LMNA
lamin A/C, the group of Lamins
Basic information
Region (hg38): 1:156082572-156140081
Previous symbols: [ "LMN1", "CMD1A", "LGMD1B", "PRO1", "LMNL1" ]
Links
Phenotypes
GenCC
Source:
- atrioventricular block (Strong), mode of inheritance: AD
- familial partial lipodystrophy, Dunnigan type (Strong), mode of inheritance: AD
- heart-hand syndrome, Slovenian type (Limited), mode of inheritance: AD
- Hutchinson-Gilford progeria syndrome (Moderate), mode of inheritance: Semidominant
- dilated cardiomyopathy 1A (Definitive), mode of inheritance: AD
- Emery-Dreifuss muscular dystrophy 2, autosomal dominant (Definitive), mode of inheritance: Semidominant
- Charcot-Marie-Tooth disease type 2B1 (Moderate), mode of inheritance: AR
- familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
- lethal restrictive dermopathy (Supportive), mode of inheritance: AD
- dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome (Supportive), mode of inheritance: AR
- familial partial lipodystrophy, Dunnigan type (Supportive), mode of inheritance: AD
- Hutchinson-Gilford progeria syndrome (Supportive), mode of inheritance: AD
- atypical Werner syndrome (Supportive), mode of inheritance: AD
- mandibuloacral dysplasia with type A lipodystrophy (Supportive), mode of inheritance: AR
- autosomal dominant Emery-Dreifuss muscular dystrophy (Supportive), mode of inheritance: AD
- autosomal recessive Emery-Dreifuss muscular dystrophy (Supportive), mode of inheritance: AR
- Charcot-Marie-Tooth disease type 2B1 (Supportive), mode of inheritance: AR
- congenital muscular dystrophy due to LMNA mutation (Supportive), mode of inheritance: AD
- heart-hand syndrome, Slovenian type (Supportive), mode of inheritance: AD
- autosomal semi-dominant severe lipodystrophic laminopathy (Supportive), mode of inheritance: Semidominant
- dilated cardiomyopathy 1A (Supportive), mode of inheritance: AD
- LMNA-related cardiocutaneous progeria syndrome (Supportive), mode of inheritance: AD
- dilated cardiomyopathy 1A (Definitive), mode of inheritance: AD
- Charcot-Marie-Tooth disease type 2B1 (Limited), mode of inheritance: AR
- Hutchinson-Gilford progeria syndrome (Definitive), mode of inheritance: AD
- Emery-Dreifuss muscular dystrophy 2, autosomal dominant (Definitive), mode of inheritance: AD
- heart-hand syndrome, Slovenian type (Moderate), mode of inheritance: AD
- restrictive dermopathy 1 (Limited), mode of inheritance: AD
- familial partial lipodystrophy, Dunnigan type (Definitive), mode of inheritance: AD
- Emery-Dreifuss muscular dystrophy 2, autosomal dominant (Strong), mode of inheritance: AD
- Hutchinson-Gilford progeria syndrome (Strong), mode of inheritance: AD
- Charcot-Marie-Tooth disease type 2B1 (Strong), mode of inheritance: AD
- Charcot-Marie-Tooth disease type 2B1 (Strong), mode of inheritance: AR
- Emery-Dreifuss muscular dystrophy 3, autosomal recessive (Strong), mode of inheritance: AR
- familial partial lipodystrophy, Dunnigan type (Strong), mode of inheritance: AD
- mandibuloacral dysplasia with type A lipodystrophy (Strong), mode of inheritance: AR
- heart-hand syndrome, Slovenian type (Strong), mode of inheritance: AD
- dilated cardiomyopathy (Definitive), mode of inheritance: AD
- arrhythmogenic right ventricular cardiomyopathy (Limited), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Hutchinson-Guilford Progeria; Cardiomyopathy, dilated, 1A; Heart-hand syndrome, Slovenian type; Emery-Dreiffus muscular dystrophy 2, autosomal dominant; Emery-Dreiffus muscular dystrophy 3, autosomal recessive; Muscular dystrophy, congenital, LMNA-related; Muscular dystrophy, limb-girdle, type 1B; Cardiomyopathy, dilated, with hypergonadotropic hypogonadism (Malouf syndrome); Lipodystrophy, familial partial, 2 (Dunnigan type) | AD/AR | Cardiovascular | Some LMNA-associated conditions can include