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UniProtKB/Swiss-Prot P02545: Variant p.Arg60Gly

Prelamin-A/C
Gene: LMNA
Variant information

Variant position:  60
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 Glycine (G) at position 60 (R60G, p.Arg60Gly).
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 glycine (G)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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:  Cardiomyopathy, dilated 1A (CMD1A) [MIM:115200]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:10580070, ECO:0000269|PubMed:11561226, ECO:0000269|PubMed:11792809, ECO:0000269|PubMed:11897440, ECO:0000269|PubMed:12486434, ECO:0000269|PubMed:12628721, ECO:0000269|PubMed:12920062, ECO:0000269|PubMed:14675861, ECO:0000269|PubMed:14684700, ECO:0000269|PubMed:15140538, ECO:0000269|PubMed:15219508, ECO:0000269|PubMed:15372542, ECO:0000269|PubMed:16061563, ECO:0000269|PubMed:18606848, ECO:0000269|PubMed:19167105, ECO:0000269|PubMed:20160190, ECO:0000269|PubMed:21846512}. 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.

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. {ECO:0000269|PubMed:10587585, ECO:0000269|PubMed:10655060, ECO:0000269|PubMed:10739751, ECO:0000269|PubMed:11792809, ECO:0000269|PubMed:12015247, ECO:0000269|PubMed:12196663, ECO:0000269|PubMed:12629077, ECO:0000269|PubMed:15372542, ECO:0000269|PubMed:17250669, ECO:0000269|PubMed:19220582, ECO:0000269|PubMed:24485160}. 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 CMD1A and FPLD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type.
Any additional useful information about the variant.

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



Sequence information

Variant position:  60
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:   DRLAVYIDRVRSLETENAGL  R LRITESEEVVSREVSGIKAA
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                         DRLAVYIDRVRSLETENAGLRLRITESEEVVSREVSGIKAA

Mouse                         DRLAVYIDRVRSLETENAGLRLRITESEEVVSREVSGIKAA

Rat                           DRLAVYIDRVRSLETENAGLRLRITESEEVVSREVSGIKAA

Pig                           DRLAVYIDRVRSLETENAGLRLRITESEEVVSREVSGIKSA

Chicken                       DRLAVYIDKVRSLELENAGLRLRITESEEVVSREVSGIKAA

Xenopus laevis                DRLAVYIDKVRSLELENARLRLRITESEDVISREVTGIKSA

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 31 – 387 IF rod
Region 1 – 130 Interaction with MLIP
Region 34 – 70 Coil 1A
Modified residue 51 – 51 Phosphoserine
Modified residue 66 – 66 Phosphoserine
Modified residue 71 – 71 Phosphoserine
Alternative sequence 1 – 99 Missing. In isoform 5.
Alternative sequence 8 – 119 Missing. In isoform 4.


Literature citations

Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease.
Fatkin D.; MacRae C.; Sasaki T.; Wolff M.R.; Porcu M.; Frenneaux M.; Atherton J.; Vidaillet H.J. Jr.; Spudich S.; De Girolami U.; Seidman J.G.; Seidman C.E.;
N. Engl. J. Med. 341:1715-1724(1999)
Cited for: VARIANTS CMD1A GLY-60; ARG-85; LYS-195 AND GLY-203; FUNCTION;

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;

Lamin A/C mutations with lipodystrophy, cardiac abnormalities, and muscular dystrophy.
van der Kooi A.J.; Bonne G.; Eymard B.; Duboc D.; Talim B.; Van der Valk M.; Reiss P.; Richard P.; Demay L.; Merlini L.; Schwartz K.; Busch H.F.M.; de Visser M.;
Neurology 59:620-623(2002)
Cited for: VARIANTS FPLD2 GLY-60 AND PRO-527;

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.