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UniProtKB/Swiss-Prot Q07837: Variant p.Met467Thr

Neutral and basic amino acid transport protein rBAT
Gene: SLC3A1
Variant information

Variant position:  467
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 Methionine (M) to Threonine (T) at position 467 (M467T, p.Met467Thr).
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 hydrophobic (M) to medium size and polar (T)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -1
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:  Cystinuria (CSNU) [MIM:220100]: An autosomal disorder characterized by impaired epithelial cell transport of cystine and dibasic amino acids (lysine, ornithine, and arginine) in the proximal renal tubule and gastrointestinal tract. The impaired renal reabsorption of cystine and its low solubility causes the formation of calculi in the urinary tract, resulting in obstructive uropathy, pyelonephritis, and, rarely, renal failure. {ECO:0000269|PubMed:10738006, ECO:0000269|PubMed:11748844, ECO:0000269|PubMed:12234283, ECO:0000269|PubMed:15635077, ECO:0000269|PubMed:16138908, ECO:0000269|PubMed:16609684, ECO:0000269|PubMed:19782624, ECO:0000269|PubMed:7539209, ECO:0000269|PubMed:7573036, ECO:0000269|PubMed:7575432, ECO:0000269|PubMed:8054986, ECO:0000269|PubMed:9186880}. 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 CSNU; loss of 80% of amino acid transport activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  467
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  685
The length of the canonical sequence.

Location on the sequence:   GPDSSRLTSRLGNQYVNVMN  M LLFTLPGTPITYYGEEIGMG
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                         GPDSSRLTSRLGNQYVNVMNMLLFTLPGTPITYYGEEIGMG

Mouse                         GPETPRLTSRVGSEYVNAMHMLLFTLPGTPITYYGEEIGMG

Rat                           GPETSRLTSRVGSEYVNAMNMLLFTLPGTPITYYGEEIGMG

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 – 685 Neutral and basic amino acid transport protein rBAT
Topological domain 109 – 685 Extracellular
Alternative sequence 392 – 685 Missing. In isoform C.


Literature citations

Genomic organization of a human cystine transporter gene (SLC3A1) and identification of novel mutations causing cystinuria.
Endsley J.K.; Phillips J.A. III; Hruska K.A.; Denneberg T.; Carlson J.; George A.L. Jr.;
Kidney Int. 51:1893-1899(1997)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANT ILE-618; VARIANTS CSNU TRP-452; HIS-461 AND THR-467;

Cystinuria caused by mutations in rBAT, a gene involved in the transport of cystine.
Calonge M.J.; Gasparini P.; Chillaron J.; Chillon M.; Gallucci M.; Rousaud F.; Zelante L.; Testar X.; Dallapiccola B.; Di Silverio F.; Barcelo P.; Estivill X.; Zorzano A.; Nunes V.; Palacin M.;
Nat. Genet. 6:420-425(1994)
Cited for: VARIANTS CSNU GLN-181; LYS-467; THR-467; THR-615; ARG-652 AND PRO-678; CHARACTERIZATION OF VARIANT THR-467;

Identification of 12 novel mutations in the SLC3A1 gene in Swedish cystinuria patients.
Harnevik L.; Fjellstedt E.; Molbaek A.; Tiselius H.-G.; Denneberg T.; Soederkvist P.;
Hum. Mutat. 18:516-525(2001)
Cited for: VARIANTS CSNU CYS-151; LYS-253; HIS-362; ARG-398; HIS-461; THR-467; VAL-481; LYS-482; ARG-510; THR-584; SER-599 AND GLU-600; VARIANT ILE-618;

Cystinuria in children: distribution and frequencies of mutations in the SLC3A1 and SLC7A9 genes.
Botzenhart E.; Vester U.; Schmidt C.; Hesse A.; Halber M.; Wagner C.; Lang F.; Hoyer P.; Zerres K.; Eggermann T.;
Kidney Int. 62:1136-1142(2002)
Cited for: VARIANTS CSNU MET-216; CYS-362; TRP-365; THR-467 AND ALA-508;

Molecular genetic analysis of SLC3A1 and SLC7A9 genes in Czech and Slovak cystinuric patients.
Skopkova Z.; Hrabincova E.; Stastna S.; Kozak L.; Adam T.;
Ann. Hum. Genet. 69:501-507(2005)
Cited for: VARIANTS CSNU ARG-140; TYR-179; MET-216; PRO-365; TRP-452; THR-467 AND TRP-547;

Large rearrangements detected by MLPA, point mutations, and survey of the frequency of mutations within the SLC3A1 and SLC7A9 genes in a cohort of 172 cystinuric Italian patients.
Bisceglia L.; Fischetti L.; Bonis P.D.; Palumbo O.; Augello B.; Stanziale P.; Carella M.; Zelante L.;
Mol. Genet. Metab. 99:42-52(2010)
Cited for: VARIANTS CSNU GLY-137; TRP-365; GLN-452; THR-467 AND TRP-547;

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.