CREB3L4 Gene - cAMP Responsive Element Binding Protein 3 Like 4
Transcriptional regulator involved in unfolded protein response and cancer
Gene Information Card
| Symbol | CREB3L4 |
|---|---|
| Full Name | cAMP responsive element binding protein 3 like 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q21.3 |
| NCBI Gene ID | 148327 ncbi.nlm.nih.gov/gene/148327 |
| Ensembl ID | ENSG00000143578 |
| UniProt ID | Q8TEY5 |
| OMIM ID | 611490 |
| HGNC ID | 18856 |
| Aliases | CREB4, AIBZIP, ATCE1, JAMP |
Description
CREB3L4 (cAMP responsive element binding protein 3 like 4) is a protein-coding gene that encodes a transcription factor belonging to the CREB/ATF family. The protein is localized to the endoplasmic reticulum (ER) membrane and functions as a sensor of ER stress, activating the unfolded protein response (UPR) by undergoing regulated intramembrane proteolysis. It is involved in cellular stress adaptation, differentiation, and has been implicated in prostate cancer and other malignancies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Prostate cancer | Overexpression and altered splicing of CREB3L4 contribute to androgen-independent growth and tumor progression | PMID: 15199144, COSMIC |
| Breast cancer | Dysregulation of CREB3L4 expression linked to ER stress and tumor cell survival | PMID: 19177215 |
| Endometrial cancer | CREB3L4 upregulation associated with poor prognosis and UPR activation | PMID: 25691885 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Prostate | 12.5 | Medium |
| Breast | 8.3 | Low |
| Endometrium | 7.1 | Low |
| Liver | 4.2 | Low |
| Testis | 6.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| PC-3 (prostate cancer) | 15.2 | High expression |
| MCF-7 (breast cancer) | 9.8 | Moderate expression |
| HepG2 (liver cancer) | 5.1 | Low expression |
| HeLa (cervical cancer) | 7.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.101C>T (p.Thr34Met) | Missense | <0.01% | Unknown functional effect |
| c.452G>A (p.Arg151His) | Missense | <0.01% | Unknown functional effect |
| c.784_785insA | Frameshift | <0.01% | Predicted loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift mutations (e.g., c.784_785insA) are predicted to cause premature truncation and loss of transcriptional activity.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in CREB3L4.
Dominant Negative (DN)
No dominant-negative mutations described for CREB3L4.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Unfolded Protein Response (UPR) - Reactome R-HSA-381119
• ATF6-alpha activates chaperones - Reactome R-HSA-381183
Protein Summary
CREB3L4 is a 395-amino acid transmembrane protein anchored in the ER membrane. Under ER stress, it is cleaved by site-1 and site-2 proteases, releasing its N-terminal cytoplasmic domain which translocates to the nucleus and activates transcription of UPR target genes. The protein contains a basic leucine zipper (bZIP) domain essential for DNA binding and dimerization. It is highly expressed in prostate epithelium and plays a role in androgen receptor signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CREB3L4 Knockout HEK293 Cell Line | EDJ-KQ255 | Human | 148327 | Details Get a Quote |
| CREB3L4 Knockout A-549 Cell Line | EDJ-KQ19494 | Human | 148327 | Details Get a Quote |
| CREB3L4 Knockout HCT 116 Cell Line | EDJ-KQ19495 | Human | 148327 | Details Get a Quote |
| CREB3L4 Knockout HeLa Cell Line | EDJ-KQ19496 | Human | 148327 | Details Get a Quote |
