U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination
    • Showing Current items.

    GCSH glycine cleavage system protein H [ Homo sapiens (human) ]

    Gene ID: 2653, updated on 27-Nov-2024

    Summary

    Go to the top of the page Help
    Official Symbol
    GCSHprovided by HGNC
    Official Full Name
    glycine cleavage system protein Hprovided by HGNC
    Primary source
    HGNC:HGNC:4208
    See related
    Ensembl:ENSG00000140905 MIM:238330; AllianceGenome:HGNC:4208
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    GCE; NKH; MMDS7
    Summary
    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]
    Expression
    Broad expression in thyroid (RPKM 44.9), kidney (RPKM 31.4) and 23 other tissues See more
    Orthologs
    mouse all
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    Go to the top of the page Help
    See GCSH in Genome Data Viewer
    Location:
    16q23.2
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (81081945..81096395, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (87143482..87157585, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (81115550..81130000, complement)

    Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene CENPN antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7749 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7750 Neighboring gene ATM interactor Neighboring gene chromosome 16 open reading frame 46 Neighboring gene uncharacterized LOC105371361 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11176 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:81110606-81111266 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:81111267-81111925 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7751 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7752 Neighboring gene RNA, U6 small nuclear 1191, pseudogene Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:81150474-81151032 Neighboring gene polycystin 1 like 2 (gene/pseudogene) Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:81171151-81171768 Neighboring gene Sharpr-MPRA regulatory region 3111 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:81191716-81192216 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:81246022-81246522 Neighboring gene ReSE screen-validated silencer GRCh37_chr16:81255488-81255706 Neighboring gene beta-carotene oxygenase 1

    Genomic regions, transcripts, and products

    Go to the top of the page Help

    Go to nucleotide: Graphics FASTA GenBank

    Expression

    Go to the top of the page Help
    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    Go to the top of the pageHelp

    Related articles in PubMed

    1. Pathogenic variants in GCSH encoding the moonlighting H-protein cause combined nonketotic hyperglycinemia and lipoate deficiency. Arribas-Carreira L, et al. Hum Mol Genet, 2023 Mar 6. PMID 36190515, Free PMC Article
    2. The primary structure of human H-protein of the glycine cleavage system deduced by cDNA cloning. Fujiwara K, et al. Biochem Biophys Res Commun, 1991 Apr 30. PMID 2025283
    3. Cloning of cDNA encoding human H-protein, a constituent of the glycine cleavage system. Hiraga K, et al. Biochem Biophys Res Commun, 1988 Mar 15. PMID 3348809
    4. Chromosomal localization, structure, single-nucleotide polymorphisms, and expression of the human H-protein gene of the glycine cleavage system (GCSH), a candidate gene for nonketotic hyperglycinemia. Kure S, et al. J Hum Genet, 2001. PMID 11450847
    5. Atypical glycine encephalopathy in an extremely low birth weight infant: description of a new mutation and clinical and electroencephalographic analysis. Pardal-Fernández JM, et al. Epileptic Disord, 2009 Mar. PMID 19299230

    See all (35) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Pathogenic variants in GCSH encoding the moonlighting H-protein cause combined nonketotic hyperglycinemia and lipoate deficiency.
      Title: Pathogenic variants in GCSH encoding the moonlighting H-protein cause combined nonketotic hyperglycinemia and lipoate deficiency.
    2. Biallelic start loss variant, c.1A > G in GCSH is associated with variant nonketotic hyperglycinemia.
      Title: Biallelic start loss variant, c.1A > G in GCSH is associated with variant nonketotic hyperglycinemia.
    3. GCSH protein is overexpressed in both, breast cancer tissue and breast cancer cell lines. A shorter (391 bp) transcript variant (Tv*) was amplified with an increased expression in healthy breast cells and a decreased expression in breast cancer samples. A GCSH-equilibrium at the transcript level is likely conceivable for optimal glycine degradation.
      Title: GCSH antisense regulation determines breast cancer cells' viability.
    4. Data indicate no mutation was found in glycine cleavage system protein-H (GCSH) and suggest that mutations in both glycine decarboxylase (GLDC) and aminomethyltransferase (AMT) are the main cause of glycine encephalopathy in Malaysian population.
      Title: Mutation analysis of glycine decarboxylase, aminomethyltransferase and glycine cleavage system protein-H genes in 13 unrelated families with glycine encephalopathy.
    5. There is no detectable glycine cleavage enzyme activity in human skin fibroblasts.
      Title: Glycine cleavage enzyme complex: molecular cloning and expression of the H-protein cDNA from cultured human skin fibroblasts.
    6. Observational study of gene-disease association. (HuGE Navigator)
      Title: Fine mapping and association studies of a high-density lipoprotein cholesterol linkage region on chromosome 16 in French-Canadian subjects.
    7. Genetic analysis showed a non-previously described mutation affecting a consensus splice site (IVS2-1G > C 3) in the AMT gene encoding the T protein of the glycine cleavage system.
      Title: Atypical glycine encephalopathy in an extremely low birth weight infant: description of a new mutation and clinical and electroencephalographic analysis.
    8. Observational study of genotype prevalence. (HuGE Navigator)
      Title: Comprehensive mutation analysis of GLDC, AMT, and GCSH in nonketotic hyperglycinemia.
    9. Heterozygous GCSH gene mutation in transient neonatal hyperglycinemia.
      Title: Heterozygous GLDC and GCSH gene mutations in transient neonatal hyperglycinemia.
    Submit: New GeneRIF Correction

