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UniProtKB/Swiss-Prot Q9NSU2: Variant p.Arg240Ser

Three-prime repair exonuclease 1
Gene: TREX1
Chromosomal location: 3p21.3
Variant information

Variant position:  240
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 Arginine (R) to Serine (S) at position 240 (R240S, p.Arg240Ser).
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 basic (R) to small size and polar (S)
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:  Systemic lupus erythematosus (SLE) [MIM:152700]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. {ECO:0000269|PubMed:17660818, ECO:0000269|PubMed:20131292, ECO:0000269|PubMed:23979357}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Enhanced immune sensing of oxidized DNA may be involved in the phototoxicity experienced by SLE patients. Exposure to UV-light produces DNA oxidative damage. Oxidized DNA being a poor TREX1 substrate, it accumulates in skin, leading to enhanced auto-immune reactivity and eventually skin lesions (PubMed:23993650). {ECO:0000269|PubMed:23993650}.
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 SLE.
Any additional useful information about the variant.

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



Sequence information

Variant position:  240
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  314
The length of the canonical sequence.

Location on the sequence:   DAHARPFGTIRPMYGVTASA  R TKPRPSAVTTTAHLATTRNT
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                         DAHARPFGTIRPMYGVTASART-KPRPSAVTTTAHLATTRNT

Mouse                         DEHARPFSTVKPMYGTPATTGTTNLRPHAATATTPLATA-N

Bovine                        DAHAKPFSTVKPMYVITTSTGT-NPRPSAVTATVPLARASD

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 – 314 Three-prime repair exonuclease 1
Region 236 – 314 Necessary for endoplasmic reticulum localization
Mutagenesis 242 – 242 K -> R. Reduces ubiquitination.


Literature citations

Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus.
Lee-Kirsch M.A.; Gong M.; Chowdhury D.; Senenko L.; Engel K.; Lee Y.A.; de Silva U.; Bailey S.L.; Witte T.; Vyse T.J.; Kere J.; Pfeiffer C.; Harvey S.; Wong A.; Koskenmies S.; Hummel O.; Rohde K.; Schmidt R.E.; Dominiczak A.F.; Gahr M.; Hollis T.; Perrino F.W.; Lieberman J.; Huebner N.;
Nat. Genet. 39:1065-1067(2007)
Cited for: VARIANTS SLE HIS-114; VAL-158; SER-227; SER-240; PRO-247; LEU-290; CYS-305 AND ALA-306; VARIANT GLY-266;

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.