cardiac anomalies, including arrhythmias and cardiomyopathy that can precede other obvious clinical signs/symptoms, and medical (eg, ICD placement) management prior to severe sequelae may be beneficial; In Hutchinson-Guilford Progeria, medical management (with farnesyltransferase inhibitors) has been shown to extend lifespan | Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dermatologic; Endocrine; Hematologic; Musculoskeletal; Neurologic | 4362786; 1205025; 3519971; 2957478; 9920078; 10080180; 10580070; 10662742; 10587585; 10814726; 10843151; 10814726; 10655060; 10739751; 11231979; 11799477; 12075506; 12768443; 12629077; 12673789; 12927431; 12702809; 12714972; 12920062; 14627682; 12788894; 12628721; 15028826; 15148145; 15317753; 15286156; 15961312; 15622532; 15668447; 16407522; 16278265; 17136397; 17250669; 17848409; 17469202; 17150192; 17325275; 17377071; 18256394; 18551513; 18364375; 18348272; 18805829; 19084400; 19283854; 21483645; 20301582 ; 20301717; 20301609; 20301300; 20301462; 22199124; 22177269; 22224630; 22240398; 22274718; 22431096; 22491857; 22700598; 22806367; 25649378; 29710166; 36507973 |
| Some allelic conditions are clinically recognizable, and in these, it is not clear if early (genetic) diagnosis would be additionally beneficial |
ClinVar
This is a list of variants' phenotypes submitted to
- Charcot-Marie-Tooth disease type 2 (183 variants)
- not provided (86 variants)
- Cardiovascular phenotype (34 variants)
- Primary dilated cardiomyopathy (18 variants)
- Dilated cardiomyopathy 1A (14 variants)
- Emery-Dreifuss muscular dystrophy 2, autosomal dominant (8 variants)
- Muscular dystrophy (5 variants)
- Familial partial lipodystrophy, Dunnigan type (5 variants)
- LMNA-related disorder (3 variants)
- Cardiomyopathy (3 variants)
- 11 conditions (3 variants)
- Congenital muscular dystrophy due to LMNA mutation (3 variants)
- Hutchinson-Gilford syndrome (3 variants)
- Primary familial dilated cardiomyopathy (2 variants)
- Dilated cardiomyopathy 1S (2 variants)
- Neuronopathy, distal hereditary motor, autosomal dominant (1 variants)
- not specified (1 variants)
- Emery-Dreifuss muscular dystrophy (1 variants)
- Neuromuscular disease (1 variants)
- See cases (1 variants)
- Charcot-Marie-Tooth disease (1 variants)
- 8 conditions (1 variants)
- Restrictive dermopathy 2 (1 variants)
- Mandibuloacral dysplasia with type A lipodystrophy (1 variants)
- Hutchinson-Gilford progeria syndrome, atypical (1 variants)
- Familial partial lipodystrophy (1 variants)
- Sudden unexplained death (1 variants)
- Emery-Dreifuss muscular dystrophy 2, autosomal dominant;Congenital muscular dystrophy due to LMNA mutation (1 variants)
- Autosomal recessive limb-girdle muscular dystrophy type 2B (1 variants)
- Primary dilated cardiomyopathy;Hutchinson-Gilford syndrome (1 variants)
- Hutchinson-Gilford progeria syndrome, childhood-onset (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the LMNA gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 286 | 298 | ||||
| missense | 57 | 117 | 643 | 818 | ||
| nonsense | 53 | 10 | 64 | |||
| start loss | 7 | |||||
| frameshift | 91 | 26 | 120 | |||
| inframe indel | 10 | 19 | 34 | |||
| splice donor/acceptor (+/-2bp) | 15 | 27 | 44 | |||
| splice region | 2 | 3 | 27 | 41 | 2 | 75 |
| non coding | 47 | 115 | 51 | 216 | ||
| Total | 234 | 191 | 721 | 402 | 53 |
Highest pathogenic variant AF is 0.00000657
Variants in LMNA
This is a list of pathogenic ClinVar variants found in the LMNA region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-156114693-C-T | Dilated cardiomyopathy 1A • Familial partial lipodystrophy, Dunnigan type • Congenital muscular dystrophy due to LMNA mutation • Charcot-Marie-Tooth disease type 2B1 • Limb-girdle muscular dystrophy, recessive • Lethal tight skin contracture syndrome • Lipoatrophy with Diabetes, Hepatic Steatosis, Hypertrophic Cardiomyopathy, and Leukomelanodermic Papules • Hutchinson-Gilford syndrome • Mandibuloacral dysplasia with type A lipodystrophy • Emery-Dreifuss muscular dystrophy 2, autosomal dominant • Emery-Dreifuss muscular dystrophy | Uncertain significance (Jan 13, 2018) | ||
