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UniProtKB/Swiss-Prot Q9NZ71: Variant p.Val745Met

Regulator of telomere elongation helicase 1
Gene: RTEL1
Variant information

Variant position:  745
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 Valine (V) to Methionine (M) at position 745 (V745M, p.Val745Met).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
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, autosomal recessive, 5 (DKCB5) [MIM:615190]: A form of dyskeratosis congenita, a rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. DKCB5 is characterized by onset of bone marrow failure and immunodeficiency in early childhood. Most patients also have growth and developmental delay and cerebellar hypoplasia, consistent with a clinical diagnosis of Hoyeraal-Hreidarsson syndrome. {ECO:0000269|PubMed:23329068, ECO:0000269|PubMed:23453664, ECO:0000269|PubMed:23591994, ECO:0000269|PubMed:23959892, ECO:0000269|PubMed:24009516}. Note=The disease is caused by mutations affecting the gene represented in this entry. RTEL1 mutations have also been found in patients with a dyskeratosis congenita-like phenotype consisting of one feature of dyskeratosis congenita and short telomeres, in the absence of the typical DKC diagnostic triad (PubMed:23329068). {ECO:0000269|PubMed:23329068}.
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 DKCB5; severe form consistent with Hoyeraal-Hreidarsson syndrome.
Any additional useful information about the variant.

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

Sequence information

Variant position:  745
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1219
The length of the canonical sequence.

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.






Caenorhabditis elegans        PKWLRNTI---SRSDTDGCALKTSR-FFKE-----------


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.

Chain 1 – 1219 Regulator of telomere elongation helicase 1
Alternative sequence 1 – 755 Missing. In isoform 5.

Literature citations

Human RTEL1 deficiency causes Hoyeraal-Hreidarsson syndrome with short telomeres and genome instability.
Le Guen T.; Jullien L.; Touzot F.; Schertzer M.; Gaillard L.; Perderiset M.; Carpentier W.; Nitschke P.; Picard C.; Couillault G.; Soulier J.; Fischer A.; Callebaut I.; Jabado N.; Londono-Vallejo A.; de Villartay J.P.; Revy P.;
Hum. Mol. Genet. 22:3239-3249(2013)

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.