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FLASH GENE
Symbol LMNA contributors: mct/ - updated : 28-09-2019
HGNC name lamin A/C
HGNC id 6636
ASSOCIATED DISORDERS
corresponding disease(s) EMD2 , LGMD1B , CMD1A , CMT2B1 , FPLD2 , MADYS1 , PRO1 , WRN2 , RDMP2 , LDHCP , EMD3 , MCPRS , HHSS
related resource Limb-Girdle Muscular Dystrophy pages
Mutation Database of Inherited Peripheral Neuropathies
Other morbid association(s)
TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
tumoral     --low  
by hypermethylation associated with poor outcome in diffuse large B-cell lymphomas
constitutional germinal mutation      
results in increased sensitivity to DNA damaging agents, an elevated DNA damage response, and a senescent phenotype
constitutional       loss of function
in striated muscle disease mutated proteins are defective in anchoring transmembrane actin-associated nuclear lines for nuclear movement
tumoral     --low  
silencing of A-type lamins by DNA methylation in some cancers could contribute to the genomic instability that drives malignancy
constitutional germinal mutation      
LMNA mutation should be considered in myopathy patients with inflammatory changes during infancy
constitutional     --over  
in osteoarthritis (OA) chondrocytes, and increased nuclear accumulation of LMNA in response to catabolic stress may account for the premature aging phenotype and apoptosis of OA chondrocytes
constitutional     --low  
depletion of LMNB1 or LMNA/Cwas sufficient to recapitulate some oncogene-induced senescence (OIS) features, including cell cycle exit and downregulation of nuclear envelope (NE) proteins 7)
Susceptibility
  • to subcutaneous abdominal abnormal adipocyte size
  • to metabolic syndrome and also higher mean fasting triglyceride and lower mean HDL-cholesterol concentrations
  • to enhanced longevity
  • Variant & Polymorphism SNP , other
  • 1908 C>T Pima Indians
  • H566H polymorphism associated with metabolic syndrome and also higher mean fasting triglyceride and lower mean HDL-cholesterol concentrations in the Old Order Amish
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    miscelleaneoussenescence 
    correction of cellular phenotypes of Hutchinson-Gilford Progeria cells by RNA interference, as potential gene therapy
    neuromuscularmyopathy 
    ERK inhibition as a therapeutic option to prevent or delay heart failure in Emery–Dreifuss muscular dystrophy and related disorders caused by mutations in LMNA
    osteoarticularbone 
    processing of prelamin A could become a new approach to regulate osteoblastogenesis and bone turnover and thus for the prevention and treatment of senile osteoporosis
    miscelleaneoussenescence 
    correction of the aberrant splicing event using a modified oligonucleotide targeted to the activated cryptic splice site (treatment inhibiting farnesylation of progerin prevents the characteristic nuclear blebbing of Hutchinson-Gilford progeria syndrome)
    cancer  
    lamins-deficient tumor cells could represent a good target for radiation therapy
    ANIMAL & CELL MODELS
  • abnormal activation of the extracellular signal-regulated kinase (ERK) branch of the mitogen-activated protein kinase (MAPK) signaling cascade in hearts of Lmna H222P ‘knock in’ mice, a model of autosomal Emery–Dreifuss muscular dystrophy
  • changes in the splicing ratio between lamin A and progerin are key factors for lifespan since heterozygous mice harboring the mutation lived longer than homozygous littermates but less than the wild-type
  • Lmna(-/-) mice display multiple tissue defects and die by 6-8 weeks of age reportedly from dilated cardiomyopathy with associated conduction defects