UniProtKB/SwissProt variant VAR

Variant information

Variant position:

264

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 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

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.

Variant rs199905054 [ dbSNP | Ensembl ]

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.

Type	Positions	Description
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;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q96MG7: Variant p.Leu264Phe