UniProtKB/Swiss-Prot P02649: Variant p.Arg246Cys

Apolipoprotein E
Gene: APOE
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Variant information Variant position:

246 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 Arginine (R) to Cysteine (C) at position 246 (R246C, p.Arg246Cys). 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 basic (R) to medium size and polar (C) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-3 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 ApoE2 Dunedin. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs121918395 [ dbSNP | Ensembl ]

Sequence information Variant position:

246 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:

QAWGERLRARMEEMGSRTRD R LDEVKEQVAEVRAKLEEQAQ 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                         QAWGERLRARMEEMGSRTRDRLDEVKEQVAEVRAKLEEQAQ

Gorilla                       QAWGERLRARMEEMGSRTRDRLDEVKEQVAEVRAKLEEQAQ

                              DALGQQLRGQLEEMSSRARGHLEEMREQIQEVRVKMEEQAD

Rhesus macaque                QA---KLRARMEEMGSRTRDRLDEVKEQVAEVRAKLEEQAQ

Chimpanzee                    QAWGERLRARMEEMGSRTRDRLDEVKEQVAEVRAKLEEQAQ

Mouse                         QAFGDRIRGRLEEVGNQARDRLEEVREHMEEVRSKMEEQTQ

Rat                           QALSDRIRGRLEEVGNQARDRLEEVREQMEEVRSKMEEQTQ

Pig                           EAWGQKLRGRLEEMGSRTRDRLDEMRDELEEVRTKVEEQGS

Bovine                        EAWRQKLHGRLEEVGVRAQDRLDKIRQQLEEVHAKVEEQGN

Rabbit                        QAWGERLRGHLEEVGSRARDRLNEVREQVEEVRVKVEEQAP

Sheep                         EAWRQKLHGRLEEVGVRAQDRLDKMRQQLEEVRSKVEEQGS

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	234 – 255	8
Region	80 – 255	8 X 22 AA approximate tandem repeats
Region	210 – 290	Lipid-binding and lipoprotein association

Literature citations
Apolipoprotein E2-Dunedin (228 Arg replaced by Cys): an apolipoprotein E2 variant with normal receptor-binding activity.
Wardell M.R.; Rall S.C. Jr.; Brennan S.O.; Nye E.R.; George P.M.; Janus E.D.; Weisgraber K.H.;
J. Lipid Res. 31:535-543(1990)
Cited for: VARIANT CYS-246;

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.