PDE1A Gene - Phosphodiesterase 1A: Function, Mutations, and Disease Associations

PDE1A encodes a calmodulin-dependent cyclic nucleotide phosphodiesterase that hydrolyzes both cAMP and cGMP. The enzyme is activated by calcium-bound calmodulin and plays a critical role in cross-talk between calcium and cyclic nucleotide signaling pathways. PDE1A is expressed in brain, heart, smooth muscle, and other tissues, and is implicated in vascular smooth muscle contraction, cardiac function, and neuronal plasticity. Alternative splicing generates multiple isoforms with distinct regulatory properties and tissue distributions.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• cGMP-PKG signaling pathway (Reactome: R-HSA-418594)

• cAMP-PKA signaling pathway (Reactome: R-HSA-163615)

• Calcium signaling pathway (KEGG: hsa04020)

• Vascular smooth muscle contraction (KEGG: hsa04270)

PDE1A is a 61 kDa protein (isoform 1) composed of 535 amino acids. It contains a conserved catalytic domain flanked by two N-terminal Ca2+/calmodulin-binding domains. The enzyme exists as a homodimer and is activated by calcium-bound calmodulin, which increases its affinity for cAMP and cGMP. PDE1A is highly expressed in brain regions such as the cerebral cortex and hippocampus, and in vascular smooth muscle. It regulates diverse processes including neurotransmitter signaling, muscle contraction, and cell proliferation. Isoforms differ in their N-terminal sequences and tissue-specific expression.