UniProtKB/SwissProt variant VAR

Variant information

Variant position:

280

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 Alanine (A) to Valine (V) at position 280 (A280V, p.Ala280Val).

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

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 HLD18; decreased function in sphingolipid biosynthetic process; reduced protein levels; increased protein degradation.

Any additional useful information about the variant.

Sequence information

Variant position:

280

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:

323

The length of the canonical sequence.

Location on the sequence:

NEHHDFPNIPGKSLPLVRKI A AEYYDNLPHYNSWIKVLYDF

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                         NEHHDFPNIPGKSLPLVRKIAAEYYDNLPHYNSWIKVLYDF

Mouse                         NEHHDFPNVPGKNLPMVRKIASEYYDDLPHYNSWIKVLYDF

Rat                           NEHHDFPNVPGKNLPLVRKIASEYYDNLPHYNSWIRVLYDF

Bovine                        NEHHDFPNIPGKSLPLVRKIAAEYYDNLPHYNSWIKVLYDF

Chicken                       NEHHDFPNIPGKSLPLVKKIAAEYYDNLPQYNSWIKVLYDF

Xenopus tropicalis            NEHHDFPSVPGKNLPLVRKIAAEYYDPLPKYSSWVKVLYDF

Caenorhabditis elegans        VEHHDFPYITGSNLPKVREIAPEYYQDWQTHDSWVGMMADF

Drosophila                    NEHHDFPAVPGSRLPEVKRIAKEFYDTMPQHTSWTRVLYDF

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	2 – 323	Sphingolipid delta(4)-desaturase DES1

Literature citations

DEGS1-associated aberrant sphingolipid metabolism impairs nervous system function in humans.
Karsai G.; Kraft F.; Haag N.; Korenke G.C.; Haenisch B.; Othman A.; Suriyanarayanan S.; Steiner R.; Knopp C.; Mull M.; Bergmann M.; Schroeder J.M.; Weis J.; Elbracht M.; Begemann M.; Hornemann T.; Kurth I.;
J. Clin. Invest. 129:1229-1239(2019)
Cited for: FUNCTION; CATALYTIC ACTIVITY; SUBCELLULAR LOCATION; INVOLVEMENT IN HLD18; VARIANT HLD18 VAL-280; CHARACTERIZATION OF VARIANT HLD18 VAL-280;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O15121: Variant p.Ala280Val