Two genes encoding steroid 21-hydroxylase are located near the genes encoding the fourth component of complement in man

Proc Natl Acad Sci U S A. 1985 Feb;82(4):1089-93. doi: 10.1073/pnas.82.4.1089.


Two genes encoding steroid 21-hydroxylase [21-OHase; steroid 21-monooxygenase; steroid, hydrogen-donor: oxygen oxidoreductase (21-hydroxylating); EC], a cytochrome P-450 enzyme, have been located within the HLA major histocompatibility complex. Congenital adrenal hyperplasia due to 21-OHase deficiency is a common inherited disorder of cortisol biosynthesis which is in genetic linkage disequilibrium with certain extended HLA haplotypes. These haplotypes include characteristic serum complement allotypes. A series of cosmid clones was isolated from a human genomic library by using a probe encoding part of the fourth component of complement, C4. These clones also hybridized with a probe encoding most of human 21-OHase. Restriction mapping and hybridization analysis showed that there are two 21-OHase genes, each located near the 3' end of one of the two C4 genes. Hybridization with probes specific for the 5' and 3' ends of the 21-OHase gene showed that the 21-OHase and C4 genes all have the same orientation. The 21-OHase genes 3' to C4A and C4B carry T aq I fragments of 3.2 and 3.7 kilobases (kb), respectively. Both of these fragments are found in genomic DNA of most individuals. In DNA from an individual with the severe, "salt-wasting" form of 21-OHase deficiency who was homozygous for HLA-A3;Bw47;C4A*1;C4B*Q0(null); DR7, the 3.7-kb Taq I fragment is absent, whereas hormonally normal individuals homozygous for HLA-A1;B8;C4A*Q0;C4B*1;DR3 do not carry the 3.2-kb Taq I fragment. These data suggest that the 21-OHase "B" gene (3.7-kb Taq I fragment) is functional, but the 21-OHase "A" gene (3.2-kb Taq I fragment) is not.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chromosome Deletion
  • Chromosome Mapping
  • Cloning, Molecular
  • Complement C4 / genetics*
  • DNA Restriction Enzymes
  • Gene Amplification
  • Genes
  • HLA Antigens / genetics
  • Humans
  • Nucleic Acid Hybridization
  • Steroid 21-Hydroxylase / genetics*
  • Steroid Hydroxylases / genetics*


  • Complement C4
  • HLA Antigens
  • Steroid Hydroxylases
  • Steroid 21-Hydroxylase
  • DNA Restriction Enzymes