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Cell biology

Stressful genetics in Crohn's disease

Nature volume 506, pages 441–442 (2014)Cite this article

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A common variant of the autophagy protein ATG16L1 is a risk factor for Crohn's disease. But the genetic alteration is revealed only when the protein is cleaved by the enzyme caspase 3 during cellular stress. See Article p.456

A single variation within the approximately six billion base pairs of human DNA is sufficient to magnify our risk of developing common complex diseases. For example, a single nucleotide change in the gene ATG16L1 is one of the strongest genetic risk factors for Crohn's disease1, a chronic inflammatory disease of the digestive tract2. On page 456 of this issue, Murthy et al.3 reveal a fascinating twist in the story of how this variant, which is present in more than 50% of the Caucasian population, may contribute to the disease. The authors report that the altered ATG16L1 protein, which contains the substitution of an alanine amino-acid residue for a threonine at position 300 (T300A), is susceptible to cleavage by the enzyme caspase 3, which is activated when a cell senses stress.

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Figure 1: Fate determination by caspase 3.

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Authors and Affiliations

  1. Arthur Kaser is in the Division of Gastroenterology and Hepatology, Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0QQ, UK.,

    Arthur Kaser

  2. Richard S. Blumberg is in the Division of Gastroenterology, Department of Medicine, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.,

    Richard S. Blumberg

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  1. Arthur Kaser
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  2. Richard S. Blumberg
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Correspondence to Arthur Kaser or Richard S. Blumberg.

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Kaser, A., Blumberg, R. Stressful genetics in Crohn's disease. Nature 506, 441–442 (2014). https://doi.org/10.1038/nature13060

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