GLDC

Protein identityUniProt · HPA

UniProt accession

P23378

Gene

GLDC

Ensembl

ENSG00000178445

Chromosome

9

Canonical length

1020 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Mitochondria

Quaternary structure

Homodimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

1020 residues, UniProt reviewed canonical sequence.

>P23378|GLDC
     1  MQSCARAWGL RLGRGVGGGR RLAGGSGPCW APRSRDSSSG GGDSAAAGAS RLLERLLPRH
    61  DDFARRHIGP GDKDQREMLQ TLGLASIDEL IEKTVPANIR LKRPLKMEDP VCENEILATL
   121  HAISSKNQIW RSYIGMGYYN CSVPQTILRN LLENSGWITQ YTPYQPEVSQ GRLESLLNYQ
   181  TMVCDITGLD MANASLLDEG TAAAEALQLC YRHNKRRKFL VDPRCHPQTI AVVQTRAKYT
   241  GVLTELKLPC EMDFSGKDVS GVLFQYPDTE GKVEDFTELV ERAHQSGSLA CCATDLLALC
   301  ILRPPGEFGV DIALGSSQRF GVPLGYGGPH AAFFAVRESL VRMMPGRMVG VTRDATGKEV
   361  YRLALQTREQ HIRRDKATSN ICTAQALLAN MAAMFAIYHG SHGLEHIARR VHNATLILSE
   421  GLKRAGHQLQ HDLFFDTLKI QCGCSVKEVL GRAAQRQINF RLFEDGTLGI SLDETVNEKD
   481  LDDLLWIFGC ESSAELVAES MGEECRGIPG SVFKRTSPFL THQVFNSYHS ETNIVRYMKK
   541  LENKDISLVH SMIPLGSCTM KLNSSSELAP ITWKEFANIH PFVPLDQAQG YQQLFRELEK
   601  DLCELTGYDQ VCFQPNSGAQ GEYAGLATIR AYLNQKGEGH RTVCLIPKSA HGTNPASAHM
   661  AGMKIQPVEV DKYGNIDAVH LKAMVDKHKE NLAAIMITYP STNGVFEENI SDVCDLIHQH
   721  GGQVYLDGAN MNAQVGICRP GDFGSDVSHL NLHKTFCIPH GGGGPGMGPI GVKKHLAPFL
   781  PNHPVISLKR NEDACPVGTV SAAPWGSSSI LPISWAYIKM MGGKGLKQAT ETAILNANYM
   841  AKRLETHYRI LFRGARGYVG HEFILDTRPF KKSANIEAVD VAKRLQDYGF HAPTMSWPVA
   901  GTLMVEPTES EDKAELDRFC DAMISIRQEI ADIEEGRIDP RVNPLKMSPH SLTCVTSSHW
   961  DRPYSREVAA FPLPFVKPEN KFWPTIARID DIYGDQHLVC TCPPMEVYES PFSEQKRASS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GLDC can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.21

Highest tissue expression

173 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GLDC.

Disease | AllUniProt

Conditions GLDC is implicated in, by any mechanism.

• Non-ketotic hyperglycinemia (NKH) MIM:605899

Disease | GeneticClinVar

488 pathogenic / likely-pathogenic of 2,623 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Glycine encephalopathy
• Glycine encephalopathy 1
• GLDC-related disorder
• Inborn genetic diseases
• Generalized epilepsy

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.11

gnomAD pLI

0

gnomAD missense Z

-1.59

DepMap mean gene effect

-0.07

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cellular response to leukemia inhibitory factor
• glycine catabolic process
• glycine decarboxylation via glycine cleavage system
• response to lipoic acid
• response to methylamine

Molecular functions

• electron transfer activity
• glycine binding
• lyase activity
• protein homodimerization activity
• pyridoxal phosphate binding
• glycine dehydrogenase (decarboxylating) activity
• pyridoxal binding

Cellular components

• glycine cleavage complex
• mitochondrial matrix
• mitochondrion
• nucleoplasm
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Pyridoxal phosphate-dependent transferase, major domain
• Pyridoxal phosphate-dependent transferase, small domain
• Pyridoxal phosphate-dependent transferase
• Aromatic amino acid beta-eliminating lyase/threonine aldolase
• Glycine dehydrogenase (decarboxylating)
• Glycine cleavage system P protein
• Glycine cleavage system P-protein, N-terminal domain
• Glycine dehydrogenase, C-terminal domain
• Beta-eliminating lyase
• Glycine cleavage system P-protein
• Glycine dehydrogenase, C-terminal domain

KeywordsUniProt

• Acetylation
• Mitochondrion
• Oxidoreductase
• Pyridoxal phosphate
• Transit peptide

InteractionsUniProt · HPA

Protein binding partners of GLDC in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• GCSH