FAM50B is a gene of currently less-defined function, but studies suggest its importance in multiple biological aspects. It has been associated with spermatogenesis, as it was among genes previously known to be associated with infertility in non-obstructive azoospermia patients [1]. Additionally, FAM50B shows a paralogous relationship with FAM50A, and co-disruption of FAM50A/FAM50B impacts cellular fitness in cancer cells [2,4].

In the context of environmental health, a quantitative linear relationship was found between children's intelligence quotients (IQs) and FAM50B DNA methylation, suggesting its potential role in lead-related neurotoxicity [3]. Moreover, abnormal DNA methylation of FAM50B has been linked to defective human spermatozoa, including asthenozoospermia and sperm DNA fragmentation, indicating its significance in male reproductive health [7,8]. In cancer research, FAM50B has emerged as an independent prognostic factor in glioblastoma and colorectal cancer, with its down-regulation inhibiting the proliferation and migration of colorectal cancer cells [9,10]. Also, FAM50B epimutations are associated with multilocus imprinting disturbances [5], and it is an imprinted gene with paternal-allele-specific expression in most tissues, and its deregulation occurs in testicular germ cell tumors [6].

In summary, FAM50B plays crucial roles in spermatogenesis, male infertility, lead-related neurotoxicity, and cancer prognosis. Studies involving its genetic manipulation in model systems, such as the co-disruption of FAM50A/FAM50B in cancer cells, help reveal its functions in these biological processes and disease conditions. The research on FAM50B provides valuable insights into various physiological and pathological mechanisms, which may contribute to the development of diagnostic and therapeutic strategies for related diseases.

References:

1. Malcher, Agnieszka, Stokowy, Tomasz, Berman, Andrea, Yatsenko, Alexander N, Kurpisz, Maciej K. 2022. Whole-genome sequencing identifies new candidate genes for nonobstructive azoospermia. In Andrology, 10, 1605-1624. doi:10.1111/andr.13269. https://pubmed.ncbi.nlm.nih.gov/36017582/

2. Köferle, Anna, Schlattl, Andreas, Hörmann, Alexandra, Mair, Barbara, Neumüller, Ralph A. . Interrogation of cancer gene dependencies reveals paralog interactions of autosome and sex chromosome-encoded genes. In Cell reports, 39, 110636. doi:10.1016/j.celrep.2022.110636. https://pubmed.ncbi.nlm.nih.gov/35417719/

3. Wan, Cong, Ma, Huimin, Liu, Jiahong, Li, Jun, Zhang, Gan. 2023. Quantitative relationships of FAM50B and PTCHD3 methylation with reduced intelligence quotients in school aged children exposed to lead: Evidence from epidemiological and in vitro studies. In The Science of the total environment, 907, 167976. doi:10.1016/j.scitotenv.2023.167976. https://pubmed.ncbi.nlm.nih.gov/37866607/

4. Thompson, Nicola A, Ranzani, Marco, van der Weyden, Louise, Jackson, Stephen P, Adams, David J. 2021. Combinatorial CRISPR screen identifies fitness effects of gene paralogues. In Nature communications, 12, 1302. doi:10.1038/s41467-021-21478-9. https://pubmed.ncbi.nlm.nih.gov/33637726/

5. Bens, Susanne, Kolarova, Julia, Beygo, Jasmin, Ammerpohl, Ole, Siebert, Reiner. 2016. Phenotypic spectrum and extent of DNA methylation defects associated with multilocus imprinting disturbances. In Epigenomics, 8, 801-16. doi:10.2217/epi-2016-0007. https://pubmed.ncbi.nlm.nih.gov/27323310/

6. Zhang, Aiping, Skaar, David A, Li, Yue, Murphy, Susan K, Jirtle, Randy L. 2011. Novel retrotransposed imprinted locus identified at human 6p25. In Nucleic acids research, 39, 5388-400. doi:10.1093/nar/gkr108. https://pubmed.ncbi.nlm.nih.gov/21421564/

7. Xu, J, Zhang, A, Zhang, Z, Xing, Q, Du, J. 2016. DNA methylation levels of imprinted and nonimprinted genes DMRs associated with defective human spermatozoa. In Andrologia, 48, 939-947. doi:10.1111/and.12535. https://pubmed.ncbi.nlm.nih.gov/26804237/

8. Zhu, Weijian, Jiang, Lei, Pan, Chengshuang, Huang, Xuefeng, Ni, Wuhua. 2021. Deoxyribonucleic acid methylation signatures in sperm deoxyribonucleic acid fragmentation. In Fertility and sterility, 116, 1297-1307. doi:10.1016/j.fertnstert.2021.06.025. https://pubmed.ncbi.nlm.nih.gov/34253331/

9. Qiu, Jiting, Wang, Chunhui, Hu, Hongkang, Ding, Xuehua, Cai, Yu. 2020. Transcriptome analysis and prognostic model construction based on splicing profiling in glioblastoma. In Oncology letters, 21, 138. doi:10.3892/ol.2020.12399. https://pubmed.ncbi.nlm.nih.gov/33552257/

10. Ding, Qiuying, Hou, Zhengping, Zhao, Zhibo, Zhao, Lei, Xiang, Yue. 2022. Identification of the prognostic signature based on genomic instability-related alternative splicing in colorectal cancer and its regulatory network. In Frontiers in bioengineering and biotechnology, 10, 841034. doi:10.3389/fbioe.2022.841034. https://pubmed.ncbi.nlm.nih.gov/35923577/