PLEC

Summary

PLEC (plectin, HGNC:9069) is a protein-coding gene on chromosome 8q24.3, encoding Plectin (Q15149). Interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes.

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 These names were superseded by plectin.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.

Source: NCBI Gene 5339 — RefSeq curated summary.

At a glance

• Gene–disease (curated): PLEC-related muscular dystrophy-epidermolysis bullosa simplex spectrum disorder (Definitive, ClinGen) — +9 more curated relationships
• GWAS associations: 59 (top 1% of genes corpus-wide)
• Clinical variants (ClinVar): 6,730 total — 106 pathogenic, 47 likely-pathogenic (top 1% of genes corpus-wide)
• Regional missense constraint (gnomAD): 1 of 6 regions constrained (≈0% of expected missense variation)
• GTEx eGene: eQTL in 48 tissues, sQTL in 14 (q < 0.05)
• Phenotypes (HPO): 146
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.73 (unconstrained)
• MANE Select transcript: NM_201384
• Interaction hub: 2,128 STRING partners (top 6% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9069
Approved symbol	PLEC
Name	plectin
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Aliases	PCN, PLTN
Ensembl gene	ENSG00000178209
Ensembl biotype	protein_coding
OMIM	601282
Entrez	5339

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 18 protein_coding, 1 retained_intron

MANE Select: ENST00000345136 · MANE Plus Clinical: ENST00000356346

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 8, TSL 3: 2, TSL 5: 2

ENST00000345136, ENST00000356346, ENST00000322810, ENST00000354589, ENST00000354958, ENST00000357649, ENST00000398774, ENST00000436759, ENST00000527096, ENST00000527303, ENST00000528025, ENST00000532346, ENST00000685198, ENST00000687971, ENST00000693060, ENST00000915283, ENST00000915284, ENST00001133391, ENST00001133392

RefSeq mRNA: 9 — MANE Select: NM_201384 NM_000445, NM_001410941, NM_201378, NM_201379, NM_201380, NM_201381, NM_201382, NM_201383, NM_201384

CCDS: CCDS43769, CCDS43770, CCDS43771, CCDS43772, CCDS43773, CCDS43774, CCDS43775, CCDS47936, CCDS94359

Canonical transcript exons

ENST00000345136 — 32 exons

Exon	Start	End
ENSE00001243927	143926784	143926882
ENSE00001243936	143926977	143927081
ENSE00001243948	143927252	143927335
ENSE00001243956	143927410	143927766
ENSE00001244001	143929646	143929829
ENSE00001244010	143929936	143930062
ENSE00001244019	143930144	143930298
ENSE00001244024	143930384	143930536
ENSE00001244034	143931534	143931659
ENSE00001244041	143931937	143932032
ENSE00001244050	143932130	143932234
ENSE00001244070	143932635	143932712
ENSE00001244123	143933197	143933351
ENSE00001244129	143933998	143934091
ENSE00001244136	143934318	143934445
ENSE00001244144	143934635	143934730
ENSE00001244151	143934810	143934929
ENSE00001244160	143935011	143935117
ENSE00001244165	143935198	143935313
ENSE00001244172	143935848	143936014
ENSE00001244232	143915153	143922395
ENSE00001295392	143929103	143929281
ENSE00001301489	143932793	143933111
ENSE00001309447	143922504	143925884
ENSE00001315328	143929414	143929571
ENSE00001319048	143927854	143927992
ENSE00001373903	143939350	143939597
ENSE00001741875	143936979	143937071
ENSE00003519962	143937165	143937242
ENSE00003574791	143938631	143938692
ENSE00003693086	143938151	143938240
ENSE00003791226	143932400	143932561

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 98.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 105.8735 / max 1621.3543, expressed in 1824 samples.

Highest expression (Bgee): sural nerve, hindlimb stylopod muscle, tibial nerve, gastrocnemius, muscle of leg.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PLEC is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 48 tissues and its splicing (sQTL) in 14 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 62 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	1.5e-130	-0.68	8:143934275:A:T
Whole Blood	eqtl	3.8e-86	-0.45	8:143921861:A:G
Thyroid	eqtl	4.8e-80	-0.53	8:143939781:C:T
Testis	eqtl	3.2e-54	-0.49	8:143921326:C:T
Lung	eqtl	3.4e-51	-0.53	8:143938038:G:A
Nerve Tibial	eqtl	2.2e-49	-0.44	8:143936137:A:G
Breast Mammary Tissue	eqtl	5.6e-45	-0.44	8:143946309:T:C
Adipose Subcutaneous	eqtl	1.1e-43	-0.33	8:143936137:A:G
Esophagus Muscularis	eqtl	4.0e-41	-0.41	8:143946309:T:C
Cells Cultured fibroblasts	sqtl	7.1e-41	-0.74	8:143939819:C:CAG
Pituitary	eqtl	4.4e-39	-0.64	8:143921861:A:G
Adipose Visceral Omentum	eqtl	1.7e-35	-0.34	8:143939725:C:G
Spleen	eqtl	2.4e-35	-0.75	8:143922240:T:G
Colon Sigmoid	eqtl	1.6e-34	-0.48	8:143946999:C:G
Brain Cerebellum	eqtl	7.2e-32	-0.56	8:143915294:A:G
Pancreas	eqtl	8.2e-28	-0.47	8:143929609:G:A
Esophagus Gastroesophageal Junction	eqtl	5.6e-27	-0.38	8:143921861:A:G
Artery Tibial	eqtl	1.1e-26	-0.29	8:143966399:C:G
Prostate	eqtl	7.6e-22	-0.47	8:143926863:T:C
Brain Hypothalamus	eqtl	3.5e-21	-0.46	8:143946309:T:C

FANTOM5 promoters

showing 10 of 24 alternative TSS:

Promoter ID	TPM avg	Samples expressed
95565	42.6967	1670
95580	11.9802	1442
95590	11.7427	1722
95588	9.5968	1453
95567	4.9991	1371
95566	4.1509	1191
95569	3.6148	1230
95585	3.2775	1254
95578	3.2751	1055
95584	2.9538	1177

