GCSH
Basic information
Region (hg38): 16:81081945-81096395
Links
Phenotypes
GenCC
Source:
- glycine encephalopathy (Strong), mode of inheritance: AR
- glycine encephalopathy (Limited), mode of inheritance: AR
- neonatal glycine encephalopathy (Supportive), mode of inheritance: AR
- infantile glycine encephalopathy (Supportive), mode of inheritance: AR
- atypical glycine encephalopathy (Supportive), mode of inheritance: Unknown
- multiple mitochondrial dysfunctions syndrome 7 (Strong), mode of inheritance: AR
- glycine encephalopathy (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Glycine encephalopathy | AR | Biochemical | There is no current effective treatment for severe disease, but children with variants associated with residual GCS enzyme activity treated aggressively early with sodium benzoate and N-methyl D-aspartate receptor site antagonists may have improved outcomes | Biochemical; Neurologic; Ophthalmologic | 6790577; 12402263; 20301531; 21470805; 33890291; 36190515 |
ClinVar
This is a list of variants' phenotypes submitted to
- Non-ketotic hyperglycinemia (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the GCSH gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 19 | 23 | ||||
| missense | 46 | 48 | ||||
| nonsense | 1 | |||||
| start loss | 2 | |||||
| frameshift | 1 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 2 | 4 | 6 | |||
| non coding | 23 | 28 | ||||
| Total | 1 | 2 | 47 | 24 | 29 |
Variants in GCSH
This is a list of pathogenic ClinVar variants found in the GCSH region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| GCSH | protein_coding | protein_coding | ENST00000315467 | 5 | 14443 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00160 | 0.709 | 125712 | 0 | 22 | 125734 | 0.0000875 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.0920 | 70 | 72.2 | 0.970 | 0.00000354 | 1068 |
| Missense in Polyphen | 12 | 20.284 | 0.59159 | 287 | ||
| Synonymous | 1.04 | 19 | 25.7 | 0.739 | 0.00000142 | 341 |
| Loss of Function | 0.791 | 5 | 7.31 | 0.684 | 3.07e-7 | 105 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000154 | 0.000149 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000163 | 0.000163 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000797 | 0.0000791 |
| Middle Eastern | 0.000163 | 0.000163 |
| South Asian | 0.000196 | 0.000196 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- 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). {ECO:0000269|PubMed:1671321}.;
- Disease
- DISEASE: 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.;
- Pathway
- Glycine, serine and threonine metabolism - Homo sapiens (human);Glyoxylate and dicarboxylate metabolism - Homo sapiens (human);Ammonia Recycling;Glycine degradation;Metabolism of amino acids and derivatives;Metabolism;Glyoxylate metabolism and glycine degradation
(Consensus)
Recessive Scores
- pRec
- 0.164
Intolerance Scores
- loftool
- 0.708
- rvis_EVS
- 0.19
- rvis_percentile_EVS
- 66.57
Haploinsufficiency Scores
- pHI
- 0.749
- hipred
- N
- hipred_score
- 0.198
- ghis
- 0.513
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- K
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.871
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Gcsh
- Phenotype
Gene ontology
- Biological process
- glycine catabolic process;protein lipoylation;glycine decarboxylation via glycine cleavage system;methylation
- Cellular component
- mitochondrion;mitochondrial matrix;glycine cleavage complex
- Molecular function
- aminomethyltransferase activity;protein binding