FAM3C
Overview
FAM3C (Family With Sequence Similarity 3 Member C) encodes a secreted cytokine-like protein. In cancer immunology, FAM3C gained attention as a source of tumor-specific neoantigens: a somatic missense mutation (c.A577G; p.K193E) generates a neoepitope recognized by patient T cells under CTLA-4 checkpoint blockade, providing proof-of-principle for neoantigen-driven antitumor immunity.
Alterations observed in the corpus
- Missense c.A577G (p.K193E) yields neoepitope TESPFEQHI, which bound patient HLA-B4402 (predicted affinity 472 nM vs. 18,323 nM for nonmutant TKSPFEQHI) and drove a polyfunctional T-cell response in melanoma patient CR9306 treated with ipilimumab/tremelimumab. PMID:25409260
Cancer types (linked)
- MEL (Melanoma): FAM3C missense mutation identified as a neoantigen source in a melanoma patient with durable complete response to CTLA-4 blockade. PMID:25409260
Co-occurrence and mutual exclusivity
- No single recurrently mutated gene defined the responder population in this study; the FAM3C neoepitope signal was at the level of shared tetrapeptide sequences across diverse genes, not at the level of individual driver genes. PMID:25409260
Therapeutic relevance
- FAM3C p.K193E neoepitope TESPFEQHI was recognized by HLA-B4402-restricted T cells and drove polyfunctional immune responses in a patient who achieved complete response to ipilimumab (CTLA-4 blockade). Supports the model that passenger mutations can function as immune determinants under checkpoint blockade. PMID:25409260
Open questions
- FAM3C is not a recurrently mutated gene across patients — its relevance is as a neoantigen source in individual patients with the right HLA allele (HLA-B4402) rather than as a general oncogene. PMID:25409260
Sources
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