UniProtKB/Swiss-Prot Q9HC29: Variant p.Arg334Gln

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

334 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 Glutamine (Q) at position 334 (R334Q, p.Arg334Gln). 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 medium size and polar (Q) 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
Variant description:

In BLAUS; somatic mosaicism in 4.9% to 11% of peripheral blood cells; hyperactive; constitutive NF-kappa-B activation in absence of muramyl dipeptide stimulation; abolishes interaction with LDOC1, ANKHD1, PPP2R3B, ENTR1 and TRIM41; decreases interaction with RIPK2 and PPP1R12C; no effect on interaction with CHMP5. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs104895461 [ dbSNP | Ensembl ]

Sequence information Variant position:

334 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:

LLWAAGQDFQEFLFVFPFSC R QLQCMAKPLSVRTLLFEHCC 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                         LLWAAGQDFQEFLFVFPFSCRQLQCMAKPLSVRTLLFEHCC

Chimpanzee                    LLWAAGRDFQEFLFVFPFSCRQLQCMAKPLSVRTLLFEHCC

Mouse                         LLWATGRSFQEFLFIFPFSCRQLQCVAKPLSLRTLLFEHCC

Bovine                        LLWASGRAFQEFLFVFPFSCRQLQCLVKPLSMRTLLFEHCC

Rabbit                        LLWATGQDFQEFLFVFPFSCRQLQCVARPLSVMTLLFEHCC

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
Domain	293 – 618	NACHT
Alternative sequence	225 – 1040	Missing. In isoform 3.
Mutagenesis	327 – 327	F -> Y. Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation.
Mutagenesis	333 – 333	C -> Y. Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation.
Mutagenesis	334 – 334	R -> A. Increased NF-kappa-B activation in response to muramyl dipeptide stimulation.
Mutagenesis	344 – 344	S -> T. Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation.

Literature citations
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; Blau syndrome polymorphisms in NOD2 identify nucleotide hydrolysis and helical domain 1 as signalling regulators.
Parkhouse R.; Boyle J.P.; Monie T.P.;
FEBS Lett. 588:3382-3389(2014)
Cited for: SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS BLAUS GLN-334; TRP-334; GLY-383; LYS-383; PHE-469; ASP-481; LEU-490; TYR-495; LEU-496; THR-513; CYS-587; ASN-605; PRO-605 AND LYS-670; CHARACTERIZATION OF VARIANTS AND CYS-471; 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; CARD15 mutations in Blau syndrome.
Miceli-Richard C.; Lesage S.; Rybojad M.; Prieur A.M.; Manouvrier-Hanu S.; Hafner R.; Chamaillard M.; Zouali H.; Thomas G.; Hugot J.-P.;
Nat. Genet. 29:19-20(2001)
Cited for: VARIANTS BLAUS GLN-334; TRP-334 AND PHE-469; NOD2-associated pediatric granulomatous arthritis, an expanding phenotype: study of an international registry and a national cohort in Spain.
Rose C.D.; Arostegui J.I.; Martin T.M.; Espada G.; Scalzi L.; Yague J.; Rosenbaum J.T.; Modesto C.; Cristina Arnal M.; Merino R.; Garcia-Consuegra J.; Carballo Silva M.A.; Wouters C.H.;
Arthritis Rheum. 60:1797-1803(2009)
Cited for: VARIANTS BLAUS GLN-334; TRP-334; LYS-383; LEU-490; TYR-495 AND CYS-587; Role of the NOD2 genotype in the clinical phenotype of Blau syndrome and early-onset sarcoidosis.
Okafuji I.; Nishikomori R.; Kanazawa N.; Kambe N.; Fujisawa A.; Yamazaki S.; Saito M.; Yoshioka T.; Kawai T.; Sakai H.; Tanizaki H.; Heike T.; Miyachi Y.; Nakahata T.;
Arthritis Rheum. 60:242-250(2009)
Cited for: VARIANTS BLAUS GLN-334; TRP-334; GLU-382; GLY-383; TYR-495; LEU-496; THR-513; PRO-605 AND LYS-670; Somatic NOD2 mosaicism in Blau syndrome.
de Inocencio J.; Mensa-Vilaro A.; Tejada-Palacios P.; Enriquez-Merayo E.; Gonzalez-Roca E.; Magri G.; Ruiz-Ortiz E.; Cerutti A.; Yaguee J.; Arostegui J.I.;
J. Allergy Clin. Immunol. 0:0-0(2015)
Cited for: VARIANT BLAUS GLN-334; VARIANT SER-268;

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.