C3orf38 is a chromosome 3 open reading frame gene with emerging roles in tumor suppression and metabolic regulation. Primary function: C3orf38 may be involved in apoptosis regulation [UniProt annotation], positioning it as a potential tumor suppressor candidate. Mechanism: The gene was identified within the 3p12.3-pcen region, a candidate tumor suppressor locus in ovarian cancer, where it exhibited expression in nontumorigenic radiation hybrids generated by chromosome 3 fragment transfer into ovarian cancer cells 1. Underexpression of related genes in this region correlated with malignant transformation, suggesting dysregulation of C3orf38 may contribute to ovarian tumorigenesis 1. Disease relevance: C3orf38 was identified as a hub gene in a tumor mutational burden-based risk model (TMBrisk) for ovarian cancer prognosis, where high expression associated with poor survival outcomes and immunosuppressive tumor microenvironments 2. Additionally, C3orf38 showed altered DNA methylation patterns in response to ketogenic diet-induced metabolic changes, suggesting epigenetic regulation in metabolic contexts 3. Clinical significance: As a TMBrisk component gene, C3orf38 demonstrates potential utility in prognostic modeling and identifying patients with immunosuppressive tumors requiring alternative therapeutic strategies in ovarian cancer.