UniProtKB/SwissProt variant VAR

Variant information

Variant position:

393

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 Tryptophan (W) to Glycine (G) at position 393 (W393G, p.Trp393Gly).

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 large size and aromatic (W) to glycine (G)

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; low sphingomyelin degradation rates.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs120074125 [ dbSNP | Ensembl ]

Sequence information

Variant position:

393

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:

PYPGLRLISLNMNFCSRENF W LLINSTDPAGQLQWLVGELQ

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                         PYPGLRLISLNMNFCSRENFWLLINSTDPAGQLQWLVGELQ

Mouse                         PRPGLRLISLNMNFCSRENFWLLINSTDPAGQLQWLVEELQ

Bovine                        PRPGLRLISLNMNFCSRENFWLLINSTDPAGQLQWLVGELQ

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
Glycosylation	397 – 397	N-linked (GlcNAc...) asparagine
Disulfide bond	387 – 433
Alternative sequence	365 – 420	Missing. In isoform 3.
Alternative sequence	377 – 420	Missing. In isoform 2.
Mutagenesis	397 – 397	N -> G. Reduces sphingomyelin phosphodiesterase activity. No effect on secretion.
Helix	392 – 395

Literature citations

A family with visceral course of Niemann-Pick disease, macular halo syndrome and low sphingomyelin degradation rate.
Sperl W.; Bart G.; Vanier M.T.; Christomanou H.; Baldissera I.; Steichensdorf E.; Paschke E.;
J. Inherit. Metab. Dis. 17:93-103(1994)
Cited for: VARIANT NPDB GLY-393;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P17405: Variant p.Trp393Gly