| 1-156114694-C-A | Lipoatrophy with Diabetes, Hepatic Steatosis, Hypertrophic Cardiomyopathy, and Leukomelanodermic Papules • Lethal tight skin contracture syndrome • Hutchinson-Gilford syndrome • Limb-girdle muscular dystrophy, recessive • Familial partial lipodystrophy • Emery-Dreifuss muscular dystrophy • Charcot-Marie-Tooth disease type 2 • Mandibuloacral dysplasia • Dilated Cardiomyopathy, Dominant • Congenital muscular dystrophy due to LMNA mutation | Uncertain significance (Jun 14, 2016) | ||
| 1-156114696-C-T | Lipoatrophy with Diabetes, Hepatic Steatosis, Hypertrophic Cardiomyopathy, and Leukomelanodermic Papules • Lethal tight skin contracture syndrome • Familial partial lipodystrophy, Dunnigan type • Hutchinson-Gilford syndrome • Emery-Dreifuss muscular dystrophy • Mandibuloacral dysplasia with type A lipodystrophy • Congenital muscular dystrophy due to LMNA mutation • Charcot-Marie-Tooth disease type 2B1 • Dilated cardiomyopathy 1A • Emery-Dreifuss muscular dystrophy 2, autosomal dominant | Conflicting classifications of pathogenicity (Aug 03, 2018) | ||
| 1-156114709-T-C | Emery-Dreifuss muscular dystrophy • Congenital muscular dystrophy due to LMNA mutation • Limb-girdle muscular dystrophy, recessive • Charcot-Marie-Tooth disease type 2B1 • Hutchinson-Gilford syndrome • Lethal tight skin contracture syndrome • Lipoatrophy with Diabetes, Hepatic Steatosis, Hypertrophic Cardiomyopathy, and Leukomelanodermic Papules • Familial partial lipodystrophy, Dunnigan type • Dilated cardiomyopathy 1A • Mandibuloacral dysplasia with type A lipodystrophy • Emery-Dreifuss muscular dystrophy 2, autosomal dominant | Uncertain significance (Jan 13, 2018) | ||
| 1-156114736-C-A | Limb-girdle muscular dystrophy, recessive • Congenital muscular dystrophy due to LMNA mutation • Dilated Cardiomyopathy, Dominant • Mandibuloacral dysplasia • Emery-Dreifuss muscular dystrophy • Lethal tight skin contracture syndrome • Lipoatrophy with Diabetes, Hepatic Steatosis, Hypertrophic Cardiomyopathy, and Leukomelanodermic Papules • Hutchinson-Gilford syndrome • Familial partial lipodystrophy • Charcot-Marie-Tooth disease type 2 | Uncertain significance (Jun 14, 2016) | ||
| 1-156114771-C-A | Benign (Mar 03, 2015) | |||
| 1-156114772-C-A | Benign (Mar 03, 2015) | |||
| 1-156114777-C-A | Lipoatrophy with Diabetes, Hepatic Steatosis, Hypertrophic Cardiomyopathy, and Leukomelanodermic Papules • Emery-Dreifuss muscular dystrophy • Familial partial lipodystrophy • Hutchinson-Gilford syndrome • Dilated Cardiomyopathy, Dominant • Charcot-Marie-Tooth disease type 2 • Congenital muscular dystrophy due to LMNA mutation • Lethal tight skin contracture syndrome • Limb-girdle muscular dystrophy, recessive • Mandibuloacral dysplasia | Uncertain significance (Jun 14, 2016) | ||
| 1-156114781-T-C | Hutchinson-Gilford syndrome • Lipoatrophy with Diabetes, Hepatic Steatosis, Hypertrophic Cardiomyopathy, and Leukomelanodermic Papules • Charcot-Marie-Tooth disease type 2B1 • Lethal tight skin contracture syndrome • Emery-Dreifuss muscular dystrophy • Congenital muscular dystrophy due to LMNA mutation • Dilated cardiomyopathy 1A • Mandibuloacral dysplasia with type A lipodystrophy • Familial partial lipodystrophy, Dunnigan type • Limb-girdle muscular dystrophy, recessive • Emery-Dreifuss muscular dystrophy 2, autosomal dominant | Uncertain significance (Jan 12, 2018) | ||
