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LMNA

lamin A/C

The LMNA gene encodes lamin A and C proteins, which are essential structural components of the nuclear envelope and play key roles in cellular stability, gene expression, and signalling pathways. The LMNA gene provides instructions for producing lamins A and C, structural proteins that form a mesh-like layer supporting the inner nuclear membrane.

Chromosome 1q22 Autosomal dominant HGNC:6636 Tier B
LMNA 1q22 p arm q arm 1

LMNA is located on the long (q) arm of chromosome 1, at band 1q22. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 1 in the library →

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Clinical tests that include this

KNOVA NIPT
LMNA is 1 of 56 genes on this panel
Prenatal NIPT screening (trisomies, microdeletions, single-gene conditions)

Overview

The LMNA gene, also known as lamin A/C, is fundamental to cellular structure and function, providing the blueprint for lamin A and lamin C proteins. These proteins are widely expressed throughout the body and are integral to the nuclear envelope, a double membrane that encloses the genetic material within a cell's nucleus. Proper functioning of LMNA-encoded proteins is vital for maintaining the nucleus's mechanical stability and for regulating various cellular processes.

Pathogenic variants within the LMNA gene can disrupt these critical functions, leading to a spectrum of inherited disorders often referred to as laminopathies. These conditions can affect multiple body systems, including muscles, fat distribution, and the heart, highlighting the gene's widespread importance in human health.

What the gene does

The LMNA gene directs the synthesis of lamin A and lamin C, two primary protein isoforms that are critical components of the nuclear lamina. The nuclear lamina is a fibrous network located just inside the inner nuclear membrane, providing mechanical support to the nucleus and playing a role in chromosomal organisation, DNA replication, and gene expression regulation. Lamin A and C are classified as intermediate filament proteins, which contribute to the cell's structural integrity and resilience.

Lamins A and C contribute to the nuclear envelope's stability, which in turn influences nuclear mechanics and cell-signalling pathways. They are involved in maintaining the shape and structural integrity of the nucleus, and their interactions with other nuclear proteins are essential for normal cellular function. Lamin A undergoes a series of processing steps, starting as prelamin A, before it becomes a mature component of the nuclear lamina. In contrast, lamin C does not require this extensive processing before integration into the nuclear structure.

Beyond their structural roles, lamins A and C are thought to participate in regulating gene activity and cell signalling. They can interact with transcription factors and chromatin, influencing how genes are switched on or off. Disruptions to these interactions or the structural integrity provided by lamins can have far-reaching effects on cellular physiology, leading to the diverse clinical presentations observed in LMNA-related disorders.

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Chromosome location

The LMNA gene is situated on chromosome 1 at band 1q22. This specific genomic location positions the gene within the long arm of chromosome 1. The gene provides instructions for a protein that is 664 amino acids in length.

Protein structure

The LMNA protein, which is 664 amino acids long, exhibits a complex domain architecture crucial for its structural and functional roles. The N-terminal region includes an Interaction with MLIP (amino acids 1-130) and a Head (amino acids 1-33), which contains a Disordered region (amino acids 1-25). Following this, a major structural component is the IF rod (amino acids 31-387), an intermediate filament rod domain. This rod domain is further segmented into Coil 1A (amino acids 34-70), Linker 1 (amino acids 71-80), Coil 1B (amino acids 81-218), Linker 2 (amino acids 219-242), and Coil 2 (amino acids 243-383). Within the Coil 2 region, a segment (amino acids 259-331) is Necessary and sufficient for the interaction with IFFO1. The protein concludes with a long C-terminal Tail (amino acids 384-664), which also contains a Disordered region (amino acids 384-442). A Nuclear localization signal (amino acids 417-422) is found within the tail, facilitating transport into the nucleus. Additionally, the tail region includes an LTD domain (amino acids 428-545) and another Disordered region (amino acids 552-576).

