LMNA Gene (Lamin A/C): Structure, Function, and Associated Diseases
Comprehensive guide to the LMNA gene, its protein products, mutations, and clinical significance in laminopathies.
Gene Information Card
| Symbol | LMNA |
|---|---|
| Full Name | Lamin A/C |
| Gene Type | Protein coding |
| Chromosomal Location | 1q22 |
| NCBI Gene ID | 4000 ncbi.nlm.nih.gov/gene/4000 |
| Ensembl ID | ENSG00000160789 |
| UniProt ID | P02545 |
| OMIM ID | 150330 |
| HGNC ID | 6636 |
| Aliases | CDCD1, CMD1A, CMT2B1, FPL, FPLD, HGPS, IDC, LDP1, LFP, LGMD1B, LMNC, LMNL1, PRO1 |
Description
The LMNA gene encodes lamin A and lamin C, two major components of the nuclear lamina, a filamentous meshwork underlying the inner nuclear membrane. These proteins provide structural support to the nucleus, regulate chromatin organization, and participate in DNA replication, transcription, and cell cycle control. Alternative splicing produces lamin A and lamin C isoforms. Mutations in LMNA cause a spectrum of diseases known as laminopathies, including Hutchinson-Gilford progeria syndrome, Emery-Dreifuss muscular dystrophy, dilated cardiomyopathy, and familial partial lipodystrophy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hutchinson-Gilford progeria syndrome (HGPS) | A de novo point mutation (c.1824C>T) activates a cryptic splice site, producing a truncated prelamin A (progerin) that is permanently farnesylated, disrupting the nuclear lamina and causing nuclear blebbing and premature aging. | ClinVar; OMIM #176670 |
| Emery-Dreifuss muscular dystrophy (EDMD) | Missense and truncating mutations in LMNA disrupt nuclear lamina integrity, leading to muscle cell fragility and progressive weakness, often with cardiac conduction defects. | ClinVar; OMIM #181350 |
| Dilated cardiomyopathy 1A (CMD1A) | Mutations in LMNA impair nuclear stability and gene regulation in cardiac myocytes, causing left ventricular dilation and systolic dysfunction, frequently with conduction system disease. | ClinVar; OMIM #115200 |
| Familial partial lipodystrophy type 2 (FPLD2) | Specific missense mutations (e.g., R482W/Q) in the lamin A/C tail disrupt adipocyte differentiation and lipid metabolism, leading to selective loss of subcutaneous fat. | ClinVar; OMIM #151660 |
| Charcot-Marie-Tooth disease type 2B1 (CMT2B1) | Homozygous LMNA mutations cause axonal neuropathy, likely due to impaired nuclear mechanics in peripheral nerves. | ClinVar; OMIM #605588 |
| Restrictive dermopathy | Severe LMNA mutations cause lethal neonatal skin and skeletal abnormalities, due to defective nuclear envelope in fibroblasts. | ClinVar; OMIM #275210 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | High | High |
| Skeletal muscle | High | High |
| Heart | High | High |
| Skin | Medium | Medium |
| Liver | Medium | Medium |
| Brain | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | High | Cervical carcinoma cell line |
| A549 | High | Lung carcinoma cell line |
| HUVEC | Medium | Endothelial cells |
| K562 | Low | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1824C>T (p.G608G) | Point mutation (cryptic splice) | De novo in HGPS | Produces progerin, a permanently farnesylated lamin A variant causing nuclear abnormalities. |
| c.568C>T (p.R190W) | Missense | Rare in EDMD | Disrupts lamin A/C dimerization, weakening nuclear lamina. |
| c.1444C>T (p.R482W) | Missense | Common in FPLD2 | Alters lamin A/C interaction with chromatin, affecting adipocyte gene expression. |
| c.357A>G (p.K117E) | Missense | Rare in CMD1A | Impairs nuclear stability in cardiac muscle, leading to dilated cardiomyopathy. |
| c.1622G>A (p.R541H) | Missense | Rare in CMT2B1 | Causes axonal degeneration due to nuclear fragility in neurons. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., frameshift, nonsense) reduce lamin A/C levels, leading to nuclear fragility and tissue-specific degeneration, as seen in some EDMD and CMD1A cases.
Gain of Function (GOF)
Gain-of-function mutations, such as the HGPS splice mutation, produce a toxic progerin protein that accumulates and disrupts nuclear function, causing premature aging.
Dominant Negative (DN)
Many missense mutations act in a dominant-negative manner, where the mutant protein interferes with the assembly of the nuclear lamina, compromising nuclear integrity and gene regulation.
View complete mutation data：
Gene Ontology (GO)
| • nuclear envelope organization | • nuclear lamina |
| • structural constituent of nuclear pore | • DNA replication |
| • chromatin organization | • cell cycle |
| • apoptosis | • mechanical stress response |
Pathways
• Nuclear Envelope Breakdown and Reformation
• Laminopathies (Disease Pathway)
• Aging and Progeria
• Muscle Contraction and Cardiac Conduction
Protein Summary
The LMNA gene produces two major isoforms, lamin A and lamin C, via alternative splicing. Lamin A is synthesized as prelamin A, which undergoes farnesylation and proteolytic cleavage to mature lamin A. Both proteins form intermediate filaments that assemble into the nuclear lamina, providing structural support and anchoring chromatin. Lamin A/C interacts with numerous nuclear proteins, including emerin, LAP2, and chromatin modifiers, influencing gene expression and DNA repair. Post-translational modifications, such as phosphorylation, regulate lamina disassembly during mitosis. Mutations in LMNA disrupt these functions, leading to a range of tissue-specific diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LMNA Knockout HEK293 Cell Line | EDJ-KQ1983 | Human | 4000 | Details Get a Quote |
| LMNA Knockout HCT 116 Cell Line | EDJ-KQ21960 | Human | 4000 | Details Get a Quote |
| LMNA Knockout HeLa Cell Line | EDJ-KQ21961 | Human | 4000 | Details Get a Quote |
| LMNA Knockout A-549 Cell Line | EDJ-KQ20664 | Human | 4000 | Details Get a Quote |
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