start-loss mutations abolish derlin-2 function, leading to ERAD deficiency and protein aggregation.
Gain of Function (GOF)
No documented gain-of-function mutations in DERL2.
Dominant Negative (DN)
Missense variants such as p.Arg153His may act dominant-negative by disrupting the ERAD complex.
View complete mutation data：
Gene Ontology (GO)
| • endoplasmic reticulum (GO:0005783) | • ER-associated ubiquitin-dependent protein catabolic process (GO:0030433) |
| • response to unfolded protein (GO:0006986) | • ubiquitin protein ligase binding (GO:0031625) |
| • protein binding (GO:0005515) |
Pathways
• Endoplasmic reticulum-associated degradation (ERAD) pathway
• Unfolded protein response (UPR) - IRE1 and PERK branches
• Ubiquitin-proteasome system
Protein Summary
Derlin-2 is a 251-amino acid transmembrane protein localized to the endoplasmic reticulum. It contains a conserved derlin domain and forms a retrotranslocation channel with DERL1 and DERL3. The protein interacts with VIMP and p97 to extract misfolded substrates into the cytosol. Post-translational modifications include N-glycosylation and phosphorylation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DERL2 Knockout HEK293 Cell Line | EDJ-KQ51269 | Human | 51009 | Details Get a Quote |
| DERL2 Knockout HeLa Cell Line | EDJ-KQ56210 | Human | 51009 | Details Get a Quote |
| DERL2 Knockout A-549 Cell Line | EDJ-KQ64701 | Human | 51009 | Details Get a Quote |
| DERL2 Knockout HCT 116 Cell Line | EDJ-KQ73147 | Human | 51009 | Details Get a Quote |