| 1-156114791-T-C | Congenital muscular dystrophy due to LMNA mutation • Hutchinson-Gilford syndrome • Mandibuloacral dysplasia with type A lipodystrophy • Emery-Dreifuss muscular dystrophy • Dilated cardiomyopathy 1A • Familial partial lipodystrophy, Dunnigan type • Lipoatrophy with Diabetes, Hepatic Steatosis, Hypertrophic Cardiomyopathy, and Leukomelanodermic Papules • Limb-girdle muscular dystrophy, recessive • Charcot-Marie-Tooth disease type 2B1 • Lethal tight skin contracture syndrome • Emery-Dreifuss muscular dystrophy 2, autosomal dominant | Likely benign (Jul 23, 2018) | ||
| 1-156114810-G-T | Emery-Dreifuss muscular dystrophy • Lipoatrophy with Diabetes, Hepatic Steatosis, Hypertrophic Cardiomyopathy, and Leukomelanodermic Papules • Mandibuloacral dysplasia • Congenital muscular dystrophy due to LMNA mutation • Hutchinson-Gilford syndrome • Charcot-Marie-Tooth disease type 2 • Lethal tight skin contracture syndrome • Dilated Cardiomyopathy, Dominant • Familial partial lipodystrophy • Limb-girdle muscular dystrophy, recessive | Uncertain significance (Jun 14, 2016) | ||
| 1-156114821-G-C | Benign (Mar 03, 2015) | |||
| 1-156114831-G-T | Hutchinson-Gilford syndrome • Lipoatrophy with Diabetes, Hepatic Steatosis, Hypertrophic Cardiomyopathy, and Leukomelanodermic Papules • Charcot-Marie-Tooth disease type 2B1 • Emery-Dreifuss muscular dystrophy • Dilated cardiomyopathy 1A • Familial partial lipodystrophy, Dunnigan type • Mandibuloacral dysplasia with type A lipodystrophy • Limb-girdle muscular dystrophy, recessive • Congenital muscular dystrophy due to LMNA mutation • Emery-Dreifuss muscular dystrophy 2, autosomal dominant • Lethal tight skin contracture syndrome • Maturity onset diabetes mellitus in young | Benign/Likely benign (Jan 12, 2018) | ||
| 1-156114857-C-A | Emery-Dreifuss muscular dystrophy • Lethal tight skin contracture syndrome • Hutchinson-Gilford syndrome • Lipoatrophy with Diabetes, Hepatic Steatosis, Hypertrophic Cardiomyopathy, and Leukomelanodermic Papules • Limb-girdle muscular dystrophy, recessive • Congenital muscular dystrophy due to LMNA mutation • Charcot-Marie-Tooth disease type 2 • Dilated Cardiomyopathy, Dominant • Mandibuloacral dysplasia • Familial partial lipodystrophy | Uncertain significance (Jun 14, 2016) | ||
| 1-156114875-T-A | Lethal tight skin contracture syndrome • Dilated cardiomyopathy 1A • Charcot-Marie-Tooth disease type 2B1 • Congenital muscular dystrophy due to LMNA mutation • Hutchinson-Gilford syndrome • Familial partial lipodystrophy, Dunnigan type • Mandibuloacral dysplasia with type A lipodystrophy • Emery-Dreifuss muscular dystrophy 2, autosomal dominant • Lipoatrophy with Diabetes, Hepatic Steatosis, Hypertrophic Cardiomyopathy, and Leukomelanodermic Papules • Emery-Dreifuss muscular dystrophy | Uncertain significance (Apr 27, 2017) | ||
| 1-156114877-C-T | Likely benign (Apr 20, 2018) | |||
| 1-156114891-C-T | not specified | Likely benign (Oct 31, 2017) | ||
| 1-156114902-C-A | Uncertain significance (May 27, 2022) | |||
| 1-156114905-C-T | Cardiomyopathy | Uncertain significance (Oct 17, 2022) | ||
| 1-156114907-A-T | not specified | Uncertain significance (Jan 20, 2017) | ||
| 1-156114908-A-G | Primary dilated cardiomyopathy | Uncertain significance (May 16, 2023) | ||
| 1-156114912-GCCGGCCATGGAGACC-G | not provided (-) | |||
| 1-156114913-C-T | Primary dilated cardiomyopathy | Uncertain significance (Feb 05, 2024) | ||
| 1-156114913-CCGGCCATGGAGACCCCGTCCCAG-C | Likely pathogenic (Jun 13, 2023) | |||
| 1-156114914-C-A | Emery-Dreifuss muscular dystrophy • Hutchinson-Gilford syndrome • Familial partial lipodystrophy • Lipoatrophy with Diabetes, Hepatic Steatosis, Hypertrophic Cardiomyopathy, and Leukomelanodermic Papules • Lethal tight skin contracture syndrome • Congenital muscular dystrophy due to LMNA mutation • Charcot-Marie-Tooth disease type 2 • Limb-girdle muscular dystrophy, recessive • Dilated Cardiomyopathy, Dominant • Mandibuloacral dysplasia | Uncertain significance (Jun 14, 2016) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| LMNA | protein_coding | protein_coding | ENST00000368300 | 12 | 57517 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.999 | 0.000605 | 125729 | 0 | 3 | 125732 | 0.0000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.37 | 269 | 403 | 0.668 | 0.0000276 | 4228 |
