The DOI matches its Crossref record; 35 of the 37 references it cites were found in a registry or an index.
Structure of human steroid 21-hydroxylase genes.
Open accessAbstract
We have determined the structure of cDNA and two genomic genes encoding steroid 21-hydroxylase [21-OHase; steroid 21-monooxygenase; steroid, hydrogen-donor:oxygen oxidoreductase (21-hydroxylating); EC 1.14.99.10]. If this cytochrome P-450 enzyme is defective, cortisol cannot be synthesized, resulting in congenital adrenal hyperplasia. The cDNA encoding this enzyme is 2.0 kilobases long, and the encoded protein is predicted to contain 494 amino acid residues with a molecular weight of 55,000. This enzyme is at most 28% homologous to other P-450 enzymes that have been studied. The 21-OHase genomic genes, which are located in the HLA major histocompatibility complex on chromosome 6, each contain 10 exons. This structure is distinct from other characterized P-450 genes, which contain 7 or 9 exons. Studies of individuals with homozygous deletions of the 21-OHase A or B genes suggest that only the B gene encodes an active enzyme. This is confirmed by the finding that the A gene has an 8-base deletion within codons 110-112, resulting in a frameshift that brings a stop codon into the reading frame at codon 130. A second frameshift and a nonsense mutation occur downstream. In contrast, the sequence of the exons of the B gene is identical to the cDNA sequence. The 21-OHase A gene is, therefore, a pseudogene.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is one of the most technically challenging monogenic conditions for molecular diagnosis, owing to the complex genomic architecture of the CYP21A2 locus and the extensive homology between the functional gene and its pseudogene.”
From Evolution of molecular diagnostic strategies for 21-hydroxylase deficiency: from classical methods to advanced genomic techniques (2026) · cites this paper as [9]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The functional gene CYP21A2, located adjacent to C4B, extends over approximately 3.4 kb and encodes a cytochrome P450 enzyme comprising 495 amino acids, whereas CYP21A1P, located adjacent to C4A, is a pseudogene containing multiple inactivating pathogenic variants that preclude proper protein expression (9, 10) (Figure 1).”
From Evolution of molecular diagnostic strategies for 21-hydroxylase deficiency: from classical methods to advanced genomic techniques (2026) · cites this paper as [9]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“CYP21A1P is transcribed but its mRNA cannot encode a functional protein owing to at least 10 deleterious mutations (143,144) including two frameshifts (8 bp deletion in exon 3, 1 bp insertion in exon 7, a nonsense mutation (p.Gln318stop; Q318X) (152), and a mutation in intron 2 that activates a cryptic splice site and causes an extra 19 nucleotides to be included in the mRNA (153).”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [143]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The most important CYP21A2 transcript begins 10-11 nucleotides before the initial AUG codon (143).”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [143]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“However, characterization of the P450c21 protein (355) and gene cloning show there is only one 21-hydroxylase encoded by a single functional gene on chromosome 6p21 (356 -359).”
From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [358]
Experimental — accuracy not yet measured
The cited source says what the claim attributes to it.
In the citing paper
“Both genes contain 10 exons and share remarkably high sequence identity, approximately 98% identity in exons and 96% in introns (9, 10).”
From Evolution of molecular diagnostic strategies for 21-hydroxylase deficiency: from classical methods to advanced genomic techniques (2026) · cites this paper as [9]
The cited source says what the claim attributes to it.
In the citing paper
“CYP21A2 and CYP21A1P both consist of 10 exons and share high nucleotide homology of about 98% and 96% in exons and introns respectively (143,144).”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [143]
The cited source says what the claim attributes to it.
In the citing paper
“The CYP21 genes consist of 10 exons (373), are about 3.4 kb long, and differ in only 87 or 88 of these bases (357-359).”
From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [358]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
DNA sequencing with chain-terminating inhibitors
Sanger, F., Nicklen, S., & Coulson, A. R. (1977) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.74.12.5463 · Cited by 68,572
Rigby, P. W. J., Dieckmann, M., Rhodes, C., & Berg, P. R. (1977) · Journal of Molecular Biology · doi:10.1016/0022-2836(77)90052-3 · Cited by 11,400
[2] New M13 vectors for cloning
Messing, J. W. (1983) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(83)01005-8 · Cited by 5,240
Colony hybridization: a method for the isolation of cloned DNAs that contain a specific gene.
Grunstein, M. R., & Hogness, D. S. (1975) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.72.10.3961 · Cited by 3,386
A rapid boiling method for the preparation of bacterial plasmids
Holmes, D. S., & Quigley, M. E. (1981) · Analytical Biochemistry · doi:10.1016/0003-2697(81)90473-5 · Cited by 3,198
The Metabolic Basis of Inherited Disease.
(1983) · Annals of Internal Medicine · doi:10.7326/0003-4819-99-3-425_3 · Cited by 2,693
Buffer gradient gels and 35S label as an aid to rapid DNA sequence determination.
Biggin, M. D., Gibson, T. J., & Hong, G. F. (1983) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.80.13.3963 · Cited by 2,320
Atlas of Protein Sequence and Structure, 1966.
Hersh, R. T., Eck, R. V., & Dayhoff, M. O. (1967) · Systematic Zoology · doi:10.2307/2412074 · Cited by 1,798
Preparative and analytical purification of DNA from agarose.
Vogelstein, B., & Gillespie, D. A. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.2.615 · Cited by 1,555
Prolonged incubation in calcium chloride improves the competence of Escherichia coli cells
Dagert, M., & Ehrlich, S. D. (1979) · Gene · doi:10.1016/0378-1119(79)90082-9 · Cited by 1,417
Research works printed but not linked: 20
- [3]3. Stanbury, J. B., Wyngaarden, J. B., Fredrickson, D. S., Goldstein, J. L. & Brown, M. S. (McGraw-Hill, New York), pp. 973-1000.
