Paired-box (PAX) genes encode a family of highly conserved transcription factors found in vertebrates and invertebrates. PAX proteins are defined by the presence of a paired domain that is evolutionarily conserved across phylogenies. Inclusion of a homeodomain and/or an octapeptide linker subdivides PAX proteins into four groups. Often termed “master regulators”, PAX proteins orchestrate tissue and organ development throughout cell differentiation and lineage determination, and are essential for tissue structure and function through maintenance of cell identity. Mutations in PAX genes are associated with myriad human diseases (e.g., microphthalmia, anophthalmia, coloboma, hypothyroidism, acute lymphoblastic leukemia). Transcriptional regulation by PAX proteins is, in part, modulated by expression of alternatively spliced transcripts. Herein, we provide a genomics update on the nine human PAX family members and PAX homologs in 16 additional species. We also present a comprehensive summary of human tissue-specific PAX transcript variant expression and describe potential functional significance of PAX isoforms. While the functional roles of PAX proteins in developmental diseases and cancer are well characterized, much remains to be understood regarding the functional roles of PAX isoforms in human health. We anticipate the analysis of tissue-specific PAX transcript variant expression presented herein can serve as a starting point for such research endeavors.

配对盒 (PAX) 基因编码脊椎动物和无脊椎动物中发现的高度保守的转录因子家族。PAX 蛋白的定义是存在一个在系统发育过程中进化保守的配对结构域。包含同源结构域和/或八肽接头将 PAX 蛋白细分为四组。PAX 蛋白通常被称为“主调节因子”，在整个细胞分化和谱系决定过程中协调组织和器官发育，并且通过维持细胞特性对于组织结构和功能至关重要。PAX基因突变与多种人类疾病有关（例如小眼症、无眼症、缺损、甲状腺功能减退症、急性淋巴细胞白血病）。PAX 蛋白的转录调节部分受到可变剪接转录物表达的调节。在此，我们提供了 9 个人类 PAX 家族成员和 16 个其他物种的 PAX 同源物的基因组学更新。我们还全面总结了人类组织特异性 PAX 转录物变异表达，并描述了 PAX 亚型的潜在功能意义。虽然 PAX 蛋白在发育疾病和癌症中的功能作用已得到很好的表征，但 PAX 亚型在人类健康中的功能作用仍有待了解。我们预计本文提出的组织特异性 PAX 转录变体表达的分析可以作为此类研究工作的起点。