Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Orphanet	Ensembl
	HGNC	UniGene	Nucleotide	OMIM		UCSC

Home Page

FLASH GENE

Symbol

LMNA

contributors: mct/ - updated : 28-09-2019

HGNC name	lamin A/C
HGNC id	6636

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed miscelleaneous senescence   correction of cellular phenotypes of Hutchinson-Gilford Progeria cells by RNA interference, as potential gene therapy neuromuscular myopathy   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 osteoarticular bone   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 miscelleaneous senescence   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