UniProtKB/SwissProt variant VAR

Variant information

Variant position:

294

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 Lysine (K) at position 294 (Q294K, p.Gln294Lys).

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 (Q) to large size and basic (K)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

1

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 NPDA; strongly reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs120074128 [ dbSNP | Ensembl ]

Sequence information

Variant position:

294

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:

MVYWTGDIPAHDVWHQTRQD Q LRALTTVTALVRKFLGPVPV

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                         MVYWTGDIPAHDVWHQTRQDQLRALTTVTALVRKFLGPVPV

Mouse                         MVYWTGDIPAHDVWQQSRQDQLRALTTITDLVRKFLGPVPV

Bovine                        MVYWTGDIPAHNIWQQSRQDQLRALTTITALVKKFLGPVPV

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
Metal binding	280 – 280	Zinc 1
Metal binding	280 – 280	Zinc 2
Helix	291 – 309

Literature citations

Two novel mutations in patients with atypical phenotypes of acid sphingomyelinase deficiency.
Pavluu H.; Elleder M.;
J. Inherit. Metab. Dis. 20:615-616(1997)
Cited for: VARIANTS NPDA LYS-294 AND PRO-343;

Acid sphingomyelinase: identification of nine novel mutations among Italian Niemann Pick type B patients and characterization of in vivo functional in-frame start codon.
Pittis M.G.; Ricci V.; Guerci V.I.; Marcais C.; Ciana G.; Dardis A.; Gerin F.; Stroppiano M.; Vanier M.T.; Filocamo M.; Bembi B.;
Hum. Mutat. 24:186-187(2004)
Cited for: VARIANTS NPDB PRO-105; PRO-227; CYS-246; THR-283; LYS-294 AND ILE-384;

Acid sphingomyelinase deficiency. Phenotype variability with prevalence of intermediate phenotype in a series of twenty-five Czech and Slovak patients. A multi-approach study.
Pavluu-Pereira H.; Asfaw B.; Poupctova H.; Ledvinova J.; Sikora J.; Vanier M.T.; Sandhoff K.; Zeman J.; Novotna Z.; Chudoba D.; Elleder M.;
J. Inherit. Metab. Dis. 28:203-227(2005)
Cited for: VARIANTS NPDA ARG-168; LEU-186; HIS-230; VAL-243; ARG-250; GLU-253; ALA-280; HIS-291; LYS-294; PRO-343; HIS-378; TRP-476; ARG-535 AND SER-579; VARIANT ARG-508; CATALYTIC ACTIVITY; CHARACTERIZATION OF VARIANTS NPDA LEU-186; GLU-253; ALA-280; LYS-294; PRO-343 AND HIS-378;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P17405: Variant p.Gln294Lys