PLEC

plectin, the group of MicroRNA protein coding host genes|Plakins

Basic information

Region (hg38): 8:143915153-143976734

Previous symbols: [ "EBS1", "PLEC1" ]

Links

ENSG00000178209 ∙ NCBI:5339 ∙ OMIM:601282 ∙ HGNC:9069 ∙ Uniprot:Q15149 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive limb-girdle muscular dystrophy type 2Q (Strong), mode of inheritance: AR
• pidermolysis 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
• pidermolysis 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
• pidermolysis 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
• pidermolysis 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

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the PLEC gene.

• not provided (20 variants)
• Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex, Ogna type;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex with nail dystrophy (6 variants)
• Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex 5C, with pyloric atresia;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex with nail dystrophy;Epidermolysis bullosa simplex, Ogna type (4 variants)
• Epidermolysis bullosa simplex with nail dystrophy (4 variants)
• Epidermolysis bullosa simplex with nail dystrophy;Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex 5C, with pyloric atresia;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex 5B, with muscular dystrophy (4 variants)
• Epidermolysis bullosa simplex 5C, with pyloric atresia (3 variants)
• Epidermolysis bullosa simplex with nail dystrophy;Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex, Ogna type;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex 5B, with muscular dystrophy (3 variants)
• Epidermolysis bullosa simplex with nail dystrophy;Epidermolysis bullosa simplex, Ogna type;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex 5C, with pyloric atresia (3 variants)
• Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex with nail dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2Q (2 variants)
• Epidermolysis bullosa simplex 5B, with muscular dystrophy (2 variants)
• Epidermolysis bullosa simplex with nail dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex, Ogna type (2 variants)
• Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex with nail dystrophy;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2Q (2 variants)
• Epidermolysis bullosa simplex with nail dystrophy;Epidermolysis bullosa simplex, Ogna type;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex 5B, with muscular dystrophy (2 variants)
• Epidermolysis bullosa simplex (2 variants)
• Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex 5C, with pyloric atresia;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex with nail dystrophy (2 variants)
• Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex with nail dystrophy;Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex 5C, with pyloric atresia;Autosomal recessive limb-girdle muscular dystrophy type 2Q (1 variants)
• Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex with nail dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex, Ogna type (1 variants)
• Epidermolysis bullosa simplex, Ogna type;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex with nail dystrophy (1 variants)
• Simplex epidermolysis bullosa_Ogna type (1 variants)
• Epidermolysis bullosa simplex, Ogna type (1 variants)
• Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex with nail dystrophy;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex 5C, with pyloric atresia (1 variants)
• Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex with nail dystrophy (1 variants)
• Epidermolysis bullosa simplex with nail dystrophy;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex 5C, with pyloric atresia;Autosomal recessive limb-girdle muscular dystrophy type 2Q (1 variants)
• Epidermolysis bullosa simplex 5C, with pyloric atresia;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex with nail dystrophy (1 variants)
• Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex, Ogna type;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex with nail dystrophy (1 variants)
• Epidermolysis bullosa simplex with nail dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex, Ogna type (1 variants)
• Epidermolysis bullosa simplex with nail dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex 5B, with muscular dystrophy (1 variants)
• Epidermolysis bullosa simplex with nail dystrophy;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex, Ogna type;Autosomal recessive limb-girdle muscular dystrophy type 2Q (1 variants)
• Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex with nail dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex 5C, with pyloric atresia (1 variants)
• Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex with nail dystrophy;Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex 5C, with pyloric atresia (1 variants)
• Epidermolysis bullosa simplex 5B, with muscular dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex with nail dystrophy;Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex 5C, with pyloric atresia (1 variants)
• Epidermolysis bullosa simplex with nail dystrophy;Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2Q (1 variants)
• Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex with nail dystrophy;Epidermolysis bullosa simplex 5C, with pyloric atresia;Autosomal recessive limb-girdle muscular dystrophy type 2Q (1 variants)
• Epidermolysis bullosa simplex with nail dystrophy;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex 5C, with pyloric atresia (1 variants)
• Epidermolysis bullosa simplex 5B, with muscular dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex with nail dystrophy;Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex, Ogna type (1 variants)
• Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex with nail dystrophy;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex 5C, with pyloric atresia (1 variants)
• Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex with nail dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex 5B, with muscular dystrophy (1 variants)
• Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex with nail dystrophy;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex, Ogna type;Autosomal recessive limb-girdle muscular dystrophy type 2Q (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.

