PICALM Gene: Function, Expression, Mutations & Disease Associations

PICALM (phosphatidylinositol binding clathrin assembly protein) encodes a clathrin assembly protein that plays a critical role in clathrin-mediated endocytosis. It is involved in the internalization of cell surface receptors and synaptic vesicle recycling. Genome-wide association studies have identified PICALM as a susceptibility locus for late-onset Alzheimer disease. The protein contains an N-terminal ANTH domain that binds phosphatidylinositol-4,5-bisphosphate and a C-terminal domain that interacts with clathrin and adaptor protein complexes.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Clathrin-mediated endocytosis (Reactome R-HSA-8856828)

• Alzheimer disease (KEGG hsa05010)

• Endocytosis (KEGG hsa04144)

PICALM is a 652-amino acid protein (UniProt Q13492) that functions as a clathrin assembly protein. It contains an N-terminal ANTH domain that binds phosphatidylinositol-4,5-bisphosphate, targeting it to the plasma membrane, and a C-terminal domain that recruits clathrin and AP-2 adaptor complexes. PICALM is essential for efficient clathrin-mediated endocytosis, including synaptic vesicle recycling and internalization of cell surface receptors. It is ubiquitously expressed with highest levels in brain. Genetic variants in PICALM are associated with Alzheimer disease risk, and chromosomal rearrangements involving PICALM are recurrent in acute leukemias.