ERCC4 Gene

ERCC4 Gene

Introduction

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">ERCC4 Gene</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>ERCC4</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>ERCC4</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Gene</td>
</tr>
<tr>
<td class="label">NCBI</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/?term=ERCC4" target="_blank">Search NCBI</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Ercc4 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.

{{- start}} [@sijbers1996]

{{- infobox [@arora2017]
| name = ERCC4 [@gregg2011]
| image = [@kuraoka2000]
| caption = DNA repair endonuclease XPF [@mcneil2015]
| gene_symbol = ERCC4 [@niedernhofer2006]
| gene_name = ERCC excision repair 4, endonuclease [@wood2010]
| chromosome = 16
| locus = 16p13.12
| ncbi_gene_id = 2072
| omim_id = 133520
| ensembl_id = ENSG00000175595
| uniprot_id = Q92889
| encoded_protein = ERCC4 Protein
}}

Overview

ERCC4 Gene

Introduction

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">ERCC4 Gene</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>ERCC4</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>ERCC4</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Gene</td>
</tr>
<tr>
<td class="label">NCBI</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/?term=ERCC4" target="_blank">Search NCBI</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Ercc4 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.

{{- start}} [@sijbers1996]

{{- infobox [@arora2017]
| name = ERCC4 [@gregg2011]
| image = [@kuraoka2000]
| caption = DNA repair endonuclease XPF [@mcneil2015]
| gene_symbol = ERCC4 [@niedernhofer2006]
| gene_name = ERCC excision repair 4, endonuclease [@wood2010]
| chromosome = 16
| locus = 16p13.12
| ncbi_gene_id = 2072
| omim_id = 133520
| ensembl_id = ENSG00000175595
| uniprot_id = Q92889
| encoded_protein = ERCC4 Protein
}}

Overview

The ERCC4 gene (also known as XPF) encodes a structure-specific endonuclease critical for nucleotide excision repair (NER). This enzyme makes the incision 5' to the DNA lesion during NER, excising a wide variety of bulky DNA adducts including UV-induced pyrimidine dimers. ERCC4 mutations cause xeroderma pigmentosum (XP-F group) and Fanconi anemia, with severe consequences for genomic stability and neurodegeneration.

Function

ERCC4 (XPF) forms a heterodimer with ERCC1 (XPF-ERCC1 complex) that functions as:

Structure-Specific Endonuclease

• Recognizes and cleaves DNA at junctions between single-stranded and double-stranded regions
• Makes 5' incisions at DNA damage sites during NER
• Essential for cleaving the damaged DNA strand during lesion removal

NER Pathway

• Part of the core NER machinery
• Works downstream of lesion recognition and DNA unwinding
• Incises damaged DNA strand 5' to the lesion
• Critical for removing UV-induced pyrimidine dimers, chemical adducts, and crosslinks

Other DNA Repair Roles

• Interstrand crosslink repair (with Fanconi anemia pathway)
• Mismatch repair (later steps)
• Telomere maintenance

Disease Associations

Xeroderma Pigmentosum (XP-F)

• ERCC4 mutations cause XP complementation group F
• Extreme photosensitivity
• 10,000-fold increased skin cancer risk
• Variable neurological degeneration

Fanconi Anemia (FA)

• ERCC4 is a Fanconi anemia complementation group gene (FANCQ)
• Chromosomal instability
• Congenital abnormalities
• Bone marrow failure
• Cancer predisposition

Neurodegeneration

• XP patients develop:
• Progressive neurodegeneration
• Ataxia
• Cognitive decline
• Hearing loss
• Accumulated DNA damage in [neurons](/entities/neurons)
• Impaired transcription-coupled repair

Cancer

• Extreme skin cancer risk (basal cell carcinoma, squamous cell carcinoma, melanoma)
• Increased internal malignancies

Expression

ERCC4 is expressed in most tissues:

• Highest in:
• Testis
• Ovary
• Bone marrow
• Skin
• Moderate expression in:
• Brain (neurons and astrocytes)
• Liver
• Kidney

• Removing transcription-blocking lesions
• Maintaining genomic integrity
• Supporting long-term neuronal survival

Therapeutic Implications

Gene Therapy

• Viral vector delivery of functional ERCC4
• CRISPR-based gene correction

Small Molecule Approaches

• DNA repair enhancers
• Antioxidants (reduce oxidative DNA damage)
• Neuroprotective strategies
• Topical DNA repair enzymes for skin protection

See Also

• [DNA Repair](/mechanisms/dna-repair-pathway)
• [Nucleotide Excision Repair](/mechanisms/nucleotide-excision-repair)
• [Fanconi Anemia Pathway](/mechanisms/fanconi-anemia-pathway)
• [Xeroderma Pigmentosum](/diseases/xeroderma-pigmentosum)
• [ERCC1 Gene](/genes/ercc1)
• [ERCC4 Protein](/proteins/ercc4-protein)

Background

The study of Ercc4 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.

External Links

• [PubMed](https://pubmed.ncbi.nlm.nih.gov/) - Biomedical literature
• [Alzheimer's Disease Neuroimaging Initiative](https://adni.loni.usc.edu/) - Research data
• [Allen Brain Atlas](https://brain-map.org/) - Brain gene expression data

References