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UniProtKB/Swiss-Prot O60832: Variant p.Thr49Met

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

Variant position:  49
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 Threonine (T) to Methionine (M) at position 49 (T49M, p.Thr49Met).
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 polar (T) to medium size and hydrophobic (M)
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:  Hoyeraal-Hreidarsson syndrome (HHS) [MIM:305000]: A clinically severe variant of dyskeratosis congenita that is characterized by multisystem involvement, early onset in utero, and often results in death in childhood. Affected individuals show intrauterine growth retardation, microcephaly, cerebellar hypoplasia, delayed development, and bone marrow failure resulting in immunodeficiency. {ECO:0000269|PubMed:10583221, ECO:0000269|PubMed:12437656, ECO:0000269|PubMed:19734544, ECO:0000269|PubMed:24914498}. 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 HHS; increases interaction with SHQ1.
Any additional useful information about the variant.

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



Sequence information

Variant position:  49
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:   EIQHAEEFLIKPESKVAKLD  T SQWPLLLKNFDKLNVRTTHY
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                         EIQHAEEFLIKPESKVAKLDTSQWPLLLKNFDKLNVRTTHY

Mouse                         EIQHAEEFLIKPESKVAQLDTSQWPLLLKNFDKLNVRTAHY

Rat                           EIQHAEDFLIKPESKAAQLDTSQWPLLLKNFDRLNVRTTHY

Chicken                       DIQHTEEFLIKPESRVAQLDTSQWPLLLKNFDKLNVLTTHY

Caenorhabditis elegans        EAQQKGSFQLPSSNETAKLDASQWPLLLKNYDKLNVRTNHY

Drosophila                    TLQKQGNFQIKPSSKIAELDTSQWPLLLKNFDKLNIRSNHY

Slime mold                    EVEQ----VIKPE-KTPILDTSKWPLLLKNYDQLSVRTGHY

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
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

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;

Unexplained aplastic anaemia, immunodeficiency, and cerebellar hypoplasia (Hoyeraal-Hreidarsson syndrome) due to mutations in the dyskeratosis congenita gene, DKC1.
Knight S.W.; Heiss N.S.; Vulliamy T.J.; Aalfs C.M.; McMahon C.; Richmond P.; Jones A.; Hennekam R.C.M.; Poustka A.; Mason P.J.; Dokal I.;
Br. J. Haematol. 107:335-339(1999)
Cited for: INVOLVEMENT IN HHS; VARIANTS HHS MET-49 AND GLY-121;

Hoyeraal-Hreidarsson syndrome with a DKC1 mutation identified by whole-exome sequencing.
Lim B.C.; Yoo S.K.; Lee S.; Shin J.Y.; Hwang H.; Chae J.H.; Hwang Y.S.; Seo J.S.; Kim J.I.; Kim K.J.;
Gene 546:425-429(2014)
Cited for: VARIANT HHS MET-49;

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.