Top tissues by expression

showing 100 of 291 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	98.79	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.19	gold quality
tibial nerve	UBERON:0001323	97.90	gold quality
gastrocnemius	UBERON:0001388	97.68	gold quality
muscle of leg	UBERON:0001383	97.49	gold quality
stromal cell of endometrium	CL:0002255	97.28	gold quality
apex of heart	UBERON:0002098	97.28	gold quality
body of tongue	UBERON:0011876	97.14	gold quality
right coronary artery	UBERON:0001625	97.06	gold quality
mucosa of stomach	UBERON:0001199	97.02	gold quality
nipple	UBERON:0002030	96.87	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.87	gold quality
triceps brachii	UBERON:0001509	96.76	gold quality
gluteal muscle	UBERON:0002000	96.75	gold quality
muscle organ	UBERON:0001630	96.62	gold quality
descending thoracic aorta	UBERON:0002345	96.35	gold quality
endometrium epithelium	UBERON:0004811	96.33	gold quality
ascending aorta	UBERON:0001496	96.24	gold quality
thoracic aorta	UBERON:0001515	96.24	gold quality
aorta	UBERON:0000947	96.10	gold quality
popliteal artery	UBERON:0002250	96.04	gold quality
tibial artery	UBERON:0007610	96.03	gold quality
left uterine tube	UBERON:0001303	95.97	gold quality
coronary artery	UBERON:0001621	95.97	gold quality
skin of abdomen	UBERON:0001416	95.90	gold quality
skin of leg	UBERON:0001511	95.88	gold quality
left coronary artery	UBERON:0001626	95.86	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.83	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.83	gold quality
lower esophagus	UBERON:0013473	95.82	gold quality
endocervix	UBERON:0000458	95.68	gold quality
dorsal root ganglion	UBERON:0000044	95.53	gold quality
diaphragm	UBERON:0001103	95.46	silver quality
granulocyte	CL:0000094	95.43	gold quality
body of uterus	UBERON:0009853	95.40	gold quality
tongue	UBERON:0001723	95.31	gold quality
pharyngeal mucosa	UBERON:0000355	95.30	gold quality
trachea	UBERON:0003126	95.24	gold quality
paraflocculus	UBERON:0005351	95.18	gold quality
skeletal muscle tissue	UBERON:0001134	95.10	gold quality
heart left ventricle	UBERON:0002084	95.09	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.07	gold quality
cardiac ventricle	UBERON:0002082	94.93	gold quality
esophagus	UBERON:0001043	94.86	gold quality
middle frontal gyrus	UBERON:0002702	94.82	gold quality
ectocervix	UBERON:0012249	94.79	gold quality
transverse colon	UBERON:0001157	94.70	gold quality
right ovary	UBERON:0002118	94.60	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.54	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.29	gold quality
zone of skin	UBERON:0000014	94.25	gold quality
fundus of stomach	UBERON:0001160	94.19	gold quality
cartilage tissue	UBERON:0002418	94.13	gold quality
muscle tissue	UBERON:0002385	94.06	gold quality
sigmoid colon	UBERON:0001159	94.01	gold quality
esophagus mucosa	UBERON:0002469	94.01	gold quality
vastus lateralis	UBERON:0001379	93.98	gold quality
quadriceps femoris	UBERON:0001377	93.95	gold quality
Brodmann (1909) area 10	UBERON:0013541	93.93	gold quality
trigeminal ganglion	UBERON:0001675	93.90	gold quality
heart	UBERON:0000948	93.89	gold quality
cerebellar vermis	UBERON:0004720	93.88	silver quality
small intestine	UBERON:0002108	93.67	gold quality
body of stomach	UBERON:0001161	93.53	gold quality
superior surface of tongue	UBERON:0007371	93.49	gold quality
right frontal lobe	UBERON:0002810	93.48	gold quality
lower esophagus mucosa	UBERON:0035834	93.47	gold quality
colon	UBERON:0001155	93.46	gold quality
cardia of stomach	UBERON:0001162	93.44	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.36	gold quality
stomach	UBERON:0000945	93.34	gold quality
upper arm skin	UBERON:0004263	93.33	gold quality
left ovary	UBERON:0002119	93.30	gold quality
right atrium auricular region	UBERON:0006631	93.17	gold quality
decidua	UBERON:0002450	93.15	gold quality
cardiac atrium	UBERON:0002081	93.08	gold quality
left ventricle myocardium	UBERON:0006566	93.05	gold quality
minor salivary gland	UBERON:0001830	93.00	gold quality
upper lobe of left lung	UBERON:0008952	92.99	gold quality
large intestine	UBERON:0000059	92.98	gold quality
mucosa of transverse colon	UBERON:0004991	92.98	gold quality
urethra	UBERON:0000057	92.97	gold quality
saphenous vein	UBERON:0007318	92.93	gold quality
thymus	UBERON:0002370	92.90	gold quality
intestine	UBERON:0000160	92.89	gold quality
metanephros cortex	UBERON:0010533	92.89	gold quality
right lung	UBERON:0002167	92.87	gold quality
myometrium	UBERON:0001296	92.81	gold quality
calcaneal tendon	UBERON:0003701	92.78	gold quality
mouth mucosa	UBERON:0003729	92.76	gold quality
uterine cervix	UBERON:0000002	92.71	gold quality
pylorus	UBERON:0001166	92.63	gold quality
colonic epithelium	UBERON:0000397	92.60	gold quality
biceps brachii	UBERON:0001507	92.59	gold quality
spleen	UBERON:0002106	92.53	gold quality
vena cava	UBERON:0004087	92.52	gold quality
upper lobe of lung	UBERON:0008948	92.46	gold quality
monocyte	CL:0000576	92.16	gold quality
saliva-secreting gland	UBERON:0001044	92.11	gold quality
layer of synovial tissue	UBERON:0007616	92.09	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-7052	yes	269.73
E-ANND-3	yes	13.54
E-CURD-112	yes	13.09
E-GEOD-110499	no	310.77
E-CURD-11	no	166.83

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	228.9	medium
Hippocampus	tissue	158.6	low
Locus coeruleus	tissue	106.9
Postcentral gyrus	tissue	98.8
Nucleus accumbens	tissue	94.1
Choroid plexus	tissue	86.6
Spinal cord	tissue	82.1
Cerebral cortex	tissue	64.0	low
Somatosensory cortex	tissue	64.0
Vagina	tissue	59.2	medium
Superior colliculi	tissue	59.2
Substantia nigra	tissue	59.0
Midbrain	tissue	58.9
Motor cortex	tissue	58.3
Thalamus	tissue	56.4
Temporal cortex	tissue	56.4
Insular cortex	tissue	56.4
Hippocampal formation	tissue	55.8
Entorhinal cortex	tissue	55.7
Prefrontal cortex	tissue	54.3
Medulla oblongata	tissue	54.1
Basal ganglia	tissue	50.9	medium
Tongue	tissue	49.7
Amygdala	tissue	49.6
Occipital cortex	tissue	49.2
Skin 1	tissue	49.0	medium
Pons	tissue	47.9
Retrosplenial and cingulate cortex	tissue	47.9
Retrosplenial cortex	tissue	47.7
Periaqueductal gray	tissue	44.6
Hypothalamus	tissue	43.4
Ventral forebrain	tissue	42.2
Putamen	tissue	41.8
Septum	tissue	37.5
Pituitary gland	tissue	36.7
Bone marrow	tissue	35.9	medium
Olfactory bulb	tissue	31.1
Corpus callosum	tissue	31.0
Cerebellum	tissue	30.6	low
Salivary gland	tissue	28.2	medium
Stomach 1	tissue	26.9	medium
Small intestine	tissue	23.4	medium
Spleen	tissue	22.9	low
Heart muscle	tissue	22.3	medium
Adipose tissue	tissue	20.9	low
Appendix	tissue	19.7	medium
Duodenum	tissue	19.5	medium
Seminal vesicle	tissue	18.4	medium
Colon	tissue	17.6	high
Pancreas	tissue	17.4	medium
Lymph node	tissue	16.6	medium
Lung	tissue	16.4	high
Urinary bladder	tissue	16.2	high
Esophagus	tissue	15.7	medium
Prostate	tissue	15.5	medium
Placenta	tissue	14.4	medium
Gallbladder	tissue	13.5	high
Endometrium 1	tissue	13.4	medium
Cervix	tissue	13.0	high
Ovary	tissue	12.8	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Area postrema (176.8), Nucleus rhomboideus (173.3), Central amygdala (165.9), Lateral amygdala (163.9), Dentate gyrus (159.7).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ELF1, TP63

miRNA regulators (miRDB)

Targeting PLEC by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 107 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363

Functional genomics

gnomAD constraint: pLI 5.95e-44, LOEUF 0.726, missense Z -2.75 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000345136 splits into 6 regions with different missense tolerance; 1 is missense-constrained (≈0% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
8:143,916,180–143,916,577	213 / 205.5	1.04	no
8:143,916,578–143,916,706	36 / 63.8	0.56	no
8:143,916,707–143,918,173	606 / 716.6	0.85	no
8:143,918,174–143,935,987	5834 / 5377.7	1.08	no
8:143,935,988–143,936,996	2 / 17.1	0.12	yes (p 2.5e-04)
8:143,936,997–143,939,461	172 / 182.7	0.94	no

Literature-anchored findings (GeneRIF, showing 40)

