The Class IIA HDACs includes HDAC4, HDAC5, HDAC7 and HDAC9. HDACs 4 and 5 have been found to most closely resemble each other while HDAC7 maintains a resemblance to both of them. There have been three discovered variants of HDAC9 including HDAC9a, HDAC9b and HDAC9c/HDRP, while more have been suspected. The variants of HDAC9 have been found to have similarities to the rest of the Class IIA HDACs. For HDAC9, the splicing variants can be seen as a way of creating a "fine-tuned mechanism" for differentiation expression levels in the cell. Different cell types may take advantage and utilize different isoforms of the HDAC9 enzyme allowing for different forms of regulation. HDACs 4, 5 and 7 have their catalytic domains located in the C-terminus along with an NLS region while HDAC9 has its catalytic domain located in the N-terminus. However, the HDAC9 variant HDAC9c/HDRP lacks a catalytic domain but has a 50% similarity to the N-terminus of HDACs 4 and 5.
For HDACs 4, 5 and 7, conserved binding domains have been discovered that bind for C-terminal binding protein (CtBP), myocyte enhancer factor 2 (MEF2) and 14-3-3. All three HDACs work to repress the myogenic transcription factor MEF2 which an essential role in muscle differentiation as a DNA binding transcription factor. Binding of HDACs to MEF2 inhibits muscle differentiation, which can be reversed by action of Ca/calmodulin-dependent kinase (CaMK) which works to dissociate the HDAC/MEF2 complex by phosphorylating the HDAC portion. They have been seen to be involved in cellular hypertrophy in muscle control differentiation as well as cellular hypertrophy in muscle and cartilage tissues. HDACs 5 and 7 have been shown to work in opposition to HDAC4 during muscle differentiation regulation so as to keep a proper level of expression. There has been evidence that these HDACs also interact with HDAC3 as a co-recruitment factor to the SMRT/N-CoR factors in the nucleus. Absence of the HDAC3 enzyme has shown to lead to inactivity which makes researchers believe that HDACs 4, 5 and 7  help the incorporation of DNA-binding recruiters for the HDAC3-containing HDAC complexes located in the nucleus. When HDAC4 is knocked out in mice, they suffer from a pronounced chondrocyte hypertrophy and die due to extreme ossification. HDAC7 has been shown to suppress Nur77-dependent apoptosis. This interaction leads to a role in clonal expansion of T cells. HDAC9 KO mice are shown to suffer from cardiac hypertrophy which is exacerbated in mice that are double KO for HDACs 9 and 5.