LMNA_HUMAN
Source: PM19886704PM23856902
Marked as 'Non-membrane protein'
Confidence: low (only semi-automatic identification from reviews) Search PubMed for
(RBC AND this entry)
Gene names: LMNA , LMN1
Protein names and data: LMNA_HUMAN , Prelamin-A/C; Lamin-A/C , 70 kDa lamin; Renal carcinoma antigen NY-REN-32; Flags: Precursor Lenght: 664 a.a.
Mass: 74139 Da
fasta formatted sequence
Function: Lamins are components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane, which is thought to provide a framework for the nuclear envelope and may also interact with chromatin. Lamin A and C are present in equal amounts in the lamina of mammals. Plays an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics. 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. Prelamin-A/C can accelerate smooth muscle cell senescence. It acts to disrupt mitosis and induce DNA damage in vascular smooth muscle cells (VSMCs), leading to mitotic failure, genomic instability, and premature senescence.
Disease: ( OMIM: 115200 150330 151660 159001 176670 181350 212112 248370 275210 605588 610140 613205 ) Emery-Dreifuss muscular dystrophy 2, autosomal dominant (EDMD2) [MIM:181350]: A form of Emery-Dreifuss muscular dystrophy, a degenerative myopathy characterized by weakness and atrophy of muscle without involvement of the nervous system, early contractures of the elbows, Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects. Note=The disease is caused by mutations affecting the gene represented in this entry. Emery-Dreifuss muscular dystrophy 3, autosomal recessive (EDMD3) [MIM:181350]: A form of Emery-Dreifuss muscular dystrophy, a degenerative myopathy characterized by weakness and atrophy of muscle without involvement of the nervous system, early contractures of the elbows, Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects. Note=The disease is caused by mutations affecting the gene represented in this entry. Cardiomyopathy, dilated 1A (CMD1A) [MIM:115200]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. Note=The disease is caused by mutations affecting the gene represented in this entry. Lipodystrophy, familial partial, 2 (FPLD2) [MIM:151660]: A disorder characterized by the loss of subcutaneous adipose tissue in the lower parts of the body (limbs, buttocks, trunk). It is accompanied by an accumulation of adipose tissue in the face and neck causing a double chin, fat neck, or cushingoid appearance. Adipose tissue may also accumulate in the axillae, back, labia majora, and intraabdominal region. Affected patients are insulin-resistant and may develop glucose intolerance and diabetes mellitus after age 20 years, hypertriglyceridemia, and low levels of high density lipoprotein cholesterol. Note=The disease is caused by mutations affecting the gene represented in this entry. Limb-girdle muscular dystrophy 1B (LGMD1B) [MIM:159001]: An autosomal dominant degenerative myopathy with age-related atrioventricular cardiac conduction disturbances, dilated cardiomyopathy, and the absence of early contractures. Characterized by slowly progressive skeletal muscle weakness of the hip and shoulder girdles. Muscle biopsy shows mild dystrophic changes. Note=The disease is caused by mutations affecting the gene represented in this entry. Charcot-Marie-Tooth disease 2B1 (CMT2B1) [MIM:605588]: A recessive axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. Nerve conduction velocities are normal or slightly reduced. Note=The disease is caused by mutations affecting the gene represented in this entry. Hutchinson-Gilford progeria syndrome (HGPS) [MIM:176670]: Rare genetic disorder characterized by features reminiscent of marked premature aging. Note=The disease is caused by mutations affecting the gene represented in this entry. HGPS is caused by the toxic accumulation of a truncated form of lamin-A/C. This mutant protein, called progerin (isoform 6), acts to deregulate mitosis and DNA damage signaling, leading to premature cell death and senescence. The mutant form is mainly generated by a silent or missense mutation