Table 1.

Familial hamartoma syndromes linked to mTOR dysregulation (39–48)

Gene	Protein	Protein Function	Disease	Clinical Features
TSC1	Hamartin (TSC1)	Binding partner for TSC2	Tuberous sclerosis	Hamartomas in skin, central nervous system, and heart; renal cysts and angiomyolipomas; lymphangiomyomatosis
TSC2	Tuberin (TSC2)	Rheb GAP	Tuberous sclerosis	Same as above
PTEN	PTEN	3′-phosphoinositide phosphatase	PTEN-hamartoma tumor syndromes	Hamartomas in multiple organs, lentigines, macrocephaly, hemihypertrophy, increased risk of breast and thyroid cancer
STK11	STK11	AMPK-dependent regulator of TSC2	Peutz-Jeghers syndrome	Hamartomas in GI tract, lentigines, increased risk of GI and non-GI carcinomas
FLCN	Folliculin (FLCN)	AMPK-dependent regulator of TSC2	BHD syndrome	Hamartomas in multiple organs (including hair follicles), lung cysts (spontaneous pneumothorax), increased risk of renal carcinomas
PKD1	Polycystin 1 (PC1)	Regulator of TSC2?	Autosomal dominant polycystic kidney disease	Renal and extrarenal cysts, cardiac valvular and vascular defects (including intracranial arterial aneurysms), hernias, colonic diverticulosis
NF1	Neurofibromin 1 (NF1)	RAS GAP	Neurofibromatosis	Neurocutaneous hamartomas, endocrine tumors, increased risk of malignant peripheral nerve tumors, sarcomas, myeloid leukemia

GI, gastrointestinal; PTEN, phosphatase and tensin homolog (PTEN-hamartoma tumor syndromes include Cowden disease, Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Lhermitte-Duclos syndrome); STK11, serine/threonine kinase 11 (also known as LKB1).