CYP21A2 Antibodies

Background

The CYP21A2 gene is located on the short arm of human chromosome 6 and is a member of the cytochrome P450 superfamily, mainly expressed in the adrenal cortex. This gene encodes 21-hydroxylase, an enzyme that plays a key catalytic role in the synthesis pathways of cortisol and aldosterone, maintaining the balance of adrenal steroid metabolism by mediating the conversion of 17-hydroxyprogesterone to 11-deoxycortisol. Because this gene is adjacent to the highly homologous pseudogene CYP21A1P, it is prone to gene conversion events, making it the most common pathogenic gene for the autosomal recessive genetic disorder - congenital adrenal hyperplasia (CAH). Since its cDNA was first cloned in 1984, research on the correlation between the gene mutation spectrum and clinical manifestations has been continuously deepened. This not only promotes the development of neonatal genetic screening and prenatal diagnosis technologies, but also facilitates the optimization of individualized glucocorticoid replacement therapy regimens, providing an important paradigm for the study of single-gene endocrine and metabolic diseases.

Structure Function Application Advantage Our Products

Structure of CYP21A2

The protein encoded by the CYP21A2 gene is cytochrome P450 family 21 subfamily A member 2, commonly known as 21-hydroxylase, with a molecular weight of approximately 52-55 kDa. The slight difference in molecular weight mainly results from protein truncation or expression loss caused by gene mutations rather than species differences, which is related to the high conservation of this gene in humans.

Species	Human	Mouse	Bovine
Gene location	6p21.33	17 B1	23q24
Main functional differences	Key enzyme in the synthesis of adrenal cortisol and aldosterone	Homologous genes are mainly responsible for corticosterone metabolism	Function and human highly homologous, participate in glucocorticoid synthesis
Related diseases	Congenital adrenal hyperplasia (CAH)	Gene knockout modeling is required	Naturally occurring CAH has not been reported

This enzyme is composed of 494 amino acids and presents a typical cytochrome P450 protein folding pattern. The core of its three-dimensional structure is a heme covalent group, which is covalently linked to the protein skeleton through a cysteine residue (Cys428) to form a catalytic active center. The substrate binding channels of 21-hydroxylase are mainly composed of secondary structural elements such as B'-C rings, F-G rings and β4 sheets. The amino acid residues in these regions jointly determine its specific recognition and binding to steroid substrates such as progesterone and 17-hydroxyprogesterone. Multiple conserved residues near the active site (such as Arg101, Asp293, Ser106, etc.) interact with steroid substrates through hydrogen bond networks, precisely localizing their C21 atoms to achieve hydroxylation reactions.

Fig. 1:Structural model of CYP21A2. Fig. 1 Structural model of CYP21A2.¹

Key structural properties of CYP21A2:

Typical P450 protein folding architecture
Hydrophobic channels guide steroid substrates to the active center
Heme iron centers catalyze the C21 hydroxylation reaction
The substrate recognition area and hemoglobin area adjacent to the catalytic specificity

Functions of CYP21A2

The core function of the CYP21A2 gene-encoded protein (21-hydroxylase) is to catalyze the synthesis of adrenal steroid hormones. Its specific functional system is as follows:

Function	Description
Synthesis of glucocorticoids	Catalyze the conversion of 17-hydroxyprogesterone to 11-deoxycortisol, which is the rate-limiting step in the cortisol synthesis pathway and is crucial for stress responses and metabolic regulation.
Synthesis of mineralocorticoids	Mediates the conversion of progesterone to 11-deoxycorticosterone, which in turn generates aldosterone, directly participating in the regulation of electrolyte balance and blood pressure in the body.
Pathological basis of CAH	The loss of this enzyme activity (in more than 90% of cases) leads to the diversion of precursor substances to the androgen pathway, causing the typical clinical manifestations of congenital adrenal hyperplasia.
Hormonal spectrum imbalance	Partial impairment of enzyme function can lead to the specific accumulation of intermediate products such as 17-hydroxyprogesterone. This unique hormone profile is the basis of neonatal screening and biochemical diagnosis.
Clinical phenotypic association	Residual enzyme activity (typically 0-50%) corresponds precisely to disease severity and forms the molecular basis for genotypic-phenotypic association studies and individualized therapy.