at codon 608 of prelamin A that causes activation of a cryptic splice donor site, resulting in production of isoform 6 with a deletion of 50 amino acids near the C terminus. Progerin lacks the conserved ZMPSTE24/FACE1 cleavage site and therefore remains permanently farnesylated. Thus, although it can enter the nucleus and associate with the nuclear envelope, it cannot incorporate normally into the nuclear lamina (PubMed:12714972). Cardiomyopathy, dilated, with hypergonadotropic hypogonadism (CMDHH) [MIM:212112]: A disorder characterized by the association of genital anomalies, hypergonadotropic hypogonadism and dilated cardiomyopathy. Patients can present other variable clinical manifestations including mental retardation, skeletal anomalies, scleroderma-like skin, graying and thinning of hair, osteoporosis. Dilated cardiomyopathy is characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Note=The disease is caused by mutations affecting the gene represented in this entry. Mandibuloacral dysplasia with type A lipodystrophy (MADA) [MIM:248370]: A disorder characterized by mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of the cranial suture, progeroid appearance, partial alopecia, soft tissue calcinosis, joint contractures, and partial lipodystrophy with loss of subcutaneous fat from the extremities. Adipose tissue in the face, neck and trunk is normal or increased. Note=The disease is caused by mutations affecting the gene represented in this entry. Lethal tight skin contracture syndrome (LTSCS) [MIM:275210]: Rare disorder mainly characterized by intrauterine growth retardation, tight and rigid skin with erosions, prominent superficial vasculature and epidermal hyperkeratosis, facial features (small mouth, small pinched nose and micrognathia), sparse/absent eyelashes and eyebrows, mineralization defects of the skull, thin dysplastic clavicles, pulmonary hypoplasia, multiple joint contractures and an early neonatal lethal course. Liveborn children usually die within the first week of life. The overall prevalence of consanguineous cases suggested an autosomal recessive inheritance. Note=The disease is caused by mutations affecting the gene represented in this entry. Heart-hand syndrome Slovenian type (HHS-Slovenian) [MIM:610140]: Heart-hand syndrome (HHS) is a clinically and genetically heterogeneous disorder characterized by the co- occurrence of a congenital cardiac disease and limb malformations. Note=The disease is caused by mutations affecting the gene represented in this entry. Muscular dystrophy congenital LMNA-related (MDCL) [MIM:613205]: A form of congenital muscular dystrophy. Patients present at birth, or within the first few months of life, with hypotonia, muscle weakness and often with joint contractures. Note=The disease is caused by mutations affecting the gene represented in this entry. Note=Defects in LMNA may cause a late-onset cardiocutaneous progeria syndrome characterized by cutaneous manifestations of aging appearing in the third decade of life, cardiac valve calcification and dysfunction, prominent atherosclerosis, and cardiomyopathy, leading to death on average in the fourth decade.
Cellular location: Nucleus. Nucleus envelope. Nucleus lamina. Nucleus, nucleoplasm. Note=Farnesylation of prelamin-A/C facilitates nuclear envelope targeting and subsequent cleaveage by ZMPSTE24/FACE1 to remove the farnesyl group produces mature lamin- A/C, which can then be inserted into the nuclear lamina. EMD is required for proper localization of non-farnesylated prelamin-A/C. Isoform C: Nucleus speckle.
Tissue specificity: In the arteries, prelamin-A/C accumulation is not observed in young healthy vessels but is prevalent in medial vascular smooth muscle cells (VSMCs) from aged individuals and in atherosclerotic lesions, where it often colocalizes with senescent and degenerate VSMCs. Prelamin-A/C expression increases with age and disease. In normal aging, the accumulation of prelamin-A/C is caused in part by the down-regulation of ZMPSTE24/FACE1 in response to oxidative stress.
