UniProtKB/SwissProt variant VAR

Variant information

Variant position:

56

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 Leucine (L) to Serine (S) at position 56 (L56S, p.Leu56Ser).

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 (L) to small size and polar (S)

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:

Dyskeratosis congenita, X-linked (DKCX) [MIM:305000]: A rare, progressive bone marrow failure syndrome characterized by the triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. {ECO:0000269|PubMed:10364516, ECO:0000269|PubMed:15304085, ECO:0000269|PubMed:17417794, ECO:0000269|PubMed:18802941, ECO:0000269|PubMed:19734544, ECO:0000269|PubMed:19879169, ECO:0000269|PubMed:21602826, ECO:0000269|PubMed:25219674, ECO:0000269|PubMed:9590285}. Note=The disease is caused by mutations affecting the gene represented in this entry. Reduced rRNA pseudouridine levels in cells from patients (PubMed:25219674). {ECO:0000269|PubMed:25219674}.

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 DKCX; due to a 2 nucleotide inversion.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121912287 [ dbSNP | Ensembl ]

Sequence information

Variant position:

56

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

Protein sequence length:

514

The length of the canonical sequence.

Location on the sequence:

FLIKPESKVAKLDTSQWPLL L KNFDKLNVRTTHYTPLACGS

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                         FLIKPESKVAKLDTSQWPLLLKNFDKLNVRTTHYTPLACGS

Mouse                         FLIKPESKVAQLDTSQWPLLLKNFDKLNVRTAHYTPLPCGS

Rat                           FLIKPESKAAQLDTSQWPLLLKNFDRLNVRTTHYTPIPCGS

Chicken                       FLIKPESRVAQLDTSQWPLLLKNFDKLNVLTTHYTPLPSGA

Caenorhabditis elegans        FQLPSSNETAKLDASQWPLLLKNYDKLNVRTNHYTPHVEGV

Drosophila                    FQIKPSSKIAELDTSQWPLLLKNFDKLNIRSNHYTPLAHGS

Slime mold                    -VIKPE-KTPILDTSKWPLLLKNYDQLSVRTGHYTPIPNGH

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	2 – 514	H/ACA ribonucleoprotein complex subunit DKC1
Cross	39 – 39	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Cross	43 – 43	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)

Literature citations

Identification of a novel mutation in DKC1 in dyskeratosis congenita.
Kurnikova M.; Shagina I.; Khachatryan L.; Schagina O.; Maschan M.; Shagin D.;
Pediatr. Blood Cancer 52:135-137(2009)
Cited for: VARIANT DKCX SER-56;

UniProtKB/Swiss-Prot O60832: Variant p.Leu56Ser