CREB3L3 Gene - cAMP Responsive Element Binding Protein 3 Like 3
Comprehensive genomic and functional analysis of CREB3L3, a transcription factor involved in unfolded protein response and lipid metabolism.
Gene Information Card
| Symbol | CREB3L3 |
|---|---|
| Full Name | cAMP responsive element binding protein 3 like 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 19p13.3 |
| NCBI Gene ID | 84699 ncbi.nlm.nih.gov/gene/84699 |
| Ensembl ID | ENSG00000167588 |
| UniProt ID | Q68CJ9 |
| OMIM ID | 611998 |
| HGNC ID | 18856 |
| Aliases | CREB-H, CREB3L3, bZIP transcription factor |
Description
CREB3L3 (cAMP responsive element binding protein 3 like 3) encodes a transcription factor of the bZIP family, primarily involved in the unfolded protein response (UPR) and regulation of lipid metabolism. It is predominantly expressed in liver and small intestine, where it activates genes involved in lipogenesis, gluconeogenesis, and acute phase response. Mutations in CREB3L3 are associated with familial combined hyperlipidemia and may contribute to metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Familial combined hyperlipidemia | Loss-of-function mutations impair lipid metabolism regulation, leading to elevated triglycerides and cholesterol. | PMID: 25282149, ClinVar |
| Hypertriglyceridemia | Reduced CREB3L3 activity disrupts VLDL secretion and lipid homeostasis. | PMID: 25282149 |
| Metabolic syndrome | Dysregulation of CREB3L3 target genes contributes to insulin resistance and hepatic steatosis. | PMID: 23415227 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Small intestine | 8.3 | Medium |
| Pancreas | 2.1 | Low |
| Kidney | 1.0 | Low |
| Adipose tissue | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocellular carcinoma cell line |
| Caco-2 | 9.8 | Colorectal adenocarcinoma cell line |
| HEK293 | 0.3 | Embryonic kidney cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.100C>T (p.Arg34*) | Nonsense | <0.01% | Loss of function; associated with hyperlipidemia |
| c.457G>A (p.Gly153Arg) | Missense | <0.01% | Impaired transcriptional activity |
| c.832delC | Frameshift | <0.01% | Truncated protein; loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg34*, c.832delC) lead to truncated or absent protein, reducing activation of lipid metabolism genes.
Gain of Function (GOF)
No gain-of-function mutations reported in CREB3L3.
Dominant Negative (DN)
Not described for CREB3L3.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Unfolded Protein Response (UPR) - Reactome R-HSA-381119
• Regulation of lipid metabolism by CREB3L3 - PMID: 23415227
Protein Summary
CREB3L3 is a 461-amino acid transcription factor with a basic leucine zipper (bZIP) domain. It localizes to the endoplasmic reticulum (ER) membrane and is cleaved upon ER stress, releasing its N-terminal domain to translocate to the nucleus and activate target genes. It plays a key role in the unfolded protein response and regulates genes involved in lipid synthesis, gluconeogenesis, and acute phase response.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CREB3L3 Knockout HEK293 Cell Line | EDJ-KQ785 | Human | 84699 | Details Get a Quote |
| CREB3L3 Knockout HeLa Cell Line | EDJ-KQ57652 | Human | 84699 | Details Get a Quote |
| CREB3L3 Knockout A-549 Cell Line | EDJ-KQ66150 | Human | 84699 | Details Get a Quote |
| CREB3L3 Knockout HCT 116 Cell Line | EDJ-KQ74577 | Human | 84699 | Details Get a Quote |
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