Serping1, also known as C1INH/C1NH, encodes C1 inhibitor. C1 inhibitor is crucial in controlling the kallikrein-kinin system, and also plays roles in the coagulation complement, contact systems, and fibrinolysis [1,2]. Its deficiency can lead to the uncontrolled activation of the kallikrein-kinin system, generating the vasoactive peptide bradykinin [1].

Mutations in SERPING1 are responsible for hereditary angioedema (C1-INH-HAE), an autosomal dominant disorder [1,2]. A comprehensive update documented 748 different SERPING1 variants, including 120 unpublished ones [1]. These variants can be heterozygous, homozygous or compound heterozygous, and some cases showed gonadal mosaicism or were de novo [1]. In addition, 58 variants were found at positions with high residue conservation among serpins, related to the mousetrap function of C1Inh [1]. C1Inh phenotype analysis identified dysfunctional serpin variants with failed serpin-protease association [1]. Also, in Chinese HAE patients, 76 different variants were identified in 90 out of 97 patients, with 35 being novel [3].

In conclusion, SERPING1 is essential for regulating the kallikrein-kinin system and other related pathways. Studies on SERPING1 mutations and their associated phenotypes in the context of hereditary angioedema have enhanced our understanding of the disease mechanism, which may contribute to more accurate diagnosis and better treatment strategies for C1-INH-HAE patients [1,2,3].

References:

1. Ponard, Denise, Gaboriaud, Christine, Charignon, Delphine, Tosi, Mario, Drouet, Christian. 2019. SERPING1 mutation update: Mutation spectrum and C1 Inhibitor phenotypes. In Human mutation, 41, 38-57. doi:10.1002/humu.23917. https://pubmed.ncbi.nlm.nih.gov/31517426/

2. Sinnathamby, Evan S, Issa, Peter P, Roberts, Logan, Shekoohi, Sahar, Kaye, Alan D. 2023. Hereditary Angioedema: Diagnosis, Clinical Implications, and Pathophysiology. In Advances in therapy, 40, 814-827. doi:10.1007/s12325-022-02401-0. https://pubmed.ncbi.nlm.nih.gov/36609679/

3. Wang, Xue, Lei, Shubin, Xu, Yingyang, Liu, Shuang, Zhi, Yuxiang. 2022. Mutation update of SERPING1 related to hereditary angioedema in the Chinese population. In Hereditas, 159, 28. doi:10.1186/s41065-022-00242-z. https://pubmed.ncbi.nlm.nih.gov/35821062/