TABLE 1.

Classes of LDLR variants.

LDLR variant classes	Type of variants	Protein/functional impact
Class I	•Early stop codons •Mutations in the promoter regions •Splicing aberrations •Large exonic deletions	Synthesis defective: Defects in LDLR protein synthesis
Class II: •Class II A •Class II B	•Missense mutations in the cysteine-rich domains •In-frame deletions/duplications •Protein truncating mutations	Transport defective: Defects in LDLR folding, maturation and transport in the secretory pathway Class IIA: Completely retained in the ER due to folding defects Class II B: Transport-competent but ER-retained due to slower processing
Class III	•Point mutations clustering in the ligand binding domain	Binding defective: Transport-competent but defective in binding to LDL
Class IV	•Mutations in the 4th and 5th domains •Complete deletion of those LDLR domains	Clustering and endocytosis defective: Impair with the clustering of ligand-bound LDLR in clathrin coated pits and endocytosis of LDLR-LDL complex
Class V	•Deletions in the EGF precursor domain	Dissociation and recycling defective: The LDLR-LDL complex is successfully internalized in the cell, but dissociation of the LDLR from the LDL does not happen leading to the degradation of LDLR along with LDL in the lysosomes (Beglova et al., 2004; Van Hoof et al., 2005)