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			50	1266	61	1377
missense	1		2777	67	33	2878
nonsense	38	21	1	1		61
start loss		1	1			2
frameshift	31	11	7			49
inframe indel			105			105
splice donor/acceptor (+/-2bp)	1	9				10
splice region			54	62	8	124
non coding			15	271	90	376
Total	71	42	2956	1605	184

Highest pathogenic variant AF is 0.00000658

Variants in PLEC

This is a list of pathogenic ClinVar variants found in the PLEC region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-143915891-G-A			Likely benign (Jul 31, 2018)
8-143916158-G-A		not specified	Benign (May 20, 2016)
8-143916167-G-A		not specified • Epidermolysis bullosa simplex with nail dystrophy • Epidermolysis bullosa simplex 5B, with muscular dystrophy • Epidermolysis bullosa simplex, Ogna type • Epidermolysis bullosa simplex 5C, with pyloric atresia • Autosomal recessive limb-girdle muscular dystrophy type 2Q	Benign (Oct 25, 2021)
8-143916180-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex with nail dystrophy	Likely benign (Nov 07, 2023)
8-143916180-G-C		Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex 5C, with pyloric atresia;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex with nail dystrophy	Conflicting classifications of pathogenicity (Jan 29, 2024)
8-143916181-G-C		Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex with nail dystrophy	Uncertain significance (Dec 20, 2023)
8-143916185-C-T		not specified • Epidermolysis bullosa simplex 5B, with muscular dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex with nail dystrophy • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 08, 2024)
8-143916186-G-A		Epidermolysis bullosa simplex, Ogna type;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex with nail dystrophy	Likely benign (Apr 05, 2021)
8-143916188-C-G		Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex with nail dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex 5C, with pyloric atresia	Uncertain significance (Mar 05, 2022)
8-143916188-CAG-C		Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex with nail dystrophy;Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex 5C, with pyloric atresia;Autosomal recessive limb-girdle muscular dystrophy type 2Q	Uncertain significance (Nov 10, 2023)
8-143916195-A-G		Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex with nail dystrophy;Epidermolysis bullosa simplex, Ogna type	Likely benign (Dec 09, 2022)
8-143916197-G-A		Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex with nail dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2Q	Uncertain significance (Jul 09, 2022)
8-143916199-C-A		Epidermolysis bullosa simplex 5C, with pyloric atresia;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex with nail dystrophy	Uncertain significance (Dec 04, 2023)
8-143916199-C-G		Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex with nail dystrophy;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex, Ogna type	Uncertain significance (Dec 30, 2021)
8-143916200-C-T		Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex, Ogna type;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex with nail dystrophy	Uncertain significance (Jun 17, 2023)
8-143916202-C-A		Epidermolysis bullosa simplex 5C, with pyloric atresia;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex with nail dystrophy	Uncertain significance (Jul 19, 2022)
8-143916206-G-A		Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex 5C, with pyloric atresia;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex with nail dystrophy;Epidermolysis bullosa simplex, Ogna type	Likely benign (Jul 02, 2022)
8-143916212-C-G		Inborn genetic diseases	Uncertain significance (Sep 27, 2021)
8-143916213-C-T		Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex with nail dystrophy;Epidermolysis bullosa simplex, Ogna type	Likely benign (Dec 12, 2022)
8-143916214-G-A		Epidermolysis bullosa simplex with nail dystrophy;Epidermolysis bullosa simplex, Ogna type;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex 5C, with pyloric atresia • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 23, 2024)
8-143916216-G-A		Epidermolysis bullosa simplex with nail dystrophy;Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex 5C, with pyloric atresia;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex 5B, with muscular dystrophy	Likely benign (Jun 01, 2022)
8-143916219-C-T			Likely benign (Jan 01, 2022)
8-143916220-C-T		Epidermolysis bullosa simplex with nail dystrophy;Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex, Ogna type;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex 5C, with pyloric atresia	Uncertain significance (Oct 10, 2021)
8-143916222-C-T		Epidermolysis bullosa simplex 5B, with muscular dystrophy;Epidermolysis bullosa simplex, Ogna type;Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex with nail dystrophy;Autosomal recessive limb-girdle muscular dystrophy type 2Q	Likely benign (Jun 01, 2024)
8-143916223-G-A		Epidermolysis bullosa simplex with nail dystrophy;Epidermolysis bullosa simplex 5C, with pyloric atresia;Epidermolysis bullosa simplex, Ogna type;Autosomal recessive limb-girdle muscular dystrophy type 2Q;Epidermolysis bullosa simplex 5B, with muscular dystrophy	Uncertain significance (Dec 21, 2023)

GnomAD

Source: gnomAD

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: dbNSFP

• 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