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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P17405: Variant p.Ile520Leu

Sphingomyelin phosphodiesterase
Gene: SMPD1
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Variant information Variant position: help 520 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 Isoleucine (I) to Leucine (L) at position 520 (I520L, p.Ile520Leu). 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 520 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 YQIDGNYSGSSHVVLDHETY I LNLTQANIPGAIPHWQLLYR 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                         YQIDGNYSGSSHVVLDHETYILNLTQANIPGAIPHWQLLYR

Mouse                         YQIDGNYPGSSHVVLDHETYILNLTQANAAGGTPSWKRLYR

Bovine                        YQIDGNYSGSSHVVLDHETYIMNLTEANEPGATPHWYLLYR

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
Modified residue 510 – 510 Phosphoserine; by PKC/PRKCD
Glycosylation 505 – 505 N-linked (GlcNAc...) asparagine
Glycosylation 522 – 522 N-linked (GlcNAc...) asparagine
Mutagenesis 505 – 505 N -> G. Loss of sphingomyelin phosphodiesterase activity. Loss of secretion.
Mutagenesis 510 – 510 S -> A. Abolishes constitutive secretion and decreases secretion in response to IL1B. No effect on lysosomal targeting. No effect on sphingomyelin phosphodiesterase activity. No effect on endolysosome location. Abolishes phosphorylation by PRKCD.
Mutagenesis 522 – 522 N -> G. Loss of sphingomyelin phosphodiesterase activity. Loss of secretion.
Beta strand 513 – 520



Literature citations
Spectrum of SMPD1 mutations in Asian-Indian patients with acid sphingomyelinase (ASM)-deficient Niemann-Pick disease.
Ranganath P.; Matta D.; Bhavani G.S.; Wangnekar S.; Jain J.M.; Verma I.C.; Kabra M.; Puri R.D.; Danda S.; Gupta N.; Girisha K.M.; Sankar V.H.; Patil S.J.; Ramadevi A.R.; Bhat M.; Gowrishankar K.; Mandal K.; Aggarwal S.; Tamhankar P.M.; Tilak P.; Phadke S.R.; Dalal A.;
Am. J. Med. Genet. A 170:2719-2730(2016)
Cited for: VARIANTS ALA-36; PHE-510 AND GLY-605; VARIANTS NPDA ARG-216; CYS-230; SER-255; ARG-319; PRO-324; ARG-343; ARG-363; HIS-391; ARG-393; SER-426; ILE-494; HIS-498; ARG-535 AND HIS-602; VARIANTS NPDB PRO-105; PHE-282; ASP-320; CYS-369; SER-465; LEU-520 AND LYS-549;
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.