HLX gene

The HLX gene (HLX stands for: H2.0 Like Homeobox) is a protein-coding gene located on chromosome 1q41. Related pathways include IL12-mediated signaling events and the causal TYROBP network in microglia. Gene Ontology (GO) annotations for this gene include sequence-specific DNA binding. An important paralog of this gene is DBX1.

The HLX gene encodes a transcription factor (homeobox protein HLX1) that is required for the TBX21/T-bet-dependent maturation of Th1 cells and for the maintenance of Th1-specific gene expression. The transcription factor is involved in embryogenesis and hematopoiesis. It enables sequence-specific DNA binding activity. It is involved in cell differentiation and the regulation of transcription by RNA polymerase II, for example in the development of the enteric nervous system and the regulation of the differentiation of T helper cells.

Furthermore, it has been shown that the encoded protein controls proliferation in embryonic cell types and hematopoietic cell lines. The HLX1 protein has been shown to be expressed in placental trophoblast cells. However, its functional role in the placenta is unknown. After CSF-1 stimulation, HLX1 mRNA expression was significantly increased in cultured trophoblast cells SGHPL-4 and HTR-8/SVNeo (p<0.001, n=3). The siRNA-mediated reduction of HLX1 mRNA levels with four independent oligonucleotides (siRNAs) resulted in significantly reduced cell proliferation in both cell lines (Rajaraman G et al. 2007).

Diseases associated with HLX include diaphragmatic hernia-short bowel asplenia syndrome and diaphragmatic eventration.

The HLX gene is expressed in a dynamic spatio-temporal expression pattern during zebrafish brain development. The homologs of this gene in the mouse and Xenopus are known to play a role in the specification of neurons in the spinal cord.

1. Hjorth JT et al. (2002) Role of hlx1 in zebrafish brain morphogenesis. Int J Dev Biol 46:583-596.
2. Rajaraman G et al. (2007) Homeobox gene HLX1 is a regulator of colony stimulating factor-1 dependent trophoblast cell proliferation. Placenta 28:991-998.
3. Suttner K et al. (2009) HLX1 gene variants influence the development of childhood asthma. J Allergy Clin Immunol 123:82-88.