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UniProtKB/Swiss-Prot P17405: Variant p.Cys91His

Sphingomyelin phosphodiesterase
Gene: SMPD1
Variant information

Variant position:  91
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 Cysteine (C) to Histidine (H) at position 91 (C91H, p.Cys91His).
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:  -3
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; requires 2 nucleotide substitutions.
Any additional useful information about the variant.



Sequence information

Variant position:  91
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:   ARLHRIVPRLRDVFGWGNLT  C PICKGLFTAINLGLKKEPNV
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                         ARLHRIVPRLRDVFGWGNLTCPICKGLFTAINLGLKKEPNV

Mouse                         VKFSAIAPPLQSAFGWQNLTCPACKVLFTALNHGLKKEPNV

Bovine                        AKFIRIAPQLQEAFGWWNLTCPTCKGLFTAIDFGLRNQASV

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
Domain 87 – 171 Saposin B-type
Glycosylation 88 – 88 N-linked (GlcNAc...) asparagine
Disulfide bond 91 – 167
Alternative sequence 106 – 106 Missing. In isoform 4.
Mutagenesis 88 – 88 N -> G. No effect on sphingomyelin phosphodiesterase activity. No effect on secretion.
Helix 90 – 105


Literature citations

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.