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P02545

- LMNA_HUMAN

UniProt

P02545 - LMNA_HUMAN

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Protein

Prelamin-A/C

Gene
LMNA, LMN1
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.2 Publications
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.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei266 – 2661Heptad change of phase
Sitei325 – 3251Stutter By similarity
Sitei330 – 3301Heptad change of phase
Sitei646 – 6472Cleavage; by endoprotease

GO - Molecular functioni

  1. protein binding Source: IntAct
  2. structural molecule activity Source: InterPro

GO - Biological processi

  1. activation of signaling protein activity involved in unfolded protein response Source: Reactome
  2. apoptotic process Source: Reactome
  3. cellular component disassembly involved in execution phase of apoptosis Source: Reactome
  4. cellular protein metabolic process Source: Reactome
  5. cellular response to hypoxia Source: UniProtKB
  6. endoplasmic reticulum unfolded protein response Source: Reactome
  7. establishment or maintenance of microtubule cytoskeleton polarity Source: BHF-UCL
  8. mitotic cell cycle Source: Reactome
  9. mitotic nuclear envelope disassembly Source: Reactome
  10. mitotic nuclear envelope reassembly Source: Reactome
  11. muscle organ development Source: UniProtKB
  12. negative regulation of extrinsic apoptotic signaling pathway Source: Ensembl
  13. negative regulation of release of cytochrome c from mitochondria Source: Ensembl
  14. positive regulation of cell aging Source: UniProtKB
  15. protein localization to nucleus Source: UniProtKB
  16. regulation of cell migration Source: BHF-UCL
  17. sterol regulatory element binding protein import into nucleus Source: Ensembl
  18. ventricular cardiac muscle cell development Source: Ensembl
Complete GO annotation...

Enzyme and pathway databases

ReactomeiREACT_13472. Breakdown of the nuclear lamina.
REACT_160242. Initiation of Nuclear Envelope Reformation.
REACT_160251. Clearance of Nuclear Envelope Membranes from Chromatin.
REACT_18273. XBP1(S) activates chaperone genes.
REACT_200828. Depolymerisation of the Nuclear Lamina.
REACT_75792. Meiotic synapsis.

Names & Taxonomyi

Protein namesi
Recommended name:
Prelamin-A/C
Cleaved into the following chain:
Alternative name(s):
70 kDa lamin
Renal carcinoma antigen NY-REN-32
Gene namesi
Name:LMNA
Synonyms:LMN1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 1

Organism-specific databases

HGNCiHGNC:6636. LMNA.

Subcellular locationi

Nucleus. Nucleus envelope. Nucleus lamina. Nucleusnucleoplasm
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.7 Publications
Isoform C : Nucleus speckle 7 Publications

GO - Cellular componenti

  1. cytoplasm Source: HPA
  2. cytosol Source: Reactome
  3. intermediate filament Source: UniProtKB
  4. lamin filament Source: Ensembl
  5. nuclear envelope Source: UniProtKB
  6. nuclear lamina Source: UniProtKB
  7. nuclear speck Source: UniProtKB-SubCell
  8. nucleoplasm Source: Reactome
  9. nucleus Source: UniProtKB
  10. perinuclear region of cytoplasm Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Intermediate filament, Nucleus

