<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">ERCC3 Gene</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>ERCC3</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>ERCC3</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=ERCC3" target="_blank">Search NCBI</a></td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/carcinoma" style="color:#ef9a9a">Carcinoma</a>, <a href="/wiki/cirrhosis" style="color:#ef9a9a">Cirrhosis</a>, <a href="/wiki/hepatocellular-carcinoma" style="color:#ef9a9a">Hepatocellular Carcinoma</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">35 edges</a></td>
</tr>
</table>
ERCC3 (Excision Repair Cross-Complementation Group 3), also known as TFIIH core component, is a DNA repair gene located on chromosome 19q13.32. The protein encodes a DNA helicase subunit of the transcription factor IIH (TFIIH) complex, which is essential for both transcription initiation and nucleotide excision repair (NER). ERCC3 plays a critical role in transcription-coupled nucleotide excision repair (TC-NER), a pathway that specifically repairs DNA lesions in actively transcribed genes.
The ERCC3 gene spans approximately 15 kb and consists of 17 exons. It encodes a 782-amino acid protein with a molecular weight of approximately 89 kDa. The protein contains seven conserved motifs characteristic of the SF2 helicase family, including the ATP-dependent DNA helicase domain. ERCC3 forms a core component of the TFIIH complex, which contains both repair and transcription activities. [@weinberg2019]
In the nervous system, ERCC3/TFIIH is essential for: [@kroker2014]
Biallelic mutations in ERCC3 cause Cockayne syndrome (CS), a rare autosomal recessive disorder characterized by progressive neurodegeneration, developmental delay, photosensitivity, and premature aging. CS patients exhibit: [@t2007]
ERCC3 polymorphisms have been associated with [Alzheimer's disease](/diseases/alzheimers-disease) (AD) risk in genome-wide association studies (GWAS). The DNA repair capacity declines with age, and impaired TC-NER may contribute to:
Evidence suggests ERCC3 variants may modify [Parkinson's disease](/diseases/parkinsons-disease) (PD) risk. DNA repair mechanisms are crucial for maintaining dopaminergic neuron viability, as these cells face high oxidative stress from dopamine metabolism.
ERCC3 and the TFIIH complex represent potential therapeutic targets:
ERCC3 is ubiquitously expressed in all human tissues, including:
ERCC3 interacts with:
ERCC3 is a critical DNA repair and transcription gene whose dysfunction leads to severe neurodegenerative phenotypes. Its role in maintaining genomic integrity in post-mitotic neurons makes it relevant to age-related neurodegenerative diseases including AD and PD.
The following diagram shows the key molecular relationships involving ERCC3 Gene discovered through SciDEX knowledge graph analysis: