UniProtKB/Swiss-Prot Q04609: Variant p.His475Tyr

Glutamate carboxypeptidase 2
Gene: FOLH1
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Variant information Variant position:

475 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Histidine (H) to Tyrosine (Y) at position 475 (H475Y, p.His475Tyr). 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
Polymorphism:

Genetic variation in FOLH1 may be associated with low folate levels and consequent hyperhomocysteinemia. This condition can result in increased risk of cardiovascular disease, neural tube defects, and cognitive deficits. Additional information on the polymorphism described.
Variant description:

Correlates with lower folate and higher homocysteine levels. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs61886492 [ dbSNP | Ensembl ]

Sequence information Variant position:

475 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

750 The length of the canonical sequence.
Location on the sequence:

SIEGNYTLRVDCTPLMYSLV H NLTKELKSPDEGFEGKSLYE 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                         SIEGNYTLRVDCTPLMYSLVHNLTKELKSPDEGFEGKSLYE

Mouse                         SIEGNYTLRVDCTPLMYSLVYNLTKELQSPDEGFEGKSLYD

Rat                           SIEGNYTLRVDCTPLMHSLVYNLTKELPSPDEGFEGKSLYD

Pig                           SIEGNYTLRVDCTPLMYSLVYNLTKELQSPDEGFEGKSLFE

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.

Type	Positions	Description
Chain	1 – 750	Glutamate carboxypeptidase 2
Topological domain	44 – 750	Extracellular
Region	274 – 587	NAALADase
Glycosylation	459 – 459	N-linked (GlcNAc...) asparagine
Glycosylation	476 – 476	N-linked (GlcNAc...) asparagine
Alternative sequence	244 – 750	Missing. In isoform PSMA-4.
Mutagenesis	459 – 459	N -> A. Loss of glycosylation. Reduces enzyme activity.
Mutagenesis	476 – 476	N -> A. Loss of glycosylation. Reduces enzyme activity.
Helix	471 – 479

Literature citations
Glutamate carboxypeptidase II: a polymorphism associated with lower levels of serum folate and hyperhomocysteinemia.
Devlin A.M.; Ling E.-H.; Peerson J.M.; Fernando S.; Clarke R.; Smith A.D.; Halsted C.H.;
Hum. Mol. Genet. 9:2837-2844(2000)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PSMA-1); VARIANT TYR-475; TISSUE SPECIFICITY;

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.