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 p... See more...

Aliases for GCSH Gene

Aliases for GCSH Gene

  • Glycine Cleavage System Protein H 2 3 5
  • Lipoic Acid-Containing Protein 2 3 4
  • Glycine Cleavage System Protein H (Aminomethyl Carrier) 2 3
  • Glycine Cleavage System H Protein, Mitochondrial 3 4
  • Mitochondrial Glycine Cleavage System H-Protein 3
  • GCE 3
  • NKH 3

External Ids for GCSH Gene

Previous GeneCards Identifiers for GCSH Gene

  • GC16M072048
  • GC16M082076
  • GC16M080854
  • GC01M165211
  • GC16M080896
  • GC16M079673
  • GC16M081115
  • GC16M066872

Summaries for GCSH Gene

Entrez Gene Summary for GCSH 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]

GeneCards Summary for GCSH Gene

GCSH (Glycine Cleavage System Protein H) is a Protein Coding gene. Diseases associated with GCSH include Glycine Encephalopathy and Atypical Glycine Encephalopathy. Among its related pathways are Carbon metabolism and Glycine, serine and threonine metabolism. Gene Ontology (GO) annotations related to this gene include enzyme binding and aminomethyltransferase activity. An important paralog of this gene is ENSG00000260643.

UniProtKB/Swiss-Prot Summary for GCSH Gene

  • The glycine cleavage system catalyzes the degradation of glycine. The H protein (GCSH) shuttles the methylamine group of glycine from the P protein (GLDC) to the T protein (GCST).

Gene Wiki entry for GCSH Gene

Additional gene information for GCSH Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GCSH Gene

Genomics for GCSH Gene

GeneHancer (GH) Regulatory Elements for GCSH Gene

Promoters and enhancers for GCSH Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH16J081094 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 757.2 +0.4 385 3.3 SP1 RBPJ POLR2A CREB1 MIXL1 NFYC ELF1 RBM39 L3MBTL2 MAX GCSH ENSG00000260643 ENSG00000284512 ATMIN PKD1L2 lnc-C16orf46-1 L13304-015 L13715-012
GH16J081090 Promoter 0.3 EPDnew 750.4 +5.7 5727 0.1 GCSH ATMIN lnc-C16orf46-1 ENSG00000284512 ENSG00000260643 L13304-015 L13715-012
GH16J081087 Promoter 0.3 EPDnew 750.4 +8.8 8752 0.1 lnc-C16orf46-1 GCSH ENSG00000284512 ENSG00000260643 L13304-015 L13715-012
GH16J081082 Promoter 0.3 EPDnew 750.4 +14.1 14054 0.1 GCSH RNU6-1191P L13304-015 L13715-012 lnc-C16orf46-1 ENSG00000260643 ENSG00000284512
GH16J081003 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 7.1 +90.3 90267 5.6 E2F8 GTF3C2 SIN3A ZBTB40 SP1 CTCF SREBF1 SIX5 LCORL SMARCE1 CMC2 CENPN ENSG00000286221 lnc-C16orf46-3 ATMIN ENSG00000260213 GCSH ENSG00000278985
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GCSH on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the GCSH gene promoter:
  • AML1a
  • ATF-2
  • CBF(2)
  • CBF-A
  • CBF-B
  • CBF-C
  • FOXD1
  • MRF-2
  • NF-kappaB1
  • S8

Genomic Locations for GCSH Gene

Genomic Locations for GCSH Gene
chr16:81,081,938-81,096,425
(GRCh38/hg38)
Size:
14,488 bases
Orientation:
Minus strand
chr16:81,115,552-81,130,008
(GRCh37/hg19)
Size:
14,457 bases
Orientation:
Minus strand

Genomic View for GCSH Gene

Genes around GCSH on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GCSH Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GCSH Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GCSH Gene

Proteins for GCSH Gene

  • Protein details for GCSH Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P23434-GCSH_HUMAN
    Recommended name:
    Glycine cleavage system H protein, mitochondrial
    Protein Accession:
    P23434
    Secondary Accessions:
    • Q9H1E9

    Protein attributes for GCSH Gene

    Size:
    173 amino acids
    Molecular mass:
    18885 Da
    Cofactor:
    Name=(R)-lipoate; Xref=ChEBI:CHEBI:83088;
    Quaternary structure:
    • Interacts with GLDC (By similarity). The glycine cleavage system is composed of four proteins: P (GLDC), T (GCST), L (DLD) and H (GCSH).

neXtProt entry for GCSH Gene

Post-translational modifications for GCSH Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for GCSH Gene

Domains & Families for GCSH Gene

Gene Families for GCSH Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Plasma proteins
  • Predicted intracellular proteins
  • Predicted secreted proteins

Suggested Antigen Peptide Sequences for GCSH Gene

GenScript: Design optimal peptide antigens:
  • Glycine cleavage system H protein, mitochondrial (GCSH_HUMAN)
  • cDNA, FLJ92251, Homo sapiens glycine cleavage system protein H (aminomethyl carrier) (GCSH), mRNA (Q53XL7_HUMAN)
  • GCSH protein (Q6IAT2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P23434

UniProtKB/Swiss-Prot:

GCSH_HUMAN :
  • Belongs to the GcvH family.
Family:
  • Belongs to the GcvH family.
genes like me logo Genes that share domains with GCSH: view

Function for GCSH Gene

Molecular function for GCSH Gene

UniProtKB/Swiss-Prot Function:
The glycine cleavage system catalyzes the degradation of glycine. The H protein (GCSH) shuttles the methylamine group of glycine from the P protein (GLDC) to the T protein (GCST).

