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

Gene ID: 2653, updated on 28-Oct-2024

Summary

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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
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Genomic context

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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

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues 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

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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.
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Phenotypes

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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
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Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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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
  
part_of glycine cleavage complex IEA
Inferred from Electronic Annotation
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

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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)

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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

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