Table 2.

Mammalian AQP mutants and their impact on disease.

AQP	Mutations	Comments	References
AQP0	Ser235Ala	Produces defects to the plasma membrane translocation that induce congenic cataracts	[122]
	Arg33Cys	Reduces the cell-to-cell adhesion that is critical for lens transparency and homeostasis, inducing congenital lens cataracts	[129]
AQP1	Thr157Ala Thr239Ala	Abolish both the water permeability and the cationic conductance increase mediated by PKC phosphorylation in Xenopus oocytes	[130]
		Impair hypotonicity-induced translocation of AQP1 to the plasma membrane of HEK cells	[131]
AQP2	Cys181Trp	Impairs the plasma membrane translocation and the mutant accumulates in the endoplasmic reticulum (ER). This mutation was observed in a patient with congenital nephrogenic diabetes insipidus (NDI)	[132]
	Ser256Asp	Phosphorylation of serine 256 allows AQP2 trafficking to the plasma membrane. Mutations in this site abrogates the protein translocation. Thus, these mutations produce NDI, due the inability of the kidneys to concentrate urine	[133]
	Ser256Ala
	Gly100Val	Both mutations were found in a Chinese family with congenital NDI, and both mutations retain AQP2 in the ER	[134]
	Gln57Pro
	Ala147Thr	These three mutations were found in patients with NDI, impair translocation to the plasma membrane, and the mutant is retained at the ER	[135]
	Thr126Met
	Asp68Ser
	Arg254Leu	This mutation lacks basopressin-mediated phosphorylation at S256, causing impaired transport to the plasma membrane. This mutation also causes NDI disease	[136]
AQP3	Tyr19Ala	Partial disruption of AQP3 basolateral localization in MDCKII cells. A portion of AQP3 remains in the cytoplasm	[137]
	Leu21Ala-Leu22Ala
	Tyr19Ala-Arg20Ala-Leu21Ala-Leu22Ala	The mutation of this N-terminal motif produces complete retention of AQP3 in the cytoplasm of transfected MDCKII cells
AQP4	Ser180Ala	Ser180 is a PKC phosphorilation site. This mutation impairs the effect and produces a reduced water-permeable protein.	[138]
	Ser111Ala	Abolishes PKG-mediated phosphorylation of AQP4 in astrocytes cultured in vitro	[139]
	Ser276Asp	This point mutation increases the rate of protein degradation. The effect was observed in AQP4-transfected MDSCK cells lysates	[140]
AQP5	Ser156Glu	This phosphomimetic mutant increases the constitutive expression of AQP5 on the membrane but does not cause significant structural changes to the protein	[67]
AQP6	N-terminus	The short N-terminus of AQP6 is involved in its intracellular localization	[94]
AQP7	Ser10Ala/T11Ala	These mutations impair PKC phosphorylation of AQP7 and its interaction with perilipin 1 affecting the correct localization of AQP7 in the plasma membrane of adipocytes	[141]
	Gly264Val	Loss of glycerol transport function that impairs the reabsorption of glycerol by the kidneys inducing hyperglyceroluria in human children	[142]
AQP9	Ser11Ala	This unphosphorylated mutant cannot be localized in the plasma membrane	[143]
	Ser11Asp	This phosphomimetic mutant enhances neutrophil polarization and chemotaxis
AQP10	His80Ala	Impairs glycerol permeability evidencing the role of His80 as a pH sensor	[71]
	Gly73Val	Impair glycerol permeability suggesting that the G73G74 motif mediates a gating mechanism between loop B and TM2 in the cytoplasmic aperture of the channel
	Gly73Phe
AQP11	Cys227Ser	Produces renal failure and death in sudden juvenile death syndrome (SJDS) in mice	[144]
		Alters the correct folding of AQP11, inducing endoplasmatic reticulum stress and apoptosis in cells of the proximal tubule	[145]