UniProtKB/Swiss-Prot P02649: Variant p.Arg269Gly

Apolipoprotein E
Gene: APOE
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Variant information Variant position:

269 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 Glycine (G) at position 269 (R269G, p.Arg269Gly). 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 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
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 ApoE3 HB. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs267606661 [ dbSNP | Ensembl ]

Sequence information Variant position:

269 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:

EVKEQVAEVRAKLEEQAQQI R LQAEAFQARLKSWFEPLVED 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                         EVKEQVAEVRAKLEEQAQQIRLQAEAFQARLKSWFEPLVED

Gorilla                       EVKEQVAEVRAKLEEQAQQIRLQAEAFQARLKSWFEPLVED

                              EMREQIQEVRVKMEEQADQIRQKAEAFQARLKSWFEPLLED

Rhesus macaque                EVKEQVAEVRAKLEEQAQQISLQAEAFQARLKSWFEPLVED

Chimpanzee                    EVKEQVAEVRAKLEEQAQQIRLQAEAFQARLKSWFEPLVED

Mouse                         EVREHMEEVRSKMEEQTQQIRLQAEIFQARLKGWFEPIVED

Rat                           EVREQMEEVRSKMEEQTQQIRLQAEIFQARIKGWFEPLVED

Pig                           EMRDELEEVRTKVEEQGSQLRLQAEAFQARLKGWFEPLVED

Bovine                        KIRQQLEEVHAKVEEQGNQMRLQAEAFQARLRSWFEPLVED

Rabbit                        EVREQVEEVRVKVEEQAPQMRLQAEAFQARLKSWFEPLVED

Sheep                         KMRQQLEEVRSKVEEQGSQIRLQAEAFQARLRSWFEPLVED

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
Region	210 – 290	Lipid-binding and lipoprotein association
Region	266 – 317	Homooligomerization
Helix	257 – 283

Literature citations
Characterization of five new mutants in the carboxyl-terminal domain of human apolipoprotein E: no cosegregation with severe hyperlipidemia.
van den Maagdenberg A.M.J.M.; Weng W.; de Bruijn I.H.; de Knijff P.; Funke H.; Smelt A.H.M.; Leuven J.A.G.; van 't Hooft F.M.; Assmann G.; Hofker M.H.; Havekes L.M.; Frants R.R.;
Am. J. Hum. Genet. 52:937-946(1993)
Cited for: VARIANTS GLU-254; GLY-269; GLU-270; HIS-292 AND ARG-314; Apolipoprotein E R112; R251G: a carboxy-terminal variant found in patients with hyperlipidemia and coronary heart disease.
Kang A.K.; Jenkins D.J.A.; Wolever T.M.S.; Huff M.W.; Maguire G.F.; Connelly P.W.; Hegele R.A.;
Mutat. Res. 382:57-65(1997)
Cited for: VARIANTS ARG-130 AND GLY-269;

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.