- [6]6. White, P. C., New, M. I. & Dupont, B. (1984) Proc. Natl. Acad. Sci. USA 81, 7505-7509.
- [7]7. White, P. C., Grossberger, D., Onufer, B. J., Chaplin, D. D., New, M. I., Dupont, B. & Strominger, J. L. (1985) Proc. Natl. Acad. Sci. USA 82, 1089-1093.
- [12]12. Grunstein, M. & Hogness, D. (1975) Proc. Natl. Acad. Sci. USA 72, 3961-3965.
- [13]13. White, P. C., New, M. I. & Dupont, B. (1984) Proc. Natl. Acad. Sci. USA 81, 1986-1990.
- [14]14. Vogelstein, B. & Gillespie, D. (1979) Proc. Natl. Acad. Sci. USA 76, 615-619.
- [20]20. Sanger, F., Nicklen, S. & Coulson, A. R. (1977) Proc. Natl. Acad. Sci. USA 74, 5463-5467.
- [21]21. Biggin, M. D., Gibson, T. J. & Hong, G. F. (1983) Proc. Natl. Acad. Sci. USA 80, 3963-3965.
- [24]24. Lewin, B. (1980) Gene Expression 2 (Wiley, New York), pp. 761-864.
- [26]26. Lipman, D. J. & Pearson, W. R. (1985) Science 228, 80-83.
- [27]27. Mizukami, Y., Sogawa, K., Suwa, Y., Muramatsu, M. & Fujii-Kuriyama, Y. (1983) Proc. Natl. Acad. Sci. USA 80, 3958-3962.
- [28]28. Sogawa, K., Gotoh, O., Kawajiri, K. & Fujii-Kuriyama, Y. (1984) Proc. Natl. Acad. Sci. USA 81, 5066-5070.
- [30]30. Dayhoff, M. 0. (National Biomedical Research Foundation, Washington, DC) Vol. 5, Suppl. 3, pp. 9-10.
- [31]31. Morohashi, K., Fujii-Kuriyama, Y., Okada, Y., Sogawa, K., Hirose, T., Inayama, S. & Omura, T. (1984) Proc. Natl. Acad. Sci. USA 81, 4647-4651.
- [33]33. Conner, B. J., Reyes, A. A., Morin, C., Itakura, K., Teplitz, R. L. & Wallace, R. B. (1983) Proc. Natl. Acad. Sci. USA 80, 278-282.
- [35]35. John, M. E., Okamura, T., Dee, A., Adler, B., John, M. C., White, P. C., Simpson, E. R. & Waterman, M. R. (1986) Biochemistry, in press.
- [36]36. Carroll, M. C., Campbell, R. D. & Porter, R. R. (1985) Proc. Natl. Acad. Sci. USA 82, 521-525.
- [38]38. Parker, K. L., Chaplin, D. D., Wong, M., Seidman, J. G., Smith, J. A. & Schimmer, B. P. (1985) Proc. Natl. Acad. Sci. USA 82, 7860-7864.
- [39]39. Werkmeister, J. M., New, M. I., Dupont, B. & White, P. C. (1986) Am. J. Hum. Genet., in press.
- [40]40. Higashi, Y., Yoshioka, H., Yamane, M., Gotoh, 0. & Fujii- Kuriyama, Y. (1986) Proc. Natl. Acad. Sci. USA 83, 2841-2845.
Cited by
Sorted by citations
The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders
Miller, W. L., & Auchus, R. J. (2011) · Endocrine Reviews · doi:10.1210/er.2010-0013 · Cited by 2,458
Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones
Payne, A. H., & Hales, D. B. (2004) · Endocrine Reviews · doi:10.1210/er.2003-0030 · Cited by 1,766
Nelson, D. R., Kamataki, T., Waxman, D. J., Guengerich, F. P., Estabrook, R. W., Feyereisen, R., Gonzalez, F. J., Coon, M. J., GUNSALUS, I. C., Gotoh, O., et al. (1993) · DNA and Cell Biology · doi:10.1089/dna.1993.12.1 · Cited by 1,647
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency*
White, P. C., & Speiser, P. W. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.3.0398 · Cited by 1,432
Self-citationMolecular biology of steroid hormone synthesis
MILLER, W. L. (1988) · Endocrine Reviews · doi:10.1210/edrv-9-3-295 · Cited by 1,397
Metadata
- Authors
- White, P. C., New, M. I., & Dupont, B.
- Affiliations
- Cornell University (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1986-07
- Volume
- 83
- Issue
- 14
- Pages
- 5111-5115
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC323900
- OpenAlex
- W1964331183
- Semantic Scholar
- ccd3407f0482a5416b4a637b0f55e07a9dd01000
- Cited by
- 569
- References
- 37
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 12 · 2023: 12 · 2022: 8 · 2021: 15 · 2020: 5 · 2019: 6 · 2018: 7 · 2017: 6 · 2016: 8 · 2015: 8 · 2014: 8 · 2013: 16 · 2012: 12
- FWCI
- 9.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA 22507, CA08478)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 00072)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Keywords
- 21-hydroxylase, CYP21, cytochrome P450, congenital adrenal hyperplasia, cDNA structure, exon-intron organization, HLA complex, chromosome 6, pseudogenes, frameshift mutation, nonsense mutation, cortisol production, gene homology
- MeSH terms
- Amino Acid Sequence, Base Sequence, Cytochrome P-450 Enzyme System, DNA, Genes, Humans, Molecular Weight, Sequence Homology, Nucleic Acid, Steroid Hydroxylases, Steroid 21-Hydroxylase
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