• cpo has a role in regulating proper nervous system function, including seizure susceptibility (PMID:15687283)
• variation for the diapause phenotype is caused by a single Lys/Ile substitution in one of the six cpo transcripts (PMID:18852464)
• There is no evidence for an association between the cpo I462K polymorphism and ovarian dormancy in Australian fruit flies. (PMID:21689187)
• The results reveal that the downstream cpo SNP does not seem to play any role in diapause induction in European Drosophila populations in contrast to the upstream coding cpo SNP. (PMID:27598401)
• Conserved binding of GCAC motifs by MEC-8, couch potato, and the RBPMS protein family has been reported (PMID:28003515)
• During polarization of peripheral blood T lymphocytes, plectin redistributes to the uropod associated with vimentin and fodrin. This vimentin-plectin-fodrin complex provides a continuous linkage from the nucleus (lamin B) to the cortical cytoskeleton. (PMID:11441066)
• The structure was solved by the molecular-replacement method. In addition, the preparation of selenomethionine-derivative crystals is described. (PMID:12136158)
• Data report the crystal structure of the actin binding domain of plectin and show that this region is sufficient for interaction with F-actin or the cytoplasmic region of integrin alpha6beta4. (PMID:12791251)
• propose a previously unrecognized function of plectin as cytoskeletal regulator of PKC signaling (dislocation of PKCdelta and elevated enzymatic activity), and possibly other signaling events, through sequestration of the scaffolding protein RACK1 (PMID:14966116)
• the involvement of desmoplakin (DP), plectin, and periplakin in the destruction of epithelial cell integrity ensures the efficient elimination of cytoskeleton, but also provides specificity for selectively targeting individual adhesion molecules (PMID:15500642)
• homozygous mutations in the plectin gene (PLEC1)in epidermolysis bullosa with pyloric atresia (PMID:15654962)
• discussion of phenotypic spectrum of plectin mutations [review] (PMID:15810881)
• the CH1 domain of the plectin-ABD associates with the groove between the two FNIII domains of beta4 (PMID:15817481)
• Co-localization, co-immunoprecipitation, and in vitro overlay analyses demonstrated direct interaction of plectin and GFAP. (PMID:16507904)
• Results describe the crystal structure of an N-terminal fragment of the plakin domain of plectin to 2.05 A resolution. (PMID:17397861)
• PLEC1 was differeentially expressed in sclerotic hippocampi compared to non-sclerotic ones. (PMID:17515952)
• A novel functional co-localisation is identified between two plakin cytolinker proteins. (PMID:17662978)
• results reveal that plectin is up-regulated in colorectal adenocarcinoma as well as in bizarre glands and locally invasive tumor nests in tubular adenoma, compared with normal colorectal mucosa (PMID:18084872)
• Thus, plectin appears to interact with CXCR4 and plays an important role in CXCR4 signaling and trafficking and HIV-1 infection. (PMID:18155192)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• Data show that intermediate filament recruitment to focal adhesions in endothelial cells requires beta3 integrin, plectin and the microtubule cytoskeleton, and is dependent on microtubule motors. (PMID:19366731)
• BRCA2-plectin interaction plays an important role in the regulation of centrosome localization and also that displacement of the centrosome may result in genomic instability and cancer development. (PMID:19709076)
• missense mutation causes structure of plectin amino terminus alteration so binding to actin and costameric proteins are attenuated (PMID:20016501)
• Plectin expression patterns determine two distinct subtypes of epidermolysis bullosa simplex (PMID:20052759)
• Autosomal recessive forms of epidermolysis bullosa simplex associated with extracutaneous manifestations, such as muscular dystrophy (MIM 226670) or pyloric atresia (MIM 612138), have been linked to genetic mutations in the gene for plectin (PMID:20447487)
• This protein has been found differentially expressed in thalami from patients with schizophrenia. (PMID:20471030)
• Plectin deficiency can indeed lead to both muscular dystrophy and pyloric atresia in an individual epidermolysis bullosa simplex (EBS) patient. (PMID:20665883)
• data show that isoform 1f of plectin plays a key role in skeletal muscle function and that disruption of the plectin 1f can cause the LGMD2 phenotype without any dermatologic component as was previously reported with mutations in constant exons of PLEC (PMID:21109228)
• mutational analysis of PLEC1 revealed a homozygous 36 nucleotide insertion (1506_1507ins36) that results in a reduced expression of PLEC1 mRNA and plectin in patients with epidermolysis bullosa simplex and congenital myasthenic syndrome. (PMID:21175599)
• The structure of the plakin domain of plectin reveals a non-canonical SH3 domain interacting with its fourth spectrin repeat. (PMID:21288893)
• degradation of plectin induced by staurosporine-treatment in liver cells resulted in cytoskeleton disruption and induced morphological changes in these cells by affecting the expression and organization of cytokeratin 18. (PMID:21420381)
• plectin deficiency might play an important role in the transformation of human liver cells (PMID:21424933)
• plectin expression was deficient in hepatocellular carcinoma and was probably through post-translational modification (PMID:21469503)
• novel esophageal squamous cell carcinoma marker plectin 1 was identified by mass spectrometry and immunohistochemical analysis (PMID:21743296)
• plectin participates in actin assembly and invasiveness in carcinoma cells in an isoform-specific manner (PMID:21821021)
• The novel FUS-plectin interaction offers new perspectives for understanding the role of FUS and plectin mutations in the pathogenesis of FUS associated diseases (PMID:22240165)
• findings suggest that plectin promotes the migration and invasion of head and neck squamous cell carcinoma (HNSCC) cells through activation of Erk 1/2 kinase and is a potential prognostic biomarker of HNSCC. (PMID:22245045)
• A linker region in the COOH-terminal end and serine residue at position 4645 may be important for the binding of plectin to intermediate filaments. (PMID:22333906)
• results confirm epidermolysis bullosa simplex-pyloric atresia is linked to mutations in distal exons 1-30 and 32 of PLEC; while epidermolysis bullosa simplex-muscular dystrophy is linked to PLEC mutations in all exons, in most cases one of the mutations affects exon 31 (PMID:23289980)
• this study is the first to demonstrate that up-regulation of vimentin and plectin expression positively correlates with the invasion and metastasis of androgen-independent PCA (PMID:23717685)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Plec	ENSMUSG00000022565
rattus_norvegicus	Plec	ENSRNOG00000023781

Paralogs (36): SYNE2 (ENSG00000054654), SPTB (ENSG00000070182), ACTN1 (ENSG00000072110), ACTN2 (ENSG00000077522), DSP (ENSG00000096696), DRP2 (ENSG00000102385), SPTBN1 (ENSG00000115306), MACF1 (ENSG00000127603), FLNC (ENSG00000128591), ACTN4 (ENSG00000130402), SYNE1 (ENSG00000131018), MICAL2 (ENSG00000133816), DTNA (ENSG00000134769), MICAL1 (ENSG00000135596), FLNB (ENSG00000136068), SPTBN5 (ENSG00000137877), DTNB (ENSG00000138101), GAS2L3 (ENSG00000139354), DST (ENSG00000151914), UTRN (ENSG00000152818), SPTBN4 (ENSG00000160460), SPTA1 (ENSG00000163554), CLMN (ENSG00000165959), PKHD1 (ENSG00000170927), SPTBN2 (ENSG00000173898), SYNE3 (ENSG00000176438), SMTNL2 (ENSG00000188176), FLNA (ENSG00000196924), SPTAN1 (ENSG00000197694), DMD (ENSG00000198947), PKHD1L1 (ENSG00000205038), DYTN (ENSG00000232125), MICAL3 (ENSG00000243156), ACTN3 (ENSG00000248746), EPPK1 (ENSG00000261150), GAS2L2 (ENSG00000270765)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1277961) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 49 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal myocardial fiber morphology	2
blistering	2
skin lesions	2
abnormal keratinocyte morphology	2
abnormal skeletal muscle fiber morphology	2
postnatal lethality, complete penetrance	2
abnormal heart morphology	1
abnormal cell morphology	1
muscle degeneration	1
myopathy	1
abnormal skin condition	1
abnormal epidermis stratum basale morphology	1
absent epidermis stratum basale	1
abnormal dermal layer morphology	1
decreased body weight	1
decreased body size	1
abnormal suckling behavior	1
postnatal growth retardation	1
edema	1
impaired wound healing	1
hemorrhage	1
abnormal T cell physiology	1
impaired skin barrier function	1
abnormal soleus morphology	1
abnormal keratinocyte physiology	1