    Phenotypes

    Go to the top of the page Help

    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Multiple mitochondrial dysfunctions syndrome 7
    MedGen: C5830586 OMIM: 620423 GeneReviews: Not available
    		Compare labs

    Variation

    Go to the top of the page Help

    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

    Go to the top of the page

    Interactions

    Go to the top of the page Help
    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Go to the top of the page Help

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables aminomethyltransferase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in glycine catabolic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in glycine decarboxylation via glycine cleavage system IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein lipoylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    part_of glycine cleavage complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrial matrix TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion HTP PubMed 
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

    Go to the top of the page Help
    Preferred Names
    glycine cleavage system H protein, mitochondrial
    Names
    glycine cleavage system protein H (aminomethyl carrier)
    lipoic acid-containing protein
    mitochondrial glycine cleavage system H-protein

    NCBI Reference Sequences (RefSeq)

    Go to the top of the page Help

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_016427.1 RefSeqGene

      Range
      5001..19429
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_541

    mRNA and Protein(s)

    1. NM_004483.5 → NP_004474.2  glycine cleavage system H protein, mitochondrial precursor

      See identical proteins and their annotated locations for NP_004474.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and is the protein-coding variant.
      Source sequence(s)
      AC092718, AV696698, BF798008, CN283809
      Consensus CDS
      CCDS10933.1
      UniProtKB/Swiss-Prot
      P23434, Q9H1E9
      UniProtKB/TrEMBL
      Q53XL7
      Related
      ENSP00000319531.3, ENST00000315467.9
      Conserved Domains (1) summary
      PRK01202
      Location:51 → 170
      PRK01202; glycine cleavage system protein GcvH

    RNA

    1. NR_033249.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate exon compared to variant 1, that causes a frameshift that makes the transcript a candidate for nonsense-mediated mRNA decay (NMD). Therefore, it is thought that this transcript does not encode a protein.
      Source sequence(s)
      AC092718, CN283805, CN283809

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000016.10 Reference GRCh38.p14 Primary Assembly

      Range
      81081945..81096395 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047433900.1 → XP_047289856.1  glycine cleavage system H protein, mitochondrial isoform X3

    2. XM_017023136.3 → XP_016878625.1  glycine cleavage system H protein, mitochondrial isoform X1

      UniProtKB/TrEMBL
      Q53XL7

    3. XM_017023137.2 → XP_016878626.1  glycine cleavage system H protein, mitochondrial isoform X2

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_025791800.1 Reference GRCh38.p14 PATCHES

      Range
      130184..144634 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054333193.1 → XP_054189168.1  glycine cleavage system H protein, mitochondrial isoform X3

    2. XM_054333191.1 → XP_054189166.1  glycine cleavage system H protein, mitochondrial isoform X1

    3. XM_054333192.1 → XP_054189167.1  glycine cleavage system H protein, mitochondrial isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060940.1 Alternate T2T-CHM13v2.0

      Range
      87143482..87157585 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054380024.1 → XP_054235999.1  glycine cleavage system H protein, mitochondrial isoform X3

    2. XM_054380022.1 → XP_054235997.1  glycine cleavage system H protein, mitochondrial isoform X1

    3. XM_054380023.1 → XP_054235998.1  glycine cleavage system H protein, mitochondrial isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P23434.2 GenPept UniProtKB/Swiss-Prot:P23434

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous