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UniProtKB/Swiss-Prot Q96MG7: Variant p.Leu264Phe

Non-structural maintenance of chromosomes element 3 homolog
Gene: NSMCE3
Variant information

Variant position:  264
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 Leucine (L) to Phenylalanine (F) at position 264 (L264F, p.Leu264Phe).
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 (L) to large size and aromatic (F)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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:  Lung disease, immunodeficiency, and chromosome breakage syndrome (LICS) [MIM:617241]: An autosomal recessive chromosome breakage syndrome associated with severe, fatal lung disease in early childhood, following viral pneumonia. LICS is characterized by combined T and B-cell immunodeficiency. Some patients may have mild dysmorphic features. {ECO:0000269|PubMed:27427983}. 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 LICS; no loss of protein stability; loss of interaction with NSMCE4; decreased interaction with NSMCE1; decreased association with the SMC5-SMC6 complex; decreased DNA repair.
Any additional useful information about the variant.

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



Sequence information

Variant position:  264
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  304
The length of the canonical sequence.

Location on the sequence:   VDYEFQWGPRTNLETSKMKV  L KFVAKVHNQDPKDWPAQYCE
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                         VD---YEFQWGPRTNLETSKMKVLKFVAKVHNQDPKDWPAQYCE

Mouse                         VD---YELQWGPRTNLETSKMKVLKFVAKVHNQDPKDWPTQ

Baker's yeast                 TDGEVISYRIGRRTQAELGLESLEKLVQEIMGLEKEQ----

Fission yeast                 NQ---FVYYIGSRAVTEISIEGLKSFVTEFFPDSDID----

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 – 304 Non-structural maintenance of chromosomes element 3 homolog
Domain 85 – 285 MAGE
Region 78 – 304 Interaction with NSMCE1
Mutagenesis 266 – 266 F -> A. Abolishes interaction with EID3.
Mutagenesis 270 – 270 V -> A. Abolishes interaction with EID3.
Helix 260 – 271


Literature citations

Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease.
van der Crabben S.N.; Hennus M.P.; McGregor G.A.; Ritter D.I.; Nagamani S.C.; Wells O.S.; Harakalova M.; Chinn I.K.; Alt A.; Vondrova L.; Hochstenbach R.; van Montfrans J.M.; Terheggen-Lagro S.W.; van Lieshout S.; van Roosmalen M.J.; Renkens I.; Duran K.; Nijman I.J.; Kloosterman W.P.; Hennekam E.; Orange J.S.; van Hasselt P.M.; Wheeler D.A.; Palecek J.J.; Lehmann A.R.; Oliver A.W.; Pearl L.H.; Plon S.E.; Murray J.M.; van Haaften G.;
J. Clin. Invest. 126:2881-2892(2016)
Cited for: VARIANTS LICS LEU-209 AND PHE-264; CHARACTERIZATION OF VARIANTS LICS LEU-209 AND PHE-264; INVOLVEMENT IN LICS; FUNCTION; SUBUNIT; INTERACTION WITH NSMCE1 AND NSMCE4;

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.