UniProtKB/Swiss-Prot P02649: Variant p.Arg292His

Apolipoprotein E
Gene: APOE
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Variant information Variant position:

292 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 Histidine (H) at position 292 (R292H, p.Arg292His). 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 (H) 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
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 ApoE4 PD. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs121918398 [ dbSNP | Ensembl ]

Sequence information Variant position:

292 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:

AEAFQARLKSWFEPLVEDMQ R QWAGLVEKVQAAVGTSAAPV 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                         AEAFQARLKSWFEPLVEDMQRQWAGLVEKVQAAVGTSA---APV

Gorilla                       AEAFQARLKSWFEPLVEDMQRQWAGLVEKVQAAMGTSA---

                              AEAFQARLKSWFEPLLEDMQRQWDGLVEKVQAAVATIP---

Rhesus macaque                AEAFQARLKSWFEPLVEDMQRQWAGLVEKVQAAVGAST---

Chimpanzee                    AEAFQARLKSWFEPLVEDMQRQWAGLVEKVQAAMGTSA---

Mouse                         AEIFQARLKGWFEPIVEDMHRQWANLMEKIQASVATNPII-

Rat                           AEIFQARIKGWFEPLVEDMQRQWANLMEKIQASVATNSIAS

Pig                           AEAFQARLKGWFEPLVEDMRRQWAGLVERMQSAVSISSS--

Bovine                        AEAFQARLRSWFEPLVEDMQRQWAGLVEKVQLALRPSP---

Rabbit                        AEAFQARLKSWFEPLVEDMQRQWAGLVEKLQAAMPSKAP--

Sheep                         AEAFQARLRSWFEPLVEDMQRQWAGLVEKVQLALHLSP---

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	266 – 317	Homooligomerization
Glycosylation	307 – 307	O-linked (GalNAc...) threonine
Glycosylation	308 – 308	O-linked (GalNAc...) serine
Helix	286 – 303

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;

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.