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UniProtKB/Swiss-Prot Q96P20: Variant p.Thr350Met

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

Variant position:  350
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 Threonine (T) to Methionine (M) at position 350 (T350M, p.Thr350Met).
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 polar (T) to medium size and hydrophobic (M)
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 MWS and CINCA; spontaneous polymerization into inflammasome speck.
Any additional useful information about the variant.

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



Sequence information

Variant position:  350
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:   ILLSSLIRKKLLPEASLLIT  T RPVALEKLQHLLDHPRHVEI
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                         ILLSSLIRKKLLPEASLLITTRPVALEKLQHLLDHPRHVEI

Rhesus macaque                ILLSSLIRKKLLPEASLLITTRPVALEKLQHLLDHPRHVEI

Mouse                         ILLSSLIRKKLLPKASLLITTRPVALEKLQHLLDHPRHVEI

Rat                           ILLSSLIRKKLLPKASLLITTRPVALEKLQHLLDHPRHVEI

Bovine                        ILLSSLIRKRLLPEASLLITTRPVALEKLQHLLGQARHVEI

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 – 1036 NACHT, LRR and PYD domains-containing protein 3
Domain 220 – 536 NACHT


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;

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;

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.