Tmem247-KO Mouse

Tmem247, a transmembrane protein-coding gene, is likely involved in multiple biological processes. While its exact function and associated pathways are not comprehensively detailed in the given references, the study of its genetic variants can provide insights into its role in biological systems [1,2].

In Tibetan highlanders, the top signal of selection was located in TMEM247. The Tibetan version has a high-frequency missense variant, rs116983452 (c.248C > T; p.Ala83Val). The T allele, from archaic ancestry, is present in over 94% of Tibetans but rare in non-Tibetans. This variant is strongly and positively correlated with altitude and significantly associated with reduced hemoglobin concentration, red blood cell count, and hematocrit. It also shows a greater effect size and better predicts adaptive traits in Tibetans compared to EPAS1 variants, with weak but significant epistatic effects when interacting with EPAS1 variants [1]. In Cronkhite-Canada syndrome (CCS) patients, TMEM247 was among 18 genes with potentially function-impacting germline variants found in over half the patients, suggesting a possible role in the pathogenesis of CCS related to innate immune responses and glycosylation [2].

In summary, TMEM247 appears to be involved in altitude-related adaptation in Tibetans, potentially through its impact on blood-related parameters. In addition, it may play a role in the pathogenesis of CCS, specifically in innate immune responses and glycosylation. The study of TMEM247 genetic variants in these contexts provides valuable insights into its biological functions and its association with specific disease-like conditions such as CCS and adaptation-related physiological changes in high-altitude populations.

References:

1. Deng, Lian, Zhang, Chao, Yuan, Kai, Su, Bing, Xu, Shuhua. 2019. Prioritizing natural-selection signals from the deep-sequencing genomic data suggests multi-variant adaptation in Tibetan highlanders. In National science review, 6, 1201-1222. doi:10.1093/nsr/nwz108. https://pubmed.ncbi.nlm.nih.gov/34691999/

2. Liu, Shuang, Zhang, Run Feng, You, Yan, Li, Ji, Qian, Jia Ming. 2022. The genomic landscape of Cronkhite-Canada syndrome: Possible clues for pathogenesis. In Journal of digestive diseases, 23, 288-294. doi:10.1111/1751-2980.13101. https://pubmed.ncbi.nlm.nih.gov/35678525/