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UniProtKB/Swiss-Prot P04114: Variant p.Arg490Trp

Apolipoprotein B-100
Gene: APOB
Chromosomal location: 2p23-p24
Variant information

Variant position:  490
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Arginine (R) to Tryptophan (W) at position 490 (R490W, p.Arg490Trp).
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 large size and aromatic (W)
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

Involvement in disease:  Hypobetalipoproteinemia, familial, 1 (FHBL1) [MIM:615558]: A disorder of lipid metabolism characterized by less than 5th percentile age- and sex-specific levels of low density lipoproteins, and dietary fat malabsorption. Clinical presentation may vary from no symptoms to severe gastrointestinal and neurological dysfunction similar to abetalipoproteinemia. {ECO:0000269|PubMed:12551903, ECO:0000269|PubMed:21981844, ECO:0000269|PubMed:27206948}. Note=The disease is caused by mutations affecting the gene represented in this entry. Most cases of FHBL1 result from nonsense mutations in the APOB gene that lead to a premature stop codon, which generate prematurely truncated apo B protein products (PubMed:21981844). {ECO:0000269|PubMed:21981844}.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In FHBL1; reduced protein secretion.
Any additional useful information about the variant.



Sequence information

Variant position:  490
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  4563
The length of the canonical sequence.

Location on the sequence:   LMEQIQDDCTGDEDYTYLIL  R VIGNMGQTMEQLTPELKSSI
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                         LMEQIQDDCTGDEDYTYLILRVIGNMGQTMEQLTPELKSSI

Mouse                         LLKQIDNECTGNEDHTFLILRVIGNMGRTMEQVMPALKSSV

Rat                           LMKQIDNECMGDEDRTFLILRVIGNMGRTMERVMPALKSSV

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 28 – 4563 Apolipoprotein B-100
Chain 28 – 2179 Apolipoprotein B-48
Domain 46 – 672 Vitellogenin
Disulfide bond 478 – 513
Mutagenesis 483 – 483 D -> N. Impairs protein secretion.
Mutagenesis 483 – 483 D -> Q. Does not affect protein secretion.
Mutagenesis 490 – 490 R -> A. Impairs protein secretion.
Mutagenesis 490 – 490 R -> K. Does not affect protein secretion.


Literature citations

A novel nontruncating APOB gene mutation, R463W, causes familial hypobetalipoproteinemia.
Burnett J.R.; Shan J.; Miskie B.A.; Whitfield A.J.; Yuan J.; Tran K.; McKnight C.J.; Hegele R.A.; Yao Z.;
J. Biol. Chem. 278:13442-13452(2003)
Cited for: VARIANT FHBL1 TRP-490; VARIANT ILE-98; CHARACTERIZATION OF VARIANT TRP-490; MUTAGENESIS OF ASP-483 AND ARG-490;

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.