Hedgehog-interacting protein (HHIP; rs1492820) is a transcriptional target and an antagonist of Hedgehog signaling; it binds with high affinity to the three mammalian Hedgehog proteins22. The mouse homolog, Hhip, is expressed in the perichondrium, including regions flanking Indian hedgehog (Ihh) expression in the appendicular and axial skeleton. Ectopic overexpression of Hhip in mouse cartilage causes severe skeletal defects, including short-limbed dwarfism, a feature reminiscent of the phenotype observed in Ihh null mice22,23.
