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UniProtKB/Swiss-Prot P17405: Variant p.Pro186Leu

Sphingomyelin phosphodiesterase
Gene: SMPD1
Variant information

Variant position:  186
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  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:  From Proline (P) to Leucine (L) at position 186 (P186L, p.Pro186Leu).
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:  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:  -3
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 NPDA; reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B.
Any additional useful information about the variant.

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



Sequence information

Variant position:  186
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  631
The length of the canonical sequence.

Location on the sequence:   TCGHWDIFSSWNISLPTVPK  P PPKPPSPPAPGAPVSRILFL
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                         TCGHWDIFSSWNISLPTVPKPPPKPPSPPAPGAPVSRILFL

Mouse                         SCGHWDIFSTWNISLPSVPKPPPKPPSPPAPGAPVSRVLFL

Bovine                        SCGHWDIFSSWNISLPAVPKPPPQPPKPPAPGSPVSRVLFL

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 47 – 631 Sphingomyelin phosphodiesterase
Glycosylation 177 – 177 N-linked (GlcNAc...) asparagine
Mutagenesis 177 – 177 N -> G. Reduces protein levels. Reduces sphingomyelin phosphodiesterase activity. No effect on secretion.


Literature citations

Acid sphingomyelinase deficiency. Phenotype variability with prevalence of intermediate phenotype in a series of twenty-five Czech and Slovak patients. A multi-approach study.
Pavluu-Pereira H.; Asfaw B.; Poupctova H.; Ledvinova J.; Sikora J.; Vanier M.T.; Sandhoff K.; Zeman J.; Novotna Z.; Chudoba D.; Elleder M.;
J. Inherit. Metab. Dis. 28:203-227(2005)
Cited for: VARIANTS NPDA ARG-168; LEU-186; HIS-230; VAL-243; ARG-250; GLU-253; ALA-280; HIS-291; LYS-294; PRO-343; HIS-378; TRP-476; ARG-535 AND SER-579; VARIANT ARG-508; CATALYTIC ACTIVITY; CHARACTERIZATION OF VARIANTS NPDA LEU-186; GLU-253; ALA-280; LYS-294; PRO-343 AND HIS-378;

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.