UniProtKB/Swiss-Prot Q9HC29: Variant p.Arg702Trp

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

702 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 Arginine (R) to Tryptophan (W) at position 702 (R702W, p.Arg702Trp). 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 large size and aromatic (W) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-3 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 IBD1 and YAOS; associated with disease susceptibility; decreased NF-kappa-B activation in response to muramyl dipeptide stimulation; no disruption of NOD2-CARD9 interaction; decreases half-life of protein; abolishes interaction with ANKHD1, ENTR1 and TRIM41; increases interaction with RIPK2 and PPP2R3B; decreases interaction with LDOC1 and PPP1R12C; no effect on interaction with CHMP5; decreased NF-kappa-B activation in response to muramyl dipeptide stimulation. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs2066844 [ dbSNP | Ensembl ]

Sequence information Variant position:

702 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:

LSREHWGLLAECQTSEKALL R RQACARWCLARSLRKHFHSI 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                         LSREHWGLLAECQTSEKALLRRQACARWCLARSLRKHFHSI

Chimpanzee                    LSREHWGLLAECQTSEKALLRRQACARWCLARSLRKHFHSI

Mouse                         LSQQHRDLLAACQVSERVLLQRQARARSCLAHSLREHFHSI

Bovine                        LSQEHRSLLAECQASETALLRRWDCVRRCLTRSLREHFRSI

Rabbit                        LSREHRDLLAACQASERSLLRRRACARWCLARSLHKHFRSI

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 – 1040	Nucleotide-binding oligomerization domain-containing protein 2
Alternative sequence	225 – 1040	Missing. In isoform 3.
Mutagenesis	690 – 690	L -> P. Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation.
Mutagenesis	691 – 691	A -> T. Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation.
Mutagenesis	710 – 710	C -> Y. Constitutive NF-kappa-B activation; when associated with R-680.
Mutagenesis	714 – 714	S -> N. Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation.
Mutagenesis	719 – 719	F -> I. Constitutive NF-kappa-B activation; when associated with R-731.

Literature citations
Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease.
Hugot J.-P.; Chamaillard M.; Zouali H.; Lesage S.; Cezard J.-P.; Belaiche J.; Almer S.; Tysk C.; O'Morain C.A.; Gassull M.; Binder V.; Finkel Y.; Cortot A.; Modigliani R.; Laurent-Puig P.; Gower-Rousseau C.; Macry J.; Colombel J.-F.; Sahbatou M.; Thomas G.;
Nature 411:599-603(2001)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2); INVOLVEMENT IN IBD1; VARIANTS IBD1 THR-140; ARG-157; CYS-235; ARG-248; ASN-291; SER-294; VAL-301; TRP-311; VAL-348; ARG-352; CYS-373; SER-414; LEU-431; VAL-432; LYS-441; THR-612; VAL-612; TRP-684; TRP-702; CYS-703; CYS-713; GLY-725; VAL-755; VAL-758; LYS-778; MET-793; LYS-843; SER-853; VAL-863; THR-885; ARG-908 AND ASP-924; VARIANTS MET-189; SER-268; SER-289; ASP-918 AND ILE-955; Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn's disease.
Inohara N.; Ogura Y.; Fontalba A.; Gutierrez O.; Pons F.; Crespo J.; Fukase K.; Inamura S.; Kusumoto S.; Hashimoto M.; Foster S.J.; Moran A.P.; Fernandez-Luna J.L.; Nunez G.;
J. Biol. Chem. 278:5509-5512(2003)
Cited for: FUNCTION; VARIANTS IBD1 TRP-702; ARG-908 AND 1007-LEU--LEU-1040 DELINS PRO; CHARACTERIZATION OF VARIANTS IBD1 TRP-702; ARG-908 AND 1007-LEU--LEU-1040 DELINS PRO; Gene-environment interaction modulated by allelic heterogeneity in inflammatory diseases.
Chamaillard M.; Philpott D.; Girardin S.E.; Zouali H.; Lesage S.; Chareyre F.; Bui T.H.; Giovannini M.; Zaehringer U.; Penard-Lacronique V.; Sansonetti P.J.; Hugot J.P.; Thomas G.;
Proc. Natl. Acad. Sci. U.S.A. 100:3455-3460(2003)
Cited for: FUNCTION; VARIANTS BLAUS GLN-334; TRP-334 AND PHE-469; VARIANTS IBD1 TRP-702; VAL-863 AND 1007-LEU--LEU-1040 DELINS PRO; CHARACTERIZATION OF VARIANTS BLAUS GLN-334; TRP-334 AND PHE-469; CHARACTERIZATION OF VARIANTS IBD1 TRP-702; VAL-863 AND 1007-LEU--LEU-1040 DELINS PRO; 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; The molecular chaperone HSP70 binds to and stabilizes NOD2, an important protein involved in Crohn disease.
Mohanan V.; Grimes C.L.;
J. Biol. Chem. 289:18987-18998(2014)
Cited for: INTERACTION WITH HSPA1A; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS IBD1 TRP-702 AND ARG-908; Characterization and Genetic Analyses of New Genes Coding for NOD2 Interacting Proteins.
Thiebaut R.; Esmiol S.; Lecine P.; Mahfouz B.; Hermant A.; Nicoletti C.; Parnis S.; Perroy J.; Borg J.P.; Pascoe L.; Hugot J.P.; Ollendorff V.;
PLoS ONE 11:E0165420-E0165420(2016)
Cited for: INTERACTION WITH ANKHD1; C10ORF67; CHMP5; DOCK7; ENTR1; KRT15; LDOC1; PPP1R12C; PPP2R3B; RIPK2; TRIM41 AND VIM; INDUCTION; CHARACTERIZATION OF VARIANTS IBD1 TRP-702 AND ARG-908; CHARACTERIZATION OF VARIANT BLAUS GLN-334; Regulation of IL-8 and IL-1beta expression in Crohn's disease associated NOD2/CARD15 mutations.
Li J.; Moran T.; Swanson E.; Julian C.; Harris J.; Bonen D.K.; Hedl M.; Nicolae D.L.; Abraham C.; Cho J.H.;
Hum. Mol. Genet. 13:1715-1725(2004)
Cited for: VARIANTS IBD1 TRP-702; ARG-908 AND 1007-LEU--LEU-1040 DELINS PRO; CHARACTERIZATION OF VARIANTS IBD1 TRP-702; ARG-908 AND 1007-LEU--LEU-1040 DELINS PRO; FUNCTION; Eight novel CARD15 variants detected by DNA sequence analysis of the CARD15 gene in 111 patients with inflammatory bowel disease.
Schnitzler F.; Brand S.; Staudinger T.; Pfennig S.; Hofbauer K.; Seiderer J.; Tillack C.; Goke B.; Ochsenkuhn T.; Lohse P.;
Immunogenetics 58:99-106(2006)
Cited for: VARIANTS IBD1 TRP-311; TRP-702; CYS-703; HIS-713; VAL-755; CYS-760; TRP-790 AND ARG-908; VARIANTS SER-268; SER-289; CYS-391; ALA-463; TRP-791; LYS-825 AND VAL-849; A new category of autoinflammatory disease associated with NOD2 gene mutations.
Yao Q.; Zhou L.; Cusumano P.; Bose N.; Piliang M.; Jayakar B.; Su L.C.; Shen B.;
Arthritis Res. Ther. 13:R148-R148(2011)
Cited for: INVOLVEMENT IN YAOS; VARIANT YAOS TRP-702;

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.