UniProtKB/SwissProt variant VAR

Variant information

Variant position:

566

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 Leucine (L) to Proline (P) at position 566 (L566P, p.Leu566Pro).

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:

-3

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 pRTA-OA; loss of localization to the plasma membrane; the retention in the cytoplasm probably explains the loss of the cotransporter activity.

Any additional useful information about the variant.

Sequence information

Variant position:

566

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

Protein sequence length:

1079

The length of the canonical sequence.

Location on the sequence:

NNFDYLEFRLWIGLWSAFLC L ILVATDASFLVQYFTRFTEE

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                         NNFDYLEFRLWIGLWSAFLCLILVATDASFLVQYFTRFTEE

Mouse                         HNFDYLEFRLWIGLWSAFMCLVLVATDASFLVQYFTRFTEE

Rat                           HSFDYLEFRLWIGLWSAFMCLILVATDASFLVQYFTRFTEE

Pig                           HNFDYLEFRLWIGLWSAFLCLILVATDASFLVQYFTRFTEE

Bovine                        HNFDYLEFRLWIGLWSAFLCLILVATDASFLVQYFTRFTEE

Rabbit                        HNFDYLEFRLWIGLWSAFLCLILVATDASFLVQYFTRFTEE

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 – 1079	Electrogenic sodium bicarbonate cotransporter 1
Transmembrane	551 – 571	Helical; Name=4
Mutagenesis	552 – 552	E -> N. Prevents membrane targeting.
Mutagenesis	554 – 554	R -> D. Prevents membrane targeting.
Mutagenesis	582 – 582	R -> N. Moderate reduction of the sodium-dependent ion transport activity.
Mutagenesis	582 – 582	R -> Q. Strong reduction of the sodium-dependent ion transport activity.
Mutagenesis	586 – 586	E -> Q. Moderate reduction of the sodium-dependent ion transport activity.

Literature citations

Proximal renal tubular acidosis and ocular pathology: a novel missense mutation in the gene (SLC4A4) for sodium bicarbonate cotransporter protein (NBCe1).
Demirci F.Y.; Chang M.H.; Mah T.S.; Romero M.F.; Gorin M.B.;
Mol. Vis. 12:324-330(2006)
Cited for: VARIANT PRTA-OA PRO-566; CHARACTERIZATION OF VARIANT PRTA-OA PRO-566; FUNCTION; SUBCELLULAR LOCATION;

Functional analysis of a novel missense NBC1 mutation and of other mutations causing proximal renal tubular acidosis.
Suzuki M.; Vaisbich M.H.; Yamada H.; Horita S.; Li Y.; Sekine T.; Moriyama N.; Igarashi T.; Endo Y.; Cardoso T.P.; de Sa L.C.; Koch V.H.; Seki G.; Fujita T.;
Pflugers Arch. 455:583-593(2008)
Cited for: VARIANT PRTA-OA ARG-530; CHARACTERIZATION OF VARIANTS PRTA-OA SER-342 SER-529; ARG-530 AND PRO-566; FUNCTION; SUBCELLULAR LOCATION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9Y6R1: Variant p.Leu566Pro