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UniProtKB/Swiss-Prot P17405: Variant p.His423Tyr

Sphingomyelin phosphodiesterase
Gene: SMPD1
Variant information

Variant position:  423
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 Histidine (H) to Tyrosine (Y) at position 423 (H423Y, p.His423Tyr).
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 medium size and polar (H) to large size and aromatic (Y)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  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:  In NPDB; abolishes enzyme activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  423
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:   GQLQWLVGELQAAEDRGDKV  H IIGHIPPGHCLKSWSWNYYR
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                         GQLQWLVGELQAAEDRGDKVHIIGHIPPGHCLKSWSWNYYR

Mouse                         GQLQWLVEELQAAENRGDKVHIIGHIPPGHCLKSWSWNYYK

Bovine                        GQLQWLVGELQAAEDRGDKVHIIGHIPPGHCLKSWSWNYYR

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
Metal binding 427 – 427 Zinc 2; via tele nitrogen
Disulfide bond 387 – 433
Beta strand 421 – 425


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;

Characterization of common SMPD1 mutations causing types A and B Niemann-Pick disease and generation of mutation-specific mouse models.
Jones I.; He X.; Katouzian F.; Darroch P.I.; Schuchman E.H.;
Mol. Genet. Metab. 95:152-162(2008)
Cited for: CHARACTERIZATION OF VARIANTS NPDA PRO-304 AND LEU-498; CHARACTERIZATION OF VARIANTS NPDB TYR-423 AND ARG-610 DEL; FUNCTION; SUBCELLULAR LOCATION; CATALYTIC ACTIVITY;

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.