What you carry at this position in your DNA and what research says about it.
Melanoma Risk: 6/10 evidence, 63 publications.
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Sample genotype (not yours): T/T
Typical Melanoma Risk and Standard Chemotherapy Response
DNA repair mechanisms operate at baseline efficiency. There is no elevated risk of skin cancer or increased sensitivity to platinum-based chemotherapy drugs.
What this genotype means: Standard DNA repair capacity; Baseline risk for melanoma.
Sample genotype (not yours): G/G
Increased Melanoma Risk and Higher Chemotherapy Toxicity Risk
Two copies of the variant allele significantly lower DNA repair capacity. This elevates the risk of skin cancer and increases the likelihood of severe side effects during chemotherapy.
What this genotype means: Reduced DNA repair efficiency; Elevated melanoma risk; Higher risk of chemotherapy side effects.
Sample genotype (not yours): T/G
Slightly Increased Melanoma Risk and Altered Chemotherapy Sensitivity
A single copy of the variant allele slightly reduces DNA repair efficiency. This leads to a mild increase in skin cancer risk and a higher likelihood of chemotherapy side effects.
What this genotype means: Slightly reduced DNA repair efficiency; Mildly elevated melanoma risk; Increased risk of chemotherapy side effects.
Gene function and biological role
Gene Function: The ERCC2 gene, also known as XPD, encodes a crucial helicase enzyme that plays a central role in the nucleotide excision repair pathway [1]. This molecular machinery is responsible for identifying and repairing DNA damage caused by ultraviolet radiation, chemical carcinogens, and environmental toxins [1] [2]. By unwinding the DNA double helix, the ERCC2 protein allows other repair factors to access and excise damaged segments, maintaining genomic stability [2]. When this pathway is compromised, unrepaired DNA lesions can accumulate, potentially leading to cellular malfunction or uncontrolled cell division [2] [3]. Consequently, variations in this gene are frequently studied in relation to cancer susceptibility and response to DNA-damaging chemotherapy drugs [3] [4].
Variant Impact: The rs13181 variant, commonly known as Lys751Gln, represents a single nucleotide change from thymine to guanine in exon 23 of the ERCC2 gene. This genetic alteration results in the substitution of the amino acid lysine with glutamine at position 751 of the ERCC2 protein. This specific position is located in the carboxyl-terminal domain, which is critical for the protein's interaction with other components of the transcription factor IIH complex. Research indicates that the glutamine-encoding G allele alters the protein's conformation and reduces overall DNA repair capacity [2]. Although the G allele is classified as benign for rare, severe genetic disorders like xeroderma pigmentosum, it acts as a low-penetrance risk factor for more common conditions [1].
Key Insight: A single genetic letter change in ERCC2 can alter how well your cells repair sun damage and influence how you might tolerate specific chemotherapy treatments.
Location: ERCC2. Chromosome 19 · 19q13.32 · 45.4 Mb
Estimated prevalence by population
Global 47.5%; European 39.2%; African 59.0%; East Asian 86.0%; South Asian 40.6%; Americas 55.7%; Ashkenazi 36.1%; Finnish 33.8%; Middle Eastern 39.6%; Amish 33.5%.
Estimated TT genotype frequency.
Global 41.8%; European 46.8%; African 35.6%; East Asian 13.4%; South Asian 46.2%; Americas 37.8%; Ashkenazi 48.0%; Finnish 48.7%; Middle Eastern 46.7%; Amish 48.8%.
Estimated TG genotype frequency.
Global 10.7%; European 14.0%; African 5.4%; East Asian 0.5%; South Asian 13.2%; Americas 6.4%; Ashkenazi 15.9%; Finnish 17.5%; Middle Eastern 13.7%; Amish 17.7%.
Estimated GG genotype frequency.
Showing effects for T/T genotype
Cancer & Oncology
Skin Cancer
Melanoma. Evidence: 3/10. Source: PMID 32277685. Typical Risk.
Lung Cancer
Lung Cancer. Evidence: 5/10. Source: PMID 23108145. Typical Risk.
Gynecological Cancers
Ovarian Cancer. Evidence: 3/10. Source: PMID 32277685. Typical Risk.
Pharmacogenomics
Chemotherapy Response
Chemotherapy Toxicity. Evidence: 6/10. Source: PMID 30914949. Typical Response.