Phenotypes From GWAS Catalog for GCSH Gene

Gene Ontology (GO) - Molecular Function for GCSH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004047 aminomethyltransferase activity TAS 3348809
GO:0005515 protein binding IPI 16189514
genes like me logo Genes that share ontologies with GCSH: view
genes like me logo Genes that share phenotypes with GCSH: view

Human Phenotype Ontology for GCSH Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

CRISPR Products

miRNA for GCSH Gene

miRTarBase miRNAs that target GCSH

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GCSH

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for GCSH Gene

Localization for GCSH Gene

Subcellular locations from UniProtKB/Swiss-Prot for GCSH Gene

Mitochondrion.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for GCSH gene
Compartment Confidence
mitochondrion 5
extracellular 1
nucleus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for GCSH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion TAS,IEA 3348809
GO:0005759 mitochondrial matrix TAS --
GO:0005960 glycine cleavage complex IEA --
genes like me logo Genes that share ontologies with GCSH: view

Pathways & Interactions for GCSH Gene

genes like me logo Genes that share pathways with GCSH: view

Gene Ontology (GO) - Biological Process for GCSH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006546 glycine catabolic process TAS 1671321
GO:0009249 protein lipoylation IDA 1671321
GO:0019464 glycine decarboxylation via glycine cleavage system IEA --
GO:0032259 methylation IEA --
genes like me logo Genes that share ontologies with GCSH: view

No data available for SIGNOR curated interactions for GCSH Gene

Drugs & Compounds for GCSH Gene

(9) Drugs for GCSH Gene - From: DrugBank and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Glycine Approved, Vet_approved Nutra Full agonist, Agonist, Target 368
Ammonia Approved Pharma 0
Carbon dioxide Approved, Investigational, Vet_approved Pharma 0
Lipoic acid Approved, Investigational Nutra 0
NADH Approved Nutra 0

(2) Additional Compounds for GCSH Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
5,10-Methylene-THF
  • (6R)-5,10-Methylenetetrahydrofolate
  • (6R)-5,10-Methylenetetrahydrofolic acid
  • 5,10-Methenyltetrahydropteroylglutamate
  • 5,10-Methylene-6-hydrofolate
  • 5,10-Methylene-6-hydrofolic acid
31690-11-6
Hydrogen Ion
  • H+
  • H(+)
  • Hydrogen cation
  • Hydron
  • Proton
genes like me logo Genes that share compounds with GCSH: view

Transcripts for GCSH Gene

mRNA/cDNA for GCSH Gene

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GCSH

Alternative Splicing Database (ASD) splice patterns (SP) for GCSH Gene

No ASD Table

Relevant External Links for GCSH Gene

GeneLoc Exon Structure for
GCSH
ECgene alternative splicing isoforms for
GCSH

Expression for GCSH Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for GCSH Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for GCSH Gene

This gene is overexpressed in Liver, secretome (23.9) and Brain (12.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for GCSH Gene



NURSA nuclear receptor signaling pathways regulating expression of GCSH Gene:

GCSH

SOURCE GeneReport for Unigene cluster for GCSH Gene:

Hs.546256

Evidence on tissue expression from TISSUES for GCSH Gene

  • Liver(4.7)
  • Muscle(4.3)
  • Nervous system(2.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for GCSH Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • nervous
  • respiratory
  • skeletal muscle
Regions:
Head and neck:
  • brain
  • epiglottis
  • head
  • neck
Thorax:
  • diaphragm
  • lung
General:
  • spinal cord
genes like me logo Genes that share expression patterns with GCSH: view

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners and mRNA Expression by UniProt/SwissProt for GCSH Gene

