The story revolves around a deaf agent, Tom Clerc (played by Insolera), from New York City who is a carrier of a powerful genetic mutation.

He is sent to Japan with his colleague, Ken Wong, to investigate crimes believed to have been committed by Japanese deaf mutants.

All deaf mutants who are carriers of this genetic mutation turn out to be superheroes with the ability to create superpowers through the use of sign language.

However, he lost a significant portion of his powers during a battle with Jux Clerc, Tom's brother and the leader of the group 1.8.8.0., an evil organization dedicated to exterminating Sign Gene mutants.

Michael Rechtshaffen of the Los Angeles Times, described the movie as one with a, "fresh, unique filmmaking voice" and a "fast-paced potpourri of stock footage combined with sign-language and stroboscopic action sequences performed by a deaf cast, video effects simulating grainy, scratchy film stock and that aforementioned all-enveloping sound mix, with an end result that proves as wildly inventive as it is empowering.

"[14] The Italian newspaper, Avvenire, declared the film will mostly likely please the younger generation, who are "accustomed to the rapid and psychedelic language of Japanese video games or cartoons".

"[22] Michela Trigari of Corriere della Sera, called Sign Gene an "experimental film" that uses science fiction as a medium to capture the imagination and "make visible what is invisible to the eyes.

"[23] Emilio Insolera appeared on the cover of Tokyo Weekender’s November 2018 issue taken by worldwide known photographer Leslie Kee[24][25] and in thirteen full pages fashion story on Vanity Fair Italia's January 2019 number 5 with Carola Insolera taken by Rosi Di Stefano.