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UniProtKB/Swiss-Prot P23378: Variant p.His580Tyr

Glycine dehydrogenase (decarboxylating), mitochondrial
Gene: GLDC
Variant information

Variant position:  580
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Histidine (H) to Tyrosine (Y) at position 580 (H580Y, p.His580Tyr).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from medium size and polar (H) to large size and aromatic (Y)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  2
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Involvement in 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. {ECO:0000269|PubMed:11286506, ECO:0000269|PubMed:11592811, ECO:0000269|PubMed:1634607, ECO:0000269|PubMed:1996985, ECO:0000269|PubMed:28244183, ECO:0000269|PubMed:28737873}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In NKH; loss of glycine catabolic process; loss of expression.
Any additional useful information about the variant.



Sequence information

Variant position:  580
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1020
The length of the canonical sequence.

Location on the sequence:   MKLNSSSELAPITWKEFANI  H PFVPLDQAQGYQQLFRELEK
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         MKLNSSSELAPITWKEFANIHPFVPLDQAQGYQQLFRELEK

Mouse                         MKLNSSSELAPITWREFANIHPFVPLDQAQGYQQLFQGLEK

Chicken                       MKLNSSAELAPISWKEFANIHPFVPLDQAQGYQQLFKDLEK

Slime mold                    MKLNATTEMYPVSWPEFNSIHPFVPANQSLGYKEMFESISN

Baker's yeast                 MKLNSTVEMMPITWPQFSNIHPFQPSNQVQGYKELITSLEK

Fission yeast                 MKLNAVTEMMPITNPLFANIHPYVPEEQAKGYRHVIEDLQL

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 36 – 1020 Glycine dehydrogenase (decarboxylating), mitochondrial


Literature citations

Nonketotic Hyperglycinemia: functional assessment of missense variants in GLDC to understand phenotypes of the disease.
Bravo-Alonso I.; Navarrete R.; Arribas-Carreira L.; Perona A.; Abia D.; Couce M.L.; Garcia-Cazorla A.; Morais A.; Domingo R.; Ramos M.A.; Swanson M.A.; Van Hove J.L.; Ugarte M.; Perez B.; Perez-Cerda C.; Rodriguez-Pombo P.;
Hum. Mutat. 38:678-691(2017)
Cited for: FUNCTION; SUBCELLULAR LOCATION; CATALYTIC ACTIVITY; INVOLVEMENT IN NKH; VARIANTS NKH LYS-146; PRO-173; ALA-267; CYS-362; TRP-373; GLU-376; TRP-461; PRO-548; TYR-580; ARG-581; ASP-624; ASP-763; GLU-768; TRP-790; HIS-866; GLY-905; THR-933 AND ARG-994; CHARACTERIZATION OF VARIANTS NKH LYS-146; PRO-173; ALA-267; CYS-362; TRP-373; GLU-376; TRP-461; PRO-548; TYR-580; ARG-581; ASP-624; ASP-763; GLU-768; TRP-790; HIS-866; GLY-905; THR-933 AND ARG-994;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.