CREBRF: CREB3 Regulatory Factor
A key regulator of endoplasmic reticulum stress and unfolded protein response, implicated in obesity, type 2 diabetes, and cancer.
Gene Information Card
| Symbol | CREBRF |
|---|---|
| Full Name | CREB3 Regulatory Factor |
| Gene Type | Protein coding |
| Chromosomal Location | 5q35.2 |
| NCBI Gene ID | 153222 ncbi.nlm.nih.gov/gene/153222 |
| Ensembl ID | ENSG00000164463 |
| UniProt ID | Q8IUR6 |
| OMIM ID | 617109 |
| HGNC ID | 26702 |
| Aliases | CREB3 regulatory factor, LRF, MGC138290 |
Description
CREBRF (CREB3 Regulatory Factor) encodes a protein that negatively regulates the unfolded protein response (UPR) by promoting the degradation of the transcription factor CREB3 (cAMP responsive element binding protein 3). It is involved in endoplasmic reticulum (ER) stress signaling, adipogenesis, and energy homeostasis. Variants in CREBRF have been associated with obesity and type 2 diabetes, particularly in Pacific Islander populations, and altered expression is observed in certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Obesity | The missense variant p.Arg457Gln (rs373863828) is associated with increased body mass index and reduced risk of type 2 diabetes, possibly through altered ER stress response and adipocyte function. | ClinVar, OMIM |
| Type 2 Diabetes | The same p.Arg457Gln variant shows a protective effect against type 2 diabetes in Samoan and other Pacific Islander populations, independent of obesity. | ClinVar, OMIM |
| Endometrial Cancer | CREBRF overexpression is observed in endometrial tumors and may promote cell proliferation and migration via modulation of the UPR. | COSMIC, NCBI Gene |
| Breast Cancer | Dysregulation of CREBRF expression has been reported in breast cancer cell lines, potentially influencing tumor growth through ER stress pathways. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 15.2 | Medium |
| Liver | 8.5 | Low |
| Pancreas | 6.1 | Low |
| Endometrium | 22.4 | High |
| Breast | 12.3 | Medium |
| Brain | 4.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 9.8 | Hepatocellular carcinoma cell line |
| MCF7 | 14.5 | Breast cancer cell line |
| HeLa | 11.2 | Cervical cancer cell line |
| K562 | 6.3 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs373863828 (p.Arg457Gln) | Missense | 0.26 in Samoans; rare in other populations | Associated with increased BMI and reduced T2D risk |
| c.1370G>A | Missense | Rare | Unknown functional effect |
| c.1123C>T | Nonsense | Rare | Predicted loss-of-function |
Mutation functional classification
Loss of Function (LOF)
Nonsense variants (e.g., c.1123C>T) are predicted to cause loss of function by introducing a premature stop codon, leading to nonsense-mediated decay or truncated protein.
Gain of Function (GOF)
The p.Arg457Gln variant is hypothesized to confer a gain-of-function effect by altering CREB3 regulation, enhancing adipogenesis and energy storage.
Dominant Negative (DN)
No dominant-negative mutations have been reported for CREBRF.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Unfolded Protein Response (UPR)
• Endoplasmic Reticulum Stress Pathway
• CREB3-mediated signaling
Protein Summary
The CREBRF protein is a 789-amino acid nuclear and cytoplasmic factor that binds to and promotes the ubiquitin-mediated degradation of CREB3, a transcription factor involved in the unfolded protein response. By attenuating CREB3 activity, CREBRF modulates ER stress signaling, influencing cellular processes such as adipogenesis, metabolism, and cell survival. The protein contains a coiled-coil domain and a C-terminal region critical for interaction with CREB3.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CREBRF Knockout HEK293 Cell Line | EDJ-KQ3827 | Human | 153222 | Details Get a Quote |
| CREBRF Knockout A-549 Cell Line | EDJ-KQ25973 | Human | 153222 | Details Get a Quote |
| CREBRF Knockout HCT 116 Cell Line | EDJ-KQ25974 | Human | 153222 | Details Get a Quote |
| CREBRF Knockout HeLa Cell Line | EDJ-KQ25975 | Human | 153222 | Details Get a Quote |
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