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The  Kallikrein  ( KLK ) gene locus encodes a family of serine proteases and is the largest contiguous cluster of protease-encoding genes attributed an evolutionary age of 330 million years. The  KLK  locus has been implicated as a high susceptibility risk loci in numerous cancer studies through the last decade. The  KLK3  gene already has established clinical relevance as a biomarker in prostate cancer prognosis through its encoded protein, prostate-specific antigen. Data mined through genome-wide association studies (GWAS) and next-generation sequencing point to many important candidate single nucleotide polymorphisms (SNPs) in  KLK3  and other  KLK  genes. SNPs in the  KLK  locus have been found to be associated with several diseases including cancer, hypertension, cardiovascular disease and atopic dermatitis. Moreover, introducing a model incorporating SNPs to improve the efficiency of prostate-specific antigen in detecting malignant states of prostate cancer has been recently suggested. Establishing the functional relevance of these newly-discovered SNPs, and their interactions with each other, through  in silico  investigations followed by experimental validation, can accelerate the discovery of diagnostic and prognostic biomarkers. In this review, we discuss the various genetic association studies on the  KLK  loci identified either through candidate gene association studies or at the GWAS and post-GWAS front to aid researchers in streamlining their search for the most significant, relevant and therapeutically promising candidate  KLK  gene and/or SNP for future investigations.

Genetic polymorphisms in the human tissue kallikrein (KLK) locus and their implication in various malignant and non-malignant diseases