The catalytic efficiency of this enzyme is determined by its coupling degree with cytochrome P450 oxidoreductase. This unique dual-enzyme system working mechanism explains why the determination of its enzyme activity must be carried out in a mitochondrial environment and also constitutes a classic model for the study of steroid hormone synthesis disorders.

Applications of CYP21A2 and CYP21A2 Antibody in Literature

1. Chi, Dung V., et al. "Novel variants of CYP21A2 in Vietnamese patients with congenital adrenal hyperplasia." Molecular Genetics & Genomic Medicine 7.5 (2019): e623. https://doi.org/10.1002/mgg3.623

This study focused on the CYP21A2 gene in 212 Vietnamese patients with congenital adrenal hyperplasia. 97.5% of pathogenic alleles were successfully detected, common genotypes such as I2g and large fragment deletions were identified, and six new pathogenic variations were discovered, deepening the understanding of genotype-phenotype associations.

2. Berry, Vanita, et al. "Pathogenic variants in the CYP21A2 gene cause isolated autosomal dominant congenital posterior polar cataracts." Ophthalmic Genetics 43.2 (2022): 218-223. https://doi.org/10.1080/13816810.2021.1998556

This study first discovered that variations in the CYP21A2 gene can lead to autosomal dominant congenital cataract. Pathogenic variants such as p.Q319* and P.257T were identified in four families and sporadic cases, expanding the pathogenic lineage of this gene (known to cause adrenal cortical hyperplasia) and suggesting that it may play an important role in the eye lens.

3. Prado, Mayara J., et al. "Characterization of mutations causing CYP21A2 deficiency in Brazilian and Portuguese populations." International Journal of Molecular Sciences 23.1 (2021): 296. https://doi.org/10.3390/ijms23010296

This study, through computational analysis and functional experiments, revealed the pathogenic mechanisms of six novel variations of the CYP21A2 gene (such as p.W202R and p.P35L). These variations, by damaging protein structure or reducing enzyme activity, respectively lead to the simple masculinization type or atypical phenotype of 21-hydroxylase deficiency, providing a basis for clinical diagnosis and management.

4. Prado, Mayara J., et al. "Variant predictions in congenital adrenal hyperplasia caused by mutations in CYP21A2." Frontiers in Pharmacology 13 (2022): 931089. https://doi.org/10.3389/fphar.2022.931089

This study evaluated the pathogenicity predictive efficacy of 13 computational tools for missense variations in the CYP21A2 gene. The results show that four tools, including CADD and ConSurf, have the best performance, with high accuracy in predicting variations that cause severe phenotypes, but low consistency in predicting variations that cause mild phenotypes, providing a reference for the classification of unknown variations in the future.

5. Maher, Jacqueline Yano, Veronica Gomez-Lobo, and Deborah P. Merke. "The management of congenital adrenal hyperplasia during preconception, pregnancy, and postpartum." Reviews in Endocrine and Metabolic Disorders 24.1 (2023): 71-83. https://doi.org/10.1007/s11154-022-09770-5

The article indicates that 21-hydroxylase deficiency is caused by mutations in the CYP21A2 gene and is an autosomal recessive inheritance. Female patients need individualized contraceptive or fertility assistance plans. Before pregnancy, glucocorticoid treatment should be optimized and genetic counseling should be received. During pregnancy, it is necessary to monitor maternal and fetal complications, adjust hormone doses in a timely manner, and the risk of fetal diseases can be evaluated through prenatal diagnosis.

Creative Biolabs: CYP21A2 Antibodies for Research

Creative Biolabs specializes in the production of high-quality CYP21A2 antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

Custom CYP21A2 Antibody Development: Tailor-made solutions to meet specific research requirements.
Bulk Production: Large-scale antibody manufacturing for industry partners.
Technical Support: Expert consultation for protocol optimization and troubleshooting.
Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our CYP21A2 antibodies, custom preparations, or technical support, contact us at email.

Reference

Prado, Mayara J., et al. "Characterization of mutations causing CYP21A2 deficiency in Brazilian and Portuguese populations." International Journal of Molecular Sciences 23.1 (2021): 296. https://doi.org/10.3390/ijms23010296