Short stature homeobox protein (SHOX) (SHOX)

The Short stature homeobox protein (SHOX) is a critical transcription factor encoded by the SHOX gene, located in the pseudoautosomal region 1 (PAR1) of the X and Y chromosomes [1, 2]. It is primarily expressed in the developing limbs and pharyngeal arches, where it regulates the proliferation and differentiation of chondrocytes within the epiphyseal growth plate [3, 5]. SHOX acts as a transcriptional activator, influencing the expression of genes involved in bone formation and skeletal patterning [5]. Haploinsufficiency of SHOX, resulting from gene deletions or point mutations, is a primary cause of short stature in Turner syndrome and is the underlying cause of Léri-Weill dyschondrosteosis and Langer mesomelic dysplasia [3, 4]. While SHOX itself is not currently targeted by direct small-molecule or biological agonists, the clinical manifestations of its deficiency are managed using recombinant human growth hormone (rhGH) [4]. rhGH therapy aims to maximize final adult height by stimulating the growth hormone/IGF-1 axis, which partially compensates for the reduced SHOX activity in the growth plates [4, 5].

Other names

Short stature homeobox-containing genePHOGSSGCLEPseudoautosomal homeobox osteogenic gene

Recombinant human growth hormone (Somatropin) acts as an agonist at the growth hormone receptor, inducing the production of Insulin-like Growth Factor 1 (IGF-1), which stimulates chondrocyte activity and longitudinal bone growth to compensate for SHOX deficiency.