Pathology & Biotechi

Involvement in diseasei

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.14 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti25 – 251R → G in EDMD2. 1 Publication
Corresponds to variant rs58327533 [ dbSNP | Ensembl ].
VAR_039746
Natural varianti25 – 251R → P in EDMD2; mis-localized in the nucleus; causes nuclear deformations and LMNB1 redistribution. 2 Publications
Corresponds to variant rs61578124 [ dbSNP | Ensembl ].
VAR_039747
Natural varianti32 – 321Missing in EDMD2. 1 Publication
VAR_039749
Natural varianti33 – 331E → G in EDMD2. 1 Publication
VAR_039751
Natural varianti35 – 351L → V in EDMD2. 1 Publication
Corresponds to variant rs56694480 [ dbSNP | Ensembl ].
VAR_039752
Natural varianti39 – 391N → S in MDCL and EDMD2. 2 Publications
VAR_063588
Natural varianti43 – 431A → T in EDMD2. 1 Publication
Corresponds to variant rs60446065 [ dbSNP | Ensembl ].
VAR_039753
Natural varianti45 – 451Y → C in EDMD2. 2 Publications
Corresponds to variant rs58436778 [ dbSNP | Ensembl ].
VAR_009971
Natural varianti50 – 501R → P in EDMD2 and MDCL. 2 Publications
Corresponds to variant rs60695352 [ dbSNP | Ensembl ].
VAR_009972
Natural varianti50 – 501R → S in EDMD2. 1 Publication
Corresponds to variant rs59931416 [ dbSNP | Ensembl ].
VAR_039754
Natural varianti63 – 631I → N in EDMD2. 2 Publications
VAR_039756
Natural varianti63 – 631I → S in EDMD2. 1 Publication
Corresponds to variant rs57793737 [ dbSNP | Ensembl ].
VAR_009974
Natural varianti65 – 651E → G in EDMD2. 1 Publication
VAR_039757
Natural varianti112 – 1121Missing in EDMD2. 2 Publications
VAR_009976
Natural varianti133 – 1331R → P in EDMD2. 1 Publication
Corresponds to variant rs60864230 [ dbSNP | Ensembl ].
VAR_017657
Natural varianti140 – 1401L → P in EDMD2. 2 Publications
VAR_039760
Natural varianti150 – 1501T → P in EDMD2. 2 Publications
Corresponds to variant rs58917027 [ dbSNP | Ensembl ].
VAR_039762
Natural varianti189 – 1891R → P in EDMD2; found also in a patient with limb-girdle muscular dystrophy; sporadic. 1 Publication
VAR_064962
Natural varianti190 – 1901R → Q in EDMD2 and CMD1A; aberrant localization with decreased nuclear rim staining and increased formation of intranuclear foci. 2 Publications
VAR_039763
Natural varianti190 – 1901R → RR in EDMD2. 1 Publication
VAR_064963
Natural varianti196 – 1994RLQT → S in EDMD2.
VAR_039766
Natural varianti206 – 2061F → L in EDMD2. 1 Publication
VAR_064964
Natural varianti222 – 2221H → P in EDMD2. 1 Publication
VAR_039769
Natural varianti222 – 2221H → Y in EDMD2. 1 Publication
Corresponds to variant rs28928901 [ dbSNP | Ensembl ].
VAR_009979
Natural varianti232 – 2321G → E in EDMD2. 1 Publication
VAR_039771
Natural varianti248 – 2481L → P in EDMD2. 1 Publication
VAR_039772
Natural varianti249 – 2491R → Q in EDMD2. 8 Publications
VAR_009980
Natural varianti249 – 2491R → W in MDCL and EDMD2; mislocalized in the nucleus; causes nuclear deformations and LMNB1 redistribution. 2 Publications
VAR_063589
Natural varianti261 – 2611Missing in EDMD2. 3 Publications
VAR_009981
Natural varianti267 – 2671Y → C in EDMD2. 1 Publication
VAR_039774
Natural varianti268 – 2681S → P in EDMD2. 1 Publication
VAR_064965
Natural varianti271 – 2711L → P in EDMD2. 1 Publication
VAR_064966
Natural varianti294 – 2941Q → P in EDMD2. 2 Publications
VAR_009982
Natural varianti295 – 2951S → P in EDMD2. 1 Publication
VAR_064967
Natural varianti303 – 3031S → P in EDMD2. 1 Publication
VAR_064968
Natural varianti336 – 3361R → Q in EDMD2. 1 Publication
VAR_009983
Natural varianti343 – 3431R → Q in EDMD2.
VAR_009984
Natural varianti355 – 3551Missing in EDMD2. 1 Publication
VAR_064969
Natural varianti358 – 3581E → 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. 5 Publications
VAR_009985
Natural varianti361 – 3611E → K in EDMD2. 1 Publication
VAR_064970
Natural varianti371 – 3711M → 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. 2 Publications
