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UniProtKB/Swiss-Prot Q9UNQ0: Variant p.Asp620Asn

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

Variant position:  620
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LB/B
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:  From Aspartate (D) to Asparagine (N) at position 620 (D620N, p.Asp620Asn).
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 medium size and polar (N)
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:  No effect on protein abundance; no effect on substrate transmembrane transport.
Any additional useful information about the variant.

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



Sequence information

Variant position:  620
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:   NNPCNYATCTGEEYLVKQGI  D LSPWGLWKNHVALACMIVIF
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                         NNPC--NYATCT---GEEYLVKQGIDLSPWGLW----------------------------------------------------------------KNHVALAC----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------MIVIF

Rhesus macaque                NNTC--NYATCT---GEEYLAKQGIDLSPWGLW--------

Mouse                         NSTCVNSYAICT---GNEYLINQGIELSPWGLW--------

Rat                           NSTCVNSYTICT---GNDYLINQGIDLSPWGLW--------

Pig                           NNTC--SFAICT---GAEYLENQGISLSAWGLW--------

Bovine                        NNTC--SYAICT---GEEFLTNQGIDISPWGLW--------

Slime mold                    PRGS-GNSSICQITRGDQFLDQLGMPQNNWFKWIDLLIVFA

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 557 – 630 Extracellular
Domain 389 – 651 ABC transmembrane type-2
Disulfide bond 603 – 603 Interchain
Alternative sequence 612 – 655 Missing. In isoform 2.
Mutagenesis 603 – 603 C -> A. Strongly reduced binding to hemin but not to PPIX.
Mutagenesis 605 – 605 Y -> A. No effect on hemin binding.


Literature citations

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;

Functional Characterization of Clinically-Relevant Rare Variants in ABCG2 Identified in a Gout and Hyperuricemia Cohort.
Toyoda Y.; Mancikova A.; Krylov V.; Morimoto K.; Pavelcova K.; Bohata J.; Pavelka K.; Pavlikova M.; Suzuki H.; Matsuo H.; Takada T.; Stiburkova B.;
Cells 8:0-0(2019)
Cited for: VARIANTS TRP-147; MET-153; LYS-360 DEL; CYS-373; ALA-421; MET-434; PRO-476; ARG-572 AND ASN-620; CHARACTERIZATION OF VARIANTS LYS-141; TRP-147; MET-153; LYS-360 DEL; CYS-373; ALA-421; MET-434; PRO-476; ARG-572 AND ASN-620; FUNCTION; CATALYTIC ACTIVITY; SUBCELLULAR LOCATION;

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.