+24 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Oryctolagus cuniculus	G1T168	100.0%	Diamond
Oryza sativa Japonica Group	P0DKK8	100.0%	Diamond
Bos taurus	Q3T0F4	100.0%	Diamond
Macaca fascicularis	Q2PFV7	99.9%	Diamond
Pongo abelii	Q5RCS6	99.8%	Diamond
Pan troglodytes	Q2KNA1	99.7%	Diamond
Gallus gallus	P05094	98.3%	Diamond
Saccharomyces cerevisiae S288C	P46784	97.1%	Diamond
Schizosaccharomyces pombe 972h-	O13614	95.8%	Diamond
Cricetulus griseus	Q9JI55	94.7%	Diamond
Canis lupus familiaris	O97592	94.6%	Diamond
Sus scrofa	Q5GN48	94.6%	Diamond
Arabidopsis thaliana	Q9SW09	93.8%	Diamond
Ictalurus punctatus	Q90YR4	92.4%	Diamond
Drosophila melanogaster	Q9VDW6	91.8%	Diamond
Xenopus laevis	Q07254	91.0%	Diamond
Anopheles gambiae	Q7PKQ5	90.1%	Diamond
Takifugu rubripes	Q2KN94	89.2%	Diamond
Tetraodon nigroviridis	Q2KN95	89.2%	Diamond
Dermatophagoides farinae	L7UZ85	80.5%	Diamond
Dictyostelium discoideum	Q550R2	79.0%	Diamond
Heterostelium album PN500	Q9Y0T3	79.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR937	ncRNA	100126338
PUF60	protein-coding	22827
SCRIB	protein-coding	23513
NRBP2	protein-coding	340371
MIR661	ncRNA	724031
EPPK1	protein-coding	83481
MIR6845	ncRNA	102466748
GRINA	protein-coding	2907
PARP10	protein-coding	84875
SPATC1	protein-coding	375686
OPLAH	protein-coding	26873

Protein

Protein identifiers

Plectin — Q15149 (reviewed: Q15149)

Alternative names: Hemidesmosomal protein 1, Plectin-1

All UniProt accessions (6): A0A8I5KSD5, A0A8I5KUE3, A0A8I5KYZ1, E9PMV1, H0YDN1, Q15149

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Homodimer or homotetramer. Interacts (via actin-binding domain) with SYNE3. Interacts (via calponin-homology (CH) 1 domain) with VIM (via rod region). Interacts (via N-terminus) with DST isoform 2 (via N-terminus). Interacts with FER. Interacts with TOR1A. Interacts with ANK3. Identified in complexes that contain VIM, EZR, AHNAK, BFSP1, BFSP2, ANK2, PLEC, PRX and spectrin. Interacts with COL17A1. Interacts with KRT14, heterodimers consisting of KRT8 and KRT18, heterodimers consisting of KRT5 and KRT14, heterodimers consisting of KRT14 and KRT15, and heterodimers consisting of KRT1 and KRT10. Interacts with DES and VIM.

Subcellular location. Cytoplasm. Cytoskeleton. Cell junction. Hemidesmosome. Cell projection. Podosome.

Tissue specificity. Widely expressed with highest levels in muscle, heart, placenta and spinal cord.

Post-translational modifications. Phosphorylated by CDK1; regulates dissociation from intermediate filaments during mitosis.

Disease relevance. Epidermolysis bullosa simplex 5C, with pyloric atresia (EBS5C) [MIM:612138] A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. EBS5C is an autosomal recessive disorder characterized by severe skin blistering at birth and congenital pyloric atresia. Death usually occurs in infancy. The disease is caused by variants affecting the gene represented in this entry. Epidermolysis bullosa simplex 5B, with muscular dystrophy (EBS5B) [MIM:226670] A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. EBS5B is an autosomal recessive disorder characterized by progressive muscular dystrophy associated with generalized skin blistering. The disease is caused by variants affecting the gene represented in this entry. Epidermolysis bullosa simplex 5A, Ogna type (EBS5A) [MIM:131950] An autosomal dominant form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. EBS5A patients manifest generalized skin bruising, skin fragility with non-scarring blistering and small hemorrhagic blisters on hands. At the ultrastructural level, EBS5A is differentiated from classical epidermolysis bullosa simplex, by the occurrence of blisters originating in basal cells above hemidesmosomes, and abnormal hemidesmosome intracellular attachment plates. The disease is caused by variants affecting the gene represented in this entry. Muscular dystrophy, limb-girdle, autosomal recessive 17 (LGMDR17) [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. The disease is caused by variants 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. Epidermolysis bullosa simplex 5D, generalized intermediate, autosomal recessive (EBS5D) [MIM:616487] A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. EBS5D patients have generalized skin blistering that heals with scarring and hyperpigmentation, and severe nail dystrophy. Mucous membranes, heart, and muscle are spared. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The N-terminus interacts with actin, the C-terminus with vimentin, desmin, GFAP, cytokeratins, lamin B; whereas both the N- and the C-terminus can bind integrin beta-4.

Similarity. Belongs to the plakin or cytolinker family.

Isoforms (9)

UniProt ID	Names	Canonical?
Q15149-1	1, Plectin-6	yes
Q15149-2	2, Plectin-1, 1c
Q15149-3	3
Q15149-4	4, Plectin-11, 1a
Q15149-5	5, Plectin-8, 1b
Q15149-6	6, Plectin-10, 1g
Q15149-7	7, Plectin-7, 1d
Q15149-8	8, Plectin-3, 1e
Q15149-9	9, Plectin-2, 1f

RefSeq proteins (9): NP_000436, NP_001397870, NP_958780, NP_958781, NP_958782, NP_958783, NP_958784, NP_958785, NP_958786* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001101	Plectin_repeat	Repeat
IPR001452	SH3_domain	Domain
IPR001589	Actinin_actin-bd_CS	Conserved_site
IPR001715	CH_dom	Domain
IPR005326	Plectin_eS10_N	Domain
IPR018159	Spectrin/alpha-actinin	Repeat
IPR035915	Plakin_repeat_sf	Homologous_superfamily
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036872	CH_dom_sf	Homologous_superfamily
IPR041573	Desmoplakin_Spectrin-like	Domain
IPR041615	Desmoplakin_SH3	Domain
IPR043197	Plakin	Family
IPR049538	PCN-like_spectrin-like_rpt	Repeat

Pfam: PF00307, PF00681, PF03501, PF17902, PF18373, PF21019, PF21020, PF21097

UniProt features (278 total): helix 60, modified residue 56, sequence conflict 41, repeat 37, sequence variant 19, region of interest 18, strand 16, splice variant 13, compositionally biased region 7, turn 6, domain 3, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

14 structures by resolution:

