CELF1 Gene

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CELF1 — CUGBP Elav-Like Family Member 1

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">CELF1 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>CELF1</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>CUGBP Elav-Like Family Member 1</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>11p11.2</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>10658</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>601998</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000131095</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9UQF0</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/cardiac-hypertrophy" style="color:#ef9a9a">Cardiac Hypertrophy</a>, <a href="/wiki/ms" style="color:#ef9a9a">Ms</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">29 edges</a></td>
</tr>
</table>

Introduction

...

CELF1 — CUGBP Elav-Like Family Member 1

Introduction

CELF1 (CUGBP Elav-Like Family Member 1) is an RNA-binding protein encoded by the CELF1 gene located on chromosome 11p11.2. It is also known as CUGBP1 (CUG-binding protein 1) and is a member of the CELF/BRUNOL family of RNA-binding proteins. CELF1 plays crucial roles in post-transcriptional regulation of gene expression, including alternative splicing, mRNA stability, and translation control. [@celf]

CELF1 dysfunction is implicated in several neurodegenerative diseases, particularly [amyotrophic lateral sclerosis (ALS)](/diseases/amyotrophic-lateral-sclerosis), [myotonic dystrophy type 1](/diseases/myotonic-dystrophy), and [Alzheimer's disease](/diseases/alzheimers-disease).[@celf] [@celfa]

The protein encoded by CELF1 is [CELF1 Protein](/proteins/celf1-protein).[@celfa] [@celf2019]

--- [@rna]

Overview

Mermaid diagram (expand to render)

CELF1 is a multifunctional RNA-binding protein that regulates gene expression at multiple levels. The protein contains three RNA recognition motifs (RRMs) that mediate sequence-specific binding to target mRNAs. CELF1 recognizes GU-rich elements (GREs) and CUG repeats in RNA, making it particularly relevant to diseases involving repeat expansions. [@celf1927]

Through its regulatory functions, CELF1 influences:

Neuronal development and function
Synaptic plasticity
Muscle fiber excitability
Stress responses

Gene Structure

Protein Structure and Function

Domain Architecture

CELF1 contains:

Three RNA Recognition Motifs (RRMs): RRM1, RRM2, and RRM3
N-terminal region: Involved in protein-protein interactions
C-terminal region: Regulatory functions

RNA Binding

CELF1 binds to:

GU-rich elements (GREs): Common in transcripts regulated during stress
CUG repeats: Pathogenic in myotonic dystrophy type 1
AU-rich elements (AREs): Found in unstable mRNAs

Post-Transcriptional Regulation

Alternative Splicing:
CELF1 regulates the splicing of numerous neuronal and muscle-specific exons. It can either promote or repress exon inclusion depending on binding site location and context.

Key splicing targets include:

[Tau (MAPT)](/genes/mapt) exon 10 (regulated in Alzheimer's)
[NMDA receptor](/entities/nmda-receptor) subunits
Calcium channel transcripts
[Autophagy](/entities/autophagy)-related transcripts

mRNA Stability:
CELF1 affects mRNA half-life by binding to AREs and GREs, generally destabilizing target transcripts.

Translation Control:
CELF1 modulates translation through:

Direct interaction with translation initiation factors
Regulation of ribosomal protein synthesis
Stress granule formation

Expression Pattern

Brain Expression

CELF1 is widely expressed in the nervous system:

Cerebral [cortex](/brain-regions/cortex): [Neurons](/entities/neurons) and glia
[Hippocampus](/brain-regions/hippocampus): CA regions and dentate gyrus
Spinal cord: Motor neurons (particularly relevant to ALS)
Cerebellum: Purkinje cells and granule cells
Brainstem: Various neuronal populations

Cellular Localization

Nucleus: Splicing regulation
Cytoplasm: Translation control
Stress granules: Formed during cellular stress
Synaptic terminals: Local translation regulation

Disease Associations

Amyotrophic Lateral Sclerosis (ALS)

CELF1 is a known ALS gene:

Mutations: D262N, E191K, and others cause familial ALS
Mechanism: Altered RNA splicing of survival motor neuron (SMN) transcripts
Pathogenesis: Toxic gain-of-function and disrupted RNA processing
Related proteins: [TDP-43 (TARDBP)](/genes/tardbp), [FUS](/entities/fus), [SMN1](/genes/smn1)

