LMNA (Lamin A/C)
LMNA encodes the nuclear lamins A and C: intermediate filaments that line the inner nuclear membrane, shape the nucleus, and organize the genome’s physical arrangement.
Function
Lamins A and C (alternative splice products of one gene) polymerize into the nuclear lamina, the meshwork under the inner nuclear membrane. The lamina gives the nucleus its mechanical properties and anchors heterochromatin: large stretches of the genome called lamina-associated domains sit against it, and their positioning correlates with transcriptional silencing. Lamin mutations change both mechanics and gene regulation at once — nuclei deform under stress, and silenced chromatin relocates. The protein is processed from a farnesylated precursor (prelamin A) whose normal maturation requires a final proteolytic step.
In aging and cancer
LMNA mutations cause Hutchinson–Gilford progeria syndrome, the segmental premature-aging disease: the classic G608G mutation creates a splice defect that leaves the farnesylated tail in place, and toxic progerin accumulates, deforming nuclei and misplacing heterochromatin. Progeria cells show the molecular phenotypes of old cells — loss of heterochromatin, DNA repair deficits, senescence — which made lamin processing a central model of biological aging. In cancer, LMNA expression is lost in aggressive tumors, and low lamin A/C correlates with nuclear deformability, invasion, and metastatic transit through small vessels.
Notes
- Human gene symbol: LMNA; UniProt P02545; 664 amino acids (lamin A); type V intermediate filament.