The three cerebral cavernous malformations (CCMs) genes namely CCM1/KRIT1, 
CCM2/MGC4607 and CCM3/PDCD10 have been identified for which mutations cause 
cerebral cavernous malformations. However, the protein products of these genes 
involved in forming CCM signaling, are still poorly understood imposing an 
urgent need to understand these genes and their signaling processes in details. 
So far involvement of CCM3/PDCD10 in the cavernous angioma has been 
characterized from biochemical and biophysical analyses. However, there is no 
comprehensive study illustrating the phylogenetic history and comprehensive 
genetic variants of CCM3/PDCD10. Herein, we explored the phylogenetic history 
and genetic variants of CCM3/PDCD10 gene. Synteny analyses revealed that 
CCM3/PDCD10 gene shared same genomic loci from Drosophila to human and the gene 
structure of CCM3/PDCD10 is conserved from human to Branchiostoma floridae for 
about 500 MYs with some changes in sea urchin and in insects. The conserved 
CCM3/PDCD10 is characterized by presence of indels in the N-terminal 
dimerization domain. We identified 951 CCM3/PDCD10 variants by analysis of 1092 
human genomes with top three variation classes belongs to 84% SNPs, 6.9% 
insertions and 6.2% deletions. We identified 22 missense mutations in the human 
CCM3/PDCD10 protein and out of which three mutations are deleterious. We also 
identified four stop-codon gaining mutations at the positions E34*, E68*, E97* 
and E140*, respectively. This study is the first comprehensive analysis of the 
CCM3/PDCD10 gene based on phylogenetic origin and genetic variants. This study 
corroborates that the evolution of CCM proteins with tubular organization 
evolvements by endothelial cells.