| *238330 | ||||||||||||||||||||||||
| GLYCINE CLEAVAGE SYSTEM H PROTEIN; GCSH | ||||||||||||||||||||||||
| HGNC Approved Gene Symbol: GCSH | ||||||||||||||||||||||||
| Cytogenetic location: 16q23.2 Genomic coordinates (GRCh37): 16:81,115,551 - 81,129,979 (from NCBI) | ||||||||||||||||||||||||
| Gene Phenotype Relationships | ||||||||||||||||||||||||
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| TEXT | ||||||||||||||||||||||||
| Description | ||||||||||||||||||||||||
| The enzyme system for cleavage of glycine (glycine cleavage system; EC 2.1.2.10), which is confined to the mitochondria, is composed of 4 protein components: P protein (a pyridoxal phosphate-dependent glycine decarboxylase; 238300), H protein (a lipoic acid-containing protein), T protein (a tetrahydrofolate-requiring enzyme; 238310), and L protein (a lipoamide dehydrogenase; 238331). Glycine encephalopathy (GCE; 605899), also called nonketotic hyperglycinemia (NKH), may be due to a defect in the H, P, or T proteins. | ||||||||||||||||||||||||
| Cloning | ||||||||||||||||||||||||
| Hiraga et al. (1988) cloned a cDNA encoding H protein from a human liver cDNA library. Koyata and Hiraga (1991) isolated a 1,192-bp cDNA that encodes the entire precursor of human H protein. Fujiwara et al. (1991) isolated a full-length GCSH cDNA encoding a precursor protein of 173 amino acids and a mature protein of 125 amino acids. By dot-blot analysis, Kure et al. (2001) found that GCSH was expressed in all 29 tissues examined. | ||||||||||||||||||||||||
| Gene Structure | ||||||||||||||||||||||||
| Kure et al. (2001) isolated and characterized a human PAC clone encoding GCSH. They found that GCSH spans 13.5 kb and contains 5 exons. | ||||||||||||||||||||||||
| Gene Function | ||||||||||||||||||||||||
| Sakata et al. (2001) reported the structure and expression of the glycine cleavage system in rat central nervous system. | ||||||||||||||||||||||||
| Mapping | ||||||||||||||||||||||||
| By fluorescence in situ hybridization, Kure et al. (2001) mapped the GCSH gene to chromosome 16q24. | ||||||||||||||||||||||||
| Molecular Genetics | ||||||||||||||||||||||||
| Hiraga et al. (1981) found a low activity for both P protein and H protein and a structural abnormality of H protein in the liver and brain of a GCE patient. In addition to atypical nonketotic hyperglycinemia, this patient had progressive degeneration of the central nervous system (Trauner et al., 1981). In the same patient, Koyata and Hiraga (1991) found in Southern analysis using the H protein cDNA probe a deletion of one SacI fragment (238330.0001). The same fragment was deleted in 1 of 7 patients with GCE resulting from deficiency of glycine decarboxylase. By direct sequencing analysis, Kure et al. (2001) identified 5 single-nucleotide polymorphisms in the GCSH gene. Applegarth and Toone (2001) reviewed the laboratory diagnosis of glycine encephalopathy and confirmed 9 mutations in the T protein (238310) and 8 mutations in the P protein. They also reviewed the 7 cases of transient NKH known at that time. | ||||||||||||||||||||||||
| ALLELIC VARIANTS (Selected Examples): | ||||||||||||||||||||||||
| Table View | ||||||||||||||||||||||||
| .0001 GLYCINE ENCEPHALOPATHY | ||||||||||||||||||||||||
| GCSH, COMPLEX REARRANGEMENT | ||||||||||||||||||||||||
| By Southern analysis using the H protein cDNA probe, Koyata and Hiraga (1991) found a deletion of one SacI fragment in a patient with glycine encephalopathy (605899) reported by Hiraga et al. (1981). The same fragment was deleted in 1 of 7 patients with NKH resulting from deficiency of glycine decarboxylase. | ||||||||||||||||||||||||
| REFERENCES | ||||||||||||||||||||||||
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