PIEZO2 (Piezo-Type Mechanosensitive Ion Channel Component 2)
PIEZO2 (piezo type mechanosensitive ion channel component 2; HGNC:26270, NCBI Gene ID 63895) is a human locus mapped to chromosome band 18p11.22-p11.21 that encodes Piezo2 homotrimeric mechanosensitive cation channel (2,752 aa per monomer). PIEZO2 acts in light touch, proprioception, baroreception & visceral interoception, together with PIEZO1 Mechanosensitive Channel Gene, Mechanosensitive Ion Channels, and Mechanoreceptors. Encodes the principal vertebrate mechanosensitive ion channel for light touch and proprioception.
Approved Symbol
PIEZO2
Chromosomal Locus
18p11.22-p11.21
Encoded Product
Piezo2 homotrimeric mechanosensitive cation channel (2,752 aa per monomer)
Distal arthrogryposis type 3/5 (GoF); PIEZO2 deficiency syndrome with proprioceptive ataxia (LoF)
Gene Structure & Expression
Genomic Organization & Cytogenetic Locus: 52-exon locus spanning over 450 kb at 18p11.22-p11.21, encoding a giant 2,752-amino-acid polypeptide with 38 transmembrane helices per protomer that assembles into a three-bladed propeller-shaped homotrimer of 114 transmembrane helices.
Cellular & Tissue Expression Profile: Expressed in cutaneous Merkel cells and low-threshold mechanoreceptor (LTMR) dorsal root ganglion neurons, muscle spindle and Golgi tendon organ proprioceptors, nodose ganglion aortic baroreceptors, and bladder stretch afferents.
Molecular Function & Pathways
Biochemical & Physiological Mechanism: Directly converts lateral lipid bilayer tension and cytoskeletal deflection into rapid, mechanically activated inward cation currents that depolarize tactile afferents, muscle proprioceptors, and Hering-Breuer pulmonary stretch receptors.
Clinical & Therapeutic Significance
Human Genetic Variants & Disease Phenotypes: Biallelic loss-of-function mutations cause autosomal recessive PIEZO2 deficiency syndrome marked by profound loss of proprioception, absent tactile vibration sense, and abolition of mechanical allodynia, whereas dominant gain-of-function variants decelerate channel inactivation and cause Gordon syndrome (distal arthrogryposis type 3) and Marden-Walker syndrome.
Therapeutic & Clinical Pharmacology: Discovered by Ardem Patapoutian (2021 Nobel Prize in Physiology or Medicine); targeted to block pathological tactile allodynia in neuropathic pain without impairing protective nociception.