Gene: PLEC

Alternate names for this Gene: EBS1|EBSMD|EBSND|EBSO|EBSOG|EBSPA|HD1|LGMD2Q|LGMDR17|PCN|PLEC1|PLEC1b|PLTN

Gene Summary: Plectin is a prominent member of an important family of structurally and in part functionally related proteins, termed plakins or cytolinkers, that are capable of interlinking different elements of the cytoskeleton. Plakins, with their multi-domain structure and enormous size, not only play crucial roles in maintaining cell and tissue integrity and orchestrating dynamic changes in cytoarchitecture and cell shape, but also serve as scaffolding platforms for the assembly, positioning, and regulation of signaling complexes (reviewed in PMID: 9701547, 11854008, and 17499243). Plectin is expressed as several protein isoforms in a wide range of cell types and tissues from a single gene located on chromosome 8 in humans (PMID: 8633055, 8698233). Until 2010, this locus was named plectin 1 (symbol PLEC1 in human; Plec1 in mouse and rat) and the gene product had been referred to as 'hemidesmosomal protein 1' or 'plectin 1, intermediate filament binding 500kDa'. These names were superseded by plectin. The plectin gene locus in mouse on chromosome 15 has been analyzed in detail (PMID: 10556294, 14559777), revealing a genomic exon-intron organization with well over 40 exons spanning over 62 kb and an unusual 5' transcript complexity of plectin isoforms. Eleven exons (1-1j) have been identified that alternatively splice directly into a common exon 2 which is the first exon to encode plectin's highly conserved actin binding domain (ABD). Three additional exons (-1, 0a, and 0) splice into an alternative first coding exon (1c), and two additional exons (2alpha and 3alpha) are optionally spliced within the exons encoding the acting binding domain (exons 2-8). Analysis of the human locus has identified eight of the eleven alternative 5' exons found in mouse and rat (PMID: 14672974); exons 1i, 1j and 1h have not been confirmed in human. Furthermore, isoforms lacking the central rod domain encoded by exon 31 have been detected in mouse (PMID:10556294), rat (PMID: 9177781), and human (PMID: 11441066, 10780662, 20052759). The short alternative amino-terminal sequences encoded by the different first exons direct the targeting of the various isoforms to distinct subcellular locations (PMID: 14559777). As the expression of specific plectin isoforms was found to be dependent on cell type (tissue) and stage of development (PMID: 10556294, 12542521, 17389230) it appears that each cell type (tissue) contains a unique set (proportion and composition) of plectin isoforms, as if custom-made for specific requirements of the particular cells. Concordantly, individual isoforms were found to carry out distinct and specific functions (PMID: 14559777, 12542521, 18541706). In 1996, a number of groups reported that patients suffering from epidermolysis bullosa simplex with muscular dystrophy (EBS-MD) lacked plectin expression in skin and muscle tissues due to defects in the plectin gene (PMID: 8698233, 8941634, 8636409, 8894687, 8696340). Two other subtypes of plectin-related EBS have been described: EBS-pyloric atresia (PA) and EBS-Ogna. For reviews of plectin-related diseases see PMID: 15810881, 19945614. Mutations in the plectin gene related to human diseases should be named based on the position in NM_000445 (variant 1, isoform 1c), unless the mutation is located within one of the other alternative first exons, in which case the position in the respective Reference Sequence should be used.

Gene is located in Chromosome: 8

Location in Chromosome : 8q24.3

Description of this Gene: plectin

Type of Gene: protein-coding

rs11783655 in PLEC gene and Body Height PMID 25282103 2014 Defining the role of common variation in the genomic and biological architecture of adult human height.

PMID 31562340 2019 Characterizing rare and low-frequency height-associated variants in the Japanese population.

PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs111730406 in PLEC gene and EPIDERMOLYSIS BULLOSA SIMPLEX WITH NAIL DYSTROPHY PMID 23289980 2013 Epidermolysis bullosa simplex with PLEC mutations: new phenotypes and new mutations.

PMID 10652002 2000 Epidermolysis bullosa: novel and de novo premature termination codon and deletion mutations in the plectin gene predict late-onset muscular dystrophy.

PMID 8830774 1996 Basic amino acid residue cluster within nuclear targeting sequence motif is essential for cytoplasmic plectin-vimentin network junctions.

PMID 19945614 2010 Plectin gene defects lead to various forms of epidermolysis bullosa simplex.

PMID 15654962 2005 Plectin gene mutations can cause epidermolysis bullosa with pyloric atresia.

rs117961539 in PLEC gene and Eosinophil count procedure PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs111730406 in PLEC gene and Epidermolysa bullosa simplex and limb girdle muscular dystrophy PMID 23289980 2013 Epidermolysis bullosa simplex with PLEC mutations: new phenotypes and new mutations.

