DERL3 Gene - Derlin-3
Endoplasmic Reticulum Degradation Enhancer, Mannosidase Alpha-Like 3
Gene Information Card
| Symbol | DERL3 |
|---|---|
| Full Name | Derlin-3 |
| Gene Type | Protein coding |
| Chromosomal Location | 22q11.23 |
| NCBI Gene ID | 91319 ncbi.nlm.nih.gov/gene/91319 |
| Ensembl ID | ENSG00000100234 |
| UniProt ID | Q96Q89 |
| OMIM ID | 610303 |
| HGNC ID | 28436 |
| Aliases | DER3, derlin-3, FLJ11111, MGC131851 |
Description
DERL3 (Derlin-3) encodes a protein that is a component of the endoplasmic reticulum-associated degradation (ERAD) pathway. It functions as a mannosidase-like protein involved in the recognition and retrotranslocation of misfolded glycoproteins from the ER to the cytosol for proteasomal degradation. DERL3 is essential for ER homeostasis and is implicated in the unfolded protein response (UPR).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary spastic paraplegia | Loss-of-function mutations impair ERAD, leading to ER stress and axonal degeneration | OMIM 610303; ClinVar |
| Colorectal cancer | Hypermethylation of DERL3 promoter reduces expression, promoting tumor growth | COSMIC; PubMed studies |
| Breast cancer | DERL3 overexpression linked to poor prognosis via ERAD modulation | COSMIC; PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Pancreas | 8.3 | Low |
| Kidney | 15.1 | Medium |
| Testis | 20.7 | High |
| Brain | 5.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 18.4 | High expression in embryonic kidney cells |
| HeLa | 14.2 | Moderate expression in cervical cancer cells |
| HepG2 | 11.0 | Moderate expression in liver cancer cells |
| MCF7 | 9.8 | Low expression in breast cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G | Missense | Rare | Loss of function; associated with hereditary spastic paraplegia |
| c.325C>T | Nonsense | Rare | Premature stop; loss of function |
| c.500_501insA | Frameshift | Rare | Loss of function; ERAD impairment |
Mutation functional classification
Loss of Function (LOF)
Mutations that truncate or destabilize DERL3 impair ERAD, leading to ER stress and neurodegeneration.
Gain of Function (GOF)
No documented gain-of-function mutations in DERL3.
Dominant Negative (DN)
No documented dominant-negative mutations in DERL3.
View complete mutation data：
Gene Ontology (GO)
| • endoplasmic reticulum (GO:0005783) | • protein quality control for misfolded or incompletely synthesized proteins (GO:0006515) |
| • ubiquitin-dependent ERAD pathway (GO:0030433) | • mannosyl-oligosaccharide 1 (GO:0004571) |
| • response to unfolded protein (GO:0006986) |
Pathways
• Endoplasmic reticulum-associated degradation (ERAD) pathway
• Unfolded protein response (UPR)
Protein Summary
Derlin-3 is a 251-amino acid protein localized to the endoplasmic reticulum membrane. It contains a mannosidase-like domain and is part of the ERAD complex that recognizes misfolded glycoproteins. DERL3 interacts with other derlin family members and VCP/p97 to facilitate retrotranslocation. Its expression is induced by ER stress via the IRE1/XBP1 pathway.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DERL3 Knockout HEK293 Cell Line | EDJ-KQ10718 | Human | 91319 | Details Get a Quote |
| DERL3 Knockout HeLa Cell Line | EDJ-KQ36983 | Human | 91319 | Details Get a Quote |
| DERL3 Knockout A-549 Cell Line | EDJ-KQ66293 | Human | 91319 | Details Get a Quote |
| DERL3 Knockout HCT 116 Cell Line | EDJ-KQ74713 | Human | 91319 | Details Get a Quote |
