The TALE never ends: A comprehensive overview of the role of PBX1, a TALE transcription factor, in human developmental defects

Hum Mutat. 2022 Sep;43(9):1125-1148. doi: 10.1002/humu.24388. Epub 2022 May 18.


PBX1 is a highly conserved atypical homeodomain transcription factor (TF) belonging to the TALE (three amino acid loop extension) family. Dimerized with other TALE proteins, it can interact with numerous partners and reach dozens of regulating sequences, suggesting its role as a pioneer factor. PBX1 is expressed throughout the embryonic stages (as early as the blastula stage) in vertebrates. In human, PBX1 germline variations are linked to syndromic renal anomalies (CAKUTHED). In this review, we summarized available data on PBX1 functions, PBX1-deficient animal models, and PBX1 germline variations in humans. Two types of genetic alterations were identified in PBX1 gene. PBX1 missense variations generate a severe phenotype including lung hypoplasia, cardiac malformations, and sexual development defects (DSDs). Conversely, truncating variants generate milder phenotypes (mainly cryptorchidism and deafness). We suggest that defects in PBX1 interactions with various partners, including proteins from the HOX (HOXA7, HOXA10, etc.), WNT (WNT9B, WNT3), and Polycomb (BMI1, EED) families are responsible for abnormal proliferation and differentiation of the embryonic mesenchyme. These alterations could explain most of the defects observed in humans. However, some phenotype variability (especially DSDs) remains poorly understood. Further studies are needed to explore the TALE family in greater depth.

Keywords: DSD; PBX1; development; genotype; phenotype; transcription factor.

Publication types

  • Review

MeSH terms

  • Animals
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins* / genetics
  • Homeodomain Proteins* / metabolism
  • Humans
  • Male
  • Phenotype
  • Pre-B-Cell Leukemia Transcription Factor 1* / genetics
  • Pre-B-Cell Leukemia Transcription Factor 1* / metabolism
  • Transcription Factors* / genetics
  • Transcription Factors* / metabolism


  • Homeodomain Proteins
  • Pre-B-Cell Leukemia Transcription Factor 1
  • Transcription Factors
  • PBX1 protein, human