UniProtKB/Swiss-Prot Q96P20: Variant p.Asp305Asn

NACHT, LRR and PYD domains-containing protein 3
Gene: NLRP3
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Variant information Variant position:

305 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 Aspartate (D) to Asparagine (N) at position 305 (D305N, p.Asp305Asn). 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
Variant description:

In CINCA and MWS; spontaneous polymerization into inflammasome speck. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs121908153 [ dbSNP | Ensembl ]

Sequence information Variant position:

305 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

1036 The length of the canonical sequence.
Location on the sequence:

PPIHKIVRKPSRILFLMDGF D ELQGAFDEHIGPLCTDWQKA 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                         PPIHKIVRKPSRILFLMDGFDELQGAFDEHIGPLCTDWQKA

Rhesus macaque                PPIRKIVSKPSRILFLMDGFDELQGAFDEHIGPLCTDWQKA

Mouse                         PPVCKILRKPSRILFLMDGFDELQGAFDEHIGEVCTDWQKA

Rat                           PPVCKILCKPSRILFLMDGFDELQGAFDEHIEEVCTDWQKA

Bovine                        PPIGKIVSKPSRILFLMDGFDELQGAFDEHTEALCTNWRKV

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 – 1036	NACHT, LRR and PYD domains-containing protein 3
Domain	220 – 536	NACHT
Modified residue	295 – 295	Phosphoserine
Mutagenesis	302 – 306	DGFDE -> AGFAAAGFNA. In Walker B mutant; abolished ATPase activity. Abolished binding to small-inhibitor MCC950.
Helix	304 – 306

Literature citations
The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response.
Baroja-Mazo A.; Martin-Sanchez F.; Gomez A.I.; Martinez C.M.; Amores-Iniesta J.; Compan V.; Barbera-Cremades M.; Yaguee J.; Ruiz-Ortiz E.; Anton J.; Bujan S.; Couillin I.; Brough D.; Arostegui J.I.; Pelegrin P.;
Nat. Immunol. 15:738-748(2014)
Cited for: SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANT FCAS1/MWS TRP-262; CHARACTERIZATION OF VARIANT CINCA ASN-305; CHARACTERIZATION OF VARIANT CINCA/MWS MET-350; MCC950 closes the active conformation of NLRP3 to an inactive state.
Tapia-Abellan A.; Angosto-Bazarra D.; Martinez-Banaclocha H.; de Torre-Minguela C.; Ceron-Carrasco J.P.; Perez-Sanchez H.; Arostegui J.I.; Pelegrin P.;
Nat. Chem. Biol. 15:560-564(2019)
Cited for: FUNCTION; CATALYTIC ACTIVITY; ACTIVITY REGULATION; MUTAGENESIS OF 302-ASP--GLU-306; CHARACTERIZATION OF VARIANT CINCA ASN-305; New mutations of CIAS1 that are responsible for Muckle-Wells syndrome and familial cold urticaria: a novel mutation underlies both syndromes.
Dode C.; Le Du N.; Cuisset L.; Letourneur F.; Berthelot J.-M.; Vaudour G.; Meyrier A.; Watts R.A.; Scott D.G.I.; Nicholls A.; Granel B.; Frances C.; Garcier F.; Edery P.; Boulinguez S.; Domergues J.-P.; Delpech M.; Grateau G.;
Am. J. Hum. Genet. 70:1498-1506(2002)
Cited for: VARIANT FCAS1 MET-200; VARIANTS MWS ASN-305; MET-350; THR-441 AND ARG-571; VARIANT FCAS1/MWS TRP-262; Chronic infantile neurological cutaneous and articular syndrome is caused by mutations in CIAS1, a gene highly expressed in polymorphonuclear cells and chondrocytes.
Feldmann J.; Prieur A.-M.; Quartier P.; Berquin P.; Certain S.; Cortis E.; Teillac-Hamel D.; Fischer A.; de Saint Basile G.;
Am. J. Hum. Genet. 71:198-203(2002)
Cited for: VARIANTS CINCA ASN-305; LYS-308; SER-311; ARG-360; ASN-438; SER-575 AND THR-664; TISSUE SPECIFICITY; De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases.
Aksentijevich I.; Nowak M.; Mallah M.; Chae J.J.; Watford W.T.; Hofmann S.R.; Stein L.; Russo R.; Goldsmith D.; Dent P.; Rosenberg H.F.; Austin F.; Remmers E.F.; Balow J.E. Jr.; Rosenzweig S.; Komarow H.; Shoham N.G.; Wood G.; Jones J.; Mangra N.; Carrero H.; Adams B.S.; Moore T.L.; Schikler K.; Hoffman H.; Lovell D.J.; Lipnick R.; Barron K.; O'Shea J.J.; Kastner D.L.; Goldbach-Mansky R.;
Arthritis Rheum. 46:3340-3348(2002)
Cited for: VARIANTS CINCA HIS-266; ASN-305; LEU-525 AND CYS-572; Clinical and genetic heterogeneity among Spanish patients with recurrent autoinflammatory syndromes associated with the CIAS1/PYPAF1/NALP3 gene.
Arostegui J.I.; Aldea A.; Modesto C.; Rua M.J.; Argueelles F.; Gonzalez-Ensenat M.A.; Ramos E.; Rius J.; Plaza S.; Vives J.; Yaguee J.;
Arthritis Rheum. 50:4045-4050(2004)
Cited for: VARIANTS FCAS1 MET-200; PRO-307 AND LYS-490; VARIANT CINCA ASN-305; VARIANT MWS MET-350; Molecular basis of the spectral expression of CIAS1 mutations associated with phagocytic cell-mediated autoinflammatory disorders CINCA/NOMID, MWS, and FCU.
Neven B.; Callebaut I.; Prieur A.-M.; Feldmann J.; Bodemer C.; Lepore L.; Derfalvi B.; Benjaponpitak S.; Vesely R.; Sauvain M.J.; Oertle S.; Allen R.; Morgan G.; Borkhardt A.; Hill C.; Gardner-Medwin J.; Fischer A.; de Saint Basile G.;
Blood 103:2809-2815(2004)
Cited for: VARIANTS CINCA LEU-262; PRO-262; ASN-305; GLY-305; SER-311; MET-350; ASP-356; PRO-407; ILE-438; CYS-572 AND PHE-634;

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.