Gene Function

Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane. Lamins provide a framework for the nuclear envelope, bridging the nuclear envelope and chromatin, thereby playing an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics. Lamin A and C also regulate matrix stiffness by conferring nuclear mechanical properties. The structural integrity of the lamina is strictly controlled by the cell cycle, as seen by the disintegration and formation of the nuclear envelope in prophase and telophase, respectively. Lamin A and C are present in equal amounts in the lamina of mammals. Also involved in DNA repair: recruited by DNA repair proteins XRCC4 and IFFO1 to the DNA double-strand breaks (DSBs) to prevent chromosome translocation by immobilizing broken DNA ends. Required for normal development of peripheral nervous system and skeletal muscle and for muscle satellite cell proliferation. Required for osteoblastogenesis and bone formation. Also prevents fat infiltration of muscle and bone marrow, helping to maintain the volume and strength of skeletal muscle and bone. Required for cardiac homeostasis Source: UniProt

Relationship to CMT

CMT2 AR
1 subtype
1q22

First described 2002

Subtype	Inheritance	Class	OMIM	Sentinel Publication
SubtypeCMT2B1	Inheritanceautosomal recessive	ClassCMT2	OMIM605588	Sentinel Publication Homozygous Defects in LMNA, Encoding Lamin A/C Nuclear-Envelope Proteins, Cause Autosomal Recessive Axonal Neuropathy in Human (Charcot-Marie-Tooth Disorder Type 2) and Mouse 2002 · 10.1086/339274

Stored Identifiers

HGNC Aliases: LMN1, CMD1A, LGMD1B, PRO1, LMNL1

hgnc_idHGNC:6636

ensembl_gene_idENSG00000160789

coords_grch38chr1:156082572-156140085

coords_grch37chr1:156052364-156109880

entrez_id4000

omim_gene150330

uniprot_idsP02545

refseq_accessionNM_170707

mane_refseqNM_170707.4

mane_ensemblENST00000368300.9

External recordsHGNC:6636OMIM 150330gnomADUniProt P02545ClinVar P/LPOrphanetMANE NM_170707.4

EvidencePanelApp GreenClinGen dosage HI 3 · Sufficient evidence

ClinVar Variants

Pathogenic and likely pathogenic variants in LMNA, as classified in ClinVar, are read live from NCBI. Only aggregate germline records are shown. Uncertain and conflicting classifications are not. Experts in CMT makes no claim to the accuracy of ClinVar data. This index is provided for informational purposes only.

Review stars are ClinVar’s measure of how well a classification is supported: four for a practice guideline, three for an expert panel review, two for agreement among multiple submitters, one for a single submitter with criteria provided, and none where no criteria were provided.

Reported in CMT

Reported in Other Diseases

Reported in a disease other than CMT. Listed apart rather than counted as CMT variants.

Variants w/o a Recorded Disease

Pathogenic or likely pathogenic in ClinVar, submitted without a disease recorded.

The Dorsal Root

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