KLK1 was first reported in relation to autosomal dominant pulmonary arterial hypertension (PAH) in 2019 (Zhu et al., PMID: 31727138). PAH is a group of diseases characterized by elevated pulmonary arterial resistance leading to right heart failure.
Summary of Genetic Evidence: Seven missense, one frameshift, one stop-gain, and one splice variant have been reported in KLK1 (Zhu et al., PMID: 31727138). These 10 probands were identified using exome sequencing in a large cohort from the National Biological Sample and Data Repository for PAH (n = 2572 cases). The mechanism of pathogenicity appears to be loss of function.
Summary of Experimental Evidence: This gene-disease association is supported by an expression experiment (PMID: 17573418). This study showed the expression of KLK1 in adult lung tissues.
In summary, the evidence for a gene-disease relationship between KLK1 and autosomal dominant PAH is limited. This classification was approved by the ClinGen Pulmonary Hypertension GCEP on 8/30/2022 (SOP Version 9).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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