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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O43586: Variant p.Glu250Lys

Proline-serine-threonine phosphatase-interacting protein 1
Gene: PSTPIP1
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Variant information Variant position: help 250 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 Glutamate (E) to Lysine (K) at position 250 (E250K, p.Glu250Lys). 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 (E) to large size and basic (K) 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 AICZC; pathogenic; markedly increased binding to MEFV. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 250 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 416 The length of the canonical sequence.
Location on the sequence: help ALWVHSNQLSMQCVKDDELY E EVRLTLEGCSIDADIDSFIQ 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                         ALWVHSNQLSMQCVKDDELYEEVRLTLEGCSIDADIDSFIQ

Mouse                         ALWVHCNQLSMQCVKDDELYEEVRLTLEGCDVEGDINGFIQ
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 – 416 Proline-serine-threonine phosphatase-interacting protein 1
Domain 5 – 264 F-BAR
Mutagenesis 232 – 232 W -> A. Abolishes binding to MEFV. Cytoplasmic filaments are finer with fewer branches.
Mutagenesis 266 – 266 D -> N. No effect on filament formation.
Helix 167 – 257



Literature citations
Brief report: genotype, phenotype, and clinical course in five patients with PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne).
Demidowich A.P.; Freeman A.F.; Kuhns D.B.; Aksentijevich I.; Gallin J.I.; Turner M.L.; Kastner D.L.; Holland S.M.;
Arthritis Rheum. 64:2022-2027(2012)
Cited for: VARIANTS PAPA THR-230 AND GLN-250; VARIANT AICZC LYS-250; INVOLVEMENT IN PAPA; INVOLVEMENT IN AICZC; Single amino acid charge switch defines clinically distinct proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1)-associated inflammatory diseases.
Holzinger D.; Fassl S.K.; de Jager W.; Lohse P.; Roehrig U.F.; Gattorno M.; Omenetti A.; Chiesa S.; Schena F.; Austermann J.; Vogl T.; Kuhns D.B.; Holland S.M.; Rodriguez-Gallego C.; Lopez-Almaraz R.; Arostegui J.I.; Colino E.; Roldan R.; Fessatou S.; Isidor B.; Poignant S.; Ito K.; Epple H.J.; Bernstein J.A.; Jeng M.; Frankovich J.; Lionetti G.; Church J.A.; Ong P.Y.; LaPlant M.; Abinun M.; Skinner R.; Bigley V.; Sachs U.J.; Hinze C.; Hoppenreijs E.; Ehrchen J.; Foell D.; Chae J.J.; Ombrello A.; Aksentijevich I.; Sunderkoetter C.; Roth J.;
J. Allergy Clin. Immunol. 136:1337-1345(2015)
Cited for: VARIANTS AICZC LYS-250 AND LYS-257; CHARACTERIZATION OF VARIANTS AICZC LYS-250 AND GLN-250; INVOLVEMENT IN AICZC; Haematological involvement associated with a mild autoinflammatory phenotype, in two patients carrying the E250K mutation of PSTPIP1.
Belelli E.; Passarelli C.; Pardeo M.; Holzinger D.; De Benedetti F.; Insalaco A.;
Clin. Exp. Rheumatol. 35 108:113-115(2017)
Cited for: VARIANT AICZC LYS-250; INVOLVEMENT IN AICZC; The expanding spectrum of clinical phenotypes associated with PSTPIP1 mutations: from PAPA to PAMI syndrome and beyond.
Kloetgen H.W.; Beltraminelli H.; Yawalkar N.; van Gijn M.E.; Holzinger D.; Borradori L.;
Br. J. Dermatol. 178:982-983(2018)
Cited for: VARIANT AICZC LYS-250; INVOLVEMENT IN AICZC; PSTPIP1-associated myeloid-related proteinemia inflammatory syndrome: A rare cause of childhood neutropenia associated with systemic inflammation and hyperzincemia.
Hashmi S.K.; Bergstrom K.; Bertuch A.A.; Despotovic J.M.; Muscal E.; Xia F.; Bi W.; Marcogliese A.; Diaz R.;
Pediatr. Blood Cancer 66:e27439-e27439(2019)
Cited for: VARIANTS AICZC LYS-250 AND LYS-257; INVOLVEMENT IN AICZC; PAMI syndrome: A rare cause that can be easily misdiagnosed.
Xu X.M.; Huang H.; Ding F.; Yang Z.; Wang J.; Jin Y.L.;
Am. J. Med. Genet. A 185:3074-3082(2021)
Cited for: VARIANT AICZC LYS-250; INVOLVEMENT IN AICZC; Strong inflammatory signatures in the neutrophils of PAMI syndrome.
Zheng W.; Fan X.; Yang Z.; Shangguan Y.; Jin T.; Liu Y.; Huang J.; Ye X.; Zhou Q.; Li X.;
Front. Immunol. 13:926087-926087(2022)
Cited for: VARIANT AICZC LYS-250; INVOLVEMENT IN AICZC;
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.