PDB	Title	Method	Resolution (Å)
4GDO	Structure of a fragment of the rod domain of plectin	X-RAY DIFFRACTION	1.7
5J1G	Structure of the spectrin repeats 7 and 8 of the plakin domain of plectin	X-RAY DIFFRACTION	1.8
2ODV	Crystal structure of a fragment of the plakin domain of plectin, Cys to Ala mutant.	X-RAY DIFFRACTION	2.05
1MB8	Crystal Structure of the actin binding domain of plectin	X-RAY DIFFRACTION	2.15
3PDY	Structure of the third and fourth spectrin repeats of the plakin domain of plectin	X-RAY DIFFRACTION	2.22
2ODU	Crystal structure of a fragment of the plakin domain of plectin	X-RAY DIFFRACTION	2.3
4Q59	Crystal structure of plectin 1a actin-binding domain	X-RAY DIFFRACTION	2.3
3F7P	Crystal structure of a complex between integrin beta4 and plectin	X-RAY DIFFRACTION	2.75
5J1H	Structure of the spectrin repeats 5 and 6 of the plakin domain of plectin	X-RAY DIFFRACTION	2.8
5J1I	Structure of the spectrin repeats 7, 8, and 9 of the plakin domain of plectin	X-RAY DIFFRACTION	2.8
3PE0	Structure of the central region of the plakin domain of plectin	X-RAY DIFFRACTION	2.95
5J1F	Structure of the spectrin repeats 5 and 6 of the plakin domain of plectin	X-RAY DIFFRACTION	3
4Q58	Crystal structure of the plectin 1a actin-binding domain/integrin beta 4 fragment complex	X-RAY DIFFRACTION	4
2N03	Solution NMR Structure plectin repeat domain 6 (4403-4606) of Plectin from Homo sapiens …	SOLUTION NMR

Predicted structure (AlphaFold)

No AlphaFold model available for Q15149 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Mutational cancer driver genes, Disease related genes, Human disease related genes, Congenital malformations, Congenital malformations of skin

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; intermediate filaments; focal adhesion sites

Antibody reliability (HPA): IH enhanced · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (56)

Type	Positions
Phosphothreonine	4411, 4539, 4623, 113, 2886, 3785, 4030
Phosphoserine	4607, 4613, 4616, 4618, 4622, 4626, 4642, 4672, 4675, 42, 42, 20, 21, 125, 149, 720, 1047, 1435, 1721, 1732, 2631, 2782, 2802, 3036, 3580, 4054, 4382, 4384, 4385, 4386, 4389, 4390, 4391, 4392, 4396, 4400, 4406
Phosphotyrosine	4615, 26, 3033, 3362, 4393
Omega-n-methylarginine	4627, 4640
N6-acetyllysine	1725, 2636, 3053, 3091, 3420

Function

Pathways and Gene Ontology

Reactome pathways

3 curated (TAS) of 11; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

11 pathways:

ID	Pathway	Evidence
R-HSA-2022090	Assembly of collagen fibrils and other multimeric structures	curated
R-HSA-264870	Caspase-mediated cleavage of cytoskeletal proteins	curated
R-HSA-446107	Type I hemidesmosome assembly	curated
R-HSA-109581	Apoptosis	—
R-HSA-111465	Apoptotic cleavage of cellular proteins	—
R-HSA-75153	Apoptotic execution phase	—
R-HSA-446728	Cell junction organization	—
R-HSA-1500931	Cell-Cell communication	—
R-HSA-1474290	Collagen formation	—
R-HSA-1474244	Extracellular matrix organization	—
R-HSA-5357801	Programmed Cell Death	—

MSigDB gene sets: 765 (showing top): MODULE_52, AP1_01, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, AAGCAAT_MIR137, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_CELL_CHEMOTAXIS, GOBP_INTERMEDIATE_FILAMENT_ORGANIZATION, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_RESPONSE_TO_FLUID_SHEAR_STRESS

GO Biological Process (39): cell morphogenesis (GO:0000902), leukocyte migration involved in immune response (GO:0002522), keratinocyte development (GO:0003334), nucleus organization (GO:0006997), mitochondrion organization (GO:0007005), intracellular protein localization (GO:0008104), gene expression (GO:0010467), fibroblast migration (GO:0010761), T cell chemotaxis (GO:0010818), skeletal myofibril assembly (GO:0014866), transmission of nerve impulse (GO:0019226), respiratory electron transport chain (GO:0022904), hemidesmosome assembly (GO:0031581), response to food (GO:0032094), peripheral nervous system myelin maintenance (GO:0032287), adherens junction organization (GO:0034332), multicellular organism growth (GO:0035264), wound healing (GO:0042060), regulation of vascular permeability (GO:0043114), protein-containing complex organization (GO:0043933), intermediate filament cytoskeleton organization (GO:0045104), intermediate filament organization (GO:0045109), sarcomere organization (GO:0045214), myoblast differentiation (GO:0045445), skeletal muscle fiber development (GO:0048741), cardiac muscle cell development (GO:0055013), establishment of skin barrier (GO:0061436), cellular response to mechanical stimulus (GO:0071260), cellular response to hydrostatic pressure (GO:0071464), cellular response to fluid shear stress (GO:0071498), tight junction organization (GO:0120193), actomyosin contractile ring assembly actin filament organization (GO:2000689), actin filament organization (GO:0007015), skeletal muscle tissue development (GO:0007519), myelination in peripheral nervous system (GO:0022011), actin cytoskeleton organization (GO:0030036), keratinocyte differentiation (GO:0030216), skin development (GO:0043588), cell motility (GO:0048870)

GO Molecular Function (11): dystroglycan binding (GO:0002162), RNA binding (GO:0003723), structural constituent of cytoskeleton (GO:0005200), structural constituent of muscle (GO:0008307), ankyrin binding (GO:0030506), identical protein binding (GO:0042802), cadherin binding (GO:0045296), actin filament binding (GO:0051015), actin binding (GO:0003779), protein binding (GO:0005515), cytoskeletal protein binding (GO:0008092)

GO Cellular Component (23): podosome (GO:0002102), cytoplasm (GO:0005737), mitochondrial outer membrane (GO:0005741), cytosol (GO:0005829), plasma membrane (GO:0005886), brush border (GO:0005903), focal adhesion (GO:0005925), sarcoplasm (GO:0016528), Z disc (GO:0030018), hemidesmosome (GO:0030056), axon (GO:0030424), dendrite (GO:0030425), sarcolemma (GO:0042383), costamere (GO:0043034), myelin sheath (GO:0043209), intermediate filament cytoskeleton (GO:0045111), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), cytoskeleton (GO:0005856), intermediate filament (GO:0005882), myofibril (GO:0030016), contractile muscle fiber (GO:0043292), cell periphery (GO:0071944)

Reactome top-level categories

8 top-level categories:

Category	Pathways
Collagen formation	1
Apoptotic cleavage of cellular proteins	1
Cell junction organization	1
Programmed Cell Death	1
Apoptotic execution phase	1
Extracellular matrix organization	1
Cell-Cell communication	1
Apoptosis	1

GO top-level categories

showing 60 of 64 GO namespaces:

Category	Terms
cellular anatomical structure	6
protein binding	3
cytoplasm	3
organelle organization	2
structural molecule activity	2
cytoskeleton	2
cytoskeletal protein binding	2
cell-substrate junction	2
neuron projection	2
anatomical structure morphogenesis	1
immune effector process	1
immune response	1
leukocyte migration	1
epithelial cell development	1
keratinocyte differentiation	1
macromolecule localization	1
macromolecule biosynthetic process	1
ameboidal-type cell migration	1
lymphocyte chemotaxis	1
T cell migration	1
myofibril assembly	1
action potential	1
cell communication	1
chemical synaptic transmission	1
nervous system process	1
electron transport chain	1
cellular respiration	1
cell-substrate junction assembly	1
response to nutrient levels	1
response to chemical	1
myelination in peripheral nervous system	1
myelin maintenance	1
cell-cell junction organization	1
multicellular organismal process	1
developmental growth	1
response to wounding	1
tissue regeneration	1
vascular process in circulatory system	1
blood circulation	1
regulation of biological quality	1
cellular component organization	1
nucleic acid binding	1
cytoskeleton organization	1
cell adhesion molecule binding	1
actin binding	1
protein-containing complex binding	1
binding	1
actin-based cell projection	1
intracellular anatomical structure	1
mitochondrial membrane	1
organelle outer membrane	1
membrane	1
cell periphery	1
microvillus	1
apical part of cell	1
cluster of actin-based cell projections	1
I band	1
dendritic tree	1
plasma membrane	1
myofibril	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 10 of 73 annotations. The rest are phylogenetic / computational / electronic (IEA).

