LMNA

LMNA is the human gene that encodes the nuclear lamins A and C, two related intermediate filament proteins that form part of the nuclear lamina on the inner surface of the nuclear envelope. The lamina provides mechanical support to the nucleus and helps organize chromatin and regulate gene expression. Lamins B1 and B2 are related lamina components encoded by the separate LMNB1 and LMNB2 genes.

Lamins A and C arise from alternative splicing of LMNA. They share an identical amino terminus but differ at the C terminus. Lamins A is produced as prelamin A and undergoes extensive post-translational processing, including farnesylation and proteolytic steps, to become mature lamin A. Lamins C, in contrast, is produced directly from splicing and does not require the same processing. The distinct processing pathways contribute to differences in function and localization within the nucleus.

LMNA plays roles in nuclear envelope integrity, chromatin organization, DNA repair, and the regulation of gene expression. The lamina participates in mechanotransduction and affects signaling pathways linked to cellular differentiation and stress responses.

Mutations in LMNA cause a spectrum of diseases known as laminopathies. These include Emery-Dreifuss muscular dystrophy type 2 (EDMD2), Dunnigan-type familial partial lipodystrophy (FPLD2), dilated cardiomyopathy, and other muscular or cardiometabolic disorders. A cryptic splice or mutation can produce progerin, a truncated form of lamin A associated with Hutchinson-Gilford progeria syndrome.