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UniProtKB/Swiss-Prot P17405: Variant p.Pro325Ala

Sphingomyelin phosphodiesterase
Gene: SMPD1
Variant information

Variant position:  325
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 Alanine (A) at position 325 (P325A, p.Pro325Ala).
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:  Change from medium size and hydrophobic (P) to small size and hydrophobic (A)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -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:  In NPDB; results in 1-4% of wild type activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  325
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:   VRKFLGPVPVYPAVGNHEST  P VNSFPPPFIEGNHSSRWLYE
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                         VRKFLGPVPVYPAVGNHESTPVNSFPPPFIEGNHSSRWLYE

Mouse                         VRKFLGPVPVYPAVGNHESTPVNGFPPPFIKGNQSSQWLYE

Bovine                        VKKFLGPVPVYPAVGNHESTPVNGFPPPFIKGNQSSHWLYE

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
Metal binding 320 – 320 Zinc 2
Glycosylation 337 – 337 N-linked (GlcNAc...) asparagine
Mutagenesis 337 – 337 N -> G. No effect on sphingomyelin phosphodiesterase activity. No effect on secretion.
Beta strand 322 – 325


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;

The acid sphingomyelinase sequence variant p.A487V is not associated with decreased levels of enzymatic activity.
Rhein C.; Naumann J.; Muehle C.; Zill P.; Adli M.; Hegerl U.; Hiemke C.; Mergl R.; Moeller H.J.; Reichel M.; Kornhuber J.;
JIMD Rep. 8:1-6(2013)
Cited for: CHARACTERIZATION OF VARIANT NPDB ALA-325; CHARACTERIZATION OF VARIANT VAL-487;

Alleged detrimental mutations in the SMPD1 gene in patients with Niemann-Pick disease.
Rhein C.; Muehle C.; Kornhuber J.; Reichel M.;
Int. J. Mol. Sci. 16:13649-13652(2015)
Cited for: CHARACTERIZATION OF VARIANT NPDB ALA-325; CHARACTERIZATION OF VARIANTS ALA-36; VAL-487 AND ARG-508; CATALYTIC ACTIVITY;

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.