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. 2001;46(7):378-84. doi: 10.1007/s100380170057.


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 13.5kb 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Oxidoreductases / genetics*
  • Amino Acid Oxidoreductases / metabolism
  • Base Sequence
  • Chromosome Mapping
  • Chromosomes, Human, Pair 16 / genetics
  • Cloning, Molecular
  • Exons
  • Glycine / blood
  • Glycine / metabolism*
  • Humans
  • Hyperglycinemia, Nonketotic / enzymology
  • Hyperglycinemia, Nonketotic / genetics*
  • In Situ Hybridization, Fluorescence
  • Introns
  • Molecular Sequence Data
  • Polymorphism, Single Nucleotide / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism


  • RNA, Messenger
  • Amino Acid Oxidoreductases
  • Glycine