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UniProtKB/Swiss-Prot P02545: Variant p.Glu358Lys

Prelamin-A/C
Gene: LMNA
Variant information

Variant position:  358
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 Glutamate (E) to Lysine (K) at position 358 (E358K, p.Glu358Lys).
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 acidic (E) 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 and MDCL; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci when transfected in C2C12 myoblasts; no obvious effect on nuclear morphology in cultured skin fibroblasts from heterozygous patients; distribution of endogenous LMNA, LMNB1 and LMNB2 are altered in cells expressing this mutant; interacts with itself and with wild-type LMNA and LMNB1; no effect on protein level.
Any additional useful information about the variant.

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



Sequence information

Variant position:  358
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:   LAEKEREMAEMRARMQQQLD  E YQELLDIKLALDMEIHAYRK
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                         LAEKEREMAEMRARMQQQLDEYQELLDIKLALDMEIHAYRK

Mouse                         LAEKEREMAEMRARMQQQLDEYQELLDIKLALDMEIHAYRK

Rat                           LAEKEREMAEMRARMQQQLDEYQELLDIKLALDMEIHAYRK

Pig                           LADKEREMAEMRARMQQQLDEYQELLDIKLALDMEIHAYRK

Chicken                       LAEKEREMAEMRARMQQQLDEYQELLDIKLALDMEINAYRK

Xenopus laevis                LADKDREMAEMRARMQQQLDEYQELLDIKLALDMEINAYRK

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 243 – 383 Coil 2
Cross 366 – 366 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Cross 378 – 378 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Helix 316 – 384


Literature citations

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;

Novel and recurrent mutations in lamin A/C in patients with Emery-Dreifuss muscular dystrophy.
Brown C.A.; Lanning R.W.; McKinney K.Q.; Salvino A.R.; Cherniske E.; Crowe C.A.; Darras B.T.; Gominak S.; Greenberg C.R.; Grosmann C.; Heydemann P.; Mendell J.R.; Pober B.R.; Sasaki T.; Shapiro F.; Simpson D.A.; Suchowersky O.; Spence J.E.;
Am. J. Med. Genet. 102:359-367(2001)
Cited for: VARIANTS EDMD2 PRO-25; THR-43; SER-50; PRO-133; 196-ARG--THR-199 DELINS SER; GLN-249; LYS-261 DEL; LYS-358; TRP-453; ILE-456; PRO-527 AND HIS-624;

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;

Nuclear envelope alterations in fibroblasts from patients with muscular dystrophy, cardiomyopathy, and partial lipodystrophy carrying lamin A/C gene mutations.
Muchir A.; Medioni J.; Laluc M.; Massart C.; Arimura T.; van der Kooi A.J.; Desguerre I.; Mayer M.; Ferrer X.; Briault S.; Hirano M.; Worman H.J.; Mallet A.; Wehnert M.; Schwartz K.; Bonne G.;
Muscle Nerve 30:444-450(2004)
Cited for: SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS EDMD2 LYS-32 DEL; SER-63; GLN-249; LYS-358; CYS-401; TRP-453 AND PRO-527; CHARACTERIZATION OF VARIANTS EDMD2 LYS-208 DEL AND HIS-377; CHARACTERIZATION OF VARIANT FPLD2 LEU-482; CHARACTERIZATION OF VARIANT CMD1A CYS-541;

De novo LMNA mutations cause a new form of congenital muscular dystrophy.
Quijano-Roy S.; Mbieleu B.; Bonnemann C.G.; Jeannet P.Y.; Colomer J.; Clarke N.F.; Cuisset J.M.; Roper H.; De Meirleir L.; D'Amico A.; Ben Yaou R.; Nascimento A.; Barois A.; Demay L.; Bertini E.; Ferreiro A.; Sewry C.A.; Romero N.B.; Ryan M.; Muntoni F.; Guicheney P.; Richard P.; Bonne G.; Estournet B.;
Ann. Neurol. 64:177-186(2008)
Cited for: VARIANTS MDCL SER-39; PRO-50; TRP-249; PRO-302; LYS-358; SER-380; PRO-453; PRO-455 AND ASP-456;

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.