Genetic variants
10 - 10 T -> I (in an atypical progeroid patient; diagnosed as Seip syndrome; dbSNP:rs57077886). VAR_039745 5707788625 - 25 R -> G (in EDMD2; dbSNP:rs58327533). VAR_039746 58327533
25 - 25 R -> P (in EDMD2; mis-localized in the nucleus; causes nuclear deformations and LMNB1 redistribution; dbSNP:rs61578124). VAR_039747 61578124
28 - 28 R -> W (in FPLD2; dbSNP:rs59914820). VAR_039748 59914820
32 - 32 Missing (in EDMD2). VAR_039749
33 - 33 E -> D (in CMT2; autosomal dominant form; dbSNP:rs57966821). VAR_039750 57966821
33 - 33 E -> G (in EDMD2). VAR_039751
35 - 35 L -> V (in EDMD2; dbSNP:rs56694480). VAR_039752 56694480
39 - 39 N -> S (in MDCL and EDMD2). VAR_063588
43 - 43 A -> T (in EDMD2; dbSNP:rs60446065). VAR_039753 60446065
45 - 45 Y -> C (in EDMD2; dbSNP:rs58436778). VAR_009971 58436778
50 - 50 R -> P (in EDMD2 and MDCL; dbSNP:rs60695352). VAR_009972 60695352
50 - 50 R -> S (in EDMD2; dbSNP:rs59931416). VAR_039754 59931416
57 - 57 A -> P (in CMDHH; phenotype originally designated as atypical Werner syndrome; dbSNP:rs28928903). VAR_017656 28928903
59 - 59 L -> R (in CMDHH). VAR_064055
60 - 60 R -> G (in CMD1A and FPLD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type; dbSNP:rs28928900). VAR_034706 28928900
62 - 62 R -> G (in FPLD2; dbSNP:rs56793579). VAR_039755 56793579
63 - 63 I -> N (in EDMD2). VAR_039756
63 - 63 I -> S (in EDMD2; dbSNP:rs57793737). VAR_009974 57793737
65 - 65 E -> G (in EDMD2). VAR_039757
85 - 85 L -> R (in CMD1A; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type; dbSNP:rs28933090). VAR_009975 28933090
89 - 89 R -> L (in CMD1A; dramatically aberrant localization with almost no nuclear rim staining and formation of intranuclear foci; dbSNP:rs59040894). VAR_039758 59040894
92 - 92 L -> F (in CMD1A). VAR_067257
97 - 97 K -> E (in CMD1A; dbSNP:rs59065411). VAR_039759 59065411
101 - 101 R -> P (in CMD1A; dramatically aberrant localization with almost no nuclear rim staining and formation of intranuclear foci). VAR_070174
112 - 112 Missing (in EDMD2). VAR_009976
133 - 133 R -> L (in FPLD2). VAR_016913
133 - 133 R -> P (in EDMD2; dbSNP:rs60864230). VAR_017657 60864230
138 - 138 E -> K (in HGPS; might be associated with early and severe strokes). VAR_070175
140 - 140 L -> P (in EDMD2). VAR_039760
140 - 140 L -> R (in HGPS; phenotype originally designated as atypical Werner syndrome; dbSNP:rs60652225). VAR_017658 60652225
143 - 143 S -> F (in HGPS; dbSNP:rs58912633). VAR_034707 58912633
143 - 143 S -> P (in CMD1A; dbSNP:rs61661343). VAR_039761 61661343
145 - 145 E -> K (in HGPS; atypical; dbSNP:rs60310264). VAR_017659 60310264
150 - 150 T -> P (in EDMD2; dbSNP:rs58917027). VAR_039762 58917027
161 - 161 E -> K (in CMD1A; dbSNP:rs28933093). VAR_017660 28933093
166 - 166 R -> P (in CMD1A; dramatically aberrant localization with almost no nuclear rim staining and formation of intranuclear foci). VAR_070176
189 - 189 R -> P (in EDMD2; found also in a patient with limb-girdle muscular dystrophy; sporadic). VAR_064962
190 - 190 R -> Q (in EDMD2 and CMD1A; aberrant localization with decreased nuclear rim staining and increased formation of intranuclear foci). VAR_039763
190 - 190 R -> RR (in EDMD2). VAR_064963
190 - 190 R -> W (in CMD1A; dbSNP:rs59026483). VAR_039764 59026483
192 - 192 D -> G (in CMD1A; dramatically increases the size of intranuclear speckles and reduces their number; this phenotype is only partially reversed by coexpression of the G-192 mutation and wild-type lamin-C; precludes insertion of lamin-C into the nuclear envelope when co- transfected with the G-192 LMNA; G-192 lamin-C expression totally disrupts the SUMO1 pattern; dbSNP:rs57045855). VAR_039765 57045855
195 - 195 N -> K (in CMD1A; dramatically aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; distribution of endogenous LMNA, LMNB1 and LMNB2 are altered in cells expressing this mutant; causes an increased loss of endogenous EMD from the nuclear envelope; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type; dbSNP:rs28933091). VAR_009977 28933091
