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UniProtKB/Swiss-Prot Q13426: Variant p.Trp43Arg

DNA repair protein XRCC4
Gene: XRCC4
Variant information

Variant position:  43
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change:  From Tryptophan (W) to Arginine (R) at position 43 (W43R, p.Trp43Arg).
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 aromatic (W) to large size and basic (R)
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

Variant description:  In SSMED; impairs the protein function in DNA double-strand break repair.
Any additional useful information about the variant.

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

Sequence information

Variant position:  43
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  336
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.




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 – 336 DNA repair protein XRCC4
Region 1 – 213 Interaction with IFFO1
Modified residue 53 – 53 Phosphoserine; by PRKDC
Mutagenesis 26 – 26 K -> E. Abolished interaction with NHEJ1/XLF; when associated with E-99.
Mutagenesis 55 – 55 E -> R. Abolished interaction with NHEJ1/XLF.
Mutagenesis 58 – 58 D -> R. Abolished interaction with NHEJ1/XLF.
Mutagenesis 61 – 61 M -> R. Abolished interaction with NHEJ1/XLF.
Mutagenesis 62 – 62 E -> R. Does not affect interaction with NHEJ1/XLF.
Beta strand 42 – 48

Literature citations

Genomic analysis of primordial dwarfism reveals novel disease genes.
Shaheen R.; Faqeih E.; Ansari S.; Abdel-Salam G.; Al-Hassnan Z.N.; Al-Shidi T.; Alomar R.; Sogaty S.; Alkuraya F.S.;
Genome Res. 24:291-299(2014)

Mutations in the NHEJ component XRCC4 cause primordial dwarfism.
Murray J.E.; van der Burg M.; Ijspeert H.; Carroll P.; Wu Q.; Ochi T.; Leitch A.; Miller E.S.; Kysela B.; Jawad A.; Bottani A.; Brancati F.; Cappa M.; Cormier-Daire V.; Deshpande C.; Faqeih E.A.; Graham G.E.; Ranza E.; Blundell T.L.; Jackson A.P.; Stewart G.S.; Bicknell L.S.;
Am. J. Hum. Genet. 96:412-424(2015)
Cited for: VARIANTS SSMED ARG-43; 161-ARG--ILE-336 DEL; 225-ARG--ILE-336 DEL AND 275-ARG--ILE-336 DEL;

XRCC4 deficiency in human subjects causes a marked neurological phenotype but no overt immunodeficiency.
Guo C.; Nakazawa Y.; Woodbine L.; Bjoerkman A.; Shimada M.; Fawcett H.; Jia N.; Ohyama K.; Li T.S.; Nagayama Y.; Mitsutake N.; Pan-Hammarstroem Q.; Gennery A.R.; Lehmann A.R.; Jeggo P.A.; Ogi T.;
J. Allergy Clin. Immunol. 136:1007-1017(2015)

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.