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UniProtKB/Swiss-Prot P17405: Variant p.Ser250Arg

Sphingomyelin phosphodiesterase
Gene: SMPD1
Variant information

Variant position:  250
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 Serine (S) to Arginine (R) at position 250 (S250R, p.Ser250Arg).
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 small size and polar (S) to large size and basic (R)
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 NPDA and NPDB; also found in patients with an intermediate form.
Any additional useful information about the variant.

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



Sequence information

Variant position:  250
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:   RRGSGLPPASRPGAGYWGEY  S KCDLPLRTLESLLSGLGPAG
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                         RRGSGLPPASRPGAGYWGEYSKCDLPLRTLESLLSGLGPAG

Mouse                         RRGSGWPPNSQKGAGFWGEYSKCDLPLRTLESLLKGLGPAG

Bovine                        RRDSGPPPASQPGAGYWGEYSKCDLPLRTLESLLSGLGPAG

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
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.
Beta strand 249 – 251


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;

Seven novel Acid sphingomyelinase gene mutations in Niemann-Pick type A and B patients.
Sikora J.; Pavluu-Pereira H.; Elleder M.; Roelofs H.; Wevers R.A.;
Ann. Hum. Genet. 67:63-70(2003)
Cited for: VARIANTS NPDA ARG-250; TYR-321; SER-465; LEU-477 AND HIS-539; VARIANTS NPDB SER-373 AND ARG-610 DEL;

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;

Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium: disease spectrum and natural course in attenuated patients.
Hollak C.E.; de Sonnaville E.S.; Cassiman D.; Linthorst G.E.; Groener J.E.; Morava E.; Wevers R.A.; Mannens M.; Aerts J.M.; Meersseman W.; Akkerman E.; Niezen-Koning K.E.; Mulder M.F.; Visser G.; Wijburg F.A.; Lefeber D.; Poorthuis B.J.;
Mol. Genet. Metab. 107:526-533(2012)
Cited for: VARIANTS NPDB HIS-91; PRO-105; PRO-163; CYS-230; SER-373; PRO-551 AND ARG-610 DEL; VARIANTS NPDA ARG-250; SER-465; LEU-477 AND HIS-539;

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.