VAR_009986
Natural varianti377 – 3771R → L in EDMD2 and LGMD1B. 2 Publications
VAR_039777
Natural varianti386 – 3861R → 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. 4 Publications
VAR_009987
Natural varianti446 – 4461D → V in EDMD2. 1 Publication
VAR_039780
Natural varianti449 – 4491G → D in EDMD2. 1 Publication
VAR_064971
Natural varianti453 – 4531R → W in EDMD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. 7 Publications
VAR_009988
Natural varianti454 – 4541L → P in EDMD2. 1 Publication
VAR_064972
Natural varianti456 – 4561N → I in EDMD2; mislocalized in the nucleus; does not alter nuclear size or shape. 2 Publications
VAR_039781
Natural varianti456 – 4561N → K in EDMD2. 1 Publication
VAR_039782
Natural varianti461 – 4611D → Y in EDMD2. 1 Publication
VAR_064973
Natural varianti467 – 4671W → R in EDMD2. 1 Publication
VAR_064974
Natural varianti469 – 4691I → T in EDMD2. 1 Publication
VAR_009990
Natural varianti520 – 5201W → S in EDMD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. 2 Publications
VAR_039784
Natural varianti527 – 5271R → 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. 10 Publications
VAR_009995
Natural varianti528 – 5281T → K in EDMD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. 4 Publications
VAR_009996
Natural varianti528 – 5281T → R in EDMD2. 2 Publications
VAR_039785
Natural varianti530 – 5301L → 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. 3 Publications
VAR_009997
Natural varianti541 – 5411R → H in EDMD2. 1 Publication
VAR_039787
Natural varianti541 – 5411R → P in EDMD2; mis-localized in the nucleus; does not alter nuclear size or shape. 1 Publication
VAR_064975
Natural varianti541 – 5411R → 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. 2 Publications
VAR_039788
Natural varianti602 – 6021G → S in EDMD2. 1 Publication
Corresponds to variant rs60662302 [ dbSNP | Ensembl ].
VAR_064976
Natural varianti624 – 6241R → H in EDMD2. 1 Publication
VAR_039791
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.2 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti225 – 2251R → Q in EDMD3. 1 Publication
VAR_067697
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.15 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti60 – 601R → G in CMD1A and FPLD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. 3 Publications
Corresponds to variant rs28928900 [ dbSNP | Ensembl ].
VAR_034706
Natural varianti85 – 851L → R in CMD1A; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. 2 Publications
Corresponds to variant rs28933090 [ dbSNP | Ensembl ].
VAR_009975
Natural varianti89 – 891R → L in CMD1A; dramatically aberrant localization with almost no nuclear rim staining and formation of intranuclear foci. 2 Publications
Corresponds to variant rs59040894 [ dbSNP | Ensembl ].
VAR_039758
Natural varianti92 – 921L → F in CMD1A. 1 Publication
VAR_067257
Natural varianti97 – 971K → E in CMD1A. 1 Publication
Corresponds to variant rs59065411 [ dbSNP | Ensembl ].
VAR_039759
Natural varianti101 – 1011R → P in CMD1A; dramatically aberrant localization with almost no nuclear rim staining and formation of intranuclear foci. 1 Publication
VAR_070174
Natural varianti143 – 1431S → P in CMD1A. 1 Publication
Corresponds to variant rs61661343 [ dbSNP | Ensembl ].
VAR_039761
Natural varianti161 – 1611E → K in CMD1A. 2 Publications
Corresponds to variant rs28933093 [ dbSNP | Ensembl ].
VAR_017660
Natural varianti166 – 1661R → P in CMD1A; dramatically aberrant localization with almost no nuclear rim staining and formation of intranuclear foci. 1 Publication
VAR_070176
Natural varianti190 – 1901R → Q in EDMD2 and CMD1A; aberrant localization with decreased nuclear rim staining and increased formation of intranuclear foci. 2 Publications
VAR_039763
Natural varianti190 – 1901R → W in CMD1A. 3 Publications
Corresponds to variant rs59026483 [ dbSNP | Ensembl ].