Myotonic Dystrophy Type 1 (DM1)

CELF1 dysregulation is central to DM1 pathogenesis:

Trigger: CTG repeat expansion in DMPK gene
Mechanism: Mutant DMPK RNA sequesters CELF1
Consequence: Loss of CELF1 function on normal targets
Phenotype: Muscle weakness, myotonia, cardiac conduction defects

Alzheimer's Disease

CELF1 contributes to AD pathogenesis:

[Tau](/proteins/tau) splicing: Regulates tau exon 10 inclusion
Alternative splicing: Affects [amyloid precursor protein](/entities/app-protein) (APP) processing
Stress responses: Involved in cellular stress pathways

Parkinson's Disease

Altered expression in PD brain
May affect [alpha-synuclein](/proteins/alpha-synuclein) RNA processing
Modulates stress granule dynamics

Cardiac Conduction Defects

Risk variants affect cardiac ion channel splicing
Relevant to both DM1-associated and isolated cardiac disease

Pathogenic Mechanisms

RNA Toxicity

In diseases with repeat expansions:

Pathogenic RNA repeats sequester CELF1
Normal RNA processing is disrupted
Loss-of-function on physiological targets

Splicing Dysregulation

Key targets affected:

Tau (MAPT): Mis-splicing leads to 3R/4R tau imbalance
SMN2: Affects motor neuron survival
Neuronal ion channels: Altered excitability

Stress Response

CELF1 participates in:

Stress granule formation
Translation shutoff during stress
Cell survival decisions

Therapeutic Implications

RNA-Targeted Therapies

Antisense oligonucleotides (ASOs) targeting CELF1
Small molecules modulating CELF1-RNA interactions
ASOs targeting toxic repeat RNAs

Gene Therapy

AAV-delivered CELF1 modulators
CRISPR-based approaches to correct splicing

Repurposing Candidates

Sodium channel modulators (for myotonia)
Stress granule inhibitors

Research Models

Cellular Models

Patient-derived iPSC neurons
Motor neuron cultures
Muscle cell models

Animal Models

Celf1 knockout mice
Transgenic CELF1 mutant mice
DM1 mouse models

Biochemical Studies

CLIP-seq for RNA targets
Proteomic analysis of CELF1 complexes

Diagnostic and Clinical Relevance

Genetic Testing

CELF1 sequencing for ALS diagnosis
Family testing for at-risk individuals

Biomarkers

CELF1 splicing events as disease biomarkers
CSF analysis for CELF1-related changes

Prognostic Indicators

Specific mutations correlate with disease progression
Splicing patterns predict outcomes
[CELF1 Protein](/proteins/celf1-protein)
[Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis)
[Myotonic Dystrophy](/diseases/myotonic-dystrophy)
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Tau Pathology](/mechanisms/tau-pathology)
[RNA-Binding Proteins in Neurodegeneration](/entities/rna-binding-proteins)
[--](/proteins/n--cadherin-protein)

External Links

[NCBI Gene: CELF1](https://www.ncbi.nlm.nih.gov/gene/10658)
[UniProt: CELF1](https://www.uniprot.org/uniprot/Q9UQF0)
[OMIM: CELF1](https://omim.org/entry/601998)
[ALS Variant Viewer: CELF1](https://alsod.iop.kcl.ac.uk/)

Background

The study of Celf1 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

[Unknown, CELF1 in ALS - Nature Neuroscience (n.d.)](https://doi.org/10.1038/nn.3657)

Unknown, CELF1 Protein - UniProt (n.d.)

[Unknown, CELF1 and Myotonic Dystrophy - Brain Research (2019)](https://doi.org/10.1016/j.brainres.2019.146619)

[Unknown, RNA Binding Proteins in Neurodegeneration - Nature Reviews Neuroscience (n.d.)](https://doi.org/10.1038/nrn3556)

[Unknown, CELF1 in Alzheimer's Disease - Acta Neuropathologica (1927)](https://doi.org/10.1007/s00401-018-1927-7)

Pathway Diagram

The following diagram shows the key molecular relationships involving CELF1 Gene discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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