Alternative titles; symbols
HGNC Approved Gene Symbol: TBXAS1
Cytogenetic location: 7q34 Genomic coordinates (GRCh38): 7:139,778,242-140,020,293 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 7q34 | Ghosal hematodiaphyseal syndrome | 231095 | Autosomal recessive | 3 |
Thromboxane synthase, a cytochrome P450 enzyme, catalyzes the conversion of the prostaglandin endoperoxide into thromboxane A2, a potent vasoconstrictor and inducer of platelet aggregation (Chase et al., 1993). In concert with prostacyclin, thromboxane A2 plays a pivotal role in the maintenance of hemostasis.
Yokoyama et al. (1991) PCR-amplified a cDNA coding for thromboxane A synthase using primers synthesized according to information on the partial amino acid sequence of the platelet enzyme. The primary structure deduced from the nucleotide sequence of the cDNA contains 533 amino acids with a predicted molecular weight of 60,487. The major mRNA from human platelets was estimated to be approximately 2.2 kb by RNA blot analysis. Miyata et al. (1994) demonstrated that the TBXAS1 gene spans more than 75 kb and consists of 13 exons and 12 introns, of which the splice donor and acceptor sites conformed to the GT/AG rule. The exon-intron boundaries of the TBXAS1 gene were similar to those of the human cytochrome P450 nifedipine oxidase gene (124010) except for introns 9 and 10.
Zhang et al. (1997) showed that exons encoding the 1.9-kb mouse thromboxane synthase mRNA are dispersed over more than 150 kb genomic DNA. The mouse gene is encoded by 13 exons ranging in size from 53 to 315 bp.
Baek et al. (1996) determined that the TBXAS1 gene, which they called TS, contains 13 exons spanning more than 150 kb. Different alleles of the ninth intron contained 13 to 20 polymorphic CA repeats. Based on Southern blot analysis, the authors reported that TBXAS1 appears to be a single-copy gene.
Using dual-color fluorescence in situ hybridization (FISH), Chase et al. (1993) localized the TBXAS1 gene to 7q34-q35. By FISH, Miyata et al. (1994) mapped the TBXAS1 gene to 7q33-q34; 7q34 may be the best estimate of the location of the gene.
Using genomic Southern analysis and FISH, Zhang et al. (1997) determined that the mouse Tbxas1 gene is present in single copy, located on chromosome 6 near the midpoint between the centromere and the kappa immunoglobulin gene.
Ghosal hematodiaphyseal dysplasia (GHDD; 231095) is a rare autosomal recessive disorder characterized by increased bone density with predominant diaphyseal involvement and aregenerative corticosteroid-sensitive anemia. Genevieve et al. (2008) identified mutations in the TBXAS1 gene in the 2 families originally reported by Isidor et al. (2007) and in 2 more families of Tunisian and Pakistani origin. The mutations involved residues conserved across species, and 3 of the 4 were located near the heme-binding domain.
In affected members of a consanguineous Algerian family with Ghosal hematodiaphyseal syndrome (GHDD; 231095) originally reported by Isidor et al. (2007), Genevieve et al. (2008) detected homozygosity for a 1463T-C transition in the TBXAS1 gene that resulted in a leu488-to-pro amino acid substitution (L488P).
In affected members of a consanguineous Tunisian family with Ghosal hematodiaphyseal syndrome (GHDD; 231095) originally reported by Isidor et al. (2007), Genevieve et al. (2008) detected homozygosity for a 248T-C transition in the TBXAS1 gene that resulted in a leu83-to-pro amino acid substitution (L83P).
In affected members of a consanguineous Tunisian family with Ghosal hematodiaphyseal syndrome (GHDD; 231095), Genevieve et al. (2008) detected homozygosity for a 1444G-T transversion in the TBXAS1 gene that resulted in a gly482-to-trp amino acid substitution (G482W).
In affected members of a consanguineous Pakistani family with Ghosal hematodiaphyseal syndrome (GHDD; 231095), Genevieve et al. (2008) detected homozygosity for a 1238G-A transition in the TBXAS1 gene that resulted in an arg413-to-glu amino acid substitution (R413E).
Baek, S. J., Lee, K.-D., Shen, R.-F. Genomic structure and polymorphism of the human thromboxane synthase-encoding gene. Gene 173: 251-256, 1996. [PubMed: 8964509] [Full Text: https://doi.org/10.1016/0378-1119(95)00881-0]
Chase, M. B., Baek, S. J., Purtell, D. C., Schwartz, S., Shen, R.-F. Mapping of the human thromboxane synthase gene (TBXAS1) to chromosome 7q34-q35 by two-color fluorescence in situ hybridization. Genomics 16: 771-773, 1993. [PubMed: 8325653] [Full Text: https://doi.org/10.1006/geno.1993.1264]
Genevieve, D., Proulle, V., Isidor, B., Bellais, S., Serre, V., Djouadi, F., Picard, C., Vignon-Savoye, C., Bader-Meunier, B., Blanche, S., de Vernejoul, M.-C., Legeai-Mallet, L., Fischer, A.-M., Le Merrer, M., Dreyfus, M., Gaussem, P., Munnich, A., Cormier-Daire, V. Thromboxane synthase mutations in an increased bone density disorder (Ghosal syndrome). Nature Genet. 40: 284-286, 2008. [PubMed: 18264100] [Full Text: https://doi.org/10.1038/ng.2007.66]
Isidor, B., Dagoneau, N., Huber, C., Genevieve, D., Bader-Meunier, B., Blanche, S., Picard, C., De Vernejoul, M. C., Munnich, A., Le Merrer, M., Cormier-Daire, V. A gene responsible for Ghosal hemato-diaphyseal dysplasia maps to chromosome 7q33-34. Hum. Genet. 121: 269-273, 2007. [PubMed: 17203301] [Full Text: https://doi.org/10.1007/s00439-006-0311-1]
Miyata, A., Yokoyama, C., Ihara, H., Bandoh, S., Takeda, O., Takahashi, E., Tanabe, T. Characterization of the human gene (TBXAS1) encoding thromboxane synthase. Europ. J. Biochem. 224: 273-279, 1994. [PubMed: 7925341] [Full Text: https://doi.org/10.1111/j.1432-1033.1994.00273.x]
Yokoyama, C., Miyata, A., Ihara, H., Ullrich, V., Tanabe, T. Molecular cloning of human platelet thromboxane A synthase. Biochem. Biophys. Res. Commun. 178: 1479-1484, 1991. [PubMed: 1714723] [Full Text: https://doi.org/10.1016/0006-291x(91)91060-p]
Zhang, L., Xiao, H., Schultz, R. A., Shen, R.-F. Genomic organization, chromosomal localization, and expression of the murine thromboxane synthase gene (Tbxas1). Genomics 45: 519-528, 1997. [PubMed: 9367676] [Full Text: https://doi.org/10.1006/geno.1997.4982]