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UniProtKB/Swiss-Prot P02545: Variant p.Ser573Leu

Prelamin-A/C
Gene: LMNA
Variant information

Variant position:  573
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 Serine (S) to Leucine (L) at position 573 (S573L, p.Ser573Leu).
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 small size and polar (S) to medium size and hydrophobic (L)
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:  Mandibuloacral dysplasia with type A lipodystrophy (MADA) [MIM:248370]: A disorder characterized by mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of the cranial suture, progeroid appearance, partial alopecia, soft tissue calcinosis, joint contractures, and partial lipodystrophy with loss of subcutaneous fat from the extremities. Adipose tissue in the face, neck and trunk is normal or increased. {ECO:0000269|PubMed:12075506, ECO:0000269|PubMed:15998779, ECO:0000269|PubMed:16278265}. 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:  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, FPLD2 and MADA.
Any additional useful information about the variant.

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



Sequence information

Variant position:  573
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:   DEDEDGDDLLHHHHGSHCSS  S GDPAEYNLRSRTVLCGTCGQ
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                         DEDE--DGDDLLHHHHGSH--CSSSGDPAEYNLRSRTVLCGTCGQ

Mouse                         NEDDDEDGEELLHHHRGSH--CSGSGDPAEYNLRSRTVLCG

Rat                           NDDEEEDGDELLHHHRGSH--CSSSGDPAEYNLRSRTVLCG

Pig                           DEDE--DGDDLLHHHHGSH--GSSSGDPAEYNLRSRTVLCG

Chicken                       DEDEEDDEVSIHHRHHHSG--CSGSADPAEYNLRSRTVLCG

Xenopus laevis                DDEDNDDMEHHHHHHHHHHDGQNSSGDPGEYNLRSRTIVCT

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
Region 384 – 664 Tail
Modified residue 568 – 568 Phosphoserine
Modified residue 571 – 571 Phosphoserine
Alternative sequence 573 – 664 Missing. In isoform C.


Literature citations

Natural history of dilated cardiomyopathy due to lamin A/C gene mutations.
Taylor M.R.G.; Fain P.R.; Sinagra G.; Robinson M.L.; Robertson A.D.; Carniel E.; Di Lenarda A.; Bohlmeyer T.J.; Ferguson D.A.; Brodsky G.L.; Boucek M.M.; Lascor J.; Moss A.C.; Li W.-L.P.; Stetler G.L.; Muntoni F.; Bristow M.R.; Mestroni L.;
J. Am. Coll. Cardiol. 41:771-780(2003)
Cited for: VARIANTS CMD1A LEU-89; HIS-377 AND LEU-573;

A homozygous mutation in the lamin A/C gene associated with a novel syndrome of arthropathy, tendinous calcinosis, and progeroid features.
Van Esch H.; Agarwal A.K.; Debeer P.; Fryns J.-P.; Garg A.;
J. Clin. Endocrinol. Metab. 91:517-521(2006)
Cited for: VARIANT MADA LEU-573;

Novel LMNA mutations seen in patients with familial partial lipodystrophy subtype 2 (FPLD2; MIM 151660).
Lanktree M.; Cao H.; Rabkin S.W.; Hanna A.; Hegele R.A.;
Clin. Genet. 71:183-186(2007)
Cited for: VARIANTS FPLD2 ASN-230; CYS-399 AND LEU-573;

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.