10 experimentally-supported GO terms:

GO term	NS	Evidence
hemidesmosome assembly	BP	direct assay
extracellular exosome	CC	high-throughput assay
focal adhesion	CC	direct assay
hemidesmosome	CC	direct assay
intermediate filament cytoskeleton	CC	direct assay
sarcolemma	CC	direct assay
RNA binding	MF	high-throughput assay
ankyrin binding	MF	physical interaction
cadherin binding	MF	high-throughput assay
structural constituent of muscle	MF	mutant phenotype

Protein interactions and networks

STRING

showing 15 of 2,128 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLEC	ITGB4	P16144	911
PLEC	SYNE3	Q6ZMZ3	879
PLEC	SYNM	O15061	838
PLEC	ITGA6	P23229	811
PLEC	COL17A1	Q9UMD9	811
PLEC	PARP10	Q53GL7	797
PLEC	DES	P17661	738
PLEC	SLMAP	Q14BN4	718
PLEC	MYOT	Q9UBF9	713
PLEC	KRT14	P02533	705
PLEC	SYNE4	Q8N205	700
PLEC	VIM	P08670	689
PLEC	GFAP	P14136	687
PLEC	PKP1	Q13835	682
PLEC	CD151	P48509	668

IntAct

Human interaction partners of PLEC in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 121 partners by confidence:

Partner	Interaction type	MIscore	Records
HTT	physical association	0.670	3
ITGB4	direct interaction	0.560	7
KRT14	physical association	0.560	1
KEAP1	direct interaction	0.540	1
SBDS	physical association	0.540	1
WNK1	physical association	0.530	2
FUS	physical association	0.520	4
ACP2	physical association	0.400	1
ACTC1	physical association	0.400	1
ACTR1A	physical association	0.400	1
ADH6	physical association	0.400	1
AHCTF1	physical association	0.400	1
ANKS4B	physical association	0.400	1
ASH1L	physical association	0.400	1
ATR	physical association	0.400	1
AXDND1	physical association	0.400	1
C2CD3	physical association	0.400	1
CASQ2	physical association	0.400	1
CCDC27	physical association	0.400	1
CCDC62	physical association	0.400	1
CDK12	physical association	0.400	1
CNPY3	physical association	0.400	1
CS	physical association	0.400	1
CTSZ	physical association	0.400	1
CTTNBP2	physical association	0.400	1
DIS3	physical association	0.400	1
DNA2	physical association	0.400	1
DNAH3	physical association	0.400	1
DNAH5	physical association	0.400	1
EWSR1	physical association	0.400	1

BioGRID (509 interactions; top human partners by supporting records): KRT18 (Proximity Label-MS; 6 records), KRT8 (Proximity Label-MS; 6 records), VIM (Proximity Label-MS; 5 records), BRCA2 (Co-fractionation; 4 records), ANK3 (Two-hybrid; 3 records), ANLN (Affinity Capture-MS; 3 records), CCDC68 (Affinity Capture-MS; 3 records), GFOD1 (Affinity Capture-MS; 3 records), MACF1 (Cross-Linking-MS (XL-MS); 3 records), MYC (Affinity Capture-MS; 3 records), NACA (Cross-Linking-MS (XL-MS); 3 records), NEFM (Affinity Capture-MS; 3 records), RPS10 (Cross-Linking-MS (XL-MS); 3 records), AAK1 (Affinity Capture-MS; 2 records), ACTA2 (Cross-Linking-MS (XL-MS); 2 records)

SIGNOR signaling

showing 3 of 5 signaling interactions:

A	Effect	B	Mechanism
CDK1	down-regulates	PLEC	phosphorylation
CyclinB/CDK1	down-regulates	PLEC	phosphorylation
TP63	“up-regulates quantity by expression”	PLEC	“transcriptional regulation”

Disease & clinical

Genetic variants

Variant evidence for PLEC: 6,730 ClinVar records (153 pathogenic / likely pathogenic); 59 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

6,730 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	106
Likely pathogenic	47
Uncertain significance	3617
Likely benign	1925
Benign	152

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 153 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
8262	NM_201384.3(PLEC):c.5917C>T (p.Arg1973Trp)	Pathogenic	criteria provided, multiple submitters, no conflicts	9
30174	NM_201384.3(PLEC):c.6874C>T (p.Arg2292Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
1320041	NM_201384.3(PLEC):c.6970C>T (p.Arg2324Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
289658	NM_201384.3(PLEC):c.7180C>T (p.Arg2394Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
620547	NM_201384.3(PLEC):c.6910C>T (p.Gln2304Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
830362	NM_201384.3(PLEC):c.6079C>T (p.Arg2027Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
501798	NM_201384.3(PLEC):c.9558_9559del (p.Glu3188fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
840189	NM_201384.3(PLEC):c.8080_8084dup (p.Ser2696fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1323468	NM_201384.3(PLEC):c.1465_1471del (p.Asn489fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2938094	NM_201384.3(PLEC):c.1675C>T (p.Arg559Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
3767316	NM_201384.3(PLEC):c.5188C>T (p.Gln1730Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
8266	NM_201384.3(PLEC):c.9004C>T (p.Arg3002Ter)	Pathogenic	criteria provided, single submitter	2
218870	NM_201384.3(PLEC):c.13297A>T (p.Lys4433Ter)	Pathogenic	criteria provided, single submitter	1
218871	NM_201384.3(PLEC):c.5932G>T (p.Glu1978Ter)	Pathogenic	criteria provided, single submitter	1
282640	NM_201384.3(PLEC):c.11287_11288del (p.Ser3763fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore PLEC’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 34 predictions of 2,386):

Position(s)	Effect	Δscore	Sites
8:143925895	acceptor_gain	1.0000
8:143925898	acceptor_gain	1.0000
8:143926782–143926783	donor_loss	1.0000	4
8:143926975–143926976	donor_loss	1.0000	5
8:143927082	acceptor_loss	1.0000	2
8:143927250–143927251	donor_loss	1.0000	5
8:143927856	donor_gain	1.0000
8:143927993–143927994	acceptor_loss	1.0000	5
8:143929101–143929102	donor_loss	1.0000	5
8:143929282–143929283	acceptor_loss	1.0000	5

AlphaMissense

6,100 missense substitutions predicted likely pathogenic (of 29,232 scored), across 2,142 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M4289	9	0.870	0.991
D4441	8	0.977	0.997
N4235	8	0.975	0.996
F4496	8	0.974	0.999
D4498	8	0.967	0.993
D4229	8	0.966	0.995
F4227	8	0.962	0.998
H4175	8	0.960	0.986
D4333	8	0.960	0.994
F4228	8	0.955	0.996
F4524	8	0.955	0.998
D4301	8	0.950	0.992
F3704	8	0.945	0.992
F4369	8	0.943	0.999
D4115	8	0.941	0.992
D4223	8	0.932	0.973
D3575	8	0.927	0.981
D3613	8	0.927	0.984
D4282	8	0.922	0.992
F4101	8	0.917	0.973

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Rectum Adenocarcinoma (validation)	favorable	0.0002
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	unfavorable	0.000342
Lung Adenocarcinoma (TCGA)	unfavorable	0.000371
Pancreatic Adenocarcinoma (TCGA)	unfavorable	0.000524

Disease associations

OMIM: gene MIM:601282 | disease phenotypes: MIM:131760, MIM:131950, MIM:226670, MIM:612138, MIM:613723, MIM:616487, MIM:226730

