UniProtKB/SwissProt variant VAR

Variant information

Variant position:

561

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

Type of variant:

LP/P [Disclaimer]

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 Arginine (R) to Glutamine (Q) at position 561 (R561Q, p.Arg561Gln).

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 large size and basic (R) to medium size and polar (Q)

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

Variant description:

In URCTU; affects urinary excretion of uridine and cytidine; decreased sodium-dependent transport of cytidine; increased protein degradation; decreased localization to the cell membrane.

Any additional useful information about the variant.

Sequence information

Variant position:

561

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

Protein sequence length:

649

The length of the canonical sequence.

Location on the sequence:

FANFSSIGIMLGGLTSMVPQ R KSDFSQIVLRALFTGACVSL

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                         FANFSSIGIMLGGLTSMVPQRKSDFSQIVLRALFTGACVSL

Rat                           FANFSSIGIMLGGLTSLVPQRRSDFSQIVLRALITGAFVSL

Pig                           FANFSSIGIMLGGLTSMVPQRKGDFSQIVLRALCTGACVSL

Rabbit                        FANLSSIGITLGGLTSMVPHRKSDLSKVVIRALFTGSCVSF

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.

Type	Positions	Description
Chain	1 – 649	Sodium/nucleoside cotransporter 1
Topological domain	559 – 569	Cytoplasmic
Alternative sequence	176 – 649	Missing. In isoform 2.
Mutagenesis	546 – 546	S -> ACRT. Unable to mediate sodium-dependent transport of uridine.
Mutagenesis	546 – 546	Missing. Unable to mediate sodium-dependent transport of uridine.

Literature citations

Deficiency of perforin and hCNT1, a novel inborn error of pyrimidine metabolism, associated with a rapidly developing lethal phenotype due to multi-organ failure.
Perez-Torras S.; Mata-Ventosa A.; Droegemoeller B.; Tarailo-Graovac M.; Meijer J.; Meinsma R.; van Cruchten A.G.; Kulik W.; Viel-Oliva A.; Bidon-Chanal A.; Ross C.J.; Wassermann W.W.; van Karnebeek C.D.M.; Pastor-Anglada M.; van Kuilenburg A.B.P.;
Biochim. Biophys. Acta 1865:1182-1191(2019)
Cited for: INVOLVEMENT IN URCTU; VARIANTS URCTU CYS-510 AND GLN-561; CHARACTERIZATION OF VARIANTS URCTU CYS-510 AND GLN-561;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O00337: Variant p.Arg561Gln