Domain map · 664 amino acids
Interaction with MLIP (1–130)IF rod (31–387)Coil 1B (81–218)Coil 2 (243–383)Necessary and sufficient for the interaction with IFFO1 (259–331)Tail (384–664)Nuclear localization signal (417–422)LTD (428–545)IF rod31–387Coil 2243–383Tail384–6641~332664
Region - functional region
Domain - independent functional unit
Motif - short conserved sequence
🧬 Explore 3D structure on AlphaFold
UniProt:P02545Length:664 aaStructure:AlphaFold

Key variants

Variants in the LMNA gene encompass a broad range of genetic changes that can impact protein function and lead to diverse health conditions. These variants can include single nucleotide changes, deletions, or insertions, all of which may alter the structure or abundance of the lamin A and C proteins. The specific location and type of variant often correlate with the particular clinical presentation, although there can be significant variability.

2,327
Total variants catalogued in ClinVar
View all on ClinVar →
547 Pathogenic / Likely pathogenic 886 Uncertain significance 627 Benign / Likely benign 267 Conflicting or other

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.1003C>T
single nucleotide variant
 p.Arg335Trp Pathogenic/Likely pathogenic ★★☆☆ Primary dilated cardiomyopathy
c.1003del
Deletion
 p.Arg335fs Pathogenic ★★☆☆ Charcot-Marie-Tooth disease type 2
c.1045C>T
single nucleotide variant
 p.Arg349Trp Pathogenic/Likely pathogenic ★★☆☆ not provided
c.104T>C
single nucleotide variant
 p.Leu35Pro Pathogenic/Likely pathogenic ★★☆☆ not provided
c.1057C>T
single nucleotide variant
 p.Gln353Ter Pathogenic ★★☆☆ not provided
c.1063C>T
single nucleotide variant
 p.Gln355Ter Pathogenic ★★☆☆ not provided
c.1072G>A
single nucleotide variant
 p.Glu358Lys Pathogenic ★★☆☆ Emery-Dreifuss muscular dystrophy 2, autosomal dominant
c.1081G>A
single nucleotide variant
 p.Glu361Lys Pathogenic ★★☆☆ not provided
c.1112_1115dup
Duplication
 p.Glu372fs Pathogenic/Likely pathogenic ★★☆☆ Primary dilated cardiomyopathy
c.1116G>C
single nucleotide variant
 p.Glu372Asp Pathogenic/Likely pathogenic ★★☆☆ Dilated cardiomyopathy 1A

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Pathogenic variants in the LMNA gene are associated with a group of conditions known as laminopathies, which include Familial dilated cardiomyopathy (all). These conditions can affect various tissues and organs, leading to a spectrum of symptoms such as muscle weakness, heart problems, and issues with fat distribution. The clinical features depend on how the specific genetic change impacts the lamin proteins' structure and function within different cell types.

Inheritance pattern

Conditions caused by pathogenic LMNA variants typically follow autosomal dominant inheritance.

♀ Affected parent 1 altered copy ♂ Unaffected parent 2 typical copies Affected Unaffected Unaffected Affected Affected Carrier Unaffected Circles = females · Squares = males

Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.

UK clinical status

The LMNA gene is routinely assessed in the UK within the NHS Genomic Medicine Service due to its established links to several serious inherited conditions. It is included in multiple PanelApp green panels, indicating strong evidence for its association with conditions like Arrhythmogenic right ventricular cardiomyopathy, Congenital muscular dystrophy, Dilated and arrhythmogenic cardiomyopathy, and Progressive cardiac conduction disease, among others. LMNA is also part of the ACMG SF v3.2 Secondary Findings list, classified as Tier 1, signifying its recognised clinical actionability for incidental findings.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Arrhythmogenic right ventricular cardiomyopathy · R133 NHS GMS → Congenital muscular dystrophy · R79 NHS GMS → Congenital myopathy · R81 NHS GMS → Dilated and arrhythmogenic cardiomyopathy · R132 NHS GMS → Fetal anomalies · R21 NHS GMS → Hereditary neuropathy or pain disorder · R78 NHS GMS → Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies · R82 NHS GMS → Monogenic diabetes · R141 NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Diet & lifestyle considerations

Research suggests that general healthy lifestyle practices may contribute to overall well-being, though there is no conclusive evidence that specific lifestyle interventions can prevent the onset or progression of LMNA-related conditions. Maintaining a balanced diet, engaging in regular, appropriate physical activity as advised by a healthcare professional, and avoiding smoking are generally recommended for cardiovascular health. Individuals with LMNA-related conditions should discuss any lifestyle changes with their healthcare provider.

