UniProtKB/Swiss-Prot P42898: Variant p.Glu429Ala

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 429 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 Glutamate (E) to Alanine (A) at position 429 (E429A, p.Glu429Ala). 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 acidic (E) to small size and hydrophobic (A) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: -1 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 MTHFR influences susceptibility to occlusive vascular disease, neural tube defects (NTD), colon cancer and acute leukemia. Additional information on the polymorphism described.
Variant description: Decreased risk for adult acute leukemia; thermolabile; decreased activity. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs1801131 [ dbSNP | Ensembl ]

Sequence information

Variant position: 429 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 656 The length of the canonical sequence.
Location on the sequence: KSKSPKEELLKMWGEELTSE E SVFEVFVLYLSGEPNRNGHK 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.
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 – 656	Methylenetetrahydrofolate reductase (NADPH)
Helix	428 – 440

Literature citations

Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS GLN-68; VAL-222; ARG-422; ALA-429; CYS-519; GLN-594 AND MET-653; A second mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects?
van der Put N.M.J.; Gabreels F.; Stevens E.M.B.; Smeitink J.A.M.; Trijbels F.J.M.; Eskes T.K.A.B.; van den Heuvel L.P.; Blom H.J.;
Am. J. Hum. Genet. 62:1044-1051(1998)
Cited for: VARIANT ALA-429; A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity.
Weisberg I.; Tran P.; Christiensen B.; Sibani S.; Rozen R.;
Mol. Genet. Metab. 64:169-172(1998)
Cited for: VARIANT ALA-429; Polymorphisms in the methylenetetrahydrofolate reductase gene are associated with susceptibility to acute leukemia in adults.
Skibola C.F.; Smith M.T.; Kane E.; Roman E.; Rollinson S.; Cartwright R.A.; Morgan G.;
Proc. Natl. Acad. Sci. U.S.A. 96:12810-12815(1999)
Cited for: VARIANTS VAL-222 AND ALA-429; ASSOCIATION WITH SUSCEPTIBILITY TO ACUTE LEUKEMIA;