Abstract
Nonketotic hyperglycinemia (NKH) is an inborn error of metabolism caused by deficiency in the glycine cleavage system (GCS); this system consists of four individual constituents, P-, T-, H-, and L-proteins. Several mutations have been identified in P- and T-protein genes, but not in the H-protein gene (GCSH), despite the presence of case reports of H-protein deficiency. To facilitate the mutational and functional analyses of GCSH, we isolated and characterized a human p1-derived artificial chromosome (PAC) clone encoding GCSH. GCSH spanned 13.5 kb and consisted of five exons. Using the PAC clone as a probe, we mapped GCSH to chromosome 16q24 by fluorescence in situ hybridization. The transcription initiation site was determined by the oligonucleotide-cap method, and potential binding sites for several transcriptional factors were found in the 5′ upstream region. Direct sequencing analysis revealed five single-nucleotide polymorphisms. The expression profiles of P-, T-, and H-protein mRNAs were studied by dot-blot analysis, using total RNA from various human tissues. GCSH was expressed in all 29 tissues examined, while T-protein mRNA was detected in 27 of the 29 tissues. In contrast, the P-protein gene was expressed in a limited number of tissues, such as liver, kidney, brain, pituitary gland, and thyroid gland, suggesting distinct transcriptional regulation of each GCS constituent.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Additional information
Received: February 28, 2001 / Accepted: April 2, 2001
Rights and permissions
About this article
Cite this article
Kure, S., Kojima, K., Kudo, T. et al. Chromosomal localization, structure, single-nucleotide polymorphisms, and expression of the human H-protein gene of the glycine cleavage system (GCSH), a candidate gene for nonketotic hyperglycinemia. J Hum Genet 46, 378–384 (2001). https://doi.org/10.1007/s100380170057
Issue Date:
DOI: https://doi.org/10.1007/s100380170057
This article is cited by
-
Metabolite-based mutualism enhances hydrogen production in a two-species microbial consortium
Communications Biology (2019)
-
GCSH antisense regulation determines breast cancer cells’ viability
Scientific Reports (2018)