VAR_039764
Natural varianti192 – 1921D → 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. 1 Publication
Corresponds to variant rs57045855 [ dbSNP | Ensembl ].
VAR_039765
Natural varianti195 – 1951N → 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. 2 Publications
Corresponds to variant rs28933091 [ dbSNP | Ensembl ].
VAR_009977
Natural varianti203 – 2031E → 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. 3 Publications
Corresponds to variant rs28933092 [ dbSNP | Ensembl ].
VAR_009978
Natural varianti203 – 2031E → K in CMD1A; decreased sumoylation; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; associated with increased cell death. 3 Publications
Corresponds to variant rs61195471 [ dbSNP | Ensembl ].
VAR_039767
Natural varianti210 – 2101I → S in CMD1A; dramatically aberrant localization with almost no nuclear rim staining and increased formation of intranuclear foci. 1 Publication
VAR_070177
Natural varianti215 – 2151L → P in CMD1A; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci. 2 Publications
VAR_039768
Natural varianti317 – 3171E → K in CMD1A. 2 Publications
VAR_039775
Natural varianti318 – 3181A → T in CMD1A; no effect on nuclear morphology and lamin A localization. 1 Publication
VAR_070179
Natural varianti349 – 3491R → L in CMD1A. 1 Publication
VAR_039776
Natural varianti388 – 3881R → H in CMD1A; no effect on nuclear morphology but restricts lamin A to the cytoplasm. 1 Publication
VAR_070180
Natural varianti399 – 3991R → C in FPLD2 and CMD1A; no effect on nuclear morphology and lamin A localization. 2 Publications
VAR_039778
Natural varianti435 – 4351R → C in CMD1A. 1 Publication
VAR_039779
Natural varianti471 – 4711R → H in CMD1A; no effect on nuclear morphology and lamin A localization. 1 Publication
VAR_070182
Natural varianti523 – 5231G → R in CMD1A. 1 Publication
VAR_067258
Natural varianti541 – 5411R → 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. 2 Publications
VAR_039788
Natural varianti573 – 5731S → L in CMD1A, FPLD2 and MADA. 3 Publications
VAR_039789
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.10 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti28 – 281R → W in FPLD2. 1 Publication
Corresponds to variant rs59914820 [ dbSNP | Ensembl ].
VAR_039748
Natural varianti60 – 601R → G in CMD1A and FPLD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. 3 Publications
Corresponds to variant rs28928900 [ dbSNP | Ensembl ].
VAR_034706
Natural varianti62 – 621R → G in FPLD2. 1 Publication
Corresponds to variant rs56793579 [ dbSNP | Ensembl ].
VAR_039755
Natural varianti133 – 1331R → L in FPLD2. 1 Publication
VAR_016913
Natural varianti230 – 2301D → N in FPLD2. 1 Publication
VAR_039770
Natural varianti399 – 3991R → C in FPLD2 and CMD1A; no effect on nuclear morphology and lamin A localization. 2 Publications
VAR_039778
Natural varianti439 – 4391R → 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. 1 Publication
VAR_070181
Natural varianti465 – 4651G → D in FPLD2. 1 Publication
VAR_009989
Natural varianti482 – 4821R → L in FPLD2. 1 Publication
VAR_009991
Natural varianti482 – 4821R → Q in FPLD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. 3 Publications
Corresponds to variant rs11575937 [ dbSNP | Ensembl ].
VAR_009992
Natural varianti482 – 4821R → 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. 4 Publications
VAR_009993
Natural varianti486 – 4861K → N in FPLD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. 1 Publication
VAR_009994
Natural varianti527 – 5271R → 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. 10 Publications
VAR_009995
Natural varianti573 – 5731S → L in CMD1A, FPLD2 and MADA. 3 Publications
VAR_039789
Natural varianti582 – 5821R → H in FPLD2. 1 Publication
Corresponds to variant rs57830985 [ dbSNP | Ensembl ].
VAR_009998
