The ARH protein is involved in cell cycle progression, possibly by affecting nuclear membrane formation through interaction with lamin B1 or other mitotic proteins, and its absence affects cell proliferation and induces premature senescence, which may play a role in the development of atherosclerosis in ARH.
Structural features of the ARH protein and its capacity to interact simultaneously with the internalization sequence of the LDL receptor, plasma membrane phospholipids, and the clathrin endocytic machinery suggest how ARH can play a pivotal role in gathering the LDL receptor into forming endocytic carrier vesicles.
Mutations in the phosphotyrosine binding domain protein ARH cause autosomal recessive hypercholesterolemia, a disorder caused by defective internalization of low density lipoprotein receptors (LDLR) in the liver.
Autosomal recessive hypercholesterolemia (ARH) is an extremely rare inherited hypercholesterolemia, the cause of which is mutations in low-density lipoprotein (LDL) receptor adaptor protein 1 (LDLRAP1) gene.
We identified a family with autosomal recessive hypercholesterolemia not explained by mutations in LDLRAP1 or other genes known to cause monogenic hypercholesterolemia.
Our results also indicate that ARH1 carrier status is present in ∼1:2500 of Sicilian inhabitants, confirming that ARH is extremely rare outside Sardinia.
Mutations in a putative low-density lipoprotein (LDL) receptor adaptor protein called ARH have been recently described in patients with autosomal recessive hypercholesterolemia (ARH).
At the age of 28 years, homozygous LDLRAP1 gene variant NM_015627.2:c.488A>C, NP_056442.2:p.(Gln163Pro) causing autosomal recessive hypercholesterolemia was determined by genetic testing.