Orthologs for GCSH Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for GCSH Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia GCSH 33 32
  • 99.04 (n)
OneToOne
cow
(Bos Taurus)
Mammalia GCSH 33
  • 90 (a)
OneToMany
LOC101905887 32
  • 89.84 (n)
-- 33
  • 87 (a)
OneToMany
-- 33
  • 87 (a)
OneToMany
-- 33
  • 85 (a)
OneToMany
-- 33
  • 80 (a)
OneToMany
-- 33
  • 79 (a)
OneToMany
dog
(Canis familiaris)
Mammalia GCSH 33 32
  • 89.6 (n)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia GCSH 33
  • 87 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Gcsh 32
  • 85.1 (n)
mouse
(Mus musculus)
Mammalia Gcsh 17 33 32
  • 83.73 (n)
chicken
(Gallus gallus)
Aves -- 33
  • 78 (a)
OneToMany
GCSH 33 32
  • 76.89 (n)
OneToMany
lizard
(Anolis carolinensis)
Reptilia GCSH 33
  • 72 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia gcsh 32
  • 70.41 (n)
zebrafish
(Danio rerio)
Actinopterygii gcsha 32
  • 68.4 (n)
gcshb 33
  • 60 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP006548 32
  • 55.77 (n)
fruit fly
(Drosophila melanogaster)
Insecta ppl 33 34 32
  • 55.07 (n)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea F52A8.5 33 34 32
  • 55.88 (n)
OneToMany
gcsh-1 33
  • 41 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes GCV3 35 33 32
  • 51.59 (n)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0A03597g 32
  • 49.46 (n)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_ADR396W 32
  • 46.61 (n)
thale cress
(Arabidopsis thaliana)
eudicotyledons AT2G35120 32
  • 54.89 (n)
rice
(Oryza sativa)
Liliopsida Os02g0170100 32
  • 56.88 (n)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes gcv3 32
  • 55.1 (n)
bread mold
(Neurospora crassa)
Ascomycetes NCU08877 32
  • 47.74 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 33
  • 31 (a)
OneToOne
Species where no ortholog for GCSH was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • oppossum (Monodelphis domestica)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for GCSH Gene

ENSEMBL:
Gene Tree for GCSH (if available)
TreeFam:
Gene Tree for GCSH (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GCSH: view image

Paralogs for GCSH Gene

Variants for GCSH Gene

Sequence variations from dbSNP and Humsavar for GCSH Gene

SNP ID Clin Chr 16 pos Variation AA Info Type
rs1443267686 uncertain-significance, Non-ketotic hyperglycinemia 81,096,202(-) C/A/T coding_sequence_variant, genic_upstream_transcript_variant, missense_variant, non_coding_transcript_variant
rs1555529308 likely-benign, Non-ketotic hyperglycinemia 81,084,598(-) A/G intron_variant
rs1567591606 uncertain-significance, Non-ketotic hyperglycinemia 81,096,262(-) A/C coding_sequence_variant, genic_upstream_transcript_variant, missense_variant, non_coding_transcript_variant
rs202181338 benign, not provided, Non-ketotic hyperglycinemia 81,084,603(-) AAAAAAAA/AAAAAAA/AAAAAAAAA intron_variant
rs386833859 likely-pathogenic, Non-ketotic hyperglycinemia 81,082,964(-) C/A coding_sequence_variant, missense_variant, splice_acceptor_variant

Structural Variations from Database of Genomic Variants (DGV) for GCSH Gene

Variant ID Type Subtype PubMed ID
esv1003113 CNV deletion 20482838
esv1126856 CNV deletion 17803354
esv2127465 CNV deletion 18987734
esv2422360 CNV duplication 17116639
esv2490578 CNV deletion 19546169
esv2714774 CNV deletion 23290073
esv2751615 CNV gain 17911159
esv3553747 CNV deletion 23714750
esv3639309 CNV loss 21293372
esv6143 CNV loss 19470904
nsv1062724 CNV gain 25217958
nsv1067144 CNV loss 25217958
nsv1070359 CNV deletion 25765185
nsv1127517 CNV deletion 24896259
nsv1138468 CNV deletion 24896259
nsv958835 CNV deletion 24416366
nsv978006 CNV duplication 23825009

Variation tolerance for GCSH Gene

Residual Variation Intolerance Score: 49.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.00; 60.15% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GCSH Gene

Human Gene Mutation Database (HGMD)
GCSH
SNPedia medical, phenotypic, and genealogical associations of SNPs for
GCSH

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GCSH Gene

Disorders for GCSH Gene

MalaCards: The human disease database

(4) MalaCards diseases for GCSH Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search GCSH in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

GCSH_HUMAN
  • Non-ketotic hyperglycinemia (NKH) [MIM:605899]: Autosomal recessive disease characterized by accumulation of a large amount of glycine in body fluid and by severe neurological symptoms. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for GCSH

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with GCSH: view

No data available for Genatlas for GCSH Gene

Publications for GCSH Gene

  1. Comprehensive mutation analysis of GLDC, AMT, and GCSH in nonketotic hyperglycinemia. (PMID: 16450403) Kure S … Matsubara Y (Human mutation 2006) 3 23 43 56
  2. The primary structure of human H-protein of the glycine cleavage system deduced by cDNA cloning. (PMID: 2025283) Fujiwara K … Motokawa Y (Biochemical and biophysical research communications 1991) 2 3 4 56
  3. The glycine cleavage system: structure of a cDNA encoding human H-protein, and partial characterization of its gene in patients with hyperglycinemias. (PMID: 1671321) Koyata H … Hiraga K (American journal of human genetics 1991) 2 3 4 56
  4. Fine mapping and association studies of a high-density lipoprotein cholesterol linkage region on chromosome 16 in French-Canadian subjects. (PMID: 19844255) Dastani Z … Genest J (European journal of human genetics : EJHG 2010) 3 43 56
  5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4 56

Products for GCSH Gene

Sources for GCSH Gene