SLCO4C1 and Melanoma

This summary evaluates the association between the SLCO4C1 gene (HGNC:23612) and melanoma (MONDO_0005105) based on evidence from case reports, multi‐patient studies, and functional assessments. In a Dutch family with a history of melanoma, rare SLCO4C1 missense variants were identified and shown to co‑segregate in affected members (PMID:31524790). Although only a single family has been reported, the recurrence of the variant in both case and multi‑patient studies supports a potential contribution to melanoma susceptibility.

The genetic evidence indicates that the variant follows an autosomal dominant inheritance pattern with co‑segregation observed in four melanoma‑affected individuals, including two additional affected relatives beyond the initial probands (PMID:31524790). One representative variant, c.1790C>T (p.Pro597Leu), was identified in these studies, and its presence in affected family members strengthens the association, albeit based on limited numbers.

However, despite the co‑segregation data, functional assessments performed using cellular models and ultraviolet exposure assays did not reveal any significant compromise in protein function or histone methyltransferase activity. These experimental findings, which failed to demonstrate a clear pathogenic mechanism, limit the functional support for the gene‑disease association (PMID:31524790).

Integrating the genetic and functional evidence, the current data suggest a limited association between SLCO4C1 variants and melanoma. The genetic findings from a single family provide initial support for a role in predisposition, yet the lack of robust functional impact and replication in larger cohorts tempers the overall confidence. Additional studies with expanded cohorts and refined functional assays will be necessary to further validate the contribution of SLCO4C1 to melanoma risk.

In summary, while the co‑segregation of the rare c.1790C>T (p.Pro597Leu) variant in SLCO4C1 among affected individuals is intriguing, the evidence remains limited. Clinicians should consider this finding as preliminary, underscoring the need for further investigation before it is integrated into routine diagnostic decision‑making.

Key Take‑home sentence: SLCO4C1 variants, particularly c.1790C>T (p.Pro597Leu), may contribute to melanoma susceptibility in select familial cases, highlighting the necessity for additional research to firmly establish their clinical relevance.

References

• Melanoma Research • 2019 • A novel germline variant in the DOT1L gene co-segregating in a Dutch family with a history of melanoma PMID:31524790

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