UniProtKB/SwissProt variant VAR

Variant information

Variant position:

295

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 Glutamine (Q) to Arginine (R) at position 295 (Q295R, p.Gln295Arg).

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

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 GGM; loss of activity.

Any additional useful information about the variant.

Sequence information

Variant position:

295

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

Protein sequence length:

664

The length of the canonical sequence.

Location on the sequence:

PWPGFIFGMSILTLWYWCTD Q VIVQRCLSAKNMSHVKGGCI

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                         PWPGFIFGMSILTLWYWCTDQVIVQRCLSAKNMSHVKGGCI

Mouse                         PWPGLIFGLAILALWYWCTDQVIVQRCLSAKNMSHVKADCT

Rat                           PWPGLIFGLSILALWYWCTDQVIVQRCLSAKNMSHVKAGCT

Rabbit                        PWPGLVFGMSILTLWYWCTDQVIVQRCLSAKNLSHVKAGCI

Sheep                         PWPGLIFGLTIISLWYWCTDQVIVQRCLSAKNMSHVKAGCI

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 – 664	Sodium/glucose cotransporter 1
Transmembrane	278 – 298	Helical
Site	300 – 300	Implicated in sodium coupling
Disulfide bond	255 – 511
Mutagenesis	287 – 287	T -> A. Acquires D-mannose, D-fructose and L-sorbose transporter activity; when associated with L-83 and C-290.
Mutagenesis	287 – 287	T -> N. Loss of D-glucose transporter activity. Has strict selectivity for D-galactose.
Mutagenesis	287 – 287	T -> SA. Has normal D-glucose and D-galactose transporter activity.
Mutagenesis	290 – 290	Y -> C. Loss of D-galactose transporter activity. Has strict selectivity for D-glucose. Acquires D-mannose, D-fructose and L-sorbose transporter activity; when associated with A-287 and L-83.
Mutagenesis	291 – 291	W -> A. Loss of D-glucose transporter activity.
Mutagenesis	292 – 292	C -> A. Has no effect on water permeability.

Literature citations

Defects in Na+/glucose cotransporter (SGLT1) trafficking and function cause glucose-galactose malabsorption.
Martin M.G.; Turk E.; Lostao M.P.; Kerner C.; Wright E.M.;
Nat. Genet. 12:216-220(1996)
Cited for: VARIANTS GGM ASN-28; GLY-28; SER-51; TRP-135; PRO-159; THR-166; 191-TYR--ALA-664 DEL; 254-LYS--ALA-664 DEL; LEU-276; TYR-292; ARG-295; SER-300; VAL-304; SER-369; 379-ARG--ALA-664 DEL; GLN-379; VAL-388; SER-405; THR-411; ARG-426; ASN-470; HIS-499 AND GLN-615; FUNCTION; TRANSPORTER ACTIVITY;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P13866: Variant p.Gln295Arg