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ERCC6L2
ERCC excision repair 6 like 2
The ERCC6L2 gene provides instructions for making a protein involved in various cellular activities, including DNA repair and maintenance of genomic stability. ERCC6L2, or ERCC excision repair 6 like 2, is a gene that codes for a protein essential for several key cellular functions.
ERCC6L2 is located on the long (q) arm of chromosome 9, at band 9q22.32. Arm ratio per GRCh38 - banding schematic.
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Overview
The ERCC6L2 gene is named for 'ERCC excision repair 6 like 2' and is instrumental in producing a protein crucial for various cellular functions. This protein is broadly involved in processes that maintain the stability and integrity of the genome. Aberrations in this gene or its protein product may affect these vital cellular mechanisms.
The ERCC6L2 gene's role extends to interactions with other cellular components, indicating its complex involvement in pathways critical for cell survival and proper functioning.
What the gene does
The protein encoded by ERCC6L2 is a helicase-like enzyme, meaning it can unwind nucleic acid strands, a fundamental process in DNA repair, replication, and transcription. Its helicase activity is crucial for correcting DNA damage and ensuring that genetic information is accurately passed on during cell division. This function is vital for preventing the accumulation of mutations that could lead to cellular dysfunction or disease. The Helicase ATP-binding domain and Helicase C-terminal domain are key to its enzymatic activity, facilitating the hydrolysis of ATP to provide energy for unwinding DNA or RNA double helices.
Furthermore, the presence of a DEAH box motif suggests its involvement in RNA metabolism or larger ribonucleoprotein complexes. The gene's contribution to DNA repair pathways underscores its importance in genome surveillance and protection against various genotoxic stresses.
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Chromosome location
The ERCC6L2 gene is situated on chromosome 9 at position 9q22.32. This precise genomic location is significant as alterations within this region could potentially impact the gene's function. The gene does not have a commonly cited exon count.
Protein structure
The ERCC6L2 protein consists of 1561 amino acids and exhibits a complex domain architecture. It includes several Disordered regions, found at amino acids 1-34, 819-860, 925-1013, and 1365-1421, which often indicate regions that are flexible and participate in protein-protein interactions. Key functional domains include the Helicase ATP-binding domain (amino acids 146-332) and the Helicase C-terminal domain (amino acids 523-673), which are essential for its helicase activity. A DEAH box motif is located within the ATP-binding domain at amino acids 283-286, characteristic of a helicase. Additionally, an Atypical PIP-box motif is present at amino acids 796-807, suggesting roles in cell cycle regulation or DNA damage response through interaction with PCNA.
Key variants
Variants in the ERCC6L2 gene can affect the structure and function of the encoded protein, potentially impacting its ability to carry out its essential roles in DNA repair and genomic stability. These genetic changes can range from single nucleotide alterations to larger deletions or insertions within the gene sequence. The clinical significance of ERCC6L2 variants varies, and further research is ongoing to fully understand their impact.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1051_1054del | p.Ala351fs | Pathogenic/Likely pathogenic | ★★☆☆ | not provided |
c.1930C>T | p.Arg644Ter | Pathogenic | ★★☆☆ | Pancytopenia-developmental delay syndrome |
c.1987C>T | p.Arg663Ter | Pathogenic | ★★☆☆ | Pancytopenia-developmental delay syndrome |
c.19C>T | p.Gln7Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Pancytopenia-developmental delay syndrome |
c.2156del | p.Gly719fs | Pathogenic | ★★☆☆ | Pancytopenia-developmental delay syndrome |
c.3763C>T | p.Arg1255Ter | Pathogenic/Likely pathogenic | ★★☆☆ | not provided |
c.1518del | p.Lys505_Tyr506insTer | Pathogenic | ★☆☆☆ | not provided |
c.2590del | p.Tyr864fs | Pathogenic | ★☆☆☆ | not provided |
c.289C>T | p.Arg97Ter | Pathogenic | ★☆☆☆ | not provided |
c.3762del | p.Glu1254fs | Pathogenic | ★☆☆☆ | not provided |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variants in the ERCC6L2 gene have been implicated in a range of inherited genetic conditions. These conditions are typically associated with disruptions in the cellular processes where the ERCC6L2 protein plays a critical role, particularly in maintaining DNA integrity. The inheritance pattern for conditions linked to ERCC6L2 variants can vary, indicating diverse genetic mechanisms.
No disease links recorded for this gene in our reference set.
UK clinical status
The ERCC6L2 gene is recognised within the UK's NHS Genomic Medicine Service, featuring on several active PanelApp green listings. These include panels for "COVID-19 research", "Cytopenia - NOT Fanconi anaemia", "Cytopenias and congenital anaemias", "DDG2P", "Haematological malignancies cancer susceptibility", "Intellectual disability (R29)", and "Primary immunodeficiency or monogenic inflammatory bowel disease (R15)". Inclusion on these panels signifies that variants in ERCC6L2 are considered to have clinical relevance for these conditions within a diagnostic setting.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the ERCC6L2 gene?
The ERCC6L2 gene provides instructions for making a protein that functions as a helicase. This protein is primarily involved in crucial cellular processes such as DNA repair and the maintenance of overall genomic stability.
Where is the ERCC6L2 gene located?
The ERCC6L2 gene is found on chromosome 9, specifically at the band designated 9q22.32. This genomic address helps pinpoint its location within the human genome.
Are ERCC6L2 variants clinically relevant in the UK?
Yes, variants in the ERCC6L2 gene are considered clinically relevant within the UK's NHS Genomic Medicine Service. The gene is listed on various green PanelApp entries for conditions such as cytopenias, intellectual disability, and haematological malignancies.