Variant position: 49 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:
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 EQVPGFTPRLAILQVGNRDD SNLYINVKLKAAEEIGIKATH
Mouse EQVPGFTPGLAILQVGDRDD SNLYINVKLKAAEEIGIKATH
Rat EQVPGFTPGLAILQVGDRDD SNLYINVKLKAAQEIGIKATH
Drosophila KQLADFVPGLRIVQVGGRED SNVYIRMKIKAATEIGIDAAH
Baker's yeast GHVPGFAPNLAIIQVGNRPD SATYVRMKRKAAEEAGIVANF
Fission yeast SVDPYFNVSLKIIQVGGRED SNVYVRMKTRAANEAGISCEH
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
1 – 935 C-1-tetrahydrofolate synthase, cytoplasmic
2 – 935 C-1-tetrahydrofolate synthase, cytoplasmic, N-terminally processed
2 – 305 Methylenetetrahydrofolate dehydrogenase and cyclohydrolase
49 – 49 S -> A. No effect on dehydrogenase and cyclohydrolase activity. Strong increase of Km for NADP.
49 – 49 S -> Q. Reduces dehydrogenase by 75% and cyclohydrolase activity by 99%. No effect on Km for NADP and for 5,10-methenyltetrahydrofolate.
52 – 52 Y -> AS. Reduces dehydrogenase activity by 99%. Reduces cyclohydrolase activity by 70%. No effect on Km for NADP and for 5,10-methenyltetrahydrofolate.
52 – 52 Y -> F. Slightly reduces dehydrogenase and cyclohydrolase activity. Increase of Km for NADP and for 5,10-methenyltetrahydrofolate.
56 – 56 K -> AIST. Decreases dehydrogenase activity over 90%. Loss of cyclohydrolase activity.
56 – 56 K -> EMQ. Moderate decrease of dehydrogenase activity. Loss of cyclohydrolase activity. Strong increase of Km for NADP. Decrease of Km for 5,10-methenyltetrahydrofolate.
56 – 56 K -> R. Reduces dehydrogenase and cyclohydrolase activity by 99%. No effect on Km for NADP and for 5,10-methenyltetrahydrofolate.
47 – 63
Characterization and review of MTHFD1 deficiency: four new patients, cellular delineation and response to folic and folinic acid treatment.
Burda P.; Kuster A.; Hjalmarson O.; Suormala T.; Buerer C.; Lutz S.; Roussey G.; Christa L.; Asin-Cayuela J.; Kollberg G.; Andersson B.A.; Watkins D.; Rosenblatt D.S.; Fowler B.; Holme E.; Froese D.S.; Baumgartner M.R.;
J. Inherit. Metab. Dis. 38:863-872(2015)
Cited for: INVOLVEMENT IN CIMAH; VARIANTS CIMAH PHE-49; 225-GLU--PHE-935 DEL AND ILE-269;
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.