Objective]Mutations in the gene that encodes the fibrosis transmembrane conductan-ce regulator (CFTR)protein can cause cystic fibrosis but the patterns of missense mutations in CFTR protein haven’t yet been reported.[Methods]The amino-acid pair predictability was used to convert the CFTR protein with its 178 missense mutations into scalar sequences,and then the substituted and substituting amino-acid pairs were analysed before and after mutation.[Re-sults]97.19% of mutations occurred in unpredictable amino acid pairs.87.08% of mutations targeted one or both substituted amino acid pairs whose actual frequency was larger than their predicted one.1 5 .1 7% mutations resulted in one or both substituting amino-acid pairs that were absent before mutation.A total of 122 mutations brought about the substituting amino-acid pairs with their actual frequency smaller than predicted one.[Conclusion]The unpredicta-ble amino-acid pairs are more sensitive to muta-tion,and the mutation trend is to narrow the difference between predicted and actual frequen-cy of amino-acid pairs,thus the composition of a-mino acid pairs becomes more randomized,which leads the human CFTR protein degenerative and causes cystic fibrosis.%【目的】编码囊性纤维化跨膜电导调节子（Cystic fibrosis transmembrane conductance regulator，CFTR）蛋白的基因突变可引起囊性纤维化，但该蛋白错义点突变的变异模式尚无报道。【方法】先用氨基酸对可预测性为指标将人CFTR蛋白及其178个错义点突变的氨基酸序列转换成标量序列，然后分析变异前后被替换掉的和替换出的氨基酸对的变化。【结果】97．19％的变异发生在不可预测的氨基酸对；87．08％的变异涉及1个或2个被替换掉的氨基酸对，其实际频率大于预测频率；15．17％的变异带来1个或2个替换出的氨基酸对，它们在正常的CFTR蛋白是不存在的；共有122个变异导致替换出的氨基酸对的实际频率小于预测频率。【结论】不可预测的氨基酸对对变异更敏感，变异的趋势是缩小氨基酸对实际频率和预测频率之间的差距，使氨基酸对的构成更加随机化，而人CFTR蛋白的这种退行性变导致了囊性纤维化。
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