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UniProtKB/Swiss-Prot P02545: Variant p.Arg401Cys

Prelamin-A/C
Gene: LMNA
Variant information

Variant position:  401
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 Cysteine (C) at position 401 (R401C, p.Arg401Cys).
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 medium size and polar (C)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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; abnormal nuclear localization in a honeycomb expression pattern in about 22% of cultured skin fibroblasts from heterozygous patients; enhances the interaction with SYNE2; no effect on nuclear localization; 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:  401
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:   EGEEERLRLSPSPTSQRSRG  R ASSHSSQTQGGGSVTKKRKL
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                         EGEEERLRLSPSPTSQRSRGRASSHSSQTQGGGSVTKKRKL

Mouse                         EGEEERLRLSPSPTSQRSRGRASSHSSQSQGGGSVTKKRKL

Rat                           EGEEERLRLSPSPTSQRSRGRASSHSSQSQGGGSVTKKRKL

Pig                           EGEEERLRLSPSPTSQRSRGRASSHSSQTQSGGSVTKKRKL

Chicken                       EGEEERLRLSPSPSSQ----RGARSSGLQHSGAGSAKKRRL

Xenopus laevis                EGEEERLRLSPSPNTQKRSARTIASHSGAHISSSASKRRRL

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 390 – 390 Phosphoserine
Modified residue 392 – 392 Phosphoserine
Modified residue 395 – 395 Phosphoserine
Modified residue 398 – 398 Phosphoserine
Modified residue 403 – 403 Phosphoserine
Modified residue 404 – 404 Phosphoserine
Modified residue 407 – 407 Phosphoserine
Modified residue 414 – 414 Phosphoserine
Cross 417 – 417 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Cross 420 – 420 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)


Literature citations

Frequent low penetrance mutations in the Lamin A/C gene, causing Emery Dreifuss muscular dystrophy.
Vytopil M.; Ricci E.; Dello Russo A.; Hanisch F.; Neudecker S.; Zierz S.; Ricotti R.; Demay L.; Richard P.; Wehnert M.; Bonne G.; Merlini L.; Toniolo D.;
Neuromuscul. Disord. 12:958-963(2002)
Cited for: VARIANTS EDMD2 LYS-32 DEL; ASN-63; GLN-336; GLN-343 AND CYS-401;

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;

Mutations in LMNA modulate the lamin A--Nesprin-2 interaction and cause LINC complex alterations.
Yang L.; Munck M.; Swamvdinathan K.; Kapinos L.E.; Noegel A.A.; Neumann S.;
PLoS ONE 8:E71850-E71850(2013)
Cited for: CHARACTERIZATION OF VARIANTS CYS-401; ASP-411; CYS-413; ILE-415; CYS-419; PRO-421 AND GLY-427; INTERACTION WITH SYNE2;

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.