KLK7 gene

The KLK7 gene (KLK7 stands for: Kallikrein Related Peptidase 7) is a protein coding gene located on chromosome 19q13.41. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, which is one of the fifteen members of the kallikrein subfamily located in a gene cluster on chromosome 19, and an important paralog of this gene is KLK5.

The KLK7 gene encodes a member of the kallikrein subfamily of serine proteases. These enzymes have diverse physiological functions and many kallikrein genes are biomarkers for cancer. The encoded protein has chymotrypsin-like activity and plays a role in the proteolysis of intercellular cohesive structures that precedes desquamation, the shedding of the outermost layer of the epidermis.

Influence on epidermal desquamation: The epidermal desquamation process is tightly regulated by the balance of activities of serine proteases of the kallikrein-related peptidase (KLK) family and their cognate inhibitor, lymphoepithelial Kazal-type related inhibitor (LEKTI), encoded by the Kazal-type 5 serine peptidase inhibitor gene. An imbalance of proteolytic activity caused by a deficiency of LEKTI leads to excessive desquamation due to increased activities of KLK5, KLK7 and KLK14 and results in Netherton syndrome (NS). Increased activity of KLKs may also be pathologic in other dermatoses such as atopic dermatitis (AD).

Potentially, treatment with a bispecific anti-KLK5/7 antibody could be a promising therapy for clinical development in Netherton syndrome and other inflammatory dermatoses (Chavarria-Smith J et al. 2022).

Cancer invasion and metastasis: The encoded protein may play a role in cancer invasion and metastasis, and increased expression of this gene is associated with unfavorable prognosis and progression of various cancers.

Polymorphisms in this gene may play a role in the development of atopic dermatitis (Yoon NY et al. 2018).

Furthermore, diseases associated with KLK7 include Netherton syndrome.

Associated metabolic pathways include the trimerization of collagen chains and the organization of the extracellular matrix. May catalyze the degradation of intercellular cohesive structures in the cornified layer of the skin during the continuous detachment of cells from the skin surface. Specific for amino acid residues with aromatic side chains in the P1 position. Cleaves the insulin A chain at '14-Tyr-|-Gln-15' and the insulin B chain at '6-Leu-|-Cys-7', '16-Tyr-|-Leu-17', '25-Phe-|-Tyr-26' and '26-Tyr-|-Thr-27'. Could play a role in the activation of precursors for inflammatory cytokines.

1. Chavarria-Smith J et al. (2022) Dual antibody inhibition of KLK5 and KLK7 for Netherton syndrome and atopic dermatitis. Sci Transl Med 14:eabp9159.
2. Komatsu N et al. (2003) Expression and localization of tissue kallikrein mRNAs in human epidermis and appendages. J Invest Dermatol 121: 542-549.
3. Matus CE et al. (2022) The family of kallikrein-related peptidases and kinin peptides as modulators of epidermal homeostasis. Am J Physiol Cell Physiol 323:C1070-C1087.
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5. Yamamoto T et al. (1987) Interstitial-tissue localization of high-molecular-weight kininogen in guinea-pig skin. Biochim Biophys Acta 916: 332-342.
6. Yoon NY et al. (2018) Simultaneous detection of barrier- and immune-related gene variations in patients with atopic dermatitis by reverse blot hybridization assay. Clin Exp Dermatol 43:430-436.