Table 1.

Tissue-specific Physiological Roles of GLIS1–3 in Disease.

Protein	Tissue	Pathology	Biological or Physiological Role	Ref.
Glis1	Skin	Psoriasis	• Highly expressed in psoriatic epidermis	Nakanishi et at. 2006
			• Promotes epidermal differentiation	Nakanishi et at. 2006
Glis2	Kidney	NPHP	• Mutation associated with NPHP in humans	Attanasio et al. 2007
			• KO mice exhibit impaired renal function and renal atrophy, fibrosis, and cysts	Attanasio et al. 2007, Kim et al. 2008
			• Modulates expression of several EMT-related genes	Attanasio et al. 2007, Kim et al. 2008
	Neurons	Neuropathies	• Expressed in primary neurons and promotes neuronal differentiation in vertebrates	Lamar et al. 2001
Glis3	Pancreas	Diabetes	• Identified as a risk locus for both type-1 and type-2 diabetes in humans	Barrett et al. 2009, Dupuis et al 2010
			• Mutation associated with NDH, characterized by neonatal diabetes, in humans	Senee et al 2006
			• KO mice exhibit hyperglycemia, hypoinsulinemia, and lack fully differentiated β-cells	Kang et al 2009b, Watanabe et al. 2009
			• KO mice exhibit dilated and cystic pancreatic ducts	Kang et al. 2009b
			• Positively regulates the expression of insulin in mature β-cells	Kang et al. 2009b, Yang et al. 2009
	Thyroid	Hypothyroidism	• Mutation associated with NDH, characterized by hypothyroidism, in humans	Senee et al. 2006
	Kidney	PKD	• Mutation associated with polycystic kidneys in humans	Senee et al. 2006
			• KO mice exhibit renal cysts and dilation of tubules and collecting ducts	Kang et al. 2009a
			• Mutation in the medaka ortholog linked to the development of PKD	Hashimoto et al. 2009
	Bone	Osteoporosis	• Promotes osteoblast and inhibits adipocyte differentiation in MSCs	Beak et al. 2007
			• Enhances the expression of FGF18, a regulator of osteogenesis and chondrogenesis	Beak et al. 2007
	Tumors	Cancer	• Expressed in malignant ependymomas and renal carcinomas	Lukashova-v. Zangen et al. 2007, Yusenko et al. 2009