The reference OMIM entry for this protein is 122500

Serpin peptidase inhibitor, clade a, member 6; serpina6
Corticosteroid-binding globulin; cbg
Transcortin

CLONING

Hammond et al. (1987) isolated a clone corresponding to the CBG gene from a human liver cDNA library. The deduced 383-residue mature protein has a molecular mass of 42.6 kD and contains 2 cysteine residues and sequences for the attachment of 6 possible N-linked oligosaccharide chains. The mRNA was relatively abundant in the liver and also present in the lung, testis, and kidney. The protein shared no sequence homology with other steroid-binding proteins, but showed remarkable sequence similarity with alpha-1-antitrypsin (AAT; 107400) and other members of the serine protease inhibitor (SERPIN) family.

GENE STRUCTURE

Underhill and Hammond (1989) determined that the CBG gene contains 5 exons distributed over approximately 19 kilobases.

MAPPING

By radioisotopic in situ hybridization, Seralini et al. (1990) localized the CBG gene to chromosome 14q31-q32.1 in the region containing 2 closely related serine protease inhibitors: alpha-1-antitrypsin and alpha-1-antichymotrypsin (AACT; 107280). These 3 genes probably evolved by duplication events. Byth et al. (1994) gave the order of genes in the serpin gene cluster in 14q32.1 as: cen--CBG-PIL (107410)--AAT--PCI (601841)--AACT--tel. Rollini and Fournier (1997) presented a detailed restriction map of a 110-kb region of genomic DNA that includes the AAT, PIL (ATR), and CBG genes, which were found to be in that order from telomere to centromere. All 3 genes are transcribed in a distal-to-proximal orientation. Within the gene cluster, ATR is approximately 12 kb downstream of AAT and CBG is approximately 57 kb downstream of AAT.

MOLECULAR GENETICS

In a 43-year-old woman with CBG deficiency (611489) who was referred for chronic asthenia and hypotension, Emptoz-Bonneton et al. (2000) identified a homozygous substitution in the CBG gene (D367N; 122500.0002), referred to as 'CBG Lyon.' She also had depression and very low serum cortisol concentration. In affected members of a large Italian Australian family with CBG deficiency, Torpy et al. (2001) identified a null mutation in the CBG gene (122500.0003). The D367N polymorphism mutation segregated independently in the same kindred. Among 32 family members there were 3 null homozygotes, 19 null heterozygotes, 2 compound heterozygotes, 3 Lyon heterozygotes, and 5 individuals without CBG mutations. Plasma immunoreactive CBG was undetectable in null homozygotes, and mean CBG levels were reduced by approximately 50% in null heterozygotes. Homozygotes and heterozygote null mutation subjects had a high prevalence of hypotension and fatigue. Among 19 adults with the null mutation, 54% had a systolic blood pressure below the third percentile. Idiopathic chronic fatigue was present in 12 of 14 adult null heterozygote subjects (86%) and in 2 of 3 null homozygotes. Five cases met the Centers for Disease Control criteria for chronic fatigue syndrome. The authors concluded that, as idiopathic fatigue disorders are associated with relatively low plasma cortisol, abnormalities of CBG may be pathogenic. Buss et al. (2007) identified a heterozygous D367N mutation in the SERPINA6 gene in a 22-year-old man with severe muscle disease associated with stress. The authors postulated that in some cases CBG deficiency may act as an autosomal dominant disorder with incomplete penetrance, although a second pathogenic mutation could not be excluded in this case. ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 122500 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).