RCCX – Wikipedia

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RCCX is a multiallelic copy number variation human DNA locus on chromosome 6p21.3.[1][2]

The RCCX abbreviation composed of the names of the genes RP (a former name for STK19 serine/threonine kinase 19),[2][3]C4, CYP21 and TNX).[4]

Structure[edit]

The number of RCCX segments varies between one and four in a chromosome,[2] with the prevalence of approximately 15% for monomodular, 75% for bimodular, and 10% for trimodular in Europeans.[5] The quadrimodular structure of the RCCX unit is very rare.[6][2][5]

In a monomodular structure, all of the genes are functional i.e. protein-coding, but if a module count is two or more, there is only one copy of each functional gene rest being non-coding pseudogenes with the exception of the C4 gene which always has active copies.[2][5] Each copy of the C4 gene, due to five adjacent nucleotide substitutions cause four amino acid changes and immunological subfunctionalization,[5] can be of one of two types: C4A and C4B.[7] Each C4 gene contains 41 exons and has a dichotomous size variation between approximately 22 kb and 16 kb, with the longer variant being the result of the integration of the endogenous retrovirus HERV-K(C4) into intron 9.[3]

The RCCX module is the most complex gene cluster in the human genome.[3][7][8] It is part of the major histocompatibility complex class III (MHC class III),[9][10] which is the most gene-dense region of the human genome, containing many genes that yet have unknown function or structure.[11][12][13][14]

References[edit]

  1. ^ Chang SF, Lee HH (2011). “Analysis of the CYP21A2 gene with intergenic recombination and multiple gene deletions in the RCCX module”. Genet Test Mol Biomarkers. 15 (1–2): 35–42. doi:10.1089/gtmb.2010.0080. PMID 21117955.
  2. ^ a b c d e Bánlaki Z, Doleschall M, Rajczy K, Fust G, Szilágyi A (October 2012). “Fine-tuned characterization of RCCX copy number variants and their relationship with extended MHC haplotypes”. Genes Immun. 13 (7): 530–5. doi:10.1038/gene.2012.29. PMID 22785613. S2CID 36582994.
  3. ^ a b c Carrozza C, Foca L, De Paolis E, Concolino P (2021). “Genes and Pseudogenes: Complexity of the RCCX Locus and Disease”. Front Endocrinol (Lausanne). 12: 709758. doi:10.3389/fendo.2021.709758. PMC 8362596. PMID 34394006.
  4. ^ Sweeten TL, Odell DW, Odell JD, Torres AR (January 2008). “C4B null alleles are not associated with genetic polymorphisms in the adjacent gene CYP21A2 in autism”. BMC Medical Genetics. 9: 1. doi:10.1186/1471-2350-9-1. PMC 2265260. PMID 18179706.
  5. ^ a b c d Bánlaki Z, Szabó JA, Szilágyi Á, Patócs A, Prohászka Z, Füst G, Doleschall M (2013). “Intraspecific evolution of human RCCX copy number variation traced by haplotypes of the CYP21A2 gene”. Genome Biol Evol. 5 (1): 98–112. doi:10.1093/gbe/evs121. PMC 3595039. PMID 23241443.
  6. ^ Tsai LP, Lee HH (September 2012). “Analysis of CYP21A1P and the duplicated CYP21A2 genes”. Gene. 506 (1): 261–2. doi:10.1016/j.gene.2012.06.045. PMID 22771554.
  7. ^ a b Doleschall M, Luczay A, Koncz K, Hadzsiev K, Erhardt É, Szilágyi Á, Doleschall Z, Németh K, Török D, Prohászka Z, Gereben B, Fekete G, Gláz E, Igaz P, Korbonits M, Tóth M, Rácz K, Patócs A (June 2017). “A unique haplotype of RCCX copy number variation: from the clinics of congenital adrenal hyperplasia to evolutionary genetics”. Eur J Hum Genet. 25 (6): 702–710. doi:10.1038/ejhg.2017.38. PMC 5477366. PMID 28401898.
  8. ^ Milner CM, Campbell RD (August 2001). “Genetic organization of the human MHC class III region”. Frontiers in Bioscience: A Journal and Virtual Library. 6: D914–26. doi:10.2741/milner. PMID 11487476.
  9. ^ Yu CY (1998). “Molecular genetics of the human MHC complement gene cluster”. Exp Clin Immunogenet. 15 (4): 213–30. doi:10.1159/000019075. PMID 10072631. S2CID 25061446.
  10. ^ Yu CY, Chung EK, Yang Y, Blanchong CA, Jacobsen N, Saxena K, Yang Z, Miller W, Varga L, Fust G (2003). “Dancing with complement C4 and the RP-C4-CYP21-TNX (RCCX) modules of the major histocompatibility complex”. Prog Nucleic Acid Res Mol Biol. Progress in Nucleic Acid Research and Molecular Biology. 75: 217–92. doi:10.1016/s0079-6603(03)75007-7. ISBN 9780125400756. PMID 14604014.
  11. ^ Xie T, Rowen L, Aguado B, Ahearn ME, Madan A, Qin S, Campbell RD, Hood L (December 2003). “Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse”. Genome Research. 13 (12): 2621–36. doi:10.1101/gr.1736803. PMC 403804. PMID 14656967.
  12. ^ Rupert KL, Rennebohm RM, Yu CY (1999). “An unequal crossover between the RCCX modules of the human MHC leading to the presence of a CYP21B gene and a tenascin TNXB/TNXA-RP2 recombinant between C4A and C4B genes in a patient with juvenile rheumatoid arthritis”. Exp Clin Immunogenet. 16 (2): 81–97. doi:10.1159/000019099. PMID 10343159. S2CID 24623016.
  13. ^ Espinosa Reyes TM, Collazo Mesa T, Lantigua Cruz PA, Agramonte Machado A, Domínguez Alonso E, Falhammar H (November 2020). “Molecular diagnosis of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency”. BMC Endocrine Disorders. 20 (1): 165. doi:10.1186/s12902-020-00643-z. PMC 7653887. PMID 33168061.
  14. ^ Lee HH (January 2005). “Chimeric CYP21P/CYP21 and TNXA/TNXB genes in the RCCX module”. Mol Genet Metab. 84 (1): 4–8. doi:10.1016/j.ymgme.2004.09.009. PMID 15639189.