| Missense in Polyphen | 46 | 116.58 | 0.39457 | 1233 | ||
| Synonymous | 0.551 | 162 | 171 | 0.946 | 0.0000109 | 1367 |
| Loss of Function | 4.75 | 2 | 30.2 | 0.0663 | 0.00000158 | 338 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000289 | 0.0000289 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000880 | 0.00000879 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- 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 (PubMed:10080180, PubMed:22431096, PubMed:10814726, PubMed:11799477, PubMed:18551513). Required for osteoblastogenesis and bone formation (PubMed:12075506, PubMed:15317753, PubMed:18611980). Also prevents fat infiltration of muscle and bone marrow, helping to maintain the volume and strength of skeletal muscle and bone (PubMed:10587585). Required for cardiac homeostasis (PubMed:10580070, PubMed:12927431, PubMed:18611980, PubMed:23666920). {ECO:0000269|PubMed:10080180, ECO:0000269|PubMed:10580070, ECO:0000269|PubMed:10587585, ECO:0000269|PubMed:10814726, ECO:0000269|PubMed:11799477, ECO:0000269|PubMed:12075506, ECO:0000269|PubMed:12927431, ECO:0000269|PubMed:15317753, ECO:0000269|PubMed:18551513, ECO:0000269|PubMed:18611980, ECO:0000269|PubMed:22431096, ECO:0000269|PubMed:23666920}.;
- Disease
- DISEASE: 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. {ECO:0000269|PubMed:10080180, ECO:0000269|PubMed:10739764, ECO:0000269|PubMed:10908904, ECO:0000269|PubMed:10939567, ECO:0000269|PubMed:11503164, ECO:0000269|PubMed:11792809, ECO:0000269|PubMed:12032588, ECO:0000269|PubMed:12467752, ECO:0000269|PubMed:12649505, ECO:0000269|PubMed:14684700, ECO:0000269|PubMed:14985400, ECO:0000269|PubMed:15372542, ECO:0000269|PubMed:15744034, ECO:0000269|PubMed:19933576, ECO:0000269|PubMed:20848652}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Emery-Dreifuss muscular dystrophy 3, autosomal recessive (EDMD3) [MIM:616516]: 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. {ECO:0000269|PubMed:22431096, ECO:0000269|PubMed:27234031}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:10580070, ECO:0000269|PubMed:11561226, ECO:0000269|PubMed:11792809, ECO:0000269|PubMed:11897440, ECO:0000269|PubMed:12486434, ECO:0000269|PubMed:12628721, ECO:0000269|PubMed:12920062, ECO:0000269|PubMed:14675861, ECO:0000269|PubMed:14684700, ECO:0000269|PubMed:15140538, ECO:0000269|PubMed:15219508, ECO:0000269|PubMed:15372542, ECO:0000269|PubMed:16061563, ECO:0000269|PubMed:18606848, ECO:0000269|PubMed:19167105, ECO:0000269|PubMed:20160190, ECO:0000269|PubMed:21846512}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:10587585, ECO:0000269|PubMed:10655060, ECO:0000269|PubMed:10739751, ECO:0000269|PubMed:11792809, ECO:0000269|PubMed:12015247, ECO:0000269|PubMed:12196663, ECO:0000269|PubMed:12629077, ECO:0000269|PubMed:15372542, ECO:0000269|PubMed:17250669, ECO:0000269|PubMed:19220582, ECO:0000269|PubMed:24485160}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:10814726, ECO:0000269|PubMed:11525883, ECO:0000269|PubMed:12032588, ECO:0000269|PubMed:12673789, ECO:0000269|PubMed:15372542, ECO:0000269|PubMed:15744034, ECO:0000269|PubMed:17136397, ECO:0000269|PubMed:27234031}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:11799477}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Hutchinson-Gilford progeria syndrome (HGPS) [MIM:176670]: Rare genetic disorder characterized by features reminiscent of marked premature aging. {ECO:0000269|PubMed:12714972, ECO:0000269|PubMed:12768443, ECO:0000269|PubMed:12927431, ECO:0000269|PubMed:15060110, ECO:0000269|PubMed:15286156, ECO:0000269|PubMed:15622532, ECO:0000269|PubMed:19933576, ECO:0000269|PubMed:21791255, ECO:0000269|PubMed:22355414, ECO:0000269|PubMed:23666920}. 