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UniProtKB/Swiss-Prot P02649: Variant p.Cys130Arg

Apolipoprotein E
Gene: APOE
Variant information

Variant position:  130
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 Cysteine (C) to Arginine (R) at position 130 (C130R, p.Cys130Arg).
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 (C) to large size and basic (R)
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

Variant description:  In HLPP3 and AD2; ApoE4, ApoE3 Leiden, ApoE3**, ApoE5-Frankfurt and ApoE5-type; ApoE3 Leiden and ApoE3** are associated with HLPP3; ApoE4 is associated with AD2; changed protein structure; no effect on binding to LDL receptor; decreased association with HDL and enrichment in VLDL and IDL; may prevent the interaction with MAP2 and MAPT; changed interaction with APP/A4 amyloid-beta peptide; increased ability to induce APP transcription; increased C-terminal proteolytic processing in neurons; decreased function in neurite outgrowth; ApoE4 is associated with higher susceptibility to SARS-CoV-2 infection in neurons and astrocytes.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  130
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:   RLSKELQAAQARLGADMEDV  C GRLVQYRGEVQAMLGQSTEE
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                         RLSKELQAAQARLGADMEDVCGRLVQYRGEVQAMLGQSTEE

Gorilla                       RLSKELQAAQARLGADMEDVRGRLAQYRGEVQAMLGQSTEE

                              RVAKELQAAQARLRSDMEDVRNRLTQYRGELQAMLGQSSEE

Rhesus macaque                RLSKELQAAQARLGADMEDVRSRLVQYRSEVQAMLGQSTEE

Chimpanzee                    RLSKELQAAQARLGADMEDVRGRLVQYRGEVQAMLGQSTEE

Mouse                         RLGKEVQAAQARLGADMEDLRNRLGQYRNEVHTMLGQSTEE

Rat                           RLAKEVQAAQARLGADMEDLRNRLGQYRNEVNTMLGQSTEE

Pig                           RLSKELQAAQARVGADMEDVRNRLVLYRSEVHNMLGQTTEE

Bovine                        RVSKELQAAQARLGSDMEDLRNRLAQYRSEVQAMLGQSTEE

Rabbit                        RLSKELQVAGA-LEADMEDVCNRLAQYRGEAQAMLGQSTEE

Sheep                         RVSKELQAAQARLGSDMEDLRNRLAQYRSEVQAMLGQSTEE

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.

TypePositionsDescription
Chain 19 – 317 Apolipoprotein E
Repeat 124 – 145 3
Region 80 – 255 8 X 22 AA approximate tandem repeats
Modified residue 143 – 143 Methionine sulfoxide
Modified residue 147 – 147 Phosphoserine; by FAM20C
Mutagenesis 127 – 127 E -> A. No effect on plasma lipoprotein distribution.
Helix 106 – 141


Literature citations

Nucleotide sequence and structure of the human apolipoprotein E gene.
Paik Y.-K.; Chang D.J.; Reardon C.A.; Davies G.E.; Mahley R.W.; Taylor J.M.;
Proc. Natl. Acad. Sci. U.S.A. 82:3445-3449(1985)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE APOE*4); VARIANT AD2 ARG-130;

Sequence diversity and large-scale typing of SNPs in the human apolipoprotein E gene.
Nickerson D.A.; Taylor S.L.; Fullerton S.M.; Weiss K.M.; Clark A.G.; Stengard J.H.; Salomaa V.; Boerwinkle E.; Sing C.F.;
Genome Res. 10:1532-1545(2000)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE APOE*3); VARIANTS PRO-46; ARG-130; CYS-163 AND CYS-176;

Apolipoprotein E distribution among human plasma lipoproteins: role of the cysteine-arginine interchange at residue 112.
Weisgraber K.H.;
J. Lipid Res. 31:1503-1511(1990)
Cited for: REGION; CHARACTERIZATION OF VARIANT ARG-130 AND ARG-176;

Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset Alzheimer disease.
Strittmatter W.J.; Weisgraber K.H.; Huang D.Y.; Dong L.M.; Salvesen G.S.; Pericak-Vance M.; Schmechel D.; Saunders A.M.; Goldgaber D.; Roses A.D.;
Proc. Natl. Acad. Sci. U.S.A. 90:8098-8102(1993)
Cited for: INTERACTION WITH APP/A4 AMYLOID-BETA PEPTIDE; CHARACTERIZATION OF VARIANT AD2 ARG-130;

Isoform-specific interactions of apolipoprotein E with the microtubule-associated protein MAP2c: implications for Alzheimer's disease.
Huang D.Y.; Goedert M.; Jakes R.; Weisgraber K.H.; Garner C.C.; Saunders A.M.; Pericak-Vance M.A.; Schmechel D.E.; Roses A.D.; Strittmatter W.J.;
Neurosci. Lett. 182:55-58(1994)
Cited for: INTERACTION WITH MAP2; CHARACTERIZATION OF VARIANT AD2 ARG-130;

Isoform-specific interactions of apolipoprotein E with microtubule-associated protein tau: implications for Alzheimer disease.
Strittmatter W.J.; Saunders A.M.; Goedert M.; Weisgraber K.H.; Dong L.M.; Jakes R.; Huang D.Y.; Pericak-Vance M.; Schmechel D.; Roses A.D.;
Proc. Natl. Acad. Sci. U.S.A. 91:11183-11186(1994)
Cited for: INTERACTION WITH MAPT; CHARACTERIZATION OF VARIANT AD2 ARG-130;

