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UniProtKB/Swiss-Prot Q9HC29: Variant p.Asp357Ala

Nucleotide-binding oligomerization domain-containing protein 2
Gene: NOD2
Variant information

Variant position:  357
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 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 Alanine (A) at position 357 (D357A, p.Asp357Ala).
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 small size and hydrophobic (A)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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:  Inflammatory bowel disease 1 (IBD1) [MIM:266600]: A chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology. It is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but most frequently it involves the terminal ileum and colon. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints. {ECO:0000269|PubMed:11385576, ECO:0000269|PubMed:15024686, ECO:0000269|PubMed:16485124, ECO:0000269|PubMed:24790089, ECO:0000269|PubMed:24960071, ECO:0000269|PubMed:27812135}. Note=Disease susceptibility is associated with variations 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 IBD1; unknown pathological significance; no disruption of NOD2-CARD9 interaction.
Any additional useful information about the variant.

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



Sequence information

Variant position:  357
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1040
The length of the canonical sequence.

Location on the sequence:   QCMAKPLSVRTLLFEHCCWP  D VGQEDIFQLLLDHPDRVLLT
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                         QCMAKPLSVRTLLFEHCCWPDVGQEDIFQLLLDHPDRVLLT

Chimpanzee                    QCMAKPLSVRTLLFEHCCWPDVGQEDIFQLLLDHPDRVLLT

Mouse                         QCVAKPLSLRTLLFEHCCWPDVAQDDVFQFLLDHPDRVLLT

Bovine                        QCLVKPLSMRTLLFEHCCWPDLGPQDVFQVLLDHPERILLT

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 – 1040 Nucleotide-binding oligomerization domain-containing protein 2
Domain 293 – 618 NACHT
Alternative sequence 225 – 1040 Missing. In isoform 3.


Literature citations

Interaction between NOD2 and CARD9 involves the NOD2 NACHT and the linker region between the NOD2 CARDs and NACHT domain.
Parkhouse R.; Boyle J.P.; Mayle S.; Sawmynaden K.; Rittinger K.; Monie T.P.;
FEBS Lett. 588:2830-2836(2014)
Cited for: INTERACTION WITH CARD9; VARIANTS IBD1 ALA-357; PHE-363 AND VAL-550; VARIANT ALA-463; CHARACTERIZATION OF VARIANTS IBD1 ARG-248; ALA-357; PHE-363; LEU-431; LYS-441; VAL-550; VAL-612 AND TRP-702; CHARACTERIZATION OF VARIANT BLAUS TRP-334; CHARACTERIZATION OF VARIANT ALA-463; MUTAGENESIS OF ASP-379;

Crohn disease: frequency and nature of CARD15 mutations in Ashkenazi and Sephardi/Oriental Jewish families.
Tukel T.; Shalata A.; Present D.; Rachmilewitz D.; Mayer L.; Grant D.; Risch N.; Desnick R.J.;
Am. J. Hum. Genet. 74:623-636(2004)
Cited for: VARIANTS IBD1 ASN-113; ALA-357; PHE-363; VAL-550 AND SER-852;

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.