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UniProtKB/Swiss-Prot P11586: Variant p.Arg293His

C-1-tetrahydrofolate synthase, cytoplasmic
Gene: MTHFD1
Variant information

Variant position:  293
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
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 Arginine (R) to Histidine (H) at position 293 (R293H, p.Arg293His).
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 large size and basic (R) to medium size and polar (H)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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

Variant description:  In NTDFS; associated with disease susceptibility.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  293
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  935
The length of the canonical sequence.

Location on the sequence:   GGVGPMTVAMLMQSTVESAK  R FLEKFKPGKWMIQYNNLNLK
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                         GGVGPMTVAMLMQSTVESAKRFLEKFKPGKWMIQYNNLNLK

Mouse                         GGVGPMTVAMLMQSTVESAQRFLQKFKPGKWTIQYNKLNLK

Rat                           GGVGPMTVAMLMQSTVESAQRFLKKFKPGKWTIQYNKLNLK

Drosophila                    GGVGPMTVAMLMKNTVRSAARFLERLAKSQWALQTLPLKPQ

Baker's yeast                 GGVGPMTVAMLMQNTLIAAKRQMEESSK-PLQIPPLPLKLL

Fission yeast                 GSVGPMTVAMLLQNVVESAVRFRKMSRKRKPTL--LPLKLQ

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 1 – 935 C-1-tetrahydrofolate synthase, cytoplasmic
Chain 2 – 935 C-1-tetrahydrofolate synthase, cytoplasmic, N-terminally processed
Helix 275 – 295


Literature citations

Molecular genetic analysis of the gene encoding the trifunctional enzyme MTHFD (methylenetetrahydrofolate-dehydrogenase, methenyltetrahydrofolate-cyclohydrolase, formyltetrahydrofolate synthetase) in patients with neural tube defects.
Hol F.A.; van der Put N.M.J.; Geurds M.P.A.; Heil S.G.; Trijbels F.J.M.; Hamel B.C.J.; Mariman E.C.M.; Blom H.J.;
Clin. Genet. 53:119-125(1998)
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO NTDFS; VARIANTS NTDFS HIS-293 AND GLN-653;

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.