What is the name of the gene that, when mutated, can cause extra toes in mice and humans?

The story behind the answer

The gene whose mutation can cause extra toes in mice and humans is Sonic hedgehog, commonly abbreviated SHH. It encodes a signaling protein that helps organize embryonic body patterning, including the formation and positioning of fingers and toes.

During limb development, SHH is produced in a specialized region called the zone of polarizing activity. Its concentration and timing help cells interpret whether they should become thumb-side or little-finger-side digits. If SHH activity appears in the wrong place or at the wrong level, an extra digit can form—a condition called polydactyly.

A common mix-up is that many human cases involve mutations in a distant regulatory enhancer rather than a change to the SHH protein-coding sequence itself. The best-known limb enhancer, called ZRS, lies roughly 1 megabase away and controls SHH expression in developing limbs. Other genes, including GLI3 and HOXD13, can also be involved in polydactyly, but SHH is the canonical answer among the choices.

Source: Wikipedia · fact-checked Aug. 2026

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