Alternative titles; symbols
HGNC Approved Gene Symbol: PTGIS
SNOMEDCT: 59621000; ICD10CM: I10; ICD9CM: 401, 401.9;
Cytogenetic location: 20q13.13 Genomic coordinates (GRCh38): 20:49,503,874-49,568,137 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 20q13.13 | Hypertension, essential | 145500 | Multifactorial | 3 |
Prostacyclin (also known as prostaglandin I2) is a potent vasodilator and inhibitor of platelet aggregation. The enzyme prostacyclin synthase (EC 5.3.99.4) catalyzes the isomerization of prostaglandin H2 (PGH2) to prostacyclin. Wang and Chen (1996) noted that although it has absorbance spectral features characteristic of the cytochrome P450s, PGIS has no monooxygenase activity and does not require an external source of electrons to initiate its enzyme reaction. Prostacyclin synthase is the single member of family 8 of the cytochrome P450 superfamily (Nelson et al., 1996).
Miyata et al. (1994) used PCR to clone the cDNA for human PGIS from aortic endothelial cell RNA. They found that the gene encodes a polypeptide of 500 amino acids with sequence homology to cholesterol 7-alpha-monooxygenase, a member of the CYP7 family of cytochrome P450s. Northern blot analysis revealed that PGIS is expressed as a 6-kb transcript which is widely expressed in human tissues. By RNA blot hybridization, Yokoyama et al. (1996) observed an additional, minor 3.3-kb mRNA.
Wang and Chen (1996) isolated and characterized the genomic DNA of the PGIS gene. They found that the gene consists of 10 exons spanning 60 kb. The authors stated that the region surrounding the transcription start site displays many features characteristic of a housekeeping gene promoter.
Yokoyama et al. (1996) demonstrated that all the splice donor and acceptor sites of the PTGIS gene conformed to the GT/AG rule. The major product of the primer extension analysis suggested that the transcription of the gene started from the positions around 49 bp upstream of the translation initiation codon.
Using a panel of human-hamster somatic hybrid DNAs, Wang and Chen (1996) determined that the PGIS gene maps to chromosome 20.
By fluorescence in situ hybridization, Yokoyama et al. (1996) mapped the PTGIS gene to 20q13.11-q13.13.
Chevalier et al. (2001) screened for mutations in the CYP8A1 gene in 130 healthy French Caucasian volunteers. They identified 5 mutations, comprising 2 previously reported silent mutations and 3 novel rare missense mutations (P38L, S118R, and R379S), in the coding sequence of the gene. In the 5-prime proximal region, they also found a variable number of tandem repeats (VNTR) polymorphism. Data confirmed the modulator effect of the VNTR polymorphism on reporter gene transcription.
Nakayama et al. (2002) stated that the PGIS gene is a candidate gene for cardiovascular disease because prostacyclin inhibits platelet aggregation, smooth muscle cell proliferation, and vasoconstriction. They also reported 3 sibs with essential hypertension who had deletion of exon 9 of the PGIS gene (601699.0001).
Nakayama et al. (2002) screened 200 patients with essential hypertension (145500) for mutations in the PGIS gene and found a T-to-C transition at the +2 position of the splice donor site of intron 9 in 1 patient. They found that the splice site mutation produced a truncated protein with a deletion in the heme-binding region, through skipping of exon 9. In the proband's sibship, 2 of 3 other sibs had the mutation and, like the proband, were hypertensive. The 2 sibs had significantly decreased urinary excretion of prostacyclin metabolites.
Chevalier, D., Cauffiez, C., Bernard, C., Lo-Guidice, J.-M., Allorge, D., Fazio, F., Ferrari, N., Libersa, C., Lhermitte, M., D'Halluin, J.-C., Broly, F. Characterization of new mutations in the coding sequence and 5-prime-untranslated region of the human prostacyclin synthase gene (CYP8A1). Hum. Genet. 108: 148-155, 2001. [PubMed: 11281454] [Full Text: https://doi.org/10.1007/s004390000444]
Miyata, A., Hara, S., Yokoyama, C., Inoue, H., Ullrich, V., Tanabe, T. Molecular cloning and expression of human prostacyclin synthase. Biochem. Biophys. Res. Commun. 200: 1728-1734, 1994. [PubMed: 8185632] [Full Text: https://doi.org/10.1006/bbrc.1994.1652]
Nakayama, T., Soma, M., Watanabe, Y., Hasimu, B., Sato, M., Aoi, N., Kosuge, K., Kanmatsuse, K., Kokubun, S., Marrow, J. D., Oates, J. A. Splicing mutation of the prostacyclin synthase gene in a family associated with hypertension. Biochem. Biophys. Res. Commun. 297: 1135-1139, 2002. [PubMed: 12372404] [Full Text: https://doi.org/10.1016/s0006-291x(02)02341-0]
Nelson, D. R., Koymans, L., Kamataki, T., Stegeman, J. J., Feyereisen, R., Waxman, D. J., Waterman, M. R., Gotoh, O., Coon, M. J., Estabrook, R. W., Gunsalus, I. C., Nebert, D. W. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics 6: 1-42, 1996. [PubMed: 8845856] [Full Text: https://doi.org/10.1097/00008571-199602000-00002]
Wang, L.-H., Chen, L. Organization of the gene encoding human prostacyclin synthase. Biochem. Biophys. Res. Commun. 226: 631-637, 1996. [PubMed: 8831668] [Full Text: https://doi.org/10.1006/bbrc.1996.1407]
Yokoyama, C., Yabuki, T., Inoue, H., Tone, Y., Hara, S., Hatae, T., Nagata, M., Takahashi, E.-I., Tanabe, T. Human gene encoding prostacyclin synthase (PTGIS): genomic organization, chromosomal localization, and promoter activity. Genomics 36: 296-304, 1996. [PubMed: 8812456] [Full Text: https://doi.org/10.1006/geno.1996.0465]