Abstract: Objective：To analyze two mutations in voltage gated chloride channel 7 gene (CLCN7) of two osteopetrosis patients using bioinformatic methods, and compare the effects of mutations on protein structure and physicochemical characteristics, so as to predict the damaging effect of the mutations on the disease development. Methods：Genomic DNA were collected from peripheral blood of two osteopetrosis patients and their family members. CLCN7 gene was PCR amplified and sequenced. NCBI website, PolyPhen-2, DNAStar, SWISS MODEL were used to analyze the effect of the mutated genes. Results：Case 1 was diagnosed as intermediate autosomal recessive osteopetrosis (IARO), and his CLCN7 gene showed a de novo homozygous mutation c.1409 C>T in exon 16, which resulted in a residue substitution from proline to leucine (c.1409 C＞T; p.Pro470Leu). Case 2 was diagnosed as autosomal dominant osteopetrosis type Ⅱ (ADOⅡ). The sequence analysis revealed a heterozygous mutation c.856 C>T in exon 10 of CLCN7 gene, which resulted in arginine to tryptophan residue substitution (c.856 C＞T; p.Arg286Trp). Both of the mutations are located in highly conserved domain among different species. The mutations cause the changes in the secondary structure, tertiary structure and physicochemical properties and so on. Conclusions：Multiple bioinformatic analyses indicate that the mutations in CLCN7 gene (c.1409 C＞T and c.856 C＞T) can change the molecule structure and affect biological function of ClC-7, which shows a damaging effect and might be the key of disease development in the patients.