GenCC curated gene-disease

10 curated gene-disease records:

Disease	Classification	Inheritance	Records
congenital myasthenic syndrome	Strong	Autosomal recessive
epidermolysis bullosa simplex 5A, Ogna type	Strong	Autosomal dominant	4
epidermolysis bullosa simplex 5B, with muscular dystrophy	Strong	Autosomal recessive	2
epidermolysis bullosa simplex 5C, with pyloric atresia	Strong	Autosomal recessive	3
autosomal recessive limb-girdle muscular dystrophy type 2Q	Strong	Autosomal recessive	3
PLEC-related muscular dystrophy-epidermolysis bullosa simplex spectrum disorder	Strong	Autosomal recessive
epidermolysis bullosa simplex	Strong	Autosomal dominant
progressive familial intrahepatic cholestasis	Moderate	Autosomal recessive
aplasia cutis congenita	Supportive	Autosomal dominant
cholestasis	Limited	Autosomal recessive

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
PLEC-related muscular dystrophy-epidermolysis bullosa simplex spectrum disorder	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (10 panels, 10 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

10 panels:

Panel	Rating
Congenital muscular dystrophy	green
Congenital myaesthenic syndrome	green
DDG2P	green
Epidermolysis bullosa	green
Epidermolysis bullosa and congenital skin fragility	green
Fetal anomalies	green
Hypotonic infant	green
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies	green
Other rare neuromuscular disorders	green
Paediatric disorders	green

Mondo (16): epidermolysis bullosa simplex (MONDO:0017610), epidermolysis bullosa simplex 5A, Ogna type (MONDO:0007555), epidermolysis bullosa simplex 5B, with muscular dystrophy (MONDO:0009181), epidermolysis bullosa simplex 5C, with pyloric atresia (MONDO:0012807), autosomal recessive limb-girdle muscular dystrophy type 2Q (MONDO:0013390), epidermolysis bullosa simplex with nail dystrophy (MONDO:0014661), myopathy (MONDO:0005336), junctional epidermolysis bullosa with pyloric atresia (MONDO:0009183), neuromuscular disease caused by qualitative or quantitative defects of plectin (MONDO:0016198), multiple sclerosis (MONDO:0005301), epidermolysis bullosa simplex 1A, generalized severe (MONDO:0007550), cholestasis (MONDO:0001751), congenital myasthenic syndrome (MONDO:0018940), aplasia cutis congenita (MONDO:0007145), progressive familial intrahepatic cholestasis (MONDO:0015762), PLEC-related muscular dystrophy-epidermolysis bullosa simplex spectrum disorder (MONDO:1060109)

Orphanet (9): Epidermolysis bullosa simplex (Orphanet:304), Epidermolysis bullosa simplex with pyloric atresia (Orphanet:158684), Plectin-related limb-girdle muscular dystrophy R17 (Orphanet:254361), Epidermolysis bullosa simplex with muscular dystrophy (Orphanet:257), PLEC-related intermediate epidermolysis bullosa simplex without extracutaneous involvement (Orphanet:79401), Junctional epidermolysis bullosa with pyloric atresia (Orphanet:79403), Qualitative or quantitative defects of plectin (Orphanet:209196), Autosomal dominant generalized epidermolysis bullosa simplex, severe form (Orphanet:79396), NON RARE IN EUROPE: Multiple sclerosis (Orphanet:802)

HPO phenotypes

showing 60 of 146 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000070	Ureterocele
HP:0000075	Renal duplication
HP:0000079	Abnormality of the urinary system
HP:0000096	Glomerular sclerosis
HP:0000110	Renal dysplasia
HP:0000126	Hydronephrosis
HP:0000164	Abnormality of the dentition
HP:0000256	Macrocephaly
HP:0000430	Underdeveloped nasal alae
HP:0000463	Anteverted nares
HP:0000478	Abnormality of the eye
HP:0000490	Deeply set eye
HP:0000491	Keratitis
HP:0000508	Ptosis
HP:0000597	Ophthalmoparesis
HP:0000602	Ophthalmoplegia
HP:0000656	Ectropion
HP:0000670	Carious teeth
HP:0000682	Abnormal dental enamel morphology
HP:0000795	Abnormality of the urethra
HP:0000951	Abnormality of the skin
HP:0000972	Palmoplantar hyperkeratosis
HP:0000978	Bruising susceptibility
HP:0000982	Palmoplantar keratoderma
HP:0000989	Pruritus
HP:0001030	Fragile skin
HP:0001034	Hypermelanotic macule
HP:0001056	Milia
HP:0001057	Aplasia cutis congenita
HP:0001060	Axillary pterygium
HP:0001075	Atrophic scars
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001284	Areflexia
HP:0001362	Calvarial skull defect
HP:0001371	Flexion contracture
HP:0001488	Bilateral ptosis
HP:0001522	Death in infancy
HP:0001561	Polyhydramnios
HP:0001596	Alopecia
HP:0001611	Hypernasal speech
HP:0001626	Abnormality of the cardiovascular system
HP:0001627	Abnormal heart morphology
HP:0001770	Toe syndactyly
HP:0001771	Achilles tendon contracture
HP:0001798	Anonychia
HP:0001804	Hypoplastic fingernail
HP:0001812	Hyperconvex fingernails
HP:0001903	Anemia
HP:0002012	Abnormality of the abdominal organs
HP:0002013	Vomiting
HP:0002015	Dysphagia
HP:0002032	Esophageal atresia
HP:0002041	Intractable diarrhea
HP:0002086	Abnormality of the respiratory system
HP:0002164	Nail dysplasia
HP:0002194	Delayed gross motor development
HP:0002206	Pulmonary fibrosis

GWAS associations

showing 30 of 59 associations:

Study	Trait	p-value
GCST90002401_102	Platelet distribution width	4e-103
GCST90002402_105	Platelet count	3e-79
GCST90002400_214	Plateletcrit	5e-47
GCST90002395_657	Mean platelet volume	2e-39
GCST004616_49	Platelet distribution width	3e-39
GCST004603_253	Platelet count	7e-33
GCST004599_261	Mean platelet volume	6e-19
GCST004607_160	Plateletcrit	2e-18
GCST010204_190	Low density lipoprotein cholesterol levels	4e-18
GCST004233_59	LDL cholesterol levels	2e-17
GCST010243_152	Apolipoprotein B levels	5e-17
GCST003818_41	Resting heart rate	1e-15
GCST004235_49	Total cholesterol levels	3e-14
GCST000759_16	LDL cholesterol	4e-13
GCST010245_10	LDL cholesterol levels	7e-13
GCST006630_60	Diastolic blood pressure	5e-12
GCST002222_49	LDL cholesterol	7e-12
GCST90014033_13	Haemorrhoidal disease	2e-11
GCST010321_96	PR interval	3e-11
GCST90002403_513	Red blood cell count	7e-11
GCST007931_41	Medication use (HMG CoA reductase inhibitors)	1e-10
GCST002898_12	LDL cholesterol	2e-10
GCST001337_24	Platelet count	5e-10
GCST90020026_251	Hip index	5e-10
GCST003194_15	Fibrinogen levels	6e-10
GCST006612_17	LDL cholesterol	6e-10
GCST000760_17	Cholesterol, total	9e-10
GCST002147_18	Fibrinogen	1e-9
GCST002647_72	Height	1e-9
GCST004122_31	Fibrinogen levels	2e-9

EFO canonical traits (from GWAS)

18 canonical traits:

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0004309	platelet count
EFO:0004314	forced expiratory volume
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width
EFO:0008378	mosquito bite reaction size measurement
EFO:0006874	antisaccade response measurement
EFO:0006336	diastolic blood pressure
EFO:0009932	HMG CoA reductase inhibitor use measurement
EFO:0009963	bipolar I disorder
EFO:0004615	apolipoprotein B measurement
EFO:0004462	PR interval
EFO:0004346	neuroimaging measurement
EFO:0004327	electrocardiography
EFO:0008373	left ventricular ejection fraction measurement
EFO:0004305	erythrocyte count
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors

