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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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CREB5
cAMP responsive element binding protein 5
Chromosome 7 · 7p15.1-p14.3
NCBI Gene: 9586Ensembl: ENSG00000146592.18HGNC: HGNC:16844UniProt: Q02930
73PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
extracellular exosomeprotein bindingpositive regulation of DNA-templated transcriptionDNA-binding transcription factor activityAbnormality of the skeletal systematopic eczemaatrial fibrillationopen-angle glaucoma
✦AI Summary

CREB5 (cAMP responsive element binding protein 5) is a transcription factor that binds to cAMP response elements and activates gene transcription. The protein functions as a key regulator in multiple pathways by directly binding to promoter regions of target genes and modulating their expression 1. CREB5 plays critical roles in cellular processes including proliferation, epithelial-mesenchymal transition (EMT), and maintenance of stem cell states. In cancer contexts, CREB5 exhibits oncogenic properties across multiple tumor types. In prostate cancer, CREB5 promotes resistance to androgen receptor-targeting therapies by physically interacting with AR and FOXA1, reprogramming nuclear protein interactions and activating Wnt signaling pathways 2. In hepatocellular carcinoma, CREB5 promotes EMT by directly binding to and upregulating tenascin-C (TNC) expression 1. CREB5 also maintains stemness in diffuse intrinsic pontine glioma through an H3.3K27M/CREB5/ID1 axis 3. Additionally, CREB5 functions in kidney injury repair processes, serving as a regulator of both successful and failed tubular repair while driving proximal tubular cell proliferation 4. The gene can be regulated by endoplasmic reticulum stress through super-enhancer mechanisms and represents a potential therapeutic target in various disease contexts.

Sources cited
1
CREB5 directly binds to promoter regions and upregulates TNC expression, promoting EMT in hepatocellular carcinoma
PMID: 39915455
2
CREB5 physically interacts with AR and FOXA1, reprogramming nuclear interactions and promoting resistance to androgen receptor-targeting therapies
PMID: 35550030
3
CREB5 maintains stemness in diffuse intrinsic pontine glioma through H3.3K27M/CREB5/ID1 axis
PMID: 40246858
4
CREB5 regulates both successful and failed tubular repair and drives proximal tubular cell proliferation after kidney injury
PMID: 39110788
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
Abnormality of the skeletal systemOpen Targets
0.50Moderate
atopic eczemaOpen Targets
0.46Moderate
atrial fibrillationOpen Targets
0.46Moderate
open-angle glaucomaOpen Targets
0.43Moderate
osteoarthritis, kneeOpen Targets
0.41Moderate
glaucomaOpen Targets
0.40Moderate
Age-related cataractOpen Targets
0.39Weak
cataractOpen Targets
0.39Weak
Myasthenia gravisOpen Targets
0.33Weak
COVID-19Open Targets
0.32Weak
adolescent idiopathic scoliosisOpen Targets
0.31Weak
tenosynovitisOpen Targets
0.31Weak
severe acute respiratory syndromeOpen Targets
0.31Weak
hair colorOpen Targets
0.29Weak
dermatitisOpen Targets
0.27Weak
placenta praeviaOpen Targets
0.25Weak
hyperpituitarismOpen Targets
0.24Weak
ovarian neoplasmOpen Targets
0.23Weak
injuryOpen Targets
0.22Weak
osteoarthritis, hipOpen Targets
0.22Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
FOSProtein interaction99%CREB3Protein interaction96%CREB3L1Protein interaction95%PPARGC1AProtein interaction95%JUNProtein interaction95%CRTC2Protein interaction94%
Tissue Expression6 tissues
Brain
100%
Lung
30%
Heart
30%
Bone Marrow
13%
Liver
4%
Ovary
4%
Gene Interaction Network
Click a node to explore
CREB5FOSCREB3CREB3L1PPARGC1AJUNCRTC2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q02930
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.42Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.27 [0.18–0.42]
RankingsWhere CREB5 stands among ~20K protein-coding genes
  • #6,454of 20,598
    Most Researched73
  • #2,225of 17,882
    Most Constrained (LOEUF)0.42 · top quartile
Genes detectedCREB5
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Anchored multiplex PCR for targeted next-generation sequencing.
PMID: 25384085
Nat Med · 2014
1.00
2
Lineage-specific regulatory changes in hypertrophic cardiomyopathy unraveled by single-nucleus RNA-seq and spatial transcriptomics.
PMID: 36646705
Cell Discov · 2023
0.90
3
CREB5 reprograms FOXA1 nuclear interactions to promote resistance to androgen receptor-targeting therapies.
PMID: 35550030
Elife · 2022
0.80
4
An oncohistone-driven H3.3K27M/CREB5/ID1 axis maintains the stemness and malignancy of diffuse intrinsic pontine glioma.
PMID: 40246858
Nat Commun · 2025
0.70
5
Epigenetic reprogramming driving successful and failed repair in acute kidney injury.
PMID: 39110788
Sci Adv · 2024
0.60