PLEC
plectin, the group of MicroRNA protein coding host genes|Plakins
Basic information
Region (hg38): 8:143915153-143976734
Previous symbols: [ "EBS1", "PLEC1" ]
Links
Phenotypes
GenCC
Source:
- autosomal recessive limb-girdle muscular dystrophy type 2Q (Strong), mode of inheritance: AR
- epidermolysis bullosa simplex 5A, Ogna type (Strong), mode of inheritance: AD
- epidermolysis bullosa simplex 5B, with muscular dystrophy (Strong), mode of inheritance: AR
- epidermolysis bullosa simplex 5C, with pyloric atresia (Strong), mode of inheritance: AR
- congenital myasthenic syndrome (Strong), mode of inheritance: AR
- epidermolysis bullosa simplex 5B, with muscular dystrophy (Strong), mode of inheritance: AR
- epidermolysis bullosa simplex 5A, Ogna type (Strong), mode of inheritance: AD
- epidermolysis bullosa simplex with nail dystrophy (Strong), mode of inheritance: AR
- aplasia cutis congenita (Supportive), mode of inheritance: AD
- epidermolysis bullosa simplex 5B, with muscular dystrophy (Supportive), mode of inheritance: AR
- epidermolysis bullosa simplex 5A, Ogna type (Supportive), mode of inheritance: AD
- epidermolysis bullosa simplex 5C, with pyloric atresia (Supportive), mode of inheritance: AR
- autosomal recessive limb-girdle muscular dystrophy type 2Q (Supportive), mode of inheritance: AR
- epidermolysis bullosa simplex 5A, Ogna type (Strong), mode of inheritance: AD
- epidermolysis bullosa simplex 5C, with pyloric atresia (Strong), mode of inheritance: AR
- autosomal recessive limb-girdle muscular dystrophy type 2Q (Strong), mode of inheritance: AR
- autosomal recessive limb-girdle muscular dystrophy (Moderate), mode of inheritance: AR
- cholestasis (Limited), mode of inheritance: AR
- epidermolysis bullosa simplex (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Muscular dystrophy, limb-girdle, autosomal recessive 17; Epidermolysis bullosa simplex 5A, Ogna type; Epidermolysis bullosa simplex 5B, with muscular dystrophy; Epidermolysis bullosa simplex 5C, with pyloric atresia; Epidermolysis bullosa simplex 5D, generalized intermediate, autosomal recessive | AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Craniofacial; Dermatologic; Gastrointestinal; Musculoskeletal | 7136614; 3355199; 2662909; 8894687; 8696340; 10446808; 10570379; 11122061; 11851880; 14675180; 15681471; 15654962; 21109228; 21263134; 21674528; 25712130 |
ClinVar
This is a list of variants' phenotypes submitted to
- Epidermolysis_bullosa_simplex_with_nail_dystrophy (5230 variants)
- Autosomal_recessive_limb-girdle_muscular_dystrophy_type_2Q (5227 variants)
- Epidermolysis_bullosa_simplex_5C,_with_pyloric_atresia (5226 variants)
- Epidermolysis_bullosa_simplex_5B,_with_muscular_dystrophy (5225 variants)
- Epidermolysis_bullosa_simplex,_Ogna_type (5218 variants)
- not_provided (2317 variants)
- Inborn_genetic_diseases (1106 variants)
- not_specified (498 variants)
- PLEC-related_disorder (347 variants)
- Junctional_epidermolysis_bullosa_with_pyloric_atresia (74 variants)
- Multiple_sclerosis (8 variants)
- Arrhythmogenic_right_ventricular_dysplasia_1 (6 variants)
- See_cases (5 variants)
- Autosomal_recessive_limb-girdle_muscular_dystrophy (5 variants)
- Epidermolysis_bullosa_simplex (4 variants)
- Abnormality_of_the_musculature (2 variants)
- Limb-girdle_muscular_dystrophy (2 variants)
- Primary_dilated_cardiomyopathy (2 variants)
- PLEC-related_epidermolysis_bullosa (2 variants)
- Simplex_epidermolysis_bullosa_Ogna_type (1 variants)
- Abnormality_of_the_skin (1 variants)
- Neuromuscular_disease_caused_by_qualitative_or_quantitative_defects_of_plectin (1 variants)
- Cholestasis (1 variants)
- Myopathy (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLEC gene is commonly pathogenic or not. These statistics are base on transcript: NM_000201384.3. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 45 | 1741 | 40 | 1827 | ||
| missense | 3159 | 266 | 19 | 3449 | ||
| nonsense | 58 | 22 | 82 | |||
| start loss | 0 | |||||
| frameshift | 37 | 13 | 54 | |||
| splice donor/acceptor (+/-2bp) | 10 | 13 | ||||
| Total | 100 | 48 | 3211 | 2007 | 59 |
Highest pathogenic variant AF is 0.000021730195
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PLEC | protein_coding | protein_coding | ENST00000322810 | 32 | 61582 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 8.35e-12 | 1.00 | 125079 | 0 | 129 | 125208 | 0.000515 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -2.57 | 3516 | 3.11e+3 | 1.13 | 0.000266 | 29384 |
| Missense in Polyphen | 960 | 935.18 | 1.0265 | 8772 | ||
| Synonymous | -11.3 | 1988 | 1.44e+3 | 1.38 | 0.000123 | 9776 |
| Loss of Function | 8.45 | 55 | 176 | 0.313 | 0.00000881 | 1941 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00130 | 0.00117 |
| Ashkenazi Jewish | 0.000499 | 0.000496 |
| East Asian | 0.00142 | 0.00139 |
| Finnish | 0.000917 | 0.000882 |
