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تسجيل

21- Hydroxylase Gene and Gene Locus

المؤلف:  Wass, J. A. H., Arlt, W., & Semple, R. K. (Eds.).

المصدر:  Oxford Textbook of Endocrinology and Diabetes

الجزء والصفحة:  3rd edition , p932-935

2026-08-12

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The CYP21A2 gene encodes for the microsomal enzyme 21- hydroxylase of 495 amino acids. CYP21A2 is localized in the HLA III region on the short arm of chromosome 6 (6p21.3), approximately 30- kilobases apart from its non- functional CYP21A1P pseudo gene. The CYP21A2 and CYP21A1P genes share a high nucleotide homology, of about 98% and 96% at exon and intron level, and consist of 10 exons. Both genes are arranged in tandem repeat with the C4A and C4B genes encoding the fourth complement factor. The C4/ CYP21A2 unit is flanked by the RP1 (STK19) gene on the telomeric side and by the TNXB gene on the centromeric side, and their truncated pseudogenes, RP2 and TNXA, forming the RCCX module (RP- C4- CYP21- TNX). The highly variable RCCX module spans about 30 kb. Most chromosomes harbour two copies of the modules with a CYP21A1P pseudogene in the telomeric module and a CYP21A2 gene in the centromeric module. However, monomodular, trimodular, or even quadrimodular haplotypes have been described (Figure 1). The reverse DNA strand from the C4 and CYP21A genes encodes for the TNXA and TNXB genes with opposite transcriptional orientation. TNXB is a very large gene consisting of 43 exons and spans 68.2 kb of DNA encoding the extracellular matrix protein, tenascin (TNX). The TNXA pseudo gene was truncated during the duplication of the ancestral RCCX module. The last exon of TNXA and TNXB is located in the 3- prime untranslated region of exon 10 of CYP21A1P and CYP21A2, respectively.

Fig1. Organization of the RCCX module at chromosome 6p21. Representative Copy Number Variants at the RCCX locus (a) non- disease variants; (b) Configurations associated with 21- hydroxylase deficiency. C4A and C4B: complement component C4A and C4B genes; CYP21A1P: steroid 21- hydroxylase pseudogene; CYP21A2: steroid 21- hydroxylase gene; TNXB: tenascin- X gene. TNXA: tenascin- X pseudogene; RP1: serine/ threonine kinase 19 gene (other names: STK19); RP2: serine/ threonine kinase 19 pseudogene (other names: STK19P); intron splice, I2G, c.293- 13A/ C>G.