Abstract
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.
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Reprinted with permission from Blake and Ziman (2014)
taken from www.genenames.org and the official mouse names are taken from . The alignment for this dendrogram is based on the amino acid sequences of proteins listed in Tables 1 and 2. Multiple sequence alignment was conducted by CLUSTALW (https://www.genome.jp/tools/clustalw/). Mma mouse, Hsa human
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Acknowledgements
We would like to thank all members of the Laboratory of Dr. Michael Robinson and Dr. Ying Chen for their continued lively discussions on these topics that led to the genesis of these analyses. We also thank the reviewers and editors for their constructive feedback on the manuscript. We sincerely apologize for not being able to include citations for all of the exceptional work of our colleagues due to space limitations.
Funding
This work was supported, in part, by National Institutes of Health Grants AA021724, AA022057, P30 ES06096, EY017963 and EY022312, and National Human Genome Research Institute (NHGRI) Grant U24HG003345 and Wellcome Trust Grant 208349/Z/17/Z. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.
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Thompson, B., Davidson, E.A., Liu, W. et al. Overview of PAX gene family: analysis of human tissue-specific variant expression and involvement in human disease. Hum Genet 140, 381–400 (2021). https://doi.org/10.1007/s00439-020-02212-9
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DOI: https://doi.org/10.1007/s00439-020-02212-9