What you carry at this position in your DNA and what research says about it.
Melanoma Risk: 10/10 evidence, 12 publications.
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Sample genotype (not yours): G/G
Typical Melanoma Risk
Typical genetic baseline is maintained at this locus. Melanoma risk and kidney function are expected to follow average population trends.
What this genotype means: Normal MITF protein SUMOylation; Standard population risk for melanoma.
Sample genotype (not yours): A/A
Significantly Increased Melanoma Risk
Significantly increased risk of melanoma and potential alterations in kidney function markers are associated with this rare genotype.
What this genotype means: Complete lack of normally SUMOylated MITF; Substantially elevated melanoma risk; Altered kidney function markers.
Sample genotype (not yours): G/A
Increased Melanoma Risk
Elevated susceptibility to melanoma and a higher likelihood of developing benign moles characterize this genotype.
What this genotype means: Impaired MITF protein SUMOylation; Increased risk of cutaneous melanoma; Higher likelihood of benign moles.
Gene function and biological role
Gene Function: The MITF gene encodes the melanocyte-inducing transcription factor, which serves as a master regulator of melanocyte development and survival [1]. It controls the expression of genes involved in pigmentation, cell proliferation, and cell death [1]. Beyond its role in skin cells, this transcription factor is expressed in other tissues, including the kidneys and retinal pigment epithelium [2]. Proper regulation of this gene is essential for maintaining normal cellular growth and preventing oncogenic transformation [1].
Variant Impact: A missense mutation in the MITF gene causes a glutamic acid to lysine substitution at position 318, commonly known as p.Glu318Lys or E318K [1]. This specific amino acid change occurs within a highly conserved SUMOylation consensus sequence, disrupting the normal post-translational modification of the protein [1]. Without proper SUMOylation, the mutant transcription factor exhibits altered binding affinity to its target genes, leading to enhanced cell migration and invasion [2]. Consequently, this variant acts as a moderate-penetrance risk modifier that predisposes carriers to cutaneous melanoma and potentially other malignancies [1].
Key Insight: Disruption of a single protein-modification site called SUMOylation can simultaneously increase the risk of both skin and kidney cancers.
Location: MITF. Chromosome 3 · 3p13 · 70.0 Mb
Estimated prevalence by population
Global 99.7%; European 99.5%; African 99.8%; East Asian 100.0%; South Asian 100.0%; Americas 99.6%; Ashkenazi 99.9%; Finnish 99.9%; Middle Eastern 100.0%; Amish 100.0%.
Estimated GG genotype frequency.
Global 0.3%; European 0.5%; African 0.2%; East Asian 0.0%; South Asian 0.0%; Americas 0.4%; Ashkenazi 0.1%; Finnish 0.1%; Middle Eastern 0.0%; Amish 0.0%.
Estimated GA genotype frequency.
Global < 0.1%; European < 0.1%; African < 0.1%; East Asian 0.0%; South Asian 0.0%; Americas < 0.1%; Ashkenazi < 0.1%; Finnish < 0.1%; Middle Eastern 0.0%; Amish 0.0%.
Estimated AA genotype frequency.
Showing effects for G/G genotype
Cancer & Oncology
Skin Cancer
Melanoma. Evidence: 10/10. Source: PMID 22012259. Typical Risk.
Organ Systems
Kidney Function & Disease
Kidney Function. Evidence: 8/10. Source: PMID 39024449. Typical Function.
Pigmentation & Appearance
Benign Moles. Evidence: 8/10. Source: PMID 39024449. Typical Count.
Cardiovascular & Metabolic
Blood Cell & Iron Traits
Hemoglobin Levels. Evidence: 7/10. Source: PMID 32327693. Typical Levels.
Showing effects for A/A genotype
Melanoma. Evidence: 10/10. Source: PMID 22012259. Elevated Risk.
Kidney Function. Evidence: 8/10. Source: PMID 39024449. Lower Function.
Benign Moles. Evidence: 8/10. Source: PMID 39024449. Higher Count.
Hemoglobin Levels. Evidence: 7/10. Source: PMID 32327693. Lower Levels.
Showing effects for G/A genotype
Melanoma. Evidence: 10/10. Source: PMID 22012259. ~2x to 5x Risk.
Kidney Function. Evidence: 8/10. Source: PMID 39024449. Slightly Lower.
Benign Moles. Evidence: 8/10. Source: PMID 39024449. Increased Count.
Hemoglobin Levels. Evidence: 7/10. Source: PMID 32327693. Slightly Lower.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Standard genetic baseline is maintained at this locus by the presence of two common G alleles. Cellular processes regulating melanocyte growth, pigmentation, and kidney function typically operate without the altered transcription activity associated with the rare variant [1]. Population studies show that individuals with this genotype do not have the elevated risk of melanoma or renal cell carcinoma linked to the E318K mutation [1]. The absence of the risk allele means that SUMOylation of the MITF protein occurs normally, keeping downstream gene expression in a balanced state [2].
Normal MITF protein SUMOylation; Standard population risk for melanoma.
Sample genotype: AA (Homozygous)
Homozygosity for the rare A allele is extremely uncommon in the general population, representing a double dose of the E318K variant. This genetic state results in a complete lack of normally SUMOylated MITF protein, which significantly enhances the transcription of genes driving cell proliferation and migration [1]. The risk of developing cutaneous melanoma is substantially elevated compared to the general population, and there may be a stronger predisposition to multiple primary melanomas [2]. Additionally, homozygous individuals may show altered kidney function markers, such as increased creatinine levels [3].
Complete lack of normally SUMOylated MITF; Substantially elevated melanoma risk; Altered kidney function markers.
Sample genotype: GA (Heterozygous)
Presence of a single A allele introduces the E318K missense variant, which impairs the normal SUMOylation of the MITF protein [1]. This molecular alteration leads to increased transcriptional activity, promoting cellular invasion, migration, and a higher count of benign moles [2]. Clinical studies indicate that heterozygous carriers have a significantly increased risk of developing cutaneous melanoma, with odds ratios typically ranging from 1.7 to over 5 depending on family history [1] [3]. Some evidence also suggests a potential, though less certain, increase in the risk of renal cell carcinoma [1].
Impaired MITF protein SUMOylation; Increased risk of cutaneous melanoma; Higher likelihood of benign moles.
Variants with shared genetic architecture
rs1126809 · TYR Gene · Chr 11 · Skin Cancer Risk
rs12203592 · IRF4 Gene · Chr 6 · Skin Cancer Risk
rs16891982 · SLC45A2 Gene · Chr 5 · Skin Cancer Risk
A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma.
A novel recurrent mutation in MITF predisposes to familial and sporadic melanoma.
Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
Content updated September 2026.
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