Table 1.

Human disease mutations that affect autophagy

Gene	Function in autophagy	Disease	Likely disease defect	Reference
Core autophagy component
Atg16L1	Core autophagy component; essential for autophagosome elongation	Crohn’s disease	Defect in bacterial clearance, increased proinflammatory cytokine secretion	Hampe, et al. 2006. Nature genetics 39: 207–11
Autophagy induction/initiation
IRGM	Autophagy induction in response to IFNγ	Crohn’s disease	Defect in bacterial clearance, abnormal lymphocytes and macrophages	Parkes, et al. 2007. Nature genetics 39: 830–32
Jumpy (MTMR14)	PI3P phosphatase, negative regulator of autophagy induction	Centronuclear myopathy	Overactive autophagy	Tosch, et al. 2006. Human molecular genetics 15: 3098
Cargo Recognition/ Autophagosome (AP) targeting
NOD2	Autophagy induction in response to MDP; targeting of Atg16L1 to bacteria	Crohn’s disease	Defect in bacterial clearance, increased proinflammatory cytokine secretion	Ogura, et al. 2001. Nature 411: 603–06
PINK1	Mitophagy	PD	Defect in mitochondrial clearance, accumulation of damaged mitochondria	Valente, et al. 2004. Science 304: 1158
Parkin	Mitophagy	PD	Defect in mitochondrial clearance, accumulation of damaged mitochondria	Kitada, et al. 1998. Nature 392: 605–08
Lysosome function
presenilin 1	Targeting of v-ATPase V0a1 to the lysosome	AD	Defect in lysosomal acidification, accumulation of protein aggregates	Sherrington, et al. 1995. Nature 375: 754–60
lysosomal α-glucosidase	Glycogen breakdown in the lysosome	Pompe diseasea	Lysosomal glycogen accumulation, defect in AP-lysosome fusion	Shen, et al. 1996. Journal of Clinical Investigation 98: 352
LAMP2B	Maintenance of lysosome function	Danon diseaseb	Defect in AP-lysosome fusion	Nishino, et al. 2000. Nature 406: 906–10

^aglycogen storage disorder, characterized by muscle atrophy and cardiomyopathy

^bX-linked hereditary disorder, characterized by cardiomyopathy and myopathy