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). {ECO:0000269|PubMed:12714972}.; DISEASE: 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. {ECO:0000269|PubMed:12927431, ECO:0000269|PubMed:17150192, ECO:0000269|PubMed:19283854}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:12075506, ECO:0000269|PubMed:15998779, ECO:0000269|PubMed:16278265}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:15317753}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:18611980}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:18551513}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:23666920}.;
- Pathway
- Dilated cardiomyopathy (DCM) - Homo sapiens (human);Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Apoptosis - Homo sapiens (human);Antiarrhythmic Pathway, Pharmacodynamics;Arrhythmogenic Right Ventricular Cardiomyopathy;Adipogenesis;Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation;XBP1(S) activates chaperone genes;Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer,s disease models;Neurodegenerative Diseases;Disease;tnfr1 signaling pathway;caspase cascade in apoptosis;induction of apoptosis through dr3 and dr4/5 death receptors;hiv-1 nef: negative effector of fas and tnf;Breakdown of the nuclear lamina;Apoptotic cleavage of cellular proteins;Apoptotic execution phase;Apoptosis;Programmed Cell Death;Depolymerisation of the Nuclear Lamina;Nuclear Envelope Breakdown;Mitotic Prophase;Initiation of Nuclear Envelope Reformation;Nuclear Envelope Reassembly;Mitotic Anaphase;Mitotic Metaphase and Anaphase;M Phase;Cell Cycle;Cell Cycle, Mitotic;Caspase Cascade in Apoptosis;Signaling by BRAF and RAF fusions;Oncogenic MAPK signaling;Diseases of signal transduction
(Consensus)
Recessive Scores
- pRec
- 0.986
Intolerance Scores
- loftool
- 0.00103
- rvis_EVS
- -0.91
- rvis_percentile_EVS
- 9.96
Haploinsufficiency Scores
- pHI
- 0.558
- hipred
- Y
- hipred_score
- 0.833
- ghis
- 0.673
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.998
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Lmna
- Phenotype
- muscle phenotype; craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; pigmentation phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; digestive/alimentary phenotype; vision/eye phenotype; immune system phenotype; skeleton phenotype; renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; reproductive system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan);
Zebrafish Information Network
- Gene name
- lmna
- Affected structure
- fat cell
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- protein import into nucleus;mitotic nuclear envelope reassembly;negative regulation of cell population proliferation;positive regulation of gene expression;regulation of cell migration;establishment or maintenance of microtubule cytoskeleton polarity;regulation of protein stability;protein localization to nucleus;IRE1-mediated unfolded protein response;ventricular cardiac muscle cell development;cellular response to hypoxia;negative regulation of mesenchymal cell proliferation;negative regulation of release of cytochrome c from mitochondria;positive regulation of cell aging;positive regulation of histone H3-K9 trimethylation;regulation of protein localization to nucleus;negative regulation of cardiac muscle hypertrophy in response to stress;negative regulation of extrinsic apoptotic signaling pathway
- Cellular component
- nucleus;nuclear envelope;lamin filament;nucleoplasm;cytosol;nuclear speck;nuclear membrane
- Molecular function
- structural molecule activity;protein binding