Apolipoprotein E-containing high density lipoprotein promotes neurite outgrowth and is a ligand for the low density lipoprotein receptor-related protein.
Fagan A.M.; Bu G.; Sun Y.; Daugherty A.; Holtzman D.M.;
J. Biol. Chem. 271:30121-30125(1996)
Cited for: FUNCTION IN NEURITE OUTGROWTH; LRP-BINDING; CHARACTERIZATION OF VARIANT AD2 ARG-130;

Apolipoprotein E fragments present in Alzheimer's disease brains induce neurofibrillary tangle-like intracellular inclusions in neurons.
Huang Y.; Liu X.Q.; Wyss-Coray T.; Brecht W.J.; Sanan D.A.; Mahley R.W.;
Proc. Natl. Acad. Sci. U.S.A. 98:8838-8843(2001)
Cited for: PTM; CHARACTERIZATION OF VARIANT AD2 ARG-130;

ApoE2, ApoE3, and ApoE4 Differentially Stimulate APP Transcription and Abeta Secretion.
Huang Y.A.; Zhou B.; Wernig M.; Suedhof T.C.;
Cell 168:427-441(2017)
Cited for: FUNCTION IN APP TRANSCRIPTION; CHARACTERIZATION OF VARIANT AD2 ARG-130;

Human apolipoprotein E. Role of arginine 61 in mediating the lipoprotein preferences of the E3 and E4 isoforms.
Dong L.M.; Wilson C.; Wardell M.R.; Simmons T.; Mahley R.W.; Weisgraber K.H.; Agard D.A.;
J. Biol. Chem. 269:22358-22365(1994)
Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 41-184 OF VARIANT AD2 ARG-130; CHARACTERIZATION OF VARIANT AD2 ARG-130; MUTAGENESIS OF ARG-79 AND GLU-127; REGION;

Interaction of the N-terminal domain of apolipoprotein E4 with heparin.
Dong J.; Peters-Libeu C.A.; Weisgraber K.H.; Segelke B.W.; Rupp B.; Capila I.; Hernaiz M.J.; LeBrun L.A.; Linhardt R.J.;
Biochemistry 40:2826-2834(2001)
Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 19-209 OF VARIANT AD2 ARG-130;

Apolipoprotein E3-Leiden contains a seven-amino acid insertion that is a tandem repeat of residues 121-127.
Wardell M.R.; Weisgraber K.H.; Havekes L.M.; Rall S.C. Jr.;
J. Biol. Chem. 264:21205-21210(1989)
Cited for: VARIANTS HLPP3 ARG-130 AND GLU-VAL-GLN-ALA-MET-LEU-GLY-145 INS;

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;

Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families.
Corder E.H.; Saunders A.M.; Strittmatter W.J.; Schmechel D.E.; Gaskell P.C.; Small G.W.; Roses A.D.; Haines J.L.; Pericak-Vance M.A.;
Science 261:921-923(1993)
Cited for: INVOLVEMENT IN AD2; VARIANT AD2 ARG-130;

Common and rare genotypes of human apolipoprotein E determined by specific restriction profiles of polymerase chain reaction-amplified DNA.
Richard P.; Thomas G.; de Zulueta M.P.; de Gennes J.-L.; Thomas M.; Cassaigne A.; Bereziat G.; Iron A.;
Clin. Chem. 40:24-29(1994)
Cited for: VARIANTS HLPP3 ARG-130; SER-154; CYS-160 AND CYS-176; VARIANT ASP-145;

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;

Virus-mediated transduction of apolipoprotein E (ApoE)-sendai develops lipoprotein glomerulopathy in ApoE-deficient mice.
Ishigaki Y.; Oikawa S.; Suzuki T.; Usui S.; Magoori K.; Kim D.H.; Suzuki H.; Sasaki J.; Sasano H.; Okazaki M.; Toyota T.; Saito T.; Yamamoto T.T.;
J. Biol. Chem. 275:31269-31273(2000)
Cited for: CHARACTERIZATION OF VARIANT LPG PRO-163; CHARACTERIZATION OF VARIANT AD2 ARG-130;

Association of extreme blood lipid profile phenotypic variation with 11 reverse cholesterol transport genes and 10 non-genetic cardiovascular disease risk factors.
Morabia A.; Cayanis E.; Costanza M.C.; Ross B.M.; Flaherty M.S.; Alvin G.B.; Das K.; Gilliam T.C.;
Hum. Mol. Genet. 12:2733-2743(2003)
Cited for: VARIANTS ARG-130 AND CYS-176;

Genetic heterogeneity of apolipoprotein E and its influence on plasma lipid and lipoprotein levels.
de Knijff P.; van den Maagdenberg A.M.J.M.; Frants R.R.; Havekes L.M.;
Hum. Mutat. 4:178-194(1994)
Cited for: REVIEW; VARIANTS LYS-31; ARG-102; ARG-130; GLN-152 AND CYS-154;

ApoE isoform-dependent SARS-CoV-2 neurotropism and cellular response.
Wang C.; Zhang M.; Garcia G.; Tian E.; Cui Q.; Chen X.; Sun G.; Wang J.; Arumugaswami V.; Shi Y.;
Cited for: POLYMORPHISM; VARIANT 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.