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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P17405: Variant p.Trp246Cys

Sphingomyelin phosphodiesterase
Gene: SMPD1
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Variant information Variant position: help 246 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 Tryptophan (W) to Cysteine (C) at position 246 (W246C, p.Trp246Cys). 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 large size and aromatic (W) to medium size and polar (C) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -2 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 NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. Any additional useful information about the variant.


Sequence information Variant position: help 246 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 631 The length of the canonical sequence.
Location on the sequence: help PLCCRRGSGLPPASRPGAGY W GEYSKCDLPLRTLESLLSGL 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                         PLCCRRGSGLPPASRPGAGYWGEYSKCDLPLRTLESLLSGL

Mouse                         PLCCRRGSGWPPNSQKGAGFWGEYSKCDLPLRTLESLLKGL

Bovine                        PLCCRRDSGPPPASQPGAGYWGEYSKCDLPLRTLESLLSGL
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 47 – 631 Sphingomyelin phosphodiesterase
Disulfide bond 229 – 252
Mutagenesis 233 – 233 S -> A. No effect on sphingomyelin phosphodiesterase activity. No effect on endolysosome location. No effect on phosphorylation by PRKCD.
Mutagenesis 250 – 250 S -> A. No effect on sphingomyelin phosphodiesterase activity. No effect on endolysosome location. No effect on phosphorylation by PRKCD.
Mutagenesis 253 – 253 D -> A. Abolished cleavage by CASP7.



Literature citations
Acid sphingomyelinase: identification of nine novel mutations among Italian Niemann Pick type B patients and characterization of in vivo functional in-frame start codon.
Pittis M.G.; Ricci V.; Guerci V.I.; Marcais C.; Ciana G.; Dardis A.; Gerin F.; Stroppiano M.; Vanier M.T.; Filocamo M.; Bembi B.;
Hum. Mutat. 24:186-187(2004)
Cited for: VARIANTS NPDB PRO-105; PRO-227; CYS-246; THR-283; LYS-294 AND ILE-384; Functional in vitro characterization of 14 SMPD1 mutations identified in Italian patients affected by Niemann Pick type B disease.
Dardis A.; Zampieri S.; Filocamo M.; Burlina A.; Bembi B.; Pittis M.G.;
Hum. Mutat. 26:164-164(2005)
Cited for: VARIANTS NPDB ALA-132 AND TYR-565; CHARACTERIZATION OF VARIANTS NPDB PRO-105; ALA-132; PRO-227; CYS-246; THR-283; TYR-565; HIS-602 AND PRO-602;
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.