UniProtKB/Swiss-Prot P02649: Variant p.Gln99Lys

Apolipoprotein E
Gene: APOE
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Variant information Variant position:

99 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B 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 99 (Q99K, p.Gln99Lys). 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
Polymorphism:

There are three common APOE alleles identified: APOE*2/APOE-epsilon2/E2, APOE*3/APOE-epsilon3/E3, and APOE*4/APOE-epsilon4/E4. The corresponding ApoE2, ApoE3 and ApoE4 isoforms differentially present Cys and Arg residues at positions 130 and 176. The most common allele in the human population is APOE*3 which sequence is the one displayed in that entry with a Cys at position 130 and an Arg at position 176. Common APOE variants influence lipoprotein metabolism in healthy individuals. Additional variants have been described and are described relative to the three common alleles. Allele APOE*4 is strongly associated with risk for severe COVID-19, increases susceptibility to SARS-CoV-2 infection in neurons and astrocytes (PubMed:33450186). Additional information on the polymorphism described.
Variant description:

In ApoE5 Frankfurt. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs1180612218 [ dbSNP | Ensembl ]

Sequence information Variant position:

99 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

317 The length of the canonical sequence.
Location on the sequence:

RALMDETMKELKAYKSELEE Q LTPVAEETRARLSKELQAAQ 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                         RALMDETMKELKAYKSELEEQLTPVAEETRARLSKELQAAQ

Gorilla                       TALMDETMKELKAYKSELEEQLTPVAEETRARLSKELQAAQ

                              TALMDETMKEVKAYKAELDEQLGPMTSETQARVAKELQAAQ

Rhesus macaque                TTLMDETMKELKAYKSELEEQLSPVAEETRARLSKELQAAQ

Chimpanzee                    TALMDETMKELKAYKSELEEQLTPVAEETRARLSKELQAAQ

Mouse                         TALMEDTMTEVKAYKKELEEQLGPVAEETRARLGKEVQAAQ

Rat                           TVLMEDTMTEVKAYKKELEEQLGPVAEETRARLAKEVQAAQ

Pig                           TELIEESMKEVKAYREELEAQLGPVTQETQARLSKELQAAQ

Bovine                        TALMEETMKEVKAYKEELEGQLGPMAQETQARVSKELQAAQ

Rabbit                        TMLMEETMKEVKAYKSELEEQLSPMAQEHRARLSKELQVAG

Sheep                         TVLMEETMKEVKAYREELEGQLAPMAQETQARVSKELQAAQ

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	19 – 317	Apolipoprotein E
Repeat	80 – 101	1
Region	80 – 255	8 X 22 AA approximate tandem repeats
Glycosylation	93 – 93	N-linked (Glc) (glycation) lysine
Mutagenesis	79 – 79	R -> T. Changes the plasma lipoprotein distribution of ApoE4 to the HDL.
Helix	97 – 99

Literature citations
Characterization of the gene for apolipoprotein E5-Frankfurt (Gln81->Lys, Cys112->Arg) by polymerase chain reaction, restriction isotyping, and temperature gradient gel electrophoresis.
Ruzicka V.; Maerz W.; Russ A.; Fisher E.; Mondorf W.; Gross W.;
Electrophoresis 14:1032-1037(1993)
Cited for: VARIANTS LYS-99 AND ARG-130;

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.