ANKRD55, the ankyrin repeat domain-55 gene, contains intronic single nucleotide polymorphisms (SNPs) associated with the risk of multiple sclerosis, rheumatoid arthritis, and other autoimmune disorders [1,2,5-8,10]. Its biological function is yet to be fully elucidated, but as ankyrin repeat domains are common protein-protein interaction platforms, it likely functions in protein complexes [1].

Genetic studies have shown associations between ANKRD55 SNPs and various autoimmune diseases. For example, in Iranian populations, the CA genotype of rs6859219 in ANKRD55 had a protective effect against multiple sclerosis, while the CC genotype was a susceptive genotype [2]. In a Chinese Han population, the A allele of rs7731626 was less frequent in dermatomyositis/polymyositis patients with interstitial lung disease, suggesting a protective role [5]. In the Iranian population, the CC genotype and C allele of rs6859219 increased the risk of rheumatoid arthritis [4]. Additionally, ANKRD55 expression levels are influenced by MS risk SNPs in different cell types, and monocytes gain the capacity to express ANKRD55 during differentiation into immature dendritic cells [3]. Bioinformatic analysis of its interactomes from recombinant overexpression in HEK293 or HeLa cells suggested functions related to nucleotide and ATP binding, nuclear transport, cell cycle, and metabolism [1].

In conclusion, ANKRD55 is associated with autoimmune diseases through its genetic polymorphisms and likely exerts functions in the formation or architecture of multiple protein complexes, regulated by (de)phosphorylation reactions [1]. The associations between ANKRD55 SNPs and autoimmune diseases, along with its potential functions in protein complexes, provide important leads for understanding the pathogenesis of these diseases and for future functional studies.

References:

1. Ugidos, Nerea, Mena, Jorge, Baquero, Sara, Elortza, Felix, Vandenbroeck, Koen. 2019. Interactome of the Autoimmune Risk Protein ANKRD55. In Frontiers in immunology, 10, 2067. doi:10.3389/fimmu.2019.02067. https://pubmed.ncbi.nlm.nih.gov/31620119/

2. Yazdanpanah, Mahboobeh, Jalilian, Nazanin, Abdollah Zadeh, Rasoul, Sahraian, Mohammad Ali, Noori-Daloii, Mohammad Reza. 2021. Investigating the association of polymorphisms of ANKRD55 and MMEL1 with susceptibility to multiple sclerosis in Iranian population. In The International journal of neuroscience, 132, 1037-1042. doi:10.1080/00207454.2020.1860964. https://pubmed.ncbi.nlm.nih.gov/33491520/

3. Mena, Jorge, Alloza, Iraide, Tulloch Navarro, Raquel, Comabella, Manuel, Vandenbroeck, Koen. 2022. Genomic Multiple Sclerosis Risk Variants Modulate the Expression of the ANKRD55-IL6ST Gene Region in Immature Dendritic Cells. In Frontiers in immunology, 12, 816930. doi:10.3389/fimmu.2021.816930. https://pubmed.ncbi.nlm.nih.gov/35111166/

4. Salehi, Rasoul, Motaghi, Mina, Salehi, Amirhossein, Karimzadeh, Hadi, Pakzad, Bahram. . Impact of Single Nucleotide Polymorphism in the ANKRD55 Gene on Occurrence and Clinical Characteristics of Rheumatoid Arthritis. In Avicenna journal of medical biotechnology, 14, 259-263. doi:10.18502/ajmb.v14i3.9833. https://pubmed.ncbi.nlm.nih.gov/36061134/

5. Li, Liubing, Chen, Si, Wen, Xiaoting, Zhang, Fengchun, Li, Yongzhe. 2017. Positive Association between ANKRD55 Polymorphism 7731626 and Dermatomyositis/Polymyositis with Interstitial Lung Disease in Chinese Han Population. In BioMed research international, 2017, 2905987. doi:10.1155/2017/2905987. https://pubmed.ncbi.nlm.nih.gov/28470010/