Pathogenic variants (disease-causing) in the CDK4 gene are associated with a significantly increased risk of cutaneous (skin) melanoma. Families with pathogenic variants in CDK4 often show multiple cases of melanoma, sometimes at younger ages than the general population. Other cancer associations are less clear, but melanoma risk is well established. Management of CDK4–related tumor risk includes regular surveillance tailored to guidelines to detect tumors early. CDK4 variants are not known to be more common in the Ashkenazi Jewish population.
Pathogenic variants in CDK4 exhibit autosomal dominant inheritance. This means there is a 50% chance the condition can be passed from generation-to-generation. First degree relatives (parents, siblings, children) have a 50% chance to have the same pathogenic variant whereas second degree relatives (grandparents, aunts/uncles, nieces/nephews, half-siblings) have a 25% chance. More distant relatives have lower chances of having the same pathogenic variant when one is identified in the family.
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Written December 2025
