HOXA1 gene

The HOXA1 gene (HOXA1 stands for: Homeobox A1) is a protein-coding gene located on chromosome 7p15.2. Two transcript variants encoding two different isoforms have been found for this gene, with only one of the isoforms containing the homeodomain region. An important paralog of this gene is HOXB1.

The HOXA1 gene encodes a sequence-specific transcription factor that regulates a variety of developmental processes, including development of the brainstem, inner and outer ear, abducens nerve and cardiovascular system, as well as morphogenesis, cognition and behavior (Tischfield MA et al. 2005). Also part of a developmental regulatory system that endows cells with specific positional identities on the anterior-posterior axis. HOXA1 acts on the anterior body structures and appears to play a role in the maintenance and/or formation of hindbrain segments. The HOXA1 transcription factor activates transcription in the presence of PBX1A and PKNOX1.

For example, the transcription factor Hoxa1 is responsible for increased levels of immunosuppressive molecules such as arginase 1 and the transcription factor STAT3 in a Borrelia infection. Although Hoxa1 and a number of other secondarily induced genes react to microbial stimuli, they do not trigger inflammatory signals but instead have an immunosuppressive effect (Petnicki-Ocwieja T et al. 2023).

Diseases associated with HOXA1 include Athabaskan brainstem dysgenesis syndrome.

In vertebrates, the genes that code for a class of transcription factors, the so-called homeobox genes, are located in clusters called A, B, C and D on four different chromosomes. The expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor that can regulate gene expression, morphogenesis and differentiation. The encoded protein may be involved in the placement of hindbrain segments in the correct position along the anterior-posterior axis during development.

1. Petnicki-Ocwieja T et al. (2023) Borrelia burgdorferi initiates early transcriptional re-programming in macrophages that supports long-term suppression of inflammation. PLoS Pathog 19:e1011886.
2. Tischfield MA et al. (2005) Homozygous HOXA1 mutations disrupt human brainstem, inner ear, cardiovascular and cognitive development. Nat Genet 37:1035-1037.