GCSH (Glycine Cleavage System H Protein)
Mitochondrial glycine decarboxylase complex component; associated with glycine encephalopathy and cancer metabolism
Gene Information Card
| Symbol | GCSH |
|---|---|
| Full Name | Glycine Cleavage System H Protein |
| Gene Type | Protein coding |
| Chromosomal Location | 16q23.2 |
| NCBI Gene ID | 2653 ncbi.nlm.nih.gov/gene/2653 |
| Ensembl ID | ENSG00000140937 |
| UniProt ID | P23434 |
| OMIM ID | 238330 |
| HGNC ID | 4208 |
| Aliases | NKH, GCE, H-protein |
Description
GCSH encodes the H protein (lipoate-containing carrier) of the mitochondrial glycine cleavage system (GCS). This multienzyme complex catalyzes the oxidative decarboxylation of glycine, producing carbon dioxide, ammonia, and a methylene group transferred to tetrahydrofolate. The H protein shuttles the methylamine intermediate between the P, T, and L proteins. Defects in GCSH cause glycine encephalopathy (nonketotic hyperglycinemia), a severe neurometabolic disorder. Altered GCSH expression is also implicated in cancer cell proliferation and metabolic reprogramming.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glycine encephalopathy (nonketotic hyperglycinemia, NKH) | Loss-of-function mutations in GCSH impair glycine cleavage, leading to toxic accumulation of glycine in brain and body fluids. | ClinVar, OMIM |
| Cancer (various types) | Upregulation of GCSH supports one-carbon metabolism and nucleotide synthesis in rapidly dividing tumor cells. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 9.8 | Medium |
| Brain | 6.2 | Medium |
| Heart | 4.1 | Low |
| Skeletal Muscle | 2.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 15.1 | High expression |
| HEK293 (embryonic kidney) | 10.4 | Moderate expression |
| SH-SY5Y (neuroblastoma) | 7.8 | Moderate expression |
| A549 (lung carcinoma) | 5.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.296C>T (p.Ser99Phe) | Missense | Rare | Loss of function; associated with NKH |
| c.1A>G (p.Met1Val) | Start loss | Rare | Loss of function; associated with NKH |
| c.433_434delAG (p.Ser145fs) | Frameshift | Rare | Loss of function; associated with NKH |
Mutation functional classification
Loss of Function (LOF)
Most reported GCSH mutations cause loss of H-protein function, impairing glycine cleavage and leading to glycine accumulation.
Gain of Function (GOF)
No gain-of-function mutations documented.
Dominant Negative (DN)
No dominant-negative mutations documented.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Glycine
• serine and threonine metabolism (KEGG: hsa00260)
• One carbon pool by folate (KEGG: hsa00670)
• Metabolic pathways (KEGG: hsa01100)
Protein Summary
The GCSH protein (H-protein) is a 173-amino-acid mitochondrial lipoate-containing carrier essential for the glycine cleavage system. It contains a lipoyl-lysine residue that accepts the methylamine group from glycine after decarboxylation by the P protein, then transfers it to the T protein. The protein is ubiquitously expressed with highest levels in liver and kidney. Mutations cause nonketotic hyperglycinemia, while overexpression in cancers supports nucleotide biosynthesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GCSH Knockout HEK293 Cell Line | EDJ-KQ50297 | Human | 2653 | Details Get a Quote |
| GCSH Knockout HeLa Cell Line | EDJ-KQ53321 | Human | 2653 | Details Get a Quote |
| GCSH Knockout A-549 Cell Line | EDJ-KQ61804 | Human | 2653 | Details Get a Quote |
| GCSH Knockout HCT 116 Cell Line | EDJ-KQ70290 | Human | 2653 | Details Get a Quote |
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