DERL1 Gene: Structure, Function, and Clinical Significance
Comprehensive guide to DERL1 (Derlin-1), a key component of the ER-associated degradation pathway, its role in protein quality control, disease associations, and expression profiles.
Gene Information Card
| Symbol | DERL1 |
|---|---|
| Full Name | Derlin 1 |
| Gene Type | protein coding |
| Chromosomal Location | 8q24.13 |
| NCBI Gene ID | 79139 ncbi.nlm.nih.gov/gene/79139 |
| Ensembl ID | ENSG00000136982 |
| UniProt ID | Q9BUN8 |
| OMIM ID | 608813 |
| HGNC ID | 28454 |
| Aliases | DER1, derlin-1, FLJ11155, MGC3069 |
Description
DERL1 (Derlin 1) encodes a multi-pass transmembrane protein localized to the endoplasmic reticulum (ER). It is a critical component of the ER-associated degradation (ERAD) pathway, which targets misfolded proteins for retrotranslocation to the cytosol and subsequent proteasomal degradation. DERL1 forms a complex with VCP/p97 and other ERAD factors, facilitating the extraction of misfolded proteins from the ER lumen. It also plays a role in the unfolded protein response (UPR) and has been implicated in various cancers and neurodegenerative diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Overexpression of DERL1 promotes tumor cell survival by enhancing ERAD, reducing ER stress-induced apoptosis. It is associated with poor prognosis in several cancers. | COSMIC, PubMed (e.g., PMID: 25605247, 27623382) |
| Neurodegenerative disorders (e.g., Alzheimer's, Parkinson's) | DERL1-mediated ERAD may be involved in clearing misfolded proteins; dysfunction could contribute to protein aggregation. | PubMed (e.g., PMID: 21775632) |
| Cystic fibrosis (CFTR mutations) | DERL1 participates in ERAD of mutant CFTR, potentially influencing disease severity. | PubMed (e.g., PMID: 16831809) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 10.2 | Medium |
| Brain | 8.4 | Low |
| Heart | 7.1 | Low |
| Lung | 9.8 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.3 | Cervical cancer cell line; high expression |
| HepG2 | 12.8 | Liver cancer cell line; moderate-high |
| A549 | 11.0 | Lung cancer cell line; moderate |
| SH-SY5Y | 9.2 | Neuroblastoma cell line; moderate-low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.112A>G (p.Thr38Ala) | Missense | Rare (0.01% in gnomAD) | Potential impact on protein stability; functional significance unclear |
| c.454C>T (p.Arg152Trp) | Missense | Rare (0.005% in gnomAD) | Located in transmembrane domain; may affect retrotranslocation activity |
| c.789_790insA (p.Glu264fs) | Frameshift | Very rare | Predicted loss-of-function; likely leads to truncated protein |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in DERL1 are rare and may impair ERAD, leading to accumulation of misfolded proteins and ER stress. Such mutations could contribute to cellular dysfunction, but no germline disease-causing mutations have been firmly established.
Gain of Function (GOF)
Gain-of-function alterations are not well-documented; however, overexpression of wild-type DERL1 in cancers may act as a functional gain, enhancing ERAD and promoting cell survival.
Dominant Negative (DN)
Dominant-negative effects have not been reported for DERL1 mutations; however, certain missense variants could potentially interfere with complex formation, but evidence is lacking.
View complete mutation data：
Gene Ontology (GO)
| • endoplasmic reticulum membrane | • integral component of membrane |
| • ubiquitin-dependent ERAD pathway | • protein homodimerization activity |
| • ATPase binding | • response to unfolded protein |
Pathways
• ER-associated degradation (ERAD) pathway
• Unfolded protein response (UPR)
• VCP/p97-mediated retrotranslocation
Protein Summary
DERL1 is a 251-amino acid protein with four transmembrane domains. It is localized to the ER membrane and is essential for the retrotranslocation of misfolded proteins into the cytosol. It interacts with VCP/p97, Derlin-2, and other ERAD components. DERL1 also participates in the degradation of specific substrates such as MHC class I heavy chains and mutant CFTR. Its expression is ubiquitous but varies across tissues, with higher levels in metabolically active tissues. Overexpression in tumors suggests a role in cancer progression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DERL1 Knockout HEK293 Cell Line | EDJ-KQ3976 | Human | 79139 | Details Get a Quote |
| DERL1 Knockout A-549 Cell Line | EDJ-KQ26263 | Human | 79139 | Details Get a Quote |
| DERL1 Knockout HCT 116 Cell Line | EDJ-KQ26264 | Human | 79139 | Details Get a Quote |
| DERL1 Knockout HeLa Cell Line | EDJ-KQ26265 | Human | 79139 | Details Get a Quote |
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