UniProtKB/SwissProt variant VAR

Variant information

Variant position:

1281

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 Arginine (R) to Tryptophan (W) at position 1281 (R1281W, p.Arg1281Trp).

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 large size and aromatic (W)

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

Involvement in disease:

Epidermolysis bullosa letalis, with pyloric atresia (EB-PA) [MIM:226730]: An autosomal recessive, frequently lethal, epidermolysis bullosa with variable involvement of skin, nails, mucosa, and with variable effects on the digestive system. It is characterized by mucocutaneous fragility, aplasia cutis congenita, and gastrointestinal atresia, which most commonly affects the pylorus. Pyloric atresia is a primary manifestation rather than a scarring process secondary to epidermolysis bullosa. {ECO:0000269|PubMed:10873890, ECO:0000269|PubMed:11251584, ECO:0000269|PubMed:11328943, ECO:0000269|PubMed:9422533, ECO:0000269|PubMed:9546354, ECO:0000269|PubMed:9792864, ECO:0000269|PubMed:9892956}. 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 EB-PA; mild form; abolishes interaction with PLEC and reduces interaction with COL17A1.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121912467 [ dbSNP | Ensembl ]

Sequence information

Variant position:

1281

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

Protein sequence length:

1822

The length of the canonical sequence.

Location on the sequence:

NDDNRPIGPMKKVLVDNPKN R MLLIENLRESQPYRYTVKAR

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                         NDDNRPIGPMKKVLVDNPKNRMLLIENLRESQPYRYTVKAR

Mouse                         NEDNRPIGPMKKVLVDNPKNRMLLIENLRESQPYRYTVKAR

Rat                           NEDNRPIGPMKKVLVDNPKNRMLLIENLRESQPYRYTVKAR

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	28 – 1822	Integrin beta-4
Topological domain	734 – 1822	Cytoplasmic
Domain	1222 – 1321	Fibronectin type-III 2
Alternative sequence	965 – 1822	Missing. In isoform Beta-4E.

Literature citations

Analysis of the interactions between BP180, BP230, plectin and the integrin alpha6beta4 important for hemidesmosome assembly.
Koster J.; Geerts D.; Favre B.; Borradori L.; Sonnenberg A.;
J. Cell Sci. 116:387-399(2003)
Cited for: FUNCTION; INTERACTION WITH COL17A1 AND DST; CHARACTERIZATION OF VARIANT TRP-1281; SUBCELLULAR LOCATION;

Novel ITGB4 mutations in lethal and nonlethal variants of epidermolysis bullosa with pyloric atresia: missense versus nonsense.
Pulkkinen L.; Rouan F.; Bruckner-Tuderman L.; Wallerstein R.; Garzon M.; Brown T.; Smith L.; Carter W.G.; Uitto J.;
Am. J. Hum. Genet. 63:1376-1387(1998)
Cited for: VARIANTS EB-PA TYR-61; CYS-252; ARG-562 AND TRP-1281;

Congenital focal segmental glomerulosclerosis associated with beta4 integrin mutation and epidermolysis bullosa.
Kambham N.; Tanji N.; Seigle R.L.; Markowitz G.S.; Pulkkinen L.; Uitto J.; D'Agati V.D.;
Am. J. Kidney Dis. 36:190-196(2000)
Cited for: VARIANT EB-PA TRP-1281;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P16144: Variant p.Arg1281Trp