UniProtKB/Swiss-Prot O60934: Variant p.Ile171Val

Nibrin
Gene: NBN
Chromosomal location: 8q21-q24
Variant information

Variant position:  171
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Unclassified
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Isoleucine (I) to Valine (V) at position 171 (I171V, p.Ile171Val).
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:  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 some childhood acute lymphoblastic leukemia patients; uncertain pathological significance; rare variant; associated with aplastic anemia at homozygosity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  171
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  754
The length of the canonical sequence.

Location on the sequence:   VMVSVKVTIKTICALICGRP  I VKPEYFTEFLKAVESKKQPP
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                         VMVSVKVTIKTICALICGRPIVKPEYFTEFLKAVESKKQPP

Mouse                         VMSAVKVTIKTICALICGRPIIKPEYFSEFLKAVESKKQPP

Rat                           AMSSVKVTIKTICALICGRPIVKPEYFSEFLKAVESKTQPP

Chicken                       IMESVKVTVKTICALICGRPIVKPEFFSELMKAVQSRQQLP

Zebrafish                     VMPTVKVTIKTICALLCCRPIVKPAFFSALSKAVQQKLPLP

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 1 – 754 Nibrin
Domain 105 – 181 BRCT
Region 111 – 328 Mediates interaction with SP100
Mutagenesis 176 – 176 Y -> A. Disrupts nuclear foci formation and block phosphorylation in response to ionizing radiation.


Literature citations

Mutations in the Nijmegen breakage syndrome gene (NBS1) in childhood acute lymphoblastic leukemia (ALL).
Varon R.; Reis A.; Henze G.; von Einsiedel H.G.; Sperling K.; Seeger K.;
Cancer Res. 61:3570-3572(2001)
Cited for: VARIANTS LEU-93; ASN-95; VAL-171; PHE-210 AND TRP-215; POSSIBLE INVOLVEMENT IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA;

First case of aplastic anemia in a Japanese child with a homozygous missense mutation in the NBS1 gene (I171V) associated with genomic instability.
Shimada H.; Shimizu K.; Mimaki S.; Sakiyama T.; Mori T.; Shimasaki N.; Yokota J.; Nakachi K.; Ohta T.; Ohki M.;
Hum. Genet. 115:372-376(2004)
Cited for: VARIANT VAL-171;

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.