UniProtKB/SwissProt variant VAR

Variant information

Variant position:

132

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 Valine (V) to Alanine (A) at position 132 (V132A, p.Val132Ala).

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 hydrophobic (V) to small size and hydrophobic (A)

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; expresses protein level comparable to wild-type SMPD1 expressing cells; retains 13% residual enzyme activity.

Any additional useful information about the variant.

Sequence information

Variant position:

132

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:

ARVGSVAIKLCNLLKIAPPA V CQSIVHLFEDDMVEVWRRSV

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                         ARVGSVAIKLCNLLKIAPPAVCQSIVHLFEDDMVEVWRRSV

Mouse                         ARVGSVAIKICKMLNIAPLDVCQSAVHLFEDDVVEVWTRSV

Bovine                        AWVGSVAIKLCVLLKIAPPAVCQSAVQLFEDDMVEVWTRSV

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.

Type	Positions	Description
Chain	47 – 631	Sphingomyelin phosphodiesterase
Domain	87 – 171	Saposin B-type
Disulfide bond	91 – 167
Disulfide bond	94 – 159
Disulfide bond	122 – 133
Mutagenesis	151 – 151	S -> A. No effect on sphingomyelin phosphodiesterase activity. No effect on subcellular location. No effect on phosphorylation by PRKCD.
Helix	130 – 150

Literature citations

Functional in vitro characterization of 14 SMPD1 mutations identified in Italian patients affected by Niemann Pick type B disease.
Dardis A.; Zampieri S.; Filocamo M.; Burlina A.; Bembi B.; Pittis M.G.;
Hum. Mutat. 26:164-164(2005)
Cited for: VARIANTS NPDB ALA-132 AND TYR-565; CHARACTERIZATION OF VARIANTS NPDB PRO-105; ALA-132; PRO-227; CYS-246; THR-283; TYR-565; HIS-602 AND PRO-602;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P17405: Variant p.Val132Ala