UniProtKB/SwissProt variant VAR

Variant information

Variant position:

219

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

Type of variant:

Disease [Disclaimer]

The variants are classified into three categories: Disease, Polymorphism and Unclassified.

Disease: Variants implicated in disease according to literature reports.
Polymorphism: Variants not reported to be implicated in disease.
Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:

From Serine (S) to Phenylalanine (F) at position 219 (S219F, p.Ser219Phe).

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 small size and polar (S) to large size and aromatic (F)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-2

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

Involvement in disease:

Familial porphyria cutanea tarda (FPCT) [MIM:176100]: A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. Familial porphyria cutanea tarda is an autosomal dominant disorder characterized by light-sensitive dermatitis, with onset in later life. It is associated with the excretion of large amounts of uroporphyrin in the urine. Iron overload is often present in association with varying degrees of liver damage. {ECO:0000269|PubMed:10338097, ECO:0000269|PubMed:10477430, ECO:0000269|PubMed:11069625, ECO:0000269|PubMed:11295834, ECO:0000269|PubMed:11719352, ECO:0000269|PubMed:2243121, ECO:0000269|PubMed:2920211, ECO:0000269|PubMed:7706766, ECO:0000269|PubMed:8896428, ECO:0000269|PubMed:9792863}. Note=The disease is caused by mutations affecting the gene represented in this entry.

The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:

In FPCT.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs982293378 [ dbSNP | Ensembl ]

Sequence information

Variant position:

219

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

Protein sequence length:

367

The length of the canonical sequence.

Location on the sequence:

LVPYLVGQVVAGAQALQLFE S HAGHLGPQLFNKFALPYIRD

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                         LVPYLVGQVVAGAQALQLFESHAGHLGPQLFNKFALPYIRD

Mouse                         LVPYLIGQVAAGAQALQLFESHAGHLGTELFSKFALPYIRD

Sheep                         LVPYLVGQVAAGAQALQLFESHAGHLGPQLFSKFALPYIRD

Zebrafish                     IVEYLLGQVKAGAQALQVFESHTGCLGPVEFKEFSLPYLRD

Drosophila                    IVDYLEMQVKAGAQMLQVFESSAEHLSKEQFLQWCVPYLKR

Slime mold                    CIDYLLGQIKAGAQALQIFDSWSNELSPAMFKEYCLPYLVQ

Baker's yeast                 AVEFLSQQVVAGAQILQVFESWGGELSSVDFDEFSLPYLRQ

Fission yeast                 TVSYLIQQVYAGAQLLQIFDSWAGELSPEDFTEYAYPYLVR

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 – 367	Uroporphyrinogen decarboxylase
Binding site	219 – 219	Substrate

Literature citations

Seven novel point mutations in the uroporphyrinogen decarboxylase (UROD) gene in patients with familial porphyria cutanea tarda (f-PCT).
Cappellini M.D.; Martinez Di Montemuros F.; Tavazzi D.; Fargion S.; Pizzuti A.; Comino A.; Cainelli T.; Fiorelli G.;
Hum. Mutat. 17:350-350(2001)
Cited for: VARIANTS FPCT GLN-142; GLN-161; PHE-219 AND SER-235;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P06132: Variant p.Ser219Phe