Background & Objectives: Non-synonymous single nucleotide polymorphism (nsSNPs) which results in disruption of protein function are used as markers in linkage and association of human proteins that might be involved in diseases and cancers .

  Methods: To study the functional effect of nsSNP in cyclooxygenase-2 (COX2 ) amino acids, the nucleotide sequences encoding COX-2 gene in cancers were extracted from the NCBI (gi|223941909) data bank (283 cases) and analyzed by SIFT, I-Mutant 2.0, SNP and GO, PANTHER and FASTSNP servers. These servers involve programs that predict the effects of amino acid substitution on protein function, stability and missense .

  Results: COX-2 is an essential enzyme for the production of pro-inflammatory prostaglandins which are relevant to cancer development and progression. The substitutions in some positions such as R228H and S428A of COX-2 in most of cancers linked to reformed protein function through disruption in enzyme active site.

  Conclusion: Amino acid substitutions as a consequence of COX-2 nsSNPs have important role in human disease. Substitutions which are located in catalytic domain are important for the enzymatic function of COX-2 and associated with higher expression of COX-2.