H3F3B, along with H3F3A, encodes the H3.3 core histone protein, which is a subtype of H3 histone. Histones are the chief protein component of DNA, helping maintain chromatin structure and regulating gene expression. They package DNA into nucleosomes, compacting the long DNA molecule within the nuclear membrane. Amino acids in histone tails, like lysine and arginine, are sites of post-translational modifications (PTMs) that regulate gene expression through chromatin remodelling and control of DNA methylation patterns [1].

Mutations in H3F3B have been identified in several malignancies. For example, H3F3B mutations (p.K36M) are highly specific to chondroblastoma, a rare primary bone tumor [2,3,4]. In a case of a non-epiphyseal cortical-based chondroblastoma involving the distal femur, the H3F3B point mutation (c.110A > T) supported the diagnosis [4]. Although H3F3A mutations are more common in giant cell tumor of bone, H3F3B gene mutations (H3.3p.Gly35Trp and H3.3p.Val36Leu) have also been reported in this tumor type [5]. Additionally, in a Chinese population, polymorphisms in the H3F3B gene (rs3214028 and rs60700976) were significantly associated with schizophrenia, and an interaction between H3F3B and NSD2 genes was related to the susceptibility to schizophrenia [6].

In conclusion, H3F3B is crucial for normal chromatin function and gene regulation through its role in histone production. Its mutations are associated with specific bone malignancies like chondroblastoma and potentially giant cell tumor of bone, and also with schizophrenia in a Chinese population. Understanding H3F3B and its mutations can provide insights into the pathogenesis of these diseases, potentially leading to better diagnostic and treatment strategies.