196 - 199 RLQT -> S (in EDMD2). VAR_039766
203 - 203 E -> G (in CMD1A; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type; decreased sumoylation; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; associated with increased cell death; dbSNP:rs28933092). VAR_009978 28933092
203 - 203 E -> K (in CMD1A; decreased sumoylation; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; associated with increased cell death; dbSNP:rs61195471). VAR_039767 61195471
206 - 206 F -> L (in EDMD2). VAR_064964
208 - 208 Missing (in LGMD1B). VAR_034708
210 - 210 I -> S (in CMD1A; dramatically aberrant localization with almost no nuclear rim staining and increased formation of intranuclear foci). VAR_070177
215 - 215 L -> P (in CMD1A; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci). VAR_039768
222 - 222 H -> P (in EDMD2). VAR_039769
222 - 222 H -> Y (in EDMD2; dbSNP:rs28928901). VAR_009979 28928901
225 - 225 R -> Q (in EDMD3). VAR_067697
230 - 230 D -> N (in FPLD2). VAR_039770
232 - 232 G -> E (in EDMD2). VAR_039771
248 - 248 L -> P (in EDMD2). VAR_039772
249 - 249 R -> Q (in EDMD2). VAR_009980
249 - 249 R -> W (in MDCL and EDMD2; mislocalized in the nucleus; causes nuclear deformations and LMNB1 redistribution). VAR_063589
260 - 260 K -> N (in CMDA1). VAR_039773
261 - 261 Missing (in EDMD2). VAR_009981
267 - 267 Y -> C (in EDMD2). VAR_039774
268 - 268 S -> P (in EDMD2). VAR_064965
271 - 271 L -> P (in EDMD2). VAR_064966
294 - 294 Q -> P (in EDMD2). VAR_009982
295 - 295 S -> P (in EDMD2). VAR_064967
298 - 298 R -> C (in CMT2B1). VAR_017661
300 - 300 D -> G (probable disease-associated mutation found in a patient with late- onset cardiocutaneous progeria syndrome; abnormal nuclear morphology with single or multple blebs, lobulation and occasional ringed or donut shaped nuclei). VAR_070178
302 - 302 L -> P (in MDCL). VAR_063590
303 - 303 S -> P (in EDMD2). VAR_064968
317 - 317 E -> K (in CMD1A). VAR_039775
318 - 318 A -> T (in CMD1A; no effect on nuclear morphology and lamin A localization). VAR_070179
336 - 336 R -> Q (in EDMD2). VAR_009983
343 - 343 R -> Q (in EDMD2). VAR_009984
349 - 349 R -> L (in CMD1A). VAR_039776
355 - 355 Missing (in EDMD2). VAR_064969
358 - 358 E -> K (in EDMD2 and MDCL; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; distribution of endogenous LMNA, LMNB1 and LMNB2 are altered in cells expressing this mutant; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type). VAR_009985
361 - 361 E -> K (in EDMD2). VAR_064970
371 - 371 M -> K (in EDMD2; dramatically aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; distribution of endogenous LMNA, LMNB1 and LMNB2 are altered in cells expressing this mutant; causes an increased loss of endogenous EMD from the nuclear envelope; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type). VAR_009986
377 - 377 R -> H (in LGMD1B). VAR_016205
377 - 377 R -> L (in EDMD2 and LGMD1B). VAR_039777
380 - 380 L -> S (in MDCL). VAR_063591
386 - 386 R -> K (in EDMD2; dramatically aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; distribution of endogenous LMNA, LMNB1 and LMNB2 are altered in cells expressing this mutant; causes an increased loss of endogenous EMD from the nuclear envelope; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type). VAR_009987
388 - 388 R -> H (in CMD1A; no effect on nuclear morphology but restricts lamin A to the cytoplasm). VAR_070180
399 - 399 R -> C (in FPLD2 and CMD1A; no effect on nuclear morphology and lamin A localization). VAR_039778
435 - 435 R -> C (in CMD1A). VAR_039779