Showing effects for G/G genotype
Melanoma. Evidence: 3/10. Source: PMID 32277685. >1.12x Increased Risk.
Lung Cancer. Evidence: 5/10. Source: PMID 23108145. Increased Risk.
Ovarian Cancer. Evidence: 3/10. Source: PMID 32277685. Increased Risk.
Chemotherapy Toxicity. Evidence: 6/10. Source: PMID 30914949. High Toxicity Risk.
Showing effects for T/G genotype
Melanoma. Evidence: 3/10. Source: PMID 32277685. ~1.12x Increased Risk.
Ovarian Cancer. Evidence: 3/10. Source: PMID 32277685. Decreased Risk.
Chemotherapy Toxicity. Evidence: 6/10. Source: PMID 30914949. Increased Risk.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Baseline DNA repair capacity is maintained by the presence of two copies of the thymine allele [1]. Standard risk levels are observed for cutaneous melanoma and other cancers [1] [2]. When undergoing platinum-based chemotherapy regimens, such as cisplatin or oxaliplatin, individuals with this genetic profile generally experience standard drug clearance and typical survival outcomes [3] [4]. The risk of severe treatment-related side effects, including kidney damage or hair loss, remains at the baseline level [3]. Because the repair machinery functions normally, cells can efficiently mend the DNA damage intentionally caused by these therapeutic agents [4]. This balanced repair capacity contributes to a standard clinical prognosis across various health outcomes [2]. Environmental factors like ultraviolet light exposure are still the primary drivers of skin damage in this group. Maintaining routine sun protection and regular skin checks represents the standard approach to long-term wellness.
Standard DNA repair capacity; Baseline risk for melanoma.
Sample genotype: GG (Homozygous)
Presence of two copies of the glutamine-encoding G allele leads to a more pronounced reduction in nucleotide excision repair efficiency [1]. This genetic profile is associated with a greater than 1.12-fold increased risk of developing cutaneous melanoma [2]. When treated with platinum-based chemotherapy agents like cisplatin, oxaliplatin, or fluorouracil, individuals with this genotype face a significantly higher risk of adverse reactions [3] [4]. These side effects frequently include severe kidney damage, hair loss, and overall systemic toxicity [3]. While the reduced repair capacity can sometimes make cancer cells more sensitive to treatment, it is also linked to decreased overall survival in several clinical cohorts [4]. Furthermore, some preliminary studies suggest an elevated risk of other malignancies, such as ovarian cancer, under this homozygous profile [2]. The accumulation of unrepaired DNA lesions from ultraviolet light or chemical exposures may occur more rapidly over time. Proactive skin monitoring and minimizing exposure to known environmental carcinogens are particularly important strategies for this group.
Reduced DNA repair efficiency; Elevated melanoma risk; Higher risk of chemotherapy side effects.
Sample genotype: TG (Heterozygous)
A single copy of the glutamine-encoding G allele is linked to a modest reduction in the body's ability to repair damaged DNA [1]. This reduction in repair efficiency is associated with a 1.12-fold increase in the risk of developing cutaneous melanoma [2]. In the context of cancer treatment, this genotype is associated with an increased risk of severe toxicities from platinum-based chemotherapies [3]. Patients receiving drugs like cisplatin or oxaliplatin may experience a higher incidence of side effects, such as kidney damage, hair loss, or general drug toxicity [3] [4]. Additionally, some clinical studies have observed decreased overall survival rates in patients with this genotype undergoing specific chemotherapy regimens [4]. Interestingly, some research suggests a potentially lower risk of ovarian cancer for individuals with this heterozygous profile, highlighting a complex biological trade-off [2]. Cellular repair processes may be slightly delayed when exposed to environmental stressors like ultraviolet radiation. Standard preventative measures such as sun protection remain highly relevant for managing overall skin health.
Slightly reduced DNA repair efficiency; Mildly elevated melanoma risk; Increased risk of chemotherapy side effects.
Variants with shared genetic architecture
rs1799793 · ERCC2 Gene · Chr 19 · DNA Repair Capacity
rs238406 · ERCC2 Gene · Chr 19 · Chemotherapy Toxicity Risk
rs4149909 · EXO1 Gene · Chr 1 · Skin Cancer Risk
The Involvement of ERCC2/XPD and ERCC6/CSB Wild Type Alleles in Protection Against Aging and Cancer.
Content updated August 2026.
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