Serpinf1, also known as the gene encoding pigment epithelium-derived factor (PEDF), is a member of the serpin family but does not exhibit typical serine protease inhibitory activity. PEDF has multiple functions including anti-tumor, anti-angiogenesis, anti-inflammation, nutrition and nerve protection, and it participates in fat metabolism [2].

In glioma, higher SERPINF1 expression is correlated with a poor overall survival rate. Knockdown of SERPINF1 can suppress the proliferation, invasion, and migration of glioma cells in vitro, and it impairs the sphere formation of glioma stem cells, suggesting its role in tumor progression and stemness [1].

In osteogenesis imperfecta (OI) type VI, SERPINF1 mutations lead to severe progressive deforming OI. For example, in-frame mutations in SERPINF1 affect the intracellular localization and secretion of PEDF, interfering with its normal function [3,5].

In otosclerosis, while some studies find no evidence for a pathogenic role of SERPINF1 variants [4], others identify SERPINF1 variants associated with the disease and reduced SERPINF1 expression in otosclerotic stapes, which might contribute to the pathophysiology [6,7].

In summary, Serpinf1 plays crucial roles in multiple biological processes and disease conditions. Its functions in tumor progression, as seen in glioma, and in bone-related disorders like OI type VI, are well-documented. In otosclerosis, the role of Serpinf1 remains somewhat controversial but emerging evidence suggests its potential involvement. Research on Serpinf1 using loss-of-function models has provided valuable insights into these disease mechanisms.

References:

1. Song, Lairong, Huo, Xulei, Li, Xiaojie, Wang, Liang, Wu, Zhen. 2023. SERPINF1 Mediates Tumor Progression and Stemness in Glioma. In Genes, 14, . doi:10.3390/genes14030580. https://pubmed.ncbi.nlm.nih.gov/36980858/

2. Zhang, Chao, Yang, Wei, Zhang, Shanshan, Li, Mian, Lu, Yanqin. . Pan-cancer analysis of osteogenesis imperfecta causing gene SERPINF1. In Intractable & rare diseases research, 11, 15-24. doi:10.5582/irdr.2021.01138. https://pubmed.ncbi.nlm.nih.gov/35261846/

3. Selina, Agnes, Kandagaddala, Madhavi, Kumar, Vignesh, Danda, Sumita, Madhuri, Vrisha. 2023. SERPINF1 gene variants causing late-onset progressive deforming osteogenesis imperfecta - A study of 18 patients from India. In Bone reports, 18, 101690. doi:10.1016/j.bonr.2023.101690. https://pubmed.ncbi.nlm.nih.gov/37425194/

4. Valgaeren, Hanne, Sommen, Manou, Beyens, Matthias, Fransen, Erik, Van Camp, Guy. 2019. Insufficient evidence for a role of SERPINF1 in otosclerosis. In Molecular genetics and genomics : MGG, 294, 1001-1006. doi:10.1007/s00438-019-01558-8. https://pubmed.ncbi.nlm.nih.gov/30968248/

5. Al-Jallad, Hadil, Palomo, Telma, Roughley, Peter, Moffatt, Pierre, Rauch, Frank. 2015. The effect of SERPINF1 in-frame mutations in osteogenesis imperfecta type VI. In Bone, 76, 115-20. doi:10.1016/j.bone.2015.04.008. https://pubmed.ncbi.nlm.nih.gov/25868797/

6. Singh, Neha, Hansdah, Kirtal, Bouzid, Amal, Masmoudi, Saber, Ramchander, Puppala Venkat. 2023. Genetic variants and altered expression of SERPINF1 confer disease susceptibility in patients with otosclerosis. In Journal of human genetics, 68, 635-642. doi:10.1038/s10038-023-01158-w. https://pubmed.ncbi.nlm.nih.gov/37308566/

7. Ziff, Joanna L, Crompton, Michael, Powell, Harry R F, Saeed, Shakeel R, Dawson, Sally J. 2016. Mutations and altered expression of SERPINF1 in patients with familial otosclerosis. In Human molecular genetics, 25, 2393-2403. doi:. https://pubmed.ncbi.nlm.nih.gov/27056980/