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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q96P20: Variant p.Asp21His

NACHT, LRR and PYD domains-containing protein 3
Gene: NLRP3
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Variant information Variant position: help 21 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Aspartate (D) to Histidine (H) at position 21 (D21H, p.Asp21His). 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: help Change from medium size and acidic (D) to medium size and polar (H) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In KEFH; does not affect ability to homooligomerize into ordered polymers. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 21 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1036 The length of the canonical sequence.
Location on the sequence: help MKMASTRCKLARYLEDLEDV D LKKFKMHLEDYPPQKGCIPL 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         MKMASTRCKLARYLEDLEDVDLKKFKMHLEDYPPQKGCIPL

Rhesus macaque                MKMASTRCKLARYLEDLEDVDLKKFKMHLEDYPPQKGCISL

Mouse                         --MTSVRCKLAQYLEDLEDVDLKKFKMHLEDYPPEKGCIPV

Rat                           MKMMSVRCKLAQYLEDLEDVDLKKFKMHLEDYPPEKGCVPI

Bovine                        MRMVSVRCKLARYLEDLEDIDFKKFKMHLEDYPSQKGCTSI
Sequence annotation in neighborhood: help 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 1 – 93 Pyrin
Modified residue 5 – 5 Phosphoserine
Modified residue 13 – 13 Phosphotyrosine
Disulfide bond 8 – 108 Redox-active
Mutagenesis 5 – 5 S -> A. Decreased phosphorylation; increased activation of the NLRP3 inflammasome.
Mutagenesis 5 – 5 S -> DE. Mimics phosphorylation state; decreased activation of the NLRP3 inflammasome.
Mutagenesis 7 – 7 R -> E. Impaired ability to homooligomerize into ordered polymers.
Mutagenesis 15 – 15 E -> R. Impaired ability to homooligomerize into ordered polymers. Complete loss of PYCARD/ASC filament nucleation.
Mutagenesis 23 – 23 K -> E. Complete loss of PYCARD/ASC filament nucleation; when associated with E-24.
Mutagenesis 24 – 24 K -> E. Complete loss of PYCARD/ASC filament nucleation; when associated with E-23.
Mutagenesis 27 – 27 M -> E. Impaired ability to homooligomerize into ordered polymers. Complete loss of PYCARD/ASC filament nucleation.
Mutagenesis 31 – 31 D -> V. Impaired ability to homooligomerize into ordered polymers. Decreased PYCARD/ASC filament nucleation.
Helix 19 – 30



Literature citations
Directionality of PYD filament growth determined by the transition of NLRP3 nucleation seeds to ASC elongation.
Hochheiser I.V.; Behrmann H.; Hagelueken G.; Rodriguez-Alcazar J.F.; Kopp A.; Latz E.; Behrmann E.; Geyer M.;
Sci. Adv. 8:eabn7583-eabn7583(2022)
Cited for: STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) OF 3-110; ACTIVITY REGULATION; INTERACTION WITH PYCARD; MUTAGENESIS OF ARG-7; GLU-15; 23-LYS-LYS-24; MET-27; ASP-31; ARG-43; HIS-51; ALA-77; ARG-80 AND ARG-81; CHARACTERIZATION OF VARIANT KEFH HIS-21; Keratoendotheliitis fugax hereditaria: a novel cryopyrin-associated periodic syndrome caused by a mutation in the nucleotide-binding domain, leucine-rich repeat family, pyrin domain-containing 3 (NLRP3) gene.
Turunen J.A.; Wedenoja J.; Repo P.; Jaervinen R.S.; Jaentti J.E.; Moertenhumer S.; Riikonen A.S.; Lehesjoki A.E.; Majander A.; Kivelae T.T.;
Am. J. Ophthalmol. 188:41-50(2018)
Cited for: VARIANT KEFH HIS-21; INVOLVEMENT IN KEFH;
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.