Glycine Decarboxylase

Alternative Names

  • GLDC
  • Glycine Cleavage System P Protein
  • GCSP
  • Glycine Dehydrogenase

Associated Diseases

Glycine Encephalopathy
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OMIM Number

238300

NCBI Gene ID

2731

Uniprot ID

P23378

Length

113,263 bases

No. of Exons

25

No. of isoforms

1

Protein Name

Glycine dehydrogenase (decarboxylating), mitochondrial

Molecular Mass

112730 Da

Amino Acid Count

120

Genomic Location

chr9:6,532,467-6,645,729

Gene Map Locus
9p24.1

Description

The GLDC gene on chromosome 9p24.1 provides instructions for making an enzyme called Glycine Dehydrogenase. This protein consists of 1,020 amino acids and weighs about 113 kDa. Glycine dehydrogenase enzyme is one of four mitochondrial proteins (P, H, T, and L) that make a large complex called glycine cleavage enzyme that catalyzes the degradation of glycine. Degradation of excess glycine is necessary for the normal development and function of nerve cells in the brain and spinal cord.

Defects in the glycine dehydrogenase enzyme result in building up of excess amounts of glycine in the brain and spinal cord. Glycine build up causes intellectual disability, seizures, and breathing difficulties characteristic of glycine encephalopathy disease.

Molecular Genetics

The GLDC gene consists of 25 coding exons and its length is approximately 113 kb. More than 40 mutations have been identified in this gene in patients with glycine encephalopathy disease. These mutations account for 80% of all cases of the disease. The most common mutations are caused by single amino acid substitutions. Also, insertion, deletion and splice site mutations have been reported to cause the disease. These mutations result in either production of a nonfunctional version of glycine dehydrogenase, or reduce but do not eliminate the enzyme's activity.

Epidemiology in the Arab World

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Variant NameCountryGenomic LocationClinical SignificanceCondition(s)HGVS ExpressionsdbSNPClinvar
NM_000170.3:c.52G>TLebanonchr9:6645448Benign,Likely Benign,Uncertain SignificanceGlycine EncephalopathyNG_016397.1:g.5245G>T; NM_000170.3:c.52G>T; NP_000161.2:p.Gly18Cys535143891367208
NM_000170.3:c.919G>TUnited Arab Emirateschr9:6604729PathogenicGlycine EncephalopathyNG_016397.1:g.45966G>T; NM_000170.3:c.919G>T; NP_000161.2:p.Glu307Ter

Other Reports

Palestine

In eight patients with glycine encephalopathy, Boneh et al. (2005) identified a homozygous T>C transition within the ATG methionine codon in exon 1 of the GLDC gene, resulting in a met1>thr (p.M1T) substitution within the initiation codon. All obligate carriers were heterozygous for the mutation and 122 control alleles did not have the mutation. The parents of patients in five of six families were first cousins. Studies of two patients showed markedly decreased GLDC mRNA levels and absence of enzyme activity. All the patients originated from an isolated population of approximately 5,000 people in a small village near Jerusalem.

In nine affected members of a large consanguineous Bedouin kindred with atypical glycine encephalopathy, Flusser et al. (2005) identified a homozygous 2607C>A transversion in exon 22 of the GLDC gene, resulting in a silent substitution (p.pro869>pro) that affects a splice site. A patient lymphoblast cell line showed abnormal GLDC DNA fragments and significantly reduced mRNA levels, consistent with a pathogenic mutation. An additional unrelated patient had the same mutation.

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