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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P17405: Variant p.Leu227Met

Sphingomyelin phosphodiesterase
Gene: SMPD1
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Variant information Variant position: help 227 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 Leucine (L) to Methionine (M) at position 227 (L227M, p.Leu227Met). 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 Similar physico-chemical property. Both residues are medium size and hydrophobic. 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. Any additional useful information about the variant.


Sequence information Variant position: help 227 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 TDLHWDHDYLEGTDPDCADP L CCRRGSGLPPASRPGAGYWG 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                         TDLHWDHDYLEGTDPDCADPLCCRRGSGLPPASRPGAGYWG

Mouse                         TDLHWDHEYLEGTDPYCADPLCCRRGSGWPPNSQKGAGFWG

Bovine                        TDLHWDHDYLEGTDPNCENPLCCRRDSGPPPASQPGAGYWG
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
Binding site 208 – 208
Binding site 210 – 210
Disulfide bond 223 – 228
Mutagenesis 225 – 225 D -> A. Does not affect cleavage by CASP7.
Mutagenesis 233 – 233 S -> A. No effect on sphingomyelin phosphodiesterase activity. No effect on endolysosome location. No effect on phosphorylation by PRKCD.
Beta strand 224 – 227



Literature citations
The demographics and distribution of type B Niemann-Pick disease: novel mutations lead to new genotype/phenotype correlations.
Simonaro C.M.; Desnick R.J.; McGovern M.M.; Wasserstein M.P.; Schuchman E.H.;
Am. J. Hum. Genet. 71:1413-1419(2002)
Cited for: VARIANTS NPDB VAL-51; TRP-94; PRO-139; ARG-159; PRO-198; CYS-202; MET-227; CYS-230; ASP-234; SER-247; ARG-250; HIS-291; ALA-325; ARG-332; ASP-359; HIS-378; LEU-378; PRO-381; VAL-415; TYR-423; ARG-433; PRO-434; CYS-437; VAL-454; ASP-458; TRP-476; LEU-477; LEU-482; ASN-490; SER-496; CYS-498; GLN-516; VAL-517; ARG-535; PRO-551; ASN-578; HIS-602 AND PRO-602; VARIANT VAL-487;
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.