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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q96NT5: Variant p.Pro425Arg

Proton-coupled folate transporter
Gene: SLC46A1
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Variant information Variant position: help 425 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Proline (P) to Arginine (R) at position 425 (P425R, p.Pro425Arg). 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: help Change from medium size and hydrophobic (P) to large size and basic (R) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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
Variant description: help In HFM; strongly decreased folate and methotrexate uptake. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 425 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 459 The length of the canonical sequence.
Location on the sequence: help TASGIFNSLYPATLNFMKGF P FLLGAGLLLIPAVLIGMLEK 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         TASGIFNSLYPATLNFMKGFPFLLGAGLLLIPAVLIGML---EK

Mouse                         MASGIFNSIYPATLNFMKGFPFLLGAGLLFIPAILIGVL--

Rat                           MASGIFNSLYPATLNFMKGFPFLLGAGLLFIPAILIGVL--

Bovine                        MASGIFNSLYPATLNLMKGFPFLLAAGLLFIPAILMGIL--

Chicken                       VATGVFNSLYPSTLHFMRGFPFLFGAILLLIPAAIMGWI--

Xenopus laevis                LATGLFNSLYPATLHFMKGFPFLLGALLLLIPAGIIGLI--

Zebrafish                     VSSGVFNALYPATLHFMKGFPFVFGAAILLIPAGIIGGLGC
Sequence annotation in neighborhood: help 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 – 459 Proton-coupled folate transporter
Transmembrane 423 – 441 Helical; Name=TM12
Mutagenesis 411 – 411 N -> ADLQ. Does not affect folate uptake.
Mutagenesis 411 – 411 N -> EHKR. Abolished folate uptake.
Mutagenesis 411 – 411 N -> T. Decreased folate uptake at low folate concentration, while folate uptake is not affected at high folate concentration.
Mutagenesis 425 – 425 P -> K. Strongly decreased folate and methotrexate uptake, while it still binds pemetrexed.



Literature citations
The spectrum of mutations in the PCFT gene, coding for an intestinal folate transporter, that are the basis for hereditary folate malabsorption.
Zhao R.; Min S.H.; Qiu A.; Sakaris A.; Goldberg G.L.; Sandoval C.; Malatack J.J.; Rosenblatt D.S.; Goldman I.D.;
Blood 110:1147-1152(2007)
Cited for: FUNCTION; SUBCELLULAR LOCATION; VARIANTS HFM SER-113; ARG-147; ARG-318; TRP-376 AND ARG-425; A P425R mutation of the proton-coupled folate transporter causing hereditary folate malabsorption produces a highly selective alteration in folate binding.
Shin D.S.; Zhao R.; Yap E.H.; Fiser A.; Goldman I.D.;
Am. J. Physiol. 302:C1405-C1412(2012)
Cited for: VARIANT HFM ARG-425; FUNCTION; TRANSPORTER ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES; CHARACTERIZATION OF VARIANT HFM ARG-425; MUTAGENESIS OF PRO-425;
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.