. Author manuscript; available in PMC: 2014 Nov 1.

Published in final edited form as: J Mol Biol. 2013 Jul 16;425(21):3919–3936. doi: 10.1016/j.jmb.2013.07.014

Table 5.

Examples of disease-related mutations that affect protein activity and function.

Gene/Protein	Disease	Mutation	Effect	Reference
ATP-binding cassette transporter (ABCA1)	Tangier disease(reduction of HDL Cholesterol in plasma)	N1800H	Changes the localization of protein, resulting in intracellular accumulation of ABCA1 and loss of interaction with ApoA-I.	193
ATP-binding cassette transporter (ABCA1)	Tangier disease(reduction of HDL Cholesterol in plasma)	W590S	Impairs dissociation of apoA-I from ABCA1, which may affect ATP-dependent lipid translocation.	194
Niemann–Pick C1-Like protein 1 (NPC1L1)	Hypocholesterolemia(reduction of LDL Cholesterol in the plasma)	T61M, S881L	Severely dysfunctional mutations; affect cholesterol uptake function, cholesterol-regulated recycling, glycosylation and stability of the protein.	195
Niemann–Pick C1-Like protein 1 (NPC1L1)		G402S, R1268H	Partially dysfunctional mutations; affect cholesterol-regulated recycling.	195
Thiazide-sensitive sodium-chloride cotransporter (SLC12A3)	Gitelman syndrome (salt wasting and low blood pressure)	G439S, G741R	Abolish sodium uptake function due to loss of localization at plasma membrane, which may be caused by incomplete glycosylation.	196
Chloride intracellular channel protein 2(CLIC2)	X-linked intellectual disability	H101Q	Stabilizes the protein, which in turn may increase ryanodine receptor activity.	44
Histone-lysine N- methyltransferase (MLL2)	Kabuki syndrome	W5065X, R5179H	May affect the epigenetic control of active chromatin states via methylation of histones.	18