Gene prioritization was conducted for genes in which recessive homozygous potentially deleterious variants were present, but the top five genes after prioritization, ABCB5, SKD2, DUS3L, HDAC10
, and LMF2, have no direct link to liver function or bile acid metabolism as far as we know (Supplementary Material Online, Table S3).
HDACs can be divided into four distinct families, of particular interest are class I (HDAC1, HDAC2, HDAC5, and HDAC8) and class II (HDAC5, HDAC6, HDAC7, HDAC9, and HDAC10
) HDACs .
In accordance with their structural diversity, HDACs are divided into four subtypes: Class I (HDAC1, HDAC2, HDAC3, and HDAC8), Class II consisting of IIa (HDAC4, HDAC5, HDAC7, and HDAC9) and IIb (HDAC6 and HDAC10
), Class III (a family of sirtuins), and Class IV (HDAC11) .
HBI-8000 inhibits cancer-associated Class I HDAC1, HDAC2, HDAC3, as well as Class IIb HDAC10
at nanomolar concentrations and stimulates accumulation of acetylated histones H3 and H4 in tumor cells.