GLDC

Chr 9AR

glycine decarboxylase

Also known as: GCE, GCE1, GCSP, HYGN1

NCBI Gene: 2731 ENSG00000178445 UniProt: P23378 OMIM: 238300

The P protein (GLDC) is a pyridoxal phosphate-dependent glycine decarboxylase that binds glycine and transfers its methylamine group to the H protein as part of the four-component mitochondrial glycine cleavage system that degrades glycine. Mutations cause glycine encephalopathy (nonketotic hyperglycinemia), a severe neurometabolic disorder with autosomal recessive inheritance. The gene shows very low constraint against loss-of-function variants, consistent with the recessive inheritance pattern of this devastating early-onset encephalopathy.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

Degradation of glycine is brought about by the glycine cleavage system, which is composed of four mitochondrial protein components: P protein (a pyridoxal phosphate-dependent glycine decarboxylase), H protein (a lipoic acid-containing protein), T protein (a tetrahydrofolate-requiring enzyme), and L protein (a lipoamide dehydrogenase). The protein encoded by this gene is the P protein, which binds to glycine and enables the methylamine group from glycine to be transferred to the T protein. Defects in this gene are a cause of nonketotic hyperglycinemia (NKH).[provided by RefSeq, Jan 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Glycine encephalopathy1MIM #605899

UniProtNon-ketotic hyperglycinemia

Clinical highlights

Gene-disease validity (ClinGen)

glycine encephalopathy · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.11

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — GLDC