| European (Non-Finnish) | 0.000326 | 0.000308 |
| Middle Eastern | 0.00142 | 0.00139 |
| South Asian | 0.000578 | 0.000556 |
| Other | 0.000530 | 0.000491 |
dbNSFP
Source:
- Function
- FUNCTION: Interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes. Could also bind muscle proteins such as actin to membrane complexes in muscle. May be involved not only in the filaments network, but also in the regulation of their dynamics. Structural component of muscle. Isoform 9 plays a major role in the maintenance of myofiber integrity. {ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:21109228}.;
- Disease
- DISEASE: Epidermolysis bullosa simplex with pyloric atresia (EBS- PA) [MIM:612138]: Autosomal recessive genodermatosis characterized by severe skin blistering at birth and congenital pyloric atresia. Death usually occurs in infancy. This disorder is allelic to MD- EBS. {ECO:0000269|PubMed:14675180, ECO:0000269|PubMed:20665883}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epidermolysis bullosa simplex, with muscular dystrophy (MD-EBS) [MIM:226670]: A form of epidermolysis bullosa characterized by the association of blister formation at the level of the hemidesmosome with late-onset muscular dystrophy. {ECO:0000269|PubMed:11159198, ECO:0000269|PubMed:20665883, ECO:0000269|PubMed:21263134, ECO:0000269|PubMed:8894687}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epidermolysis bullosa simplex, Ogna type (O-EBS) [MIM:131950]: A form of intraepidermal epidermolysis bullosa characterized by generalized skin bruising, skin fragility with non-scarring blistering and small hemorrhagic blisters on hands. At the ultrastructural level, it is differentiated from classical cases of K-EBS, WC-EBS and DM-EBS, by the occurrence of blisters originating in basal cells above hemidesmosomes, and abnormal hemidesmosome intracellular attachment plates. {ECO:0000269|PubMed:11851880}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Limb-girdle muscular dystrophy 2Q (LGMD2Q) [MIM:613723]: A form of limb-girdle muscular dystrophy characterized by early childhood onset of proximal muscle weakness. Limb-girdle muscular dystrophies are characterized by proximal weakness, weakness of the hip and shoulder girdles and prominent asymmetrical quadriceps femoris and biceps brachii atrophy. {ECO:0000269|PubMed:21109228, ECO:0000269|PubMed:25556389, ECO:0000269|PubMed:27234031}. Note=The disease is caused by mutations affecting the gene represented in this entry. A 9 bp deletion containing the initiation codon in exon 1f of PLEC have been found in limb-girdle muscular dystrophy patients. The mutation results in deficient expression of isoform 9 and disorganization of the myofibers, without any effect on the skin.; DISEASE: Epidermolysis bullosa simplex with nail dystrophy (EBSND) [MIM:616487]: A form of epidermolysis bullosa, a dermatologic disorder characterized by skin blistering. EBSND patients also manifest nail dystrophy. {ECO:0000269|PubMed:25712130}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Assembly of collagen fibrils and other multimeric structures;Alpha6Beta4Integrin;Collagen formation;Extracellular matrix organization;Caspase-mediated cleavage of cytoskeletal proteins;Apoptotic cleavage of cellular proteins;Apoptotic execution phase;Apoptosis;Programmed Cell Death;EGFR1;Type I hemidesmosome assembly;Cell junction organization;Cell-Cell communication
(Consensus)
Recessive Scores
- pRec
- 0.299
Intolerance Scores
- loftool
- 0.00999
- rvis_EVS
- -6.57
- rvis_percentile_EVS
- 0.03
Haploinsufficiency Scores
- pHI
- 0.273
- hipred
- Y
- hipred_score
- 0.637
- ghis
- 0.545
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.948
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |
Mouse Genome Informatics
- Gene name
- Plec
- 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; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; normal 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); 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); hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system 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);
Zebrafish Information Network
- Gene name
- plecb
- Affected structure
- skeletal muscle
- Phenotype tag
- abnormal
- Phenotype quality
- refractivity
Gene ontology
- Biological process
- hemidesmosome assembly;wound healing;intermediate filament cytoskeleton organization
- Cellular component
- cytoplasm;cytosol;intermediate filament;plasma membrane;brush border;focal adhesion;membrane;sarcoplasm;hemidesmosome;sarcolemma;costamere;intermediate filament cytoskeleton;perinuclear region of cytoplasm;extracellular exosome
- Molecular function
- RNA binding;actin binding;structural molecule activity;structural constituent of cytoskeleton;protein binding;structural constituent of muscle;ankyrin binding;cadherin binding