HOXD

HOXD refers to the HOXD gene cluster, one of the four HOX gene clusters in vertebrates. The HOXD cluster encodes a set of transcription factors that contain a homeobox DNA-binding domain and regulate patterning during embryonic development, particularly along the anterior-posterior axis and in limb formation.

In humans, the HOXD cluster is located on chromosome 2 and is organized in a linear array. Expression of HOXD genes shows spatial and temporal patterns during development; regulatory elements within and near the cluster, as well as distant enhancers, influence where and when individual HOXD genes are active. The concept of collinearity—gene order correlating with expression domains—applies to the cluster, though regulatory interactions are complex and tissue-specific.

Functional roles of HOXD genes include contributions to axial skeleton patterning and limb morphogenesis, where they act in concert with other HOX clusters. Perturbations in expression can disrupt limb or digit formation and cause segmentation defects in the spine. The specific roles of individual HOXD genes can vary by tissue and developmental stage.

Clinical significance is seen in congenital malformations linked to HOXD genes. HOXD13, in particular, is associated with synpolydactyly; expansions of a polyalanine tract in HOXD13 cause SPD type 1. More subtle regulatory changes can also contribute to limb anomalies. Altered HOXD expression has been observed in various cancers, reflecting roles in cell differentiation and proliferation.

Research notes: Because HOXD genes share regulatory landscapes and may coordinate with HOXA and HOXB clusters, understanding their interactions remains an active area in developmental biology and medical genetics.