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UniProtKB/Swiss-Prot P02545: Variant p.Thr528Lys

Prelamin-A/C
Gene: LMNA
Variant information

Variant position:  528
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 Threonine (T) to Lysine (K) at position 528 (T528K, p.Thr528Lys).
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 medium size and polar (T) to large size and basic (K)
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

Variant description:  In EDMD2; 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:  528
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:   PPTDLVWKAQNTWGCGNSLR  T ALINSTGEEVAMRKLVRSVT
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                         PPTDLVWKAQNTWGCGNSLRTALINSTGEEVAMRKLVRSVT

Mouse                         PPTDLVWKAQNTWGCGSSLRTALINSTGEEVAMRKLVRSLT

Rat                           PPTDLVWKAQNTWGCGTSLRTALINATGEEVAMRKLVRSLT

Pig                           PPADLVWKSQNTWGCGNSLRTALINSTGEEVAMRKLVRSVT

Chicken                       PPSDVVWKAQSSWGSGDSLRTALINSNGEEVAMRKLVRTVI

Xenopus laevis                PPSDLVWKAQSSWGTGDSIRTALLTSSNEEVAMRKLVRTVV

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 510 – 510 Phosphothreonine
Modified residue 533 – 533 Phosphoserine
Modified residue 546 – 546 Phosphoserine
Modified residue 548 – 548 Phosphothreonine
Beta strand 526 – 531


Literature citations

Different mutations in the LMNA gene cause autosomal dominant and autosomal recessive Emery-Dreifuss muscular dystrophy.
Raffaele di Barletta M.; Ricci E.; Galluzzi G.; Tonali P.; Mora M.; Morandi L.; Romorini A.; Voit T.; Orstavik K.H.; Merlini L.; Trevisan C.; Biancalana V.; Housmanowa-Petrusewicz I.; Bione S.; Ricotti R.; Schwartz K.; Bonne G.; Toniolo D.;
Am. J. Hum. Genet. 66:1407-1412(2000)
Cited for: VARIANTS EDMD2 TYR-222; GLN-249; GLN-336; TRP-453; THR-469; PRO-527 AND LYS-528;

Clinical and molecular genetic spectrum of autosomal dominant Emery-Dreifuss muscular dystrophy due to mutations of the lamin A/C gene.
Bonne G.; Mercuri E.; Muchir A.; Urtizberea A.; Becane H.M.; Recan D.; Merlini L.; Wehnert M.; Boor R.; Reuner U.; Vorgerd M.; Wicklein E.M.; Eymard B.; Duboc D.; Penisson-Besnier I.; Cuisset J.M.; Ferrer X.; Desguerre I.; Lacombe D.; Bushby K.; Pollitt C.; Toniolo D.; Fardeau M.; Schwartz K.; Muntoni F.;
Ann. Neurol. 48:170-180(2000)
Cited for: VARIANTS EDMD2 CYS-45; PRO-50; SER-63; GLU-112 DEL; PRO-222; GLU-232; GLN-249; LYS-261 DEL; PRO-294; LYS-358; LYS-371; LYS-386; TRP-453; LYS-456; SER-520; PRO-527 AND LYS-528;

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;

Novel LMNA mutations in patients with Emery-Dreifuss muscular dystrophy and functional characterization of four LMNA mutations.
Scharner J.; Brown C.A.; Bower M.; Iannaccone S.T.; Khatri I.A.; Escolar D.; Gordon E.; Felice K.; Crowe C.A.; Grosmann C.; Meriggioli M.N.; Asamoah A.; Gordon O.; Gnocchi V.F.; Ellis J.A.; Mendell J.R.; Zammit P.S.;
Hum. Mutat. 32:152-167(2011)
Cited for: VARIANTS EDMD2 SER-39; CYS-45; PRO-150; PRO-189; ARG-190 INS; LEU-206; TRP-249; GLN-249; PRO-268; PRO-271; PRO-294; PRO-295; PRO-303; GLN-355 DEL; LYS-358; LYS-361; LYS-386; ASP-449; TRP-453; PRO-454; TYR-461; ARG-467; PRO-527; LYS-528; ARG-528; SER-541; PRO-541; SER-602 AND CYS-644; CHARACTERIZATION OF VARIANTS EDMD2 PRO-25; TRP-249; ILE-456 AND PRO-541;

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.