UniProtKB/Swiss-Prot P02545: Variant p.Arg190Gln

Prelamin-A/C
Gene: LMNA
Chromosomal location: 1q21.2-q21.3
Variant information

Variant position:  190
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Arginine (R) to Glutamine (Q) at position 190 (R190Q, p.Arg190Gln).
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 (Q)
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 CMD1A; aberrant localization with decreased nuclear rim staining and increased formation of intranuclear foci.
Any additional useful information about the variant.



Sequence information

Variant position:  190
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:   AKLEAALGEAKKQLQDEMLR  R VDAENRLQTMKEELDFQKNI
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                         AKLEAALGEAKKQLQDEMLRRVDAENRLQTMKEELDFQKNI

Mouse                         AKLEAALGEAKKQLQDEMLRRVDAENRLQTLKEELDFQKNI

Rat                           AKLEAALGEAKKQLQDEMLRRVDAENRLQTLKEELDFQKNI

Pig                           AKLEAALGEAKKQLQDEMLRRVDAENRLQTLKEELDFQKNI

Chicken                       AKLEGALSEAKKQLQDEMLRRVDAENRLQTLKEELEFQKNI

Xenopus laevis                AKLEASLADTKKQLQDEMLRRVDTENRNQTLKEELEFQKSI

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 34 – 383 Rod
Region 81 – 218 Coil 1B
Modified residue 171 – 171 N6-acetyllysine; alternate
Modified residue 171 – 171 N6-succinyllysine; alternate
Modified residue 201 – 201 N6-acetyllysine; alternate
Cross 201 – 201 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate
Mutagenesis 201 – 201 K -> L. Decreased sumoylation; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; associated with increased cell death.


Literature citations

Morphological analysis of 13 LMNA variants identified in a cohort of 324 unrelated patients with idiopathic or familial dilated cardiomyopathy.
Cowan J.; Li D.; Gonzalez-Quintana J.; Morales A.; Hershberger R.E.;
Circ. Cardiovasc. Genet. 3:6-14(2010)
Cited for: SUBCELLULAR LOCATION; VARIANTS CMD1A LEU-89; PRO-101; PRO-166; GLN-190; LYS-203; SER-210; PRO-215; THR-318; HIS-388; CYS-399 AND HIS-471;

Lamin A N-terminal phosphorylation is associated with myoblast activation: impairment in Emery-Dreifuss muscular dystrophy.
Cenni V.; Sabatelli P.; Mattioli E.; Marmiroli S.; Capanni C.; Ognibene A.; Squarzoni S.; Maraldi N.M.; Bonne G.; Columbaro M.; Merlini L.; Lattanzi G.;
J. Med. Genet. 42:214-220(2005)
Cited for: VARIANT LGMD1B HIS-377; VARIANTS EDMD2 ASN-63; PRO-140; GLN-190; GLN-249 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.