CREBBP Gene

CREBBP Gene

Introduction

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">CREBBP Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>CREBBP</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>CREB Binding Protein</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>16p13.3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>1387</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>600140</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000105383</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q92793 (CREBBP)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/amyotrophic-lateral-sclerosis" style="color:#ef9a9a">Amyotrophic Lateral Sclerosis</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/carcinoma" style="color:#ef9a9a">Carcinoma</a>, <a href="/wiki/colorectal-cancer" style="color:#ef9a9a">Colorectal Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">374 edges</a></td>
</tr>
</table>

Crebbp Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

CREBBP Gene

Introduction

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">CREBBP Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>CREBBP</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>CREB Binding Protein</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>16p13.3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>1387</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>600140</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000105383</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q92793 (CREBBP)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/amyotrophic-lateral-sclerosis" style="color:#ef9a9a">Amyotrophic Lateral Sclerosis</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/carcinoma" style="color:#ef9a9a">Carcinoma</a>, <a href="/wiki/colorectal-cancer" style="color:#ef9a9a">Colorectal Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">374 edges</a></td>
</tr>
</table>

Crebbp Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

Gene Information

Normal Function

• Acetylates histones H3/H4 to open chromatin
• Acetylates transcription factors (p53, [NF-κB](/entities/nf-kb), CREB)
• Functions as transcriptional coactivator
• Essential for:
• Learning and memory
• Synaptic plasticity
• Neuronal survival
• Embryonic development
• Interacts with CBP (they are the same protein)

Disease Associations

Alzheimer's Disease

• CREBBP/CBP levels decline in AD brain
• Essential for memory consolidation
• Acetylates [tau](/proteins/tau) and reduces aggregation
• May be therapeutic target

Huntington's Disease

• Mutant [huntingtin](/proteins/huntingtin-protein) sequesters CREBBP
• Contributes to transcriptional dysregulation
• Restoring CREBBP function is therapeutic strategy

Rubinstein-Taybi Syndrome

• Heterozygous CREBBP mutations cause RTS
• Intellectual disability, distinctive features
• Haploinsufficiency

Expression

• Brain: [Cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), cerebellum
• Ubiquitously in peripheral tissues
• Nuclear localization

Therapeutic Implications

• [HDAC](/entities/hdac-enzymes) inhibitors: Increase histone acetylation
• CBP activators: Under development
• Gene therapy: AAV-CREBBP for neuroprotection

Expression Pattern

CREBBP shows broad expression across tissues:

• Brain: High in cerebral cortex, hippocampus (CA1-CA3), cerebellum (Purkinje cells)
• [Neurons](/entities/neurons): Expressed in most neuronal subtypes including pyramidal cells, interneurons
• Glia: Present in [astrocytes](/entities/astrocytes) and [microglia](/entities/microglia)
• Peripheral: Liver (highest), kidney, heart, lung, skeletal muscle

Molecular Function

CREBBP (CREB-binding protein) is a master transcriptional coactivator:

• Acetylates histone H3K27, H3K9
• Remodels chromatin for transcription
• HAT activity required for learning/memory

• Interacts with CREB, p53, NF-κB, HIF-1α
• Bridges transcription factors to basal machinery
• Essential for activity-dependent gene expression

• Forms heterodimers with p300
• Multiple domains for protein interactions
• Bromodomain recognizes acetyl-lysine

• Integrates cAMP, calcium, growth factor signals
• Coordinates transcriptional responses
• Dysregulation affects neuroplasticity

Role in Neurodegeneration

• [Alzheimer's Disease](/diseases/alzheimers-disease): Reduced CBP in neurons, therapeutic potential
• Huntington's Disease: Mutant [HTT](/genes/htt) sequesters CBP
• FTD/ALS: [TDP-43](/proteins/tdp-43) affects CBP function

Animal Models

Key findings from model systems:

• Heterozygous knockout mice: Viable, model for Rubinstein-Taybi syndrome
• Neuron-specific knockouts: Severe memory deficits, impaired [LTP](/mechanisms/long-term-potentiation)
• Conditional knockouts: Reversible deficits
• Knock-in models: Disease-causing mutations recapitulate phenotype
• Rescue studies: Demonstrate CBP haploinsufficiency role

Therapeutic Implications

CREBBP is a therapeutic target:

• HDAC inhibitors: Increase histone acetylation, may compensate
• Small molecule activators: HAT activity enhancers in development
• Gene therapy: AAV-CREBBP delivery being explored
• Combination approaches: With neurotrophic factors

Key Publications

External Links

• [NCBI Gene: CREBBP](https://www.ncbi.nlm.nih.gov/gene/1387)
• [UniProt: CREBBP](https://www.uniprot.org/uniprot/Q92793)

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Huntington's Disease](/diseases/huntingtons)
• [Rubinstein-Taybi Syndrome](/diseases/rubinstein-taybi-syndrome)
• [CREB1](/proteins/creb1-protein)
• [EP300](/proteins/ep300-protein)

Background

The study of Crebbp Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

References

[@goodman2000]: Goodman RH, Smolik S. (2000). CBP/p300 in cell growth, transformation, and development. Genes Dev. 14(13):1553-1577. PMID: 10859150(https://pubmed.ncbi.nlm.nih.gov/10859150/)

[@kalkhoven2004]: Kalkhoven E. (2004). CBP and p300: HATs for different occasions. Biochem Pharmacol. 68(6):1145-1155. PMID: 15313432(https://pubmed.ncbi.nlm.nih.gov/15313432/)

[@veitia2003]: Veitia RA. (2003). Balancing acts: the role of transcriptional coactivators in disease. Trends Genet. 19(5):263-268. PMID: 12711215(https://pubmed.ncbi.nlm.nih.gov/12711215/)

Pathway Diagram

Pathway Diagram

The following diagram shows the key molecular relationships involving CREBBP Gene discovered through SciDEX knowledge graph analysis: