Disease relevance of TMPRSS4

• A novel transmembrane serine protease (TMPRSS3) overexpressed in pancreatic cancer [1].
• Thus, TMPRSS3 is a novel membrane-bound serine protease overexpressed in cancer, which may be of importance for processes involved in metastasis formation and tumor invasion [1].
• CONCLUSION: Mutations of TMPRSS3 contribute to hearing loss in many communities worldwide and account for 1.8% (8 of 449) of Pakistani families segregating congenital deafness as an autosomal recessive trait [2].

High impact information on TMPRSS4

• In the Xenopus oocyte expression system, proteolytic processing of TMPRSS3 was associated with increased ENaC mediated currents [3].
• The epithelial amiloride-sensitive sodium channel (ENaC), which is expressed in many sodium-reabsorbing tissues including the inner ear and is regulated by membrane-bound channel activating serine proteases (CAPs), is a potential substrate of TMPRSS3 [3].
• Transient expression of wild-type or tagged TMPRSS3 protein showed a primary localization in the endoplasmic reticulum [3].
• The 2.3-kb mRNA of the gene, named TMPRSS3, is strongly expressed in a subset of pancreatic cancer and various other cancer tissues, and its expression correlates with the metastatic potential of the clonal SUIT-2 pancreatic cancer cell lines [1].
• The AUC was 0.956 for ECM1 and 0.926 for TMPRSS4 [4].

Biological context of TMPRSS4

• The allele frequencies of the TMPRSS4 c.4-7A>G, NPHP4 c.2818-2A>T, and ORCTL4 c.517-2A>C polymorphisms in a Japanese population were determined to be 0.42, 0.10, and 0.27, respectively, by PCR-SSCP analysis [5].
• Therefore, in this study, splice-site variants of the transmembrane serine protease gene TMPRSS4, nephronophthisis gene NPHP4, and organic-cation transporter gene ORCTL4, were selected from the dbSNP single nucleotide polymorphism database as candidates to identify genetic polymorphisms associated with a structural change in their mRNA transcripts [5].
• The mutant TMPRSS3 harboring the novel R216L missense mutation within the predicted cleavage site of the protein fails to undergo proteolytic cleavage and is unable to activate ENaC, thus providing evidence that pre-cleavage of TMPRSS3 is mandatory for normal function [6].
• The three families with the highest LOD score for linkage to chromosome 21q22.3 were shown to harbor P404L, R216L, or Q398X mutations, suggesting that mutations in TMPRSS3 are a considerable contributor to non-syndromic deafness in the Turkish population [6].
• METHODS: We enrolled families segregating recessive hearing loss from Pakistan and Newfoundland. Microsatellite markers flanking the TMPRSS3 locus were used for linkage analysis [2].

Anatomical context of TMPRSS4

• CONCLUSIONS: ECM1 and TMPRSS4 are excellent diagnostic markers of malignant thyroid nodules and may be used to improve the diagnostic accuracy of FNA biopsy [4].

Other interactions of TMPRSS4

• Effect of splice-site polymorphisms of the TMPRSS4, NPHP4 and ORCTL4 genes on their mRNA expression [5].
• Within these, 140 were also identified in PDAC by others, such as Galectin-1, Galectin-3, and MT-SP2 [7].

Analytical, diagnostic and therapeutic context of TMPRSS4

• ECM1 and TMPRSS4 are diagnostic markers of malignant thyroid neoplasms and improve the accuracy of fine needle aspiration biopsy [4].

References