UniProtKB/SwissProt variant VAR

Variant information

Variant position:

520

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 Valine (V) to Phenylalanine (F) at position 520 (V520F, p.Val520Phe).

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 hydrophobic (V) to large size and aromatic (F)

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 CF.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs77646904 [ dbSNP | Ensembl ]

Sequence information

Variant position:

520

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

Protein sequence length:

1480

The length of the canonical sequence.

Location on the sequence:

GTIKENIIFGVSYDEYRYRS V IKACQLEEDISKFAEKDNIV

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                         GTIKENIIFGVSYDEYRYRSVIKACQLEEDISKFAEKDNIV

Gorilla                       GTIKENIIFGVSYDEYRYRSVIKACQLEEDISKFAEKDNIV

Rhesus macaque                GTIKENIIFGVSYDEYRYRSVINACQLEEDISKFAEKDNIV

Chimpanzee                    GTIKENIIFGVSYDEYRYRSVIKACQLEEDISKFAEKDNIV

Mouse                         GTIKENIIFGVSYDEYRYKSVVKACQLQQDITKFAEQDNTV

Rat                           GTIKENIIFGVSYDEYRYKSVVKACQLQEDITKFAEQDNTV

Pig                           GTIKENIIFGVSYDEYRYRSVIKACQLEEDISKFAEKDNIV

Bovine                        GTIKDNIIFGVSYDEYRYRSVIKACQLEEDISKFAEKDNVV

Rabbit                        GTIKENIIFGVSYDEYRYKSVIKACQLEEDISKFTEKDNTV

Sheep                         GTIKDNIIFGVSYDEYRYRSVIKACQLEEDISKFSEKDNIV

Horse                         GTIKENIIFGVSYDEYRYRSVIKACQLEEDISKFAEKDNIV

Xenopus laevis                GTIKENIVFGVSYDQYRYLSVIKACQLEEDISKFPEKDNTV

Zebrafish                     GTIRDNILFGLTYDEYRYKSVVKACQLEEDLAALPEKDKTP

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 – 1480	Cystic fibrosis transmembrane conductance regulator
Topological domain	359 – 858	Cytoplasmic
Domain	423 – 646	ABC transporter 1
Lipidation	524 – 524	S-palmitoyl cysteine
Mutagenesis	508 – 508	F -> R. Impaired maturation of glycan chains indicating impaired trafficking from the endoplasmic reticulum to the cell membrane.
Mutagenesis	508 – 508	Missing. Abolishes MARCHF2-mediated degradation.
Mutagenesis	539 – 539	I -> T. Enhances trafficking from the endoplasmic reticulum to the cell membrane.
Helix	514 – 523

Literature citations

Three novel mutations in the cystic fibrosis gene detected by chemical cleavage: analysis of variant splicing and a nonsense mutation.
Jones C.T.; McIntosh I.; Keston M.; Ferguson A.; Brock D.J.H.;
Hum. Mol. Genet. 1:11-17(1992)
Cited for: VARIANTS CF PHE-520 AND HIS-1291;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P13569: Variant p.Val520Phe