CREB3L1: A Key Regulator of Unfolded Protein Response and Bone Development
Comprehensive genomic and functional analysis of the CREB3L1 gene, its role in osteogenesis imperfecta, and implications in cancer biology.
Gene Information Card
| Symbol | CREB3L1 |
|---|---|
| Full Name | cAMP responsive element binding protein 3 like 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 11p11.2 |
| NCBI Gene ID | 90993 ncbi.nlm.nih.gov/gene/90993 |
| Ensembl ID | ENSG00000157613 |
| UniProt ID | Q96BA8 |
| OMIM ID | 616215 |
| HGNC ID | 18856 |
| Aliases | OASIS, CREB-H, CREB3, CREB3L1 |
Description
CREB3L1 (cAMP responsive element binding protein 3 like 1), also known as OASIS, is a transcription factor that belongs to the CREB/ATF family. It is primarily localized to the endoplasmic reticulum (ER) membrane and is activated upon ER stress through regulated intramembrane proteolysis. Once cleaved, its N-terminal domain translocates to the nucleus to regulate genes involved in the unfolded protein response (UPR), bone matrix formation, and cell differentiation. Mutations in CREB3L1 are associated with osteogenesis imperfecta type XVI, and its dysregulation has been implicated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Osteogenesis Imperfecta Type XVI | Loss-of-function mutations in CREB3L1 impair the transcription of collagen type I and other bone matrix proteins, leading to brittle bones and skeletal deformities. | OMIM #616215; multiple case reports with homozygous or compound heterozygous mutations |
| Breast Cancer | Overexpression of CREB3L1 has been observed in breast cancer cell lines, potentially promoting metastasis through regulation of UPR target genes. | COSMIC; literature on CREB3L1 in cancer cell lines |
| Glioma | CREB3L1 expression is altered in glioblastoma, contributing to tumor progression via ER stress signaling. | NCBI Gene expression studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone | 12.5 | Medium |
| Salivary gland | 8.3 | Low |
| Pancreas | 6.1 | Low |
| Liver | 4.7 | Low |
| Brain | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 15.2 | High expression |
| U2OS (osteosarcoma) | 10.8 | Moderate expression |
| HepG2 (liver cancer) | 7.4 | Low expression |
| SH-SY5Y (neuroblastoma) | 5.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1042C>T (p.Arg348*) | Nonsense | <0.01% | Loss of function; truncated protein lacking transactivation domain |
| c.1A>G (p.Met1?) | Missense | <0.01% | Loss of start codon; no protein production |
| c.832G>A (p.Gly278Arg) | Missense | <0.01% | Likely loss of function; impaired DNA binding |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations in CREB3L1 lead to loss of transcriptional activity, causing osteogenesis imperfecta type XVI.
Gain of Function (GOF)
Not well documented; overexpression in some cancers may confer gain-of-function effects via UPR activation.
Dominant Negative (DN)
No dominant-negative mutations have been reported for CREB3L1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Unfolded Protein Response (UPR) - Reactome R-HSA-381119
• ATF6-alpha activates chaperones - Reactome R-HSA-381183
• Collagen biosynthesis and modifying enzymes - Reactome R-HSA-1650814
Protein Summary
CREB3L1 is a 519-amino acid protein with an N-terminal basic leucine zipper (bZIP) domain and a C-terminal transmembrane domain that anchors it to the ER membrane. Under ER stress, it is cleaved by site-1 and site-2 proteases, releasing the N-terminal fragment that enters the nucleus to activate UPR target genes such as BiP, CHOP, and collagen type I. The protein plays a critical role in osteoblast differentiation and bone matrix production.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CREB3L1 Knockout HEK293 Cell Line | EDJ-KQ783 | Human | 90993 | Details Get a Quote |
| CREB3L1 Knockout A-549 Cell Line | EDJ-KQ19489 | Human | 90993 | Details Get a Quote |
| CREB3L1 Knockout HeLa Cell Line | EDJ-KQ19490 | Human | 90993 | Details Get a Quote |
| CREB3L1 Knockout HCT 116 Cell Line | EDJ-KQ74704 | Human | 90993 | Details Get a Quote |
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