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.7 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti208 – 2081Missing in LGMD1B. 1 Publication
VAR_034708
Natural varianti377 – 3771R → H in LGMD1B. 5 Publications
VAR_016205
Natural varianti377 – 3771R → L in EDMD2 and LGMD1B. 2 Publications
VAR_039777
Natural varianti481 – 4811Y → H in LGMD1B. 1 Publication
VAR_039783
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.2 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti298 – 2981R → C in CMT2B1. 1 Publication
VAR_017661
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 (1 Publication).9 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti138 – 1381E → K in HGPS; might be associated with early and severe strokes. 1 Publication
VAR_070175
Natural varianti140 – 1401L → R in HGPS; phenotype originally designated as atypical Werner syndrome. 1 Publication
Corresponds to variant rs60652225 [ dbSNP | Ensembl ].
VAR_017658
Natural varianti143 – 1431S → F in HGPS. 1 Publication
Corresponds to variant rs58912633 [ dbSNP | Ensembl ].
VAR_034707
Natural varianti145 – 1451E → K in HGPS; atypical. 1 Publication
Corresponds to variant rs60310264 [ dbSNP | Ensembl ].
VAR_017659
Natural varianti471 – 4711R → C in HGPS. 1 Publication
Corresponds to variant rs28928902 [ dbSNP | Ensembl ].
VAR_017662
Natural varianti527 – 5271R → C in HGPS. 1 Publication
VAR_017663
Natural varianti542 – 5421K → N in HGPS. 1 Publication
VAR_034710
Natural varianti608 – 6081G → S in HGPS; reduced binding to SUN1; may affect splicing by activating a cryptic splice donor site. 3 Publications
VAR_017664
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.4 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti57 – 571A → P in CMDHH; phenotype originally designated as atypical Werner syndrome. 1 Publication
Corresponds to variant rs28928903 [ dbSNP | Ensembl ].
VAR_017656
Natural varianti59 – 591L → R in CMDHH. 2 Publications
VAR_064055
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.4 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti527 – 5271R → H in MADA. 1 Publication
VAR_018727
Natural varianti529 – 5291A → V in MADA. 1 Publication
VAR_034709
Natural varianti573 – 5731S → L in CMD1A, FPLD2 and MADA. 3 Publications
VAR_039789
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.2 Publications
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.1 Publication
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.2 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti39 – 391N → S in MDCL and EDMD2. 2 Publications
VAR_063588
Natural varianti50 – 501R → P in EDMD2 and MDCL. 2 Publications
Corresponds to variant rs60695352 [ dbSNP | Ensembl ].
VAR_009972
Natural varianti249 – 2491R → W in MDCL and EDMD2; mislocalized in the nucleus; causes nuclear deformations and LMNB1 redistribution. 2 Publications
VAR_063589
Natural varianti302 – 3021L → P in MDCL. 1 Publication
VAR_063590
Natural varianti358 – 3581E → 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. 5 Publications
VAR_009985
Natural varianti380 – 3801L → S in MDCL. 1 Publication
VAR_063591
Natural varianti453 – 4531R → P in MDCL. 1 Publication
VAR_063592
Natural varianti455 – 4551R → P in MDCL. 1 Publication
VAR_063593
Natural varianti456 – 4561N → D in MDCL. 1 Publication
VAR_063594
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.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi201 – 2011K → L: Decreased sumoylation; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; associated with increased cell death. 1 Publication
Mutagenesisi644 – 6441R → A: Does not affect tail cleavage. 1 Publication
Mutagenesisi647 – 6471L → R: Completely inhibits tail cleavage. 1 Publication
Mutagenesisi648 – 6481L → A: Completely inhibits tail cleavage. 1 Publication
Mutagenesisi650 – 6501N → A: Partially inhibits tail cleavage. 1 Publication
Mutagenesisi661 – 6611C → S: Loss of interaction with NARF. Abolishes farnesylation. 2 Publications

