Tapbp, also known as TAP-binding protein or tapasin, is an integral component of the peptide-loading complex. It plays a crucial role in bridging MHC class I molecules to the transporter associated with antigen processing (TAP) in the endoplasmic reticulum, thus facilitating the presentation of peptides on the cell surface. This process is fundamental to the immune system's ability to recognize and respond to pathogens and cancer cells [4,6].

Genetic variations in TAPBP have been associated with multiple diseases. In malaria, two SNPs (rs111686073 and rs59097151) that regulate TAPBP mRNA expression are associated with lower Plasmodium falciparum parasite prevalence and clinical malaria incidence, specifically among individuals with tapasin-dependent HLA-I allotypes [1]. In cervical cancer, the SNP rs1059288 in the 3' UTR of TAPBP is associated with increased cancer susceptibility. The risk G allele increases m6A modification of TAPBP, leading to its overexpression, which promotes cancer cell growth, migration, and drug resistance [2]. Additionally, TAPBP has been identified as one of the proteins with cross-cancer effects, and its circulating levels may be causally associated with certain site-specific cancers [3]. Moreover, TAPBP deficiency in humans causes reduced cell surface expression of MHC-I, leading to an inborn error of immunity with phenotypes similar to TAP deficiencies, such as bronchiectasis and recurrent respiratory tract infections [5]. In chronic rhinosinusitis, the TAPBP polymorphism rs2282851 is associated with an increased risk of the disease [7]. In aspirin-exacerbated respiratory disease, TAPBP polymorphisms may play a role in its development [8]. Higher TAPBP expression is predictive of better progression-free survival in patients with DNA mismatch repair deficiency metastatic colorectal cancer treated with COX inhibitors and anti-PD-1 therapy [9].

In conclusion, Tapbp is essential for the peptide-loading and presentation process of MHC class I molecules, which is critical for immune function. Studies on genetic variations and deficiencies of Tapbp have revealed its associations with various diseases, including malaria, cervical cancer, multiple site-specific cancers, inborn errors of immunity, chronic rhinosinusitis, aspirin-exacerbated respiratory disease, and metastatic colorectal cancer. These findings contribute to our understanding of disease mechanisms and potential biomarker discovery.

References:

1. Walker-Sperling, Victoria, Digitale, Jean C, Viard, Mathias, Feeney, Margaret E, Carrington, Mary. 2022. Genetic variation that determines TAPBP expression levels associates with the course of malaria in an HLA allotype-dependent manner. In Proceedings of the National Academy of Sciences of the United States of America, 119, e2205498119. doi:10.1073/pnas.2205498119. https://pubmed.ncbi.nlm.nih.gov/35858344/

2. Hu, Jing, Wang, Shizhi, Zhang, Xing, Lu, Yiran, Jin, Hua. 2024. A genetic variant in the TAPBP gene enhances cervical cancer susceptibility by increasing m6A modification. In Archives of toxicology, 98, 3425-3438. doi:10.1007/s00204-024-03820-4. https://pubmed.ncbi.nlm.nih.gov/38992170/

3. Sun, Jing, Luo, Jia, Jiang, Fangyuan, Ding, Yuan, Li, Xue. . Exploring the cross-cancer effect of circulating proteins and discovering potential intervention targets for 13 site-specific cancers. In Journal of the National Cancer Institute, 116, 565-573. doi:10.1093/jnci/djad247. https://pubmed.ncbi.nlm.nih.gov/38039160/

4. Teng, Michelle S, Stephens, Richard, Du Pasquier, Louis, Lindquist, Jonathan A, Trowsdale, John. . A human TAPBP (TAPASIN)-related gene, TAPBP-R. In European journal of immunology, 32, 1059-68. doi:. https://pubmed.ncbi.nlm.nih.gov/11920573/

5. Elsayed, Abdulwahab, von Hardenberg, Sandra, Atschekzei, Faranaz, Ringshausen, Felix C, Sogkas, Georgios. 2024. Phenotypic and pathomechanistic overlap between tapasin and TAP deficiencies. In The Journal of allergy and clinical immunology, 154, 1069-1075. doi:10.1016/j.jaci.2024.06.003. https://pubmed.ncbi.nlm.nih.gov/38866210/

6. Landis, Eric D, Palti, Yniv, Dekoning, Jenefer, Phillips, Ruth B, Hansen, John D. 2006. Identification and regulatory analysis of rainbow trout tapasin and tapasin-related genes. In Immunogenetics, 58, 56-69. doi:. https://pubmed.ncbi.nlm.nih.gov/16447046/

7. Alromaih, Saud, Mfuna-Endam, Leandra, Bosse, Yohan, Filali-Mouhim, Abdelali, Desrosiers, Martin. 2013. CD8A gene polymorphisms predict severity factors in chronic rhinosinusitis. In International forum of allergy & rhinology, 3, 605-11. doi:10.1002/alr.21174. https://pubmed.ncbi.nlm.nih.gov/23640800/

8. Cho, Sung-hwan, Park, Jong-Sook, Park, Byung Lae, Shin, Hyoung Doo, Park, Choon-Sik. . Association analysis of tapasin polymorphisms with aspirin-exacerbated respiratory disease in asthmatics. In Pharmacogenetics and genomics, 23, 341-8. doi:10.1097/FPC.0b013e328361d4bb. https://pubmed.ncbi.nlm.nih.gov/23736108/

9. Wu, Zehua, Zhang, Yuanzhe, Cheng, Yi, Zhang, Jianwei, Deng, Yanhong. 2024. PD-1 blockade plus COX inhibitors in dMMR metastatic colorectal cancer: Clinical, genomic, and immunologic analyses from the PCOX trial. In Med (New York, N.Y.), 5, 998-1015.e6. doi:10.1016/j.medj.2024.05.002. https://pubmed.ncbi.nlm.nih.gov/38795703/