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UniProtKB/Swiss-Prot Q96NT5: Variant p.Gly338Arg

Proton-coupled folate transporter
Gene: SLC46A1
Variant information

Variant position:  338
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Glycine (G) to Arginine (R) at position 338 (G338R, p.Gly338Arg).
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 glycine (G) to large size and basic (R)
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

Involvement in disease:  Hereditary folate malabsorption (HFM) [MIM:229050]: Rare autosomal recessive disorder characterized by impaired intestinal folate absorption with folate deficiency resulting in anemia, hypoimmunoglobulinemia with recurrent infections, and recurrent or chronic diarrhea. In many patients, neurological abnormalities such as seizures or mental retardation become apparent during early childhood, attributed to impaired transport of folates into the central nervous system. When diagnosed early, the disorder can be treated by administration of folate. If untreated, it can be fatal and, if treatment is delayed, the neurological defects can become permanent. {ECO:0000269|PubMed:17129779, ECO:0000269|PubMed:17446347, ECO:0000269|PubMed:18559978, ECO:0000269|PubMed:20686069, ECO:0000269|PubMed:20805364, ECO:0000269|PubMed:21333572}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In HFM; loss of function measured as methotrexate uptake.
Any additional useful information about the variant.

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



Sequence information

Variant position:  338
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  459
The length of the canonical sequence.

Location on the sequence:   SLLALKLLQYCLADAWVAEI  G LAFNILGMVVFAFATITPLM
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                         SLLALKLLQYCLADAWVAEIGLAFNILGMVVFAFATITPLM

Mouse                         SLLGLRLLQFCLADTWVAEIGLAFNILGMVVFAFATITPLM

Rat                           SLLGLRLLQFCLADTWVAEIGLAFNILGMVVFAFATITPLM

Bovine                        SLLGLRLLQYCLADTWVAEIGLVFNILGMMVFAFATITPLM

Xenopus laevis                SLAGLRLFQLCLADSWVAEMGFISNISGLVVISLASTTPIM

Zebrafish                     SLTGLRAMQCCLEDSWVALVGLTSNMVGLVVISVADTTALM

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 – 459 Proton-coupled folate transporter
Transmembrane 332 – 356 Helical


Literature citations

Identification of novel mutations in the proton-coupled folate transporter (PCFT-SLC46A1) associated with hereditary folate malabsorption.
Shin D.S.; Mahadeo K.; Min S.H.; Diop-Bove N.; Clayton P.; Zhao R.; Goldman I.D.;
Mol. Genet. Metab. 103:33-37(2011)
Cited for: VARIANTS HFM ASP-335 AND ARG-338; CHARACTERIZATION OF VARIANTS HFM ASP-335 AND ARG-338;

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.