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UniProtKB/Swiss-Prot O60832: Variant p.Met350Thr

H/ACA ribonucleoprotein complex subunit DKC1
Gene: DKC1
Chromosomal location: Xq28
Variant information

Variant position:  350
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 Methionine (M) to Threonine (T) at position 350 (M350T, p.Met350Thr).
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 (M) to medium size and polar (T)
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

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; decreases interaction with SHQ1.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  350
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:   NQEIVVITTKGEAICMAIAL  M TTAVISTCDHGIVAKIKRVI
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                         NQEIVVITTKGEAICMAIALMTTAVISTCDHGIVAKIKRVI

Mouse                         NQEIVVITTKGEAICMAIALMTTAVISTCDHGIVAKIKRVI

Rat                           NQEVVVITTKGEAVCVAIALMTTAVISTCDHGVVAKIKRVI

Chicken                       KQEIVVITTKGEAICLAIALMTTAVISTCDHGVVAKIKRVI

Caenorhabditis elegans        GKEIVIMSTKGEAICIAIAQMNTSTIASVDHGVVAKSKRVI

Drosophila                    DQEIVICTTKGEAICLAIALMTTATMASCDHGVVAKIKRVI

Slime mold                    NEEVVLITTKGEAIAIGIAQMTTASMATCDHGVVATIKRVI

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.

TypePositionsDescription
Chain 2 – 514 H/ACA ribonucleoprotein complex subunit DKC1
Domain 296 – 371 PUA
Mutagenesis 353 – 353 A -> R. Increases interaction with SHQ1.


Literature citations

X-linked dyskeratosis congenita is predominantly caused by missense mutations in the DKC1 gene.
Knight S.W.; Heiss N.S.; Vulliamy T.J.; Greschner S.; Stavrides G.; Pai G.S.; Lestringant G.; Varma N.; Mason P.J.; Dokal I.; Poustka A.;
Am. J. Hum. Genet. 65:50-58(1999)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANTS DKCX VAL-2; GLU-39; LYS-41; THR-65; ALA-66; VAL-321; ILE-350; THR-350; VAL-353 AND ARG-402;

Pathogenic NAP57 mutations decrease ribonucleoprotein assembly in dyskeratosis congenita.
Grozdanov P.N.; Fernandez-Fuentes N.; Fiser A.; Meier U.T.;
Hum. Mol. Genet. 18:4546-4551(2009)
Cited for: INTERACTION WITH SHQ1; CHARACTERIZATION OF VARIANTS DKCX ALA-66; ILE-350; THR-350 AND VAL-353; CHARACTERIZATION OF VARIANTS HHS MET-49 AND GLY-121; MUTAGENESIS OF ALA-353;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.