439 - 439 R -> C (in FPLD2; increase in nuclear blebbing and formation of honeycomb-like structures in the nuclei with no accumulation of prelamin A in skin fibroblasts; causes oligomerization of the C-terminal globular domain of lamins A and C under no-reducing conditions and increases binding affinity for DNA; increases sensitivity to oxidative stress; no significant differences in stability and structure compared with the wild-type). VAR_070181
446 - 446 D -> V (in EDMD2). VAR_039780
449 - 449 G -> D (in EDMD2). VAR_064971
453 - 453 R -> P (in MDCL). VAR_063592
453 - 453 R -> W (in EDMD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type). VAR_009988
454 - 454 L -> P (in EDMD2). VAR_064972
455 - 455 R -> P (in MDCL). VAR_063593
456 - 456 N -> D (in MDCL). VAR_063594
456 - 456 N -> I (in EDMD2; mislocalized in the nucleus; does not alter nuclear size or shape). VAR_039781
456 - 456 N -> K (in EDMD2). VAR_039782
461 - 461 D -> Y (in EDMD2). VAR_064973
465 - 465 G -> D (in FPLD2). VAR_009989
467 - 467 W -> R (in EDMD2). VAR_064974
469 - 469 I -> T (in EDMD2). VAR_009990
471 - 471 R -> C (in HGPS; dbSNP:rs28928902). VAR_017662 28928902
471 - 471 R -> H (in CMD1A; no effect on nuclear morphology and lamin A localization). VAR_070182
481 - 481 Y -> H (in LGMD1B). VAR_039783
482 - 482 R -> L (in FPLD2). VAR_009991
482 - 482 R -> Q (in FPLD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type; dbSNP:rs11575937). VAR_009992 11575937
482 - 482 R -> W (in FPLD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type; decreases binding affinity for DNA; increases sensitivity to oxidative stress). VAR_009993
486 - 486 K -> N (in FPLD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type). VAR_009994
520 - 520 W -> S (in EDMD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type). VAR_039784
523 - 523 G -> R (in CMD1A). VAR_067258
527 - 527 R -> C (in HGPS). VAR_017663
527 - 527 R -> H (in MADA). VAR_018727
527 - 527 R -> P (in EDMD2 and FPLD2; interacts with itself and with wild-type LMNA and LMNB1; reduced binding to SUN1; no decrease in the stability compared with wild-type). VAR_009995
528 - 528 T -> K (in EDMD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type). VAR_009996
528 - 528 T -> R (in EDMD2). VAR_039785
529 - 529 A -> V (in MADA). VAR_034709
530 - 530 L -> P (in EDMD2; interacts with itself and with wild-type LMNA and LMNB1; reduced binding to SUN1; no decrease in the stability compared with wild-type). VAR_009997
541 - 541 R -> C (in apical left ventricular aneurysm). VAR_039786
541 - 541 R -> H (in EDMD2). VAR_039787
541 - 541 R -> P (in EDMD2; mis-localized in the nucleus; does not alter nuclear size or shape). VAR_064975
541 - 541 R -> S (in EDMD2 and CMD1A; modest and non-specific nuclear membrane alterations; the phenotype is entirely reversed by coexpression of the S-541 mutation and wild-type lamin-C). VAR_039788
542 - 542 K -> N (in HGPS). VAR_034710
573 - 573 S -> L (in CMD1A, FPLD2 and MADA). VAR_039789
578 - 578 E -> V (in an atypical progeroid patient; diagnosed as Werner syndrome). VAR_039790
582 - 582 R -> H (in FPLD2; dbSNP:rs57830985). VAR_009998 57830985
602 - 602 G -> S (in EDMD2; dbSNP:rs60662302). VAR_064976 60662302
608 - 608 G -> S (in HGPS; reduced binding to SUN1; may affect splicing by activating a cryptic splice donor site). VAR_017664
624 - 624 R -> H (in EDMD2). VAR_039791
644 - 644 R -> C (in an atypical progeroid patient; diagnosed as Hutchinson-Gilford progeria syndrome; partially inhibits tail cleavage). VAR_039792
Database cross-references
UniProt: P02545Ensembl: ENST00000347559
Ensembl: ENST00000361308
Ensembl: ENST00000368300
Ensembl: ENST00000368301
Ensembl: ENST00000448611
Ensembl: ENST00000508500
MIM: 115200
MIM: 150330
MIM: 151660
MIM: 159001
MIM: 176670
MIM: 181350
MIM: 212112
MIM: 248370
MIM: 275210
MIM: 605588
MIM: 610140
MIM: 613205
neXtProt: NX_P02545
Antibodypedia: P02545 (may not find the protein thus also not any antibody)
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