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UniProtKB/Swiss-Prot Q9NSU2: Variant p.Asp18Asn

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

Variant position:  18
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 Aspartate (D) to Asparagine (N) at position 18 (D18N, p.Asp18Asn).
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 acidic (D) to medium size and polar (N)
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:  Aicardi-Goutieres syndrome 1 (AGS1) [MIM:225750]: A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood. {ECO:0000269|PubMed:16845398, ECO:0000269|PubMed:17293595, ECO:0000269|PubMed:17357087, ECO:0000269|PubMed:17846997, ECO:0000269|PubMed:18045533, ECO:0000269|PubMed:20131292, ECO:0000269|PubMed:20799324, ECO:0000269|PubMed:23979357}. 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.

Involvement in disease:  Chilblain lupus 1 (CHBL1) [MIM:610448]: A rare cutaneous form of lupus erythematosus. Affected individuals present with painful bluish-red papular or nodular lesions of the skin in acral locations precipitated by cold and wet exposure at temperatures less than 10 degrees centigrade. {ECO:0000269|PubMed:17357087, ECO:0000269|PubMed:17440703}. 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 CHBL1 and AGS1; loss of function.
Any additional useful information about the variant.

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



Sequence information

Variant position:  18
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:   MGSQALPPGPMQTLIFF  D MEATGLPFSQPKVTELCLLA
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                         MGSQALPPGPMQTLIFFDMEATGLPFSQPKVTELCLLA

Mouse                         MGSQTLPHGHMQTLIFLDLEATGLPSSRPEVTELCLLA

Bovine                        MGSRALPPGPVQTLIFLDLEATGLPFSQPKITELCLLA

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
Metal binding 18 – 18 Magnesium 1
Metal binding 18 – 18 Magnesium 2
Metal binding 20 – 20 Magnesium 1
Alternative sequence 1 – 1 M -> MGPGARRQGRIVQGRPEMCFCPPPTPLPPLRILTLGTHTPTPCSSPGSAAGTYPTM. In isoform 1.
Mutagenesis 30 – 30 K -> R. Reduces ubiquitination.


Literature citations

A mutation in TREX1 that impairs susceptibility to granzyme A-mediated cell death underlies familial chilblain lupus.
Lee-Kirsch M.A.; Chowdhury D.; Harvey S.; Gong M.; Senenko L.; Engel K.; Pfeiffer C.; Hollis T.; Gahr M.; Perrino F.W.; Lieberman J.; Hubner N.;
J. Mol. Med. 85:531-537(2007)
Cited for: VARIANT CHBL1 ASN-18; CHARACTERIZATION OF VARIANT CHBL1 ASN-18;

A de novo p.Asp18Asn mutation in TREX1 in a patient with Aicardi-Goutieres syndrome.
Haaxma C.A.; Crow Y.J.; van Steensel M.A.; Lammens M.M.; Rice G.I.; Verbeek M.M.; Willemsen M.A.;
Am. J. Med. Genet. A 152:2612-2617(2010)
Cited for: VARIANT AGS1 ASN-18;

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.