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UniProtKB/Swiss-Prot P17405: Variant p.Gln525His

Sphingomyelin phosphodiesterase
Gene: SMPD1
Variant information

Variant position:  525
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 Glutamine (Q) to Histidine (H) at position 525 (Q525H, p.Gln525His).
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 polar.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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 64% of wild-type activity.
Any additional useful information about the variant.



Sequence information

Variant position:  525
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:   NYSGSSHVVLDHETYILNLT  Q ANIPGAIPHWQLLYRARETY
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                         NYSGSSHVVLDHETYILNLTQANIPGAIPHWQLLYRARETY

Mouse                         NYPGSSHVVLDHETYILNLTQANAAGGTPSWKRLYRARETY

Bovine                        NYSGSSHVVLDHETYIMNLTEANEPGATPHWYLLYRARETY

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
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.
Helix 523 – 526


Literature citations

Identification and characterization of eight novel SMPD1 mutations causing types A and B Niemann-Pick disease.
Desnick J.P.; Kim J.; He X.; Wasserstein M.P.; Simonaro C.M.; Schuchman E.H.;
Mol. Med. 16:316-321(2010)
Cited for: VARIANTS NPDA ARG-211 AND HIS-253; VARIANTS NPDB MET-314; ARG-427 AND HIS-525; CHARACTERIZATION OF VARIANTS NPDA ARG-211 AND HIS-253; CHARACTERIZATION OF VARIANTS NPDB MET-314; ARG-427 AND HIS-525;

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.