Fam167a, also known as C8orf13, is a gene that has been linked to multiple biological processes and diseases. It activates the noncanonical NF-κB pathway, and genetic polymorphisms in the Fam167A-BLK region are associated with autoimmune diseases, suggesting its role in immune-related mechanisms [1,2,3,4,5,6,7,8,9,10].

In a study on chronic myeloid leukemia (CML), in vitro and in vivo mouse experiments were carried out. It was found that Fam167A activates the noncanonical NF-κB pathway by binding to desmoglein-1 (DSG1), blocking the ubiquitination of NF-κB-inducing kinase (NIK) and upregulating it. Neutralization of Fam167A in a mouse tumor model reduced noncanonical NF-κB activity and restored cell sensitivity to tyrosine kinase inhibitors (TKIs), revealing its crucial role in BCR-ABL-independent TKI resistance in CML [1].

In conclusion, Fam167a plays a significant role in the noncanonical NF-κB signaling pathway activation. The in vivo mouse model studies have specifically shown its importance in CML, highlighting its potential as a target and biomarker for BCR-ABL-independent TKI resistance in this disease [1].

References:

1. Yang, Taewoo, Sim, Kyu-Young, Ko, Gwang-Hoon, Kim, Hyeoung-Joon, Park, Sung-Gyoo. 2022. FAM167A is a key molecule to induce BCR-ABL-independent TKI resistance in CML via noncanonical NF-κB signaling activation. In Journal of experimental & clinical cancer research : CR, 41, 82. doi:10.1186/s13046-022-02298-1. https://pubmed.ncbi.nlm.nih.gov/35241148/

2. Song, Rong-Hua, Li, Qian, Jia, Xi, Wang, Bin, Zhang, Jin-An. 2018. Polymorphisms of FAM167A-BLK Region Confer Risk of Autoimmune Thyroid Disease. In DNA and cell biology, 37, 932-940. doi:10.1089/dna.2018.4344. https://pubmed.ncbi.nlm.nih.gov/30351170/

3. Zhou, Yingbo, Li, Xiangpei, Wang, Guosheng, Li, Xiaomei. 2016. Association of FAM167A-BLK rs2736340 Polymorphism with Susceptibility to Autoimmune Diseases: A Meta-Analysis. In Immunological investigations, 45, 336-48. doi:10.3109/08820139.2016.1157812. https://pubmed.ncbi.nlm.nih.gov/27105348/

4. Liu, Yun, Ke, Xia, Kang, Hou-Yong, Shen, Yang, Hong, Su-Ling. 2016. Genetic risk of TNFSF4 and FAM167A-BLK polymorphisms in children with asthma and allergic rhinitis in a Han Chinese population. In The Journal of asthma : official journal of the Association for the Care of Asthma, 53, 567-75. doi:10.3109/02770903.2015.1108437. https://pubmed.ncbi.nlm.nih.gov/27088737/

5. Sun, Fei, Li, Ping, Chen, Hua, Li, Yongzhe, Zhang, Fengchun. 2013. Association studies of TNFSF4, TNFAIP3 and FAM167A-BLK polymorphisms with primary Sjogren's syndrome in Han Chinese. In Journal of human genetics, 58, 475-9. doi:10.1038/jhg.2013.26. https://pubmed.ncbi.nlm.nih.gov/23635951/

6. Mentlein, L, Thorlacius, G E, Meneghel, L, Espinosa, A, Wahren-Herlenius, M. 2018. The rheumatic disease-associated FAM167A-BLK locus encodes DIORA-1, a novel disordered protein expressed highly in bronchial epithelium and alveolar macrophages. In Clinical and experimental immunology, 193, 167-177. doi:10.1111/cei.13138. https://pubmed.ncbi.nlm.nih.gov/29663334/

7. Ito, Ikue, Kawaguchi, Yasushi, Kawasaki, Aya, Hara, Masako, Tsuchiya, Naoyuki. . Association of the FAM167A-BLK region with systemic sclerosis. In Arthritis and rheumatism, 62, 890-5. doi:10.1002/art.27303. https://pubmed.ncbi.nlm.nih.gov/20131239/

8. Eleftheriou, D, Levin, M, Shingadia, D, Klein, N J, Brogan, P A. 2013. Management of Kawasaki disease. In Archives of disease in childhood, 99, 74-83. doi:10.1136/archdischild-2012-302841. https://pubmed.ncbi.nlm.nih.gov/24162006/

9. Sun, Fei, Xu, Juanjuan, Wu, Ziyan, Li, Yongzhe, Zhang, Fengchun. 2013. Polymorphisms in the FAM167A-BLK, but not BANK1, are associated with primary Sjögren's syndrome in a Han Chinese population. In Clinical and experimental rheumatology, 31, 704-10. doi:. https://pubmed.ncbi.nlm.nih.gov/23899688/

10. Nordmark, G, Kristjansdottir, G, Theander, E, Jonsson, R, Syvänen, A-C. 2010. Association of EBF1, FAM167A(C8orf13)-BLK and TNFSF4 gene variants with primary Sjögren's syndrome. In Genes and immunity, 12, 100-9. doi:10.1038/gene.2010.44. https://pubmed.ncbi.nlm.nih.gov/20861858/