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UniProtKB/Swiss-Prot Q9UNQ0: Variant p.Val12Met

Broad substrate specificity ATP-binding cassette transporter ABCG2
Gene: ABCG2
Variant information

Variant position:  12
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Polymorphism
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 Valine (V) to Methionine (M) at position 12 (V12M, p.Val12Met).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
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

Polymorphism:  Genetic variations in ABCG2 define the blood group Junior system (JR) [MIM:614490]. Individuals with Jr(a-) blood group lack the Jr(a) antigen on their red blood cells. These individuals may have anti-Jr(a) antibodies in their serum, which can cause transfusion reactions or hemolytic disease of the fetus or newborn. Although the clinical significance of the Jr(a-) blood group has been controversial, severe fatal hemolytic disease of the newborn has been reported. The Jr(a-) phenotype has a higher frequency in individuals of Asian descent, compared to those of European descent. The Jr(a-) phenotype is inherited as an autosomal recessive trait.Genetic variations in ABCG2 influence the variance in serum uric acid concentrations and define the serum uric acid concentration quantitative trait locus 1 (UAQTL1) [MIM:138900]. Excess serum accumulation of uric acid can lead to the development of gout, a common disorder characterized by tissue deposition of monosodium urate crystals as a consequence of hyperuricemia (PubMed:18834626, PubMed:19506252, PubMed:20368174). -
Additional information on the polymorphism described.

Variant description:  Found in Jr(a-) blood group phenotype.
Any additional useful information about the variant.

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



Sequence information

Variant position:  12
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  655
The length of the canonical sequence.

Location on the sequence:   MSSSNVEVFIP  V SQGNTNGFPATASNDLKAFT
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                         MSSSNVEVFIPVSQGNTNGFPATAS-NDLKAFT---

Rhesus macaque                MSSSNVEVFIPMSQENTNGFPTTTS-NDRKAF

Mouse                         MSSSNDHVLVPMSQRNNNGLPRTNS-RAVRTL

Rat                           MSSSNDHVLVPMSQRNKNGLPGMSS-RGARTL

Pig                           MSSNSYQVSIPMSKRNTNGLPGSSS-NELKTS

Bovine                        MSSNSYEVSIPMSKK-LNGIPETTS-KDLQTL

Slime mold                    PEIGNDEI--PLQEFGQKSFAADNTIGGMQSI

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 – 655 Broad substrate specificity ATP-binding cassette transporter ABCG2
Topological domain 1 – 395 Cytoplasmic


Literature citations

Submission
SeattleSNPs variation discovery resource;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS MET-12; LYS-141; HIS-296 AND THR-528;

ABCG2 null alleles define the Jr(a-) blood group phenotype.
Zelinski T.; Coghlan G.; Liu X.Q.; Reid M.E.;
Nat. Genet. 44:131-132(2012)
Cited for: POLYMORPHISM; INVOLVEMENT IN JR; VARIANT MET-12;

Catalog of 605 single-nucleotide polymorphisms (SNPs) among 13 genes encoding human ATP-binding cassette transporters: ABCA4, ABCA7, ABCA8, ABCD1, ABCD3, ABCD4, ABCE1, ABCF1, ABCG1, ABCG2, ABCG4, ABCG5, and ABCG8.
Iida A.; Saito S.; Sekine A.; Mishima C.; Kitamura Y.; Kondo K.; Harigae S.; Osawa S.; Nakamura Y.;
J. Hum. Genet. 47:285-310(2002)
Cited for: VARIANTS MET-12 AND LYS-141;

Natural allelic variants of breast cancer resistance protein (BCRP) and their relationship to BCRP expression in human intestine.
Zamber C.P.; Lamba J.K.; Yasuda K.; Farnum J.; Thummel K.; Schuetz J.D.; Schuetz E.G.;
Pharmacogenetics 13:19-28(2003)
Cited for: VARIANTS MET-12; LYS-141; LEU-206 AND TYR-590;

Single nucleotide polymorphisms modify the transporter activity of ABCG2.
Morisaki K.; Robey R.W.; Oezvegy-Laczka C.; Honjo Y.; Polgar O.; Steadman K.; Sarkadi B.; Bates S.E.;
Cancer Chemother. Pharmacol. 56:161-172(2005)
Cited for: CHARACTERIZATION OF VARIANTS MET-12; LYS-141 AND ASN-620;

Genetic variation and haplotype structure of the ABC transporter gene ABCG2 in a Japanese population.
Maekawa K.; Itoda M.; Sai K.; Saito Y.; Kaniwa N.; Shirao K.; Hamaguchi T.; Kunitoh H.; Yamamoto N.; Tamura T.; Minami H.; Kubota K.; Ohtsu A.; Yoshida T.; Saijo N.; Kamatani N.; Ozawa S.; Sawada J.;
Drug Metab. Pharmacokinet. 21:109-121(2006)
Cited for: VARIANTS MET-12; LEU-13; LYS-141; GLN-160; ARG-354; LEU-431; ASN-441 AND LEU-489;

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.