RETREG3 (Reticulophagy Regulator 3)
Gene encoding a reticulophagy receptor involved in endoplasmic reticulum turnover and cellular stress responses.
Gene Information Card
| Symbol | RETREG3 |
|---|---|
| Full Name | Reticulophagy Regulator 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q21.31 |
| NCBI Gene ID | 100130872 ncbi.nlm.nih.gov/gene/100130872 |
| Ensembl ID | ENSG00000187608 |
| UniProt ID | Q9BQD7 |
| OMIM ID | 620193 |
| HGNC ID | 25923 |
| Aliases | FAM134C, C17orf42, FLJ38663 |
Description
RETREG3 (Reticulophagy Regulator 3), also known as FAM134C, encodes a member of the reticulophagy receptor family. The protein localizes to the endoplasmic reticulum (ER) membrane and mediates selective autophagy of ER fragments (ER-phagy), contributing to ER turnover and homeostasis. It contains a reticulon homology domain (RHD) that induces membrane curvature and an LC3-interacting region (LIR) for autophagosome recruitment.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary sensory and autonomic neuropathy type I (HSAN1) | Loss-of-function mutations in RETREG3 impair ER-phagy, leading to ER stress and neuronal degeneration. | ClinVar; OMIM |
| Neurodegenerative disorders (general) | Dysregulation of ER-phagy via RETREG3 variants may contribute to protein aggregation and cellular toxicity. | NCBI Gene; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Adipose tissue | 8.2 | Low |
| Liver | 6.1 | Low |
| Kidney | 9.8 | Low |
| Testis | 15.3 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.1 | Embryonic kidney cells |
| SH-SY5Y | 14.7 | Neuroblastoma cell line |
| HepG2 | 7.3 | Hepatocellular carcinoma cells |
| HeLa | 9.5 | Cervical cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.520C>T (p.Arg174*) | Nonsense | <0.01% | Premature stop, loss of function |
| c.689G>A (p.Arg230Gln) | Missense | <0.01% | Impaired LIR motif, reduced autophagy |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg174*) lead to truncated protein lacking functional domains, causing ER-phagy deficiency.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Missense mutations in the LIR motif (e.g., p.Arg230Gln) may act dominant-negative by disrupting autophagosome recruitment.
View complete mutation data：
Gene Ontology (GO)
| • endoplasmic reticulum (GO:0005783) | • autophagosome (GO:0005776) |
| • response to endoplasmic reticulum stress (GO:0034976) | • reticulophagy (GO:0061709) |
| • identical protein binding (GO:0042802) |
Pathways
• Reticulophagy (ER-phagy)
• Autophagy – lysosome pathway
Protein Summary
RETREG3 (FAM134C) is a 497-amino acid transmembrane protein with a reticulon homology domain (RHD) that induces ER membrane curvature and an LC3-interacting region (LIR) that binds autophagosomal LC3/GABARAP family proteins. It functions as a receptor for selective ER autophagy, targeting damaged or excess ER sheets for lysosomal degradation. The protein is widely expressed, with highest levels in brain and testis. Mutations in RETREG3 are associated with hereditary sensory and autonomic neuropathy type I (HSAN1) due to impaired ER turnover.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RETREG3 Knockout HEK293 Cell Line | EDJ-KQ15038 | Human | 162427 | Details Get a Quote |
| RETREG3 Knockout A-549 Cell Line | EDJ-KQ45580 | Human | 162427 | Details Get a Quote |
| RETREG3 Knockout HCT 116 Cell Line | EDJ-KQ45581 | Human | 162427 | Details Get a Quote |
| RETREG3 Knockout HeLa Cell Line | EDJ-KQ45582 | Human | 162427 | Details Get a Quote |
