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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P17405: Variant p.Tyr539His

Sphingomyelin phosphodiesterase
Gene: SMPD1
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Variant information Variant position: help 539 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 Tyrosine (Y) to Histidine (H) at position 539 (Y539H, p.Tyr539His). 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 (Y) to medium size and polar (H) 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 NPDA. Any additional useful information about the variant.


Sequence information Variant position: help 539 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 YILNLTQANIPGAIPHWQLL Y RARETYGLPNTLPTAWHNLV 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                         YILNLTQANIPGAIPHWQLLYRARETYGLPNTLPTAWHNLV

Mouse                         YILNLTQANAAGGTPSWKRLYRARETYGLPDAMPASWHNLV

Bovine                        YIMNLTEANEPGATPHWYLLYRARETYGLPNALPTAWHDLV
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
Chain 254 – 631 Sphingomyelin phosphodiesterase, processed form
Glycosylation 522 – 522 N-linked (GlcNAc...) asparagine
Mutagenesis 522 – 522 N -> G. Loss of sphingomyelin phosphodiesterase activity. Loss of secretion.
Beta strand 536 – 540



Literature citations
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 (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.