Supplement considerations

There is no scientific evidence to suggest that specific dietary supplements can prevent, treat, or cure LMNA-related conditions. While some supplements are marketed for cardiovascular health or muscle support, their effectiveness in the context of genetic conditions like those associated with LMNA variants is not established. Individuals should consult a healthcare professional before taking any supplements, as some may interact with medications or have unintended side effects.

Frequently asked questions

What is the LMNA gene?

The LMNA gene provides instructions for making lamin A and lamin C proteins, which are crucial structural components of the nuclear envelope in cells. These proteins help maintain the nucleus's shape and integrity, and are involved in regulating gene expression.

What conditions are associated with LMNA gene variants?

Pathogenic variants in the LMNA gene are linked to a group of disorders known as laminopathies, which can include Familial dilated cardiomyopathy (all). These conditions can affect various body systems, including the heart and muscles.

How are LMNA variants inherited?

LMNA-related conditions are typically inherited in an autosomal dominant pattern. This means that a person needs only one copy of the altered gene in each cell to be affected.

What is the nuclear envelope?

The nuclear envelope is a double membrane that surrounds the nucleus of eukaryotic cells, separating the genetic material from the rest of the cell. Lamin A and C proteins form a structural network, the nuclear lamina, that supports this envelope.

Can lifestyle changes prevent LMNA-related conditions?

While a healthy lifestyle is generally beneficial for overall health, there is no conclusive evidence that specific lifestyle changes can prevent the onset or progression of conditions caused by LMNA gene variants. Any lifestyle modifications should be discussed with a healthcare provider.

References

  1. Petillo R, D'Ambrosio P, Torella A. Novel mutations in LMNA A/C gene and associated phenotypes. Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology. 2015. PMID: 27199538
  2. Guénantin AC, Briand N, Bidault G. Nuclear envelope-related lipodystrophies. Seminars in cell & developmental biology. 2014. PMID: 24384368
  3. Carboni N, Mateddu A, Marrosu G. Genetic and clinical characteristics of skeletal and cardiac muscle in patients with lamin A/C gene mutations. Muscle & nerve. 2013. PMID: 23450819
  4. Bonne G, Quijano-Roy S. Emery-Dreifuss muscular dystrophy, laminopathies, and other nuclear envelopathies. Handbook of clinical neurology. 2013. PMID: 23622360
  5. Carboni N, Politano L, Floris M. Overlapping syndromes in laminopathies: a meta-analysis of the reported literature. Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology. 2013. PMID: 23853504
  6. Bidault G, Vatier C, Capeau J. LMNA-linked lipodystrophies: from altered fat distribution to cellular alterations. Biochemical Society transactions. 2011. PMID: 22103520
  7. Garg A, Subramanyam L, Agarwal AK. Atypical progeroid syndrome due to heterozygous missense LMNA mutations. The Journal of clinical endocrinology and metabolism. 2009. PMID: 19875478
  8. Quijano-Roy S, Mbieleu B, Bönnemann CG. De novo LMNA mutations cause a new form of congenital muscular dystrophy. Annals of neurology. 2008. PMID: 18551513
  9. Navarro CL, De Sandre-Giovannoli A, Bernard R. Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identify restrictive dermopathy as a lethal neonatal laminopathy. Human molecular genetics. 2004. PMID: 15317753
  10. De Sandre-Giovannoli A, Bernard R, Cau P. Lamin a truncation in Hutchinson-Gilford progeria. Science (New York, N.Y.). 2003. PMID: 12702809
  11. Eriksson M, Brown WT, Gordon LB. Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature. 2003. PMID: 12714972
  12. Novelli G, Muchir A, Sangiuolo F. Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A/C. American journal of human genetics. 2002. PMID: 12075506
  13. Muchir A, Bonne G, van der Kooi AJ. Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbances (LGMD1B). Human molecular genetics. 2000. PMID: 10814726
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 18 October 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .