Another class of highly intolerant genes predicted by EvoTol but not RVIS are those which belong to the ATP-binding cassette (ABC) family of transmembrane transporters, such as ABCA10 a cholesterol responsive gene (48), ABCA13 or ABCB6 previously involved in cardiovascular disease, such as atherosclerosis (49). The gene discussed is ABCB6; the disease is cardiovascular disorder.