HOMER1 Gene - Structure, Function, and Clinical Significance

HOMER1 encodes a member of the Homer family of scaffold proteins that regulate group I metabotropic glutamate receptor (mGluR1/5) signaling and synaptic plasticity. The protein contains an N-terminal Ena/VASP homology 1 (EVH1) domain that binds proline-rich motifs in target proteins and a C-terminal coiled-coil domain mediating multimerization. Alternative splicing generates isoforms with distinct C-termini, including a short dominant-negative isoform (HOMER1A) induced by neuronal activity. HOMER1 is involved in calcium signaling, dendritic spine morphogenesis, and behavioral responses to drugs of abuse.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Metabotropic glutamate receptor signaling (Reactome: R-HSA-420092)

• Long-term depression (Reactome: R-HSA-438066)

• CREB phosphorylation (Reactome: R-HSA-111931)

HOMER1 is a scaffold protein that links metabotropic glutamate receptors (mGluR1/5) to intracellular calcium stores and signaling complexes. It plays a critical role in synaptic plasticity, dendritic spine morphology, and neuronal excitability. The protein has multiple isoforms generated by alternative splicing, with HOMER1A acting as an activity-induced dominant-negative regulator. Dysregulation of HOMER1 is implicated in neuropsychiatric disorders including schizophrenia, bipolar disorder, and autism spectrum disorder.