PMID 19945614 2010 Plectin gene defects lead to various forms of epidermolysis bullosa simplex.

PMID 8830774 1996 Basic amino acid residue cluster within nuclear targeting sequence motif is essential for cytoplasmic plectin-vimentin network junctions.

PMID 10652002 2000 Epidermolysis bullosa: novel and de novo premature termination codon and deletion mutations in the plectin gene predict late-onset muscular dystrophy.

PMID 15654962 2005 Plectin gene mutations can cause epidermolysis bullosa with pyloric atresia.

rs111730406 in PLEC gene and Epidermolysis Bullosa Simplex With Pyloric Atresia PMID 23289980 2013 Epidermolysis bullosa simplex with PLEC mutations: new phenotypes and new mutations.

PMID 10652002 2000 Epidermolysis bullosa: novel and de novo premature termination codon and deletion mutations in the plectin gene predict late-onset muscular dystrophy.

PMID 8830774 1996 Basic amino acid residue cluster within nuclear targeting sequence motif is essential for cytoplasmic plectin-vimentin network junctions.

PMID 19945614 2010 Plectin gene defects lead to various forms of epidermolysis bullosa simplex.

PMID 15654962 2005 Plectin gene mutations can cause epidermolysis bullosa with pyloric atresia.

rs111730406 in PLEC gene and Epidermolysis bullosa simplex, Ogna type PMID 23289980 2013 Epidermolysis bullosa simplex with PLEC mutations: new phenotypes and new mutations.

PMID 8830774 1996 Basic amino acid residue cluster within nuclear targeting sequence motif is essential for cytoplasmic plectin-vimentin network junctions.

PMID 10652002 2000 Epidermolysis bullosa: novel and de novo premature termination codon and deletion mutations in the plectin gene predict late-onset muscular dystrophy.

PMID 19945614 2010 Plectin gene defects lead to various forms of epidermolysis bullosa simplex.

PMID 15654962 2005 Plectin gene mutations can cause epidermolysis bullosa with pyloric atresia.

PMID 11851880 2002 A site-specific plectin mutation causes dominant epidermolysis bullosa simplex Ogna: two identical de novo mutations.

rs11780978 in PLEC gene and Fibrinogen assay PMID 26561523 2016 A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration.

rs1065837 in PLEC gene and Forced expiratory volume function PMID 26634245 2015 A genome-wide association study identifies risk loci for spirometric measures among smokers of European and African ancestry.

rs11136336 in PLEC gene and Lean body mass PMID 30593698 2019 Genomics of body fat percentage may contribute to sex bias in anorexia nervosa.

rs11136341 in PLEC gene and Low density lipoprotein cholesterol measurement PMID 20686565 2010 Biological, clinical and population relevance of 95 loci for blood lipids.

PMID 29507422 2018 A large electronic-health-record-based genome-wide study of serum lipids.

PMID 24097068 2013 Discovery and refinement of loci associated with lipid levels.

PMID 30275531 2018 Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program.

PMID 28334899 2017 Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels.

rs111730406 in PLEC gene and MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 2Q PMID 23289980 2013 Epidermolysis bullosa simplex with PLEC mutations: new phenotypes and new mutations.

PMID 8830774 1996 Basic amino acid residue cluster within nuclear targeting sequence motif is essential for cytoplasmic plectin-vimentin network junctions.

PMID 10652002 2000 Epidermolysis bullosa: novel and de novo premature termination codon and deletion mutations in the plectin gene predict late-onset muscular dystrophy.

PMID 19945614 2010 Plectin gene defects lead to various forms of epidermolysis bullosa simplex.

PMID 15654962 2005 Plectin gene mutations can cause epidermolysis bullosa with pyloric atresia.

rs11780978 in PLEC gene and Osteoarthritis of hip PMID 29559693 2018 Genome-wide analyses using UK Biobank data provide insights into the genetic architecture of osteoarthritis.

rs6995402 in PLEC gene and Platelet Count measurement PMID 22139419 2011 New gene functions in megakaryopoiesis and platelet formation.

PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

rs7819099 in PLEC gene and Red Blood Cell Count measurement PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs11136341 in PLEC gene and Serum LDL cholesterol measurement PMID 20686565 2010 Biological, clinical and population relevance of 95 loci for blood lipids.

PMID 24097068 2013 Discovery and refinement of loci associated with lipid levels.

rs11136341 in PLEC gene and Serum total cholesterol measurement PMID 20686565 2010 Biological, clinical and population relevance of 95 loci for blood lipids.

PMID 29507422 2018 A large electronic-health-record-based genome-wide study of serum lipids.

PMID 24097068 2013 Discovery and refinement of loci associated with lipid levels.

PMID 30275531 2018 Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program.

PMID 28334899 2017 Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels.

rs73715570 in PLEC gene and Systolic Pressure PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.