GCSH

Protein identityUniProt · HPA

UniProt accession

P23434

Gene

GCSH

Ensembl

ENSG00000140905

Chromosome

16

Canonical length

173 aa

Protein class

Disease related genes, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins

Subcellular location

Vesicles

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 H protein, which transfers the methylamine group of glycine from the P protein to the T protein. Defects in this gene are a cause of nonketotic hyperglycinemia (NKH). Two transcript variants, one protein-coding and the other probably not protein-coding,have been found for this gene. Also, several transcribed and non-transcribed pseudogenes of this gene exist throughout the genome.[provided by RefSeq, Jan 2010]

Canonical amino-acid sequenceUniProt

173 residues, UniProt reviewed canonical sequence.

>P23434|GCSH
     1  MALRVVRSVR ALLCTLRAVP SPAAPCPPRP WQLGVGAVRT LRTGPALLSV RKFTEKHEWV
    61  TTENGIGTVG ISNFAQEALG DVVYCSLPEV GTKLNKQDEF GALESVKAAS ELYSPLSGEV
   121  TEINEALAEN PGLVNKSCYE DGWLIKMTLS NPSELDELMS EEAYEKYIKS IEE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GCSH 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)

0.42

Highest tissue expression

134 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GCSH.

Disease | AllUniProt

Conditions GCSH is implicated in, by any mechanism.

• Multiple mitochondrial dysfunctions syndrome 7 (MMDS7) MIM:620423

Disease | GeneticClinVar

11 pathogenic / likely-pathogenic of 150 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Multiple mitochondrial dysfunctions syndrome 7
• Glycine encephalopathy
• GCSH-related disorder

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)

1.42

gnomAD pLI

0

gnomAD missense Z

0.09

DepMap mean gene effect

-0.34

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

• glycine decarboxylation via glycine cleavage system

Cellular components

• glycine cleavage complex
• mitochondrial matrix
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Biotin/lipoyl attachment
• 2-oxo acid dehydrogenase, lipoyl-binding site
• Single hybrid motif
• Glycine cleavage system H-protein/Simiate
• Glycine cleavage H-protein
• Glycine cleavage system H-protein
• Glycine cleavage system H-protein, subgroup

KeywordsUniProt

• Lipoyl
• Mitochondrion
• Neurodegeneration
• Transit peptide

InteractionsUniProt · HPA

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

• GLDC