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

Summary

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
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Genomic context

Location:: 16q23.2

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (81081945..81096395, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (87143482..87157585, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (81115550..81130000, complement)

Chromosome 16 - NC_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
Observational study of genotype prevalence. (HuGE Navigator)
Title: Comprehensive mutation analysis of GLDC, AMT, and GCSH in nonketotic hyperglycinemia.
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	not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH65079 (e-PCR)
- UniSTS:91783

D16S2649 (e-PCR)
- UniSTS:152256

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	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
is_active_in cytoplasm	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
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

NG_016427.1 RefSeqGene

Range

5001..19429

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GenBank, FASTA, Sequence Viewer (Graphics), LRG_541

mRNA and Protein(s)

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

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_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000016.10 Reference GRCh38.p14 Primary Assembly

Range

81081945..81096395 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047433900.1 → XP_047289856.1 glycine cleavage system H protein, mitochondrial isoform X3
XM_017023136.3 → XP_016878625.1 glycine cleavage system H protein, mitochondrial isoform X1

UniProtKB/TrEMBL

Q53XL7
XM_017023137.2 → XP_016878626.1 glycine cleavage system H protein, mitochondrial isoform X2

Reference GRCh38.p14 PATCHES

Genomic

NW_025791800.1 Reference GRCh38.p14 PATCHES

Range

130184..144634 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054333193.1 → XP_054189168.1 glycine cleavage system H protein, mitochondrial isoform X3
XM_054333191.1 → XP_054189166.1 glycine cleavage system H protein, mitochondrial isoform X1
XM_054333192.1 → XP_054189167.1 glycine cleavage system H protein, mitochondrial isoform X2

Alternate T2T-CHM13v2.0

Genomic

NC_060940.1 Alternate T2T-CHM13v2.0

Range

87143482..87157585 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054380024.1 → XP_054235999.1 glycine cleavage system H protein, mitochondrial isoform X3
XM_054380022.1 → XP_054235997.1 glycine cleavage system H protein, mitochondrial isoform X1
XM_054380023.1 → XP_054235998.1 glycine cleavage system H protein, mitochondrial isoform X2