UniProtKB/Swiss-Prot P02545: Variant p.Gly465Asp

Prelamin-A/C
Gene: LMNA
Chromosomal location: 1q21.2-q21.3
Variant information

Variant position:  465
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Glycine (G) to Aspartate (D) at position 465 (G465D, p.Gly465Asp).
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 glycine (G) to medium size and acidic (D)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -1
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:  Lipodystrophy, familial partial, 2 (FPLD2) [MIM:151660]: A disorder characterized by the loss of subcutaneous adipose tissue in the lower parts of the body (limbs, buttocks, trunk). It is accompanied by an accumulation of adipose tissue in the face and neck causing a double chin, fat neck, or cushingoid appearance. Adipose tissue may also accumulate in the axillae, back, labia majora, and intraabdominal region. Affected patients are insulin-resistant and may develop glucose intolerance and diabetes mellitus after age 20 years, hypertriglyceridemia, and low levels of high density lipoprotein cholesterol. Note=The disease is caused by mutations affecting the gene represented in this entry.
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 FPLD2.
Any additional useful information about the variant.



Sequence information

Variant position:  465
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:   VDEEGKFVRLRNKSNEDQSM  G NWQIKRQNGDDPLLTYRFPP
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                         VDEEGKFVRLRNKSNEDQSMGNWQIKRQNGDDPLLTYRFPP

Mouse                         VDEEGKFVRLRNKSNEDQSMGNWQIRRQNGDDPLMTYRFPP

Rat                           VDEEGKFVRLRNKSNEDQSMGNWQIKRQNGDDPLMTYRFPP

Pig                           VDEEGKFVRLRNKSNEDQSMGNWQIKRQNGDDPLLTYRFPP

Chicken                       VDLEGRFVRLRNKSNEDQALGNWQVKRQNGDDPPLTYRFPP

Xenopus laevis                VDPEGKYVRLRNKSNEDQSLGNWQIKRQIGDETPIVYKFPP

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 432 – 545 LTD
Region 384 – 664 Tail
Modified residue 450 – 450 N6-acetyllysine
Modified residue 457 – 457 N6-acetyllysine
Modified residue 458 – 458 Phosphoserine
Modified residue 463 – 463 Phosphoserine
Helix 464 – 466


Literature citations

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;

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.