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UniProtKB/Swiss-Prot Q96NT5: Variant p.Asp156Tyr

Proton-coupled folate transporter
Gene: SLC46A1
Variant information

Variant position:  156
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 Aspartate (D) to Tyrosine (Y) at position 156 (D156Y, p.Asp156Tyr).
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 (D) to large size and aromatic (Y)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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:  156
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:   QLQLHVGYFVLGRILCALLG  D FGGLLAASFASVADVSSSRS
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                         QLQLHVGYFVLGRILCALLGDFGGLLAASFASVADVSSSRS

Mouse                         QLELHVGFFVLGRALCALLGDFNGLLAASFASVADVSSNHS

Rat                           QLQLHIGFFVLGRALCALLGDFNGLLAASFASVADVSSNHS

Bovine                        QLHLHIGYLVLGRILCALLGDFSGLLAASFASVADVSSSRT

Xenopus laevis                YQELHVGYFLIGRFISGISGDFNMILAGCFAYIADVSDRQS

Zebrafish                     YLKLPVFWFLIGRICSGLSGDFNAILAGCFAYVADTSERGS

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 146 – 168 Helical
Mutagenesis 156 – 156 D -> E. Does not affect methotrexate uptake.
Mutagenesis 156 – 156 D -> FKNVW. Loss of methotrexate uptake.
Mutagenesis 156 – 156 D -> G. 2-fold reduction of methotrexate uptake.
Mutagenesis 156 – 156 D -> S. 8-fold reduction of methotrexate uptake.


Literature citations

Functional roles of aspartate residues of the proton-coupled folate transporter (PCFT-SLC46A1); a D156Y mutation causing hereditary folate malabsorption.
Shin D.S.; Min S.H.; Russell L.; Zhao R.; Fiser A.; Goldman I.D.;
Blood 116:5162-5169(2010)
Cited for: VARIANT HFM TYR-156; CHARACTERIZATION OF VARIANT HFM TYR-156; MUTAGENESIS OF ASP-109 AND ASP-156;

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.