GenAge entry for LMNA (Homo sapiens)

Entry selected based on evidence directly linking the gene product to ageing in humans

Gene name (HAGRID: 14)

HGNC symbol
LMNA 
Aliases
HGPS; LMN1; CMD1A; LGMD1B; PRO1; LMNL1 
Common name
lamin A/C 

Potential relevance to the human ageing process

Main reason for selection
Entry selected based on evidence directly linking the gene product to ageing in humans
Description

LMNA encodes both lamin A and C (lamin A/C), two components of the lamina, a layer of the inner nuclear membrane that may interact with chromatin [174]. Hutchinson-Gilford's progeroid syndrome, caused by a mutation in LMNA, is characterized by features resembling accelerated ageing [17]. Cells from Hutchinson-Gilford's progeroid syndrome patients are characterised by accumulation of abnormally shaped nuclei, accumulation of DNA damage and premature senescence [4328]. LMNA mutations (such as the G608G mutation) generate more accessible splicing donor sites and lead to the production of an alternatively spliced product of LMNA called progerin, normally found in ageing cells. Progerin binds directly to lamin A/C and induces profound nuclear aberrations in human cells.

Mice Lmna mutants containing the G690G mutation, which also display an increased ratio of progerin/Lamin A, have shorter lifespan compared to the wild-type ( ~40% in heterozygous mice, and ~83% in homozygous mice), while mice with Lmna LCS, a knock-in mutation responsible for specifically not-producing progerin, display an increased lifespan (~13% in heterozygous mice and ~10% in homozygous mice) [3548]. Lamin A/C are TP53BP1 binding proteins that promote TP53BP1 nuclear retention. Lmna knockout mouse embryonic fibroblasts are deficient in TP53BP1 and are unable to carry out the NHEJ DNA repair pathway [4328].

In flies LamC mutations are a model of human LMNA mutations. These flies demonstrate premature aging in adult flight muscles and have decreased levels of specific mitochondrial protein transcripts and progressive mitochondrial degradation. Several transcripts required for mitochondrial integrity and function exit the nucleus via nuclear envelop budding. Abnormal lamina organisation due to LamC mutation may prevent the egress of these RNAs [4375]. Thus, absence of LMNA may accelerate aging due to an impaired response to DNA damage and mitochondrial dysfunction.

Overall, LMNA is one of the most promising candidates for a gene related to human ageing.

Cytogenetic information

Cytogenetic band
1q22
Location
156,114,670 bp to 156,140,089 bp
Orientation
Plus strand
Display region using the UCSC Genome Browser (GRCh38/hg38)

Protein information

Gene Ontology
Process: GO:0007077; mitotic nuclear envelope disassembly
GO:0007084; mitotic nuclear envelope reassembly
GO:0030334; regulation of cell migration
GO:0030951; establishment or maintenance of microtubule cytoskeleton polarity
GO:0034504; protein localization to nucleus
GO:0035105; sterol regulatory element binding protein import into nucleus
GO:0036498; IRE1-mediated unfolded protein response
GO:0055015; ventricular cardiac muscle cell development
GO:0071456; cellular response to hypoxia
GO:0072201; negative regulation of mesenchymal cell proliferation
GO:0090201; negative regulation of release of cytochrome c from mitochondria
And 4 more GO terms
Cellular component: GO:0005634; nucleus
GO:0005635; nuclear envelope
GO:0005638; lamin filament
GO:0005654; nucleoplasm
GO:0005737; cytoplasm
GO:0005829; cytosol
GO:0016607; nuclear speck
GO:0031012; extracellular matrix
GO:0031965; nuclear membrane
Function: GO:0005198; structural molecule activity
GO:0005515; protein binding
Show all GO terms

Protein interactions and network

Protein-protein interacting partners in GenAge
TP53, LMNA, MYC, EGF, PARP1, RPA1, VCP, TOP2A, UBE2I, PML, PRKCA, PRKDC, XRCC6, RB1, EMD, PCMT1, LMNB1, H2AFX, CTNNB1, SIRT6, CISD2, SIRT7
STRING interaction network
Protein-Protein network diagram for LMNA

Retrieve sequences for LMNA

ORF
ORF
CDS
CDS

Homologs in model organisms

Caenorhabditis elegans
lmn-1
Danio rerio
lmna
Drosophila melanogaster
LamC
Mus musculus
Lmna
Rattus norvegicus
Lmna

In other databases

GenAge model organism genes
  • A homolog of this gene for Caenorhabditis elegans is present as lmn-1
  • A homolog of this gene for Mus musculus is present as Lmna
LongevityMap
  • This gene is present as LMNA

Selected references

External links

EPD
ORF Accession
NM_170707
CDS Accession
NP_733821
OMIM
150330
HPRD
01035
Ensembl
LMNA
UniProt/Swiss-Prot
LMNA_HUMAN
GeneCards
LMNA
Entrez Gene
4000
UniGene
594444
GenAtlas
LMNA
Internet
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