Keywords - Diseasei

Cardiomyopathy, Charcot-Marie-Tooth disease, Congenital muscular dystrophy, Disease mutation, Emery-Dreifuss muscular dystrophy, Limb-girdle muscular dystrophy, Neurodegeneration, Neuropathy

Organism-specific databases

MIMi115200. phenotype.
151660. phenotype.
159001. phenotype.
176670. phenotype.
181350. phenotype.
212112. phenotype.
248370. phenotype.
275210. phenotype.
605588. phenotype.
610140. phenotype.
613205. phenotype.
Orphaneti79474. Atypical Werner syndrome.
280365. Autosomal codominant severe lipodystrophic laminopathy.
98853. Autosomal dominant Emery-Dreifuss muscular dystrophy.
264. Autosomal dominant limb-girdle muscular dystrophy type 1B.
98855. Autosomal recessive Emery-Dreifuss muscular dystrophy.
98856. Charcot-Marie-Tooth disease type 2B1.
157973. Congenital muscular dystrophy due to LMNA mutation.
2229. Dilated cardiomyopathy - hypergonadotropic hypogonadism.
300751. Familial dilated cardiomyopathy with conduction defect due to LMNA mutation.
293899. Familial isolated arrhythmogenic ventricular dysplasia, biventricular form.
293888. Familial isolated arrhythmogenic ventricular dysplasia, left dominant form.
293910. Familial isolated arrhythmogenic ventricular dysplasia, right dominant form.
2348. Familial partial lipodystrophy, Dunnigan type.
79084. Familial partial lipodystrophy, Kobberling type.
168796. Heart-hand syndrome, Slovenian type.
740. Hutchinson-Gilford progeria syndrome.
137871. Laminopathy type Decaudain-Vigouroux.
54260. Left ventricular noncompaction.
1662. Lethal restrictive dermopathy.
363618. LMNA-related cardiocutaneous progeria syndrome.
90153. Mandibuloacral dysplasia with type A lipodystrophy.
99706. Progeria-associated arthropathy.
PharmGKBiPA231.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 661661Prelamin-A/CPRO_0000398835Add
BLAST
Chaini1 – 646646Lamin-A/CPRO_0000063810Add
BLAST
Propeptidei647 – 66115Removed in Lamin-A/C formPRO_0000398836Add
BLAST
Propeptidei662 – 6643Removed in Prelamin-A/C form and in Lamin-A/C formPRO_0000403442

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionine1 Publication
Modified residuei3 – 31Phosphothreonine1 Publication
Modified residuei12 – 121Phosphoserine2 Publications
Modified residuei18 – 181Phosphoserine1 Publication
Modified residuei19 – 191Phosphothreonine3 Publications
Modified residuei22 – 221Phosphoserine4 Publications
Modified residuei32 – 321N6-acetyllysine; alternate By similarity
Modified residuei32 – 321N6-succinyllysine; alternate By similarity
Modified residuei108 – 1081N6-acetyllysine1 Publication
Modified residuei123 – 1231N6-acetyllysine By similarity
Modified residuei135 – 1351N6-acetyllysine By similarity
Modified residuei155 – 1551N6-acetyllysine By similarity
Modified residuei171 – 1711N6-acetyllysine; alternate By similarity
Modified residuei171 – 1711N6-succinyllysine; alternate By similarity
Modified residuei201 – 2011N6-acetyllysine; alternate By similarity
Cross-linki201 – 201Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate1 Publication
Modified residuei212 – 2121Phosphoserine1 Publication
Modified residuei260 – 2601N6-acetyllysine By similarity
Modified residuei270 – 2701N6-acetyllysine1 Publication
Modified residuei277 – 2771Phosphoserine2 Publications
Modified residuei301 – 3011Phosphoserine2 Publications
Modified residuei311 – 3111N6-acetyllysine1 Publication
Modified residuei390 – 3901Phosphoserine4 Publications