Overview of PAX gene family: analysis of human tissue-specific variant expression and involvement in human disease

Hum Genet. 2021 Mar;140(3):381-400. doi: 10.1007/s00439-020-02212-9. Epub 2020 Jul 29.


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.

Publication types

  • Review

MeSH terms

  • Alternative Splicing
  • Animals
  • Chromosome Mapping
  • Evolution, Molecular
  • Genetic Predisposition to Disease*
  • Humans
  • Paired Box Transcription Factors / genetics*
  • Phylogeny
  • RNA, Messenger / genetics
  • Transcription, Genetic


  • Paired Box Transcription Factors
  • RNA, Messenger