ACTG2

ACTG2, or actin gamma 2, is a protein-coding gene in humans that encodes the smooth muscle–specific gamma-actin isoform. Gamma-actin proteins are members of the actin family and form microfilaments that contribute to the structure and contractility of the cytoskeleton in smooth muscle cells. The ACTG2-encoded protein is primarily expressed in visceral smooth muscle, including the gastrointestinal tract and urinary bladder, and participates in actin filament networks that mediate contraction and help maintain cell shape.

Genetics and disease: Variants in ACTG2 have been linked to visceral smooth muscle dysfunction. Pathogenic variants, often missense changes, can disrupt actin filament formation and actin–myosin interaction, leading to reduced motility of the gastrointestinal and urinary tracts. Clinically, ACTG2 mutations are associated with chronic intestinal pseudo-obstruction, megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS), and related abdominal and bladder dysfunction. Inheritance is typically autosomal dominant, with many reported cases arising de novo, though familial cases exist.

Mechanism and protein interactions: As a structural component of the smooth muscle cytoskeleton, gamma-actin interacts with myosin and actin-binding proteins to form contractile filaments. It participates in maintaining cell integrity during smooth muscle contraction and may be involved in remodeling in response to physiological stimuli.

Evolution and expression: ACTG2 is part of the vertebrate actin gene family and shows high sequence conservation with other actin isoforms. Expression patterns support tissue-restricted roles in smooth muscle, particularly in the gastrointestinal tract and urinary system, where proper cytoskeletal function is essential for motility.