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UniProtKB/Swiss-Prot P02545: Variant p.Arg482Trp

Prelamin-A/C
Gene: LMNA
Variant information

Variant position:  482
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 482 (R482W, p.Arg482Trp).
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

Variant description:  In FPLD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type; decreases binding affinity for DNA; increases sensitivity to oxidative stress.
Any additional useful information about the variant.

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



Sequence information

Variant position:  482
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  664
The length of the canonical sequence.

Location on the sequence:   QSMGNWQIKRQNGDDPLLTY  R FPPKFTLKAGQVVTIWAAGA
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                         QSMGNWQIKRQNGDDPLLTYRFPPKFTLKAGQVVTIWAAGA

Mouse                         QSMGNWQIRRQNGDDPLMTYRFPPKFTLKAGQVVTIWASGA

Rat                           QSMGNWQIKRQNGDDPLMTYRFPPKFTLKAGQVVTIWASGA

Pig                           QSMGNWQIKRQNGDDPLLTYRFPPKFTLKAGQVVTIWAAGA

Chicken                       QALGNWQVKRQNGDDPPLTYRFPPKFTLKAGQAVTIWASGA

Xenopus laevis                QSLGNWQIKRQIGDETPIVYKFPPRLTLKAGQTVTIWASGA

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 1 – 661 Prelamin-A/C
Chain 1 – 646 Lamin-A/C
Domain 428 – 545 LTD
Region 384 – 664 Tail
Modified residue 463 – 463 Phosphoserine
Modified residue 496 – 496 Phosphothreonine
Cross 470 – 470 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Cross 486 – 486 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Beta strand 479 – 482


Literature citations

The R439C mutation in LMNA causes lamin oligomerization and susceptibility to oxidative stress.
Verstraeten V.L.; Caputo S.; van Steensel M.A.; Duband-Goulet I.; Zinn-Justin S.; Kamps M.; Kuijpers H.J.; Ostlund C.; Worman H.J.; Briede J.J.; Le Dour C.; Marcelis C.L.; van Geel M.; Steijlen P.M.; van den Wijngaard A.; Ramaekers F.C.; Broers J.L.;
J. Cell. Mol. Med. 13:959-971(2009)
Cited for: SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS FPLD2 CYS-439 AND TRP-482;

Mutational and haplotype analyses of families with familial partial lipodystrophy (Dunnigan variety) reveal recurrent missense mutations in the globular C-terminal domain of lamin A/C.
Speckman R.A.; Garg A.; Du F.; Bennett L.; Veile R.; Arioglu E.; Taylor S.I.; Lovett M.; Bowcock A.M.;
Am. J. Hum. Genet. 66:1192-1198(2000)
Cited for: VARIANTS FPLD2 ASP-465; GLN-482; TRP-482 AND HIS-582;

LMNA, encoding lamin A/C, is mutated in partial lipodystrophy.
Shackleton S.; Lloyd D.J.; Jackson S.N.J.; Evans R.; Niermeijer M.F.; Singh B.M.; Schmidt H.; Brabant G.; Kumar S.; Durrington P.N.; Gregory S.; O'Rahilly S.; Trembath R.C.;
Nat. Genet. 24:153-156(2000)
Cited for: VARIANTS FPLD2 LEU-482 AND TRP-482;

Properties of lamin A mutants found in Emery-Dreifuss muscular dystrophy, cardiomyopathy and Dunnigan-type partial lipodystrophy.
Oestlund C.; Bonne G.; Schwartz K.; Worman H.J.;
J. Cell Sci. 114:4435-4445(2001)
Cited for: CHARACTERIZATION OF VARIANTS CMD1A GLY-60; ARG-85; LYS-195 AND GLY-203; CHARACTERIZATION OF VARIANTS EDMD2 LYS-358; LYS-371; LYS-386; TRP-453; SER-520; PRO-527; LYS-528 AND PRO-530; CHARACTERIZATION OF VARIANTS FPLD2 GLN-482; TRP-482 AND ASN-486;

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.