8 disease descriptors:

Descriptor	Name	Tree numbers
D002779	Cholestasis	C06.130.120.135
D016110	Epidermolysis Bullosa Simplex	C16.131.831.493.180; C16.320.850.275.180; C17.800.804.493.180; C17.800.827.275.180; C17.800.865.410.180
D009103	Multiple Sclerosis	C10.114.375.500; C10.314.350.500; C20.111.258.250.500
D020294	Myasthenic Syndromes, Congenital	C10.668.758.800; C16.320.590
C535955	Epidermolysa bullosa simplex and limb girdle muscular dystrophy *(supp.)*
C567408	Epidermolysis Bullosa Simplex With Pyloric Atresia *(supp.)*
C535962	Epidermolysis bullosa simplex, Ogna type *(supp.)*
C535377	Epidermolysis bullosa with pyloric atresia *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1293240 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

128 measured of 136 human assays (154 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
4-(4-aminophenylsulfonamido)-1-benzenesulfonamide	KI	109 nM
3-chloranyl-N-[2-chloranyl-5-(trifluoromethyl)phenyl]-6-(3,5-dimethylpyrazol-1-yl)pyridine-2-carboxamide	EC50	240 nM
SMR000067268	IC50	408 nM
cid_1912988	IC50	498 nM
cid_3759952	EC50	1090 nM
CHEMBL5653589	KD	1440 nM
MLS000588669	IC50	1610 nM
MLS000537607	EC50	1800 nM
N-[4-(4-morpholinylsulfonyl)phenyl]-6-oxo-1H-pyridine-3-carboxamide	IC50	1890 nM
SMR000277284	IC50	2570 nM
MLS000576933	IC50	3550 nM
MLS000664114	IC50	3590 nM
(2S)-3-phenyl-2-[[(2S)-2-[3-(3,5,9-trimethyl-7-oxidanylidene-furo[3,2-g]chromen-6-yl)propanoylamino]propanoyl]amino]propanoic acid	IC50	3600 nM
4-[(2-ethoxybenzyl)amino]phenol	EC50	3630 nM
[3-[(E)-3-methoxyprop-1-enyl]-7-methyl-6,8-dioxoisochromen-7-yl] furan-2-carboxylate	IC50	3700 nM
(2S)-2-[[2-(3-benzyl-4,8-dimethyl-2-oxochromen-7-yl)oxyacetyl]amino]-3-phenylpropanoic acid	IC50	3860 nM
2-(diethylamino)ethyl 4-[[(Z)-2-cyano-2-[4-(2-oxochromen-3-yl)-1,3-thiazol-2-yl]ethenyl]amino]benzoate	IC50	4120 nM
cid_5989040	IC50	4300 nM
4-[3-[(4-phenylbenzoyl)amino]phenoxy]phthalic acid	IC50	4440 nM
4-bromanyl-N-[(3-bromophenyl)methylideneamino]benzamide	IC50	4510 nM
3-(4-nitrophenyl)-2H-phthalazine-1,4-dione	IC50	5220 nM
MLS000588665	IC50	5230 nM
SMR000497405	IC50	5580 nM
(E)-N-[[4-[(5-ethyl-1,3,4-thiadiazol-2-yl)sulfamoyl]phenyl]carbamothioyl]-3-(4-propan-2-ylphenyl)prop-2-enamide	IC50	6160 nM
SMR000162332	IC50	6710 nM
1-(ethylamino)-3-methyl-3H-naphtho[1,2,3-de]quinoline-2,7-dione	IC50	7290 nM
2-[4-[[5-(4-chlorophenyl)-6-ethoxycarbonyl-7-methyl-3-oxidanylidene-5H-[1,3]thiazolo[3,2-a]pyrimidin-2-ylidene]methyl]phenoxy]ethanoic acid	IC50	8420 nM
MLS000936640	IC50	10900 nM
MLS001196487	IC50	11300 nM
3-[3,4-dihydro-1H-isoquinolin-2-yl-[1-(2-methoxyethyl)-5-tetrazolyl]methyl]-7-methoxy-1H-quinolin-2-one	IC50	11800 nM
MLS000779218	IC50	12200 nM
4-[(4-hydroxyanilino)methylene]-2,2,5,5-tetramethyldihydro-3(2H)-furanone	IC50	12200 nM
(5Z)-5-[[4-(dimethylamino)phenyl]methylidene]-4-(4-methoxyanilino)-1,3-thiazol-2-one	IC50	12700 nM
5-bromanyl-N-(3-cyano-1-phenyl-pyrrolo[3,2-b]quinoxalin-2-yl)furan-2-carboxamide	IC50	14000 nM
MLS000714144	IC50	14300 nM
3-[(E)-(5-chloro-2-hydroxyphenyl)diazenyl]-4,5-dihydroxynaphthalene-2,7-disulfonate	EC50	16300 nM
N-butyl-N-[(6-methoxy-2-oxo-1H-quinolin-3-yl)methyl]-4-methylbenzenesulfonamide	IC50	17200 nM
2-[4-[(2-oxo-8-prop-2-enylchromene-3-carbonyl)amino]phenyl]acetic acid	IC50	17300 nM
MLS001003216	IC50	18300 nM
4-[1,3-bis(oxidanylidene)-3a,4,7,7a-tetrahydroisoindol-2-yl]-N-(4-bromophenyl)benzamide	IC50	18600 nM
3-{4-Chloro-5-[(2-chloro-benzoyl)-hydrazonomethyl]-2-oxo-thiazol-3-ylmethyl}-benzoic acid methyl ester	IC50	19000 nM
SMR000208086	IC50	19600 nM
SMR000434079	IC50	23200 nM
3-(4-tert-butylphenyl)-3-{[(4-fluorophenyl)acetyl]amino}propanoic acid	IC50	25600 nM
1-Amino-4-hydroxy-anthraquinone	IC50	25700 nM
1,5-dimethyl-4-[(4-oxidanylidenecyclohexa-2,5-dien-1-ylidene)amino]-2-phenyl-pyrazol-3-one	IC50	31600 nM
3-(1,3-dioxoisoindol-2-yl)-N-(4-sulfamoylphenyl)benzamide	IC50	40200 nM
MLS000589117	IC50	40600 nM
5-[(5E)-5-[[3,4-bis(phenylmethoxy)phenyl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]pentanoic acid	IC50	45400 nM
N-[(E)-2-(5-chloro-3-ethyl-1,3-benzothiazol-3-ium-2-yl)ethenyl]-N-methylaniline;perchlorate	EC50	49800 nM

ChEMBL bioactivities

57 potent at pChembl≥5 of 113 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.96	Kd	11.04	nM	CHEMBL5653589
7.96	ED50	11.04	nM	CHEMBL5653589
5.82	IC50	1518	nM	CHEMBL88326
5.81	IC50	1560	nM	CHEMBL1511181
5.80	IC50	1600	nM	CHEMBL1405964
5.75	IC50	1792	nM	CHEMBL1993173
5.75	IC50	1771	nM	CHEMBL1503523
5.73	IC50	1852	nM	CHEMBL1334149
5.72	IC50	1893	nM	CHEMBL1585746
5.69	IC50	2041	nM	CHEMBL1354019
5.68	IC50	2094	nM	CHEMBL1389315
5.67	IC50	2138	nM	CHEMBL2028186
5.67	IC50	2165	nM	CHEMBL1304979
5.64	IC50	2307	nM	CHEMBL1300620
5.62	IC50	2391	nM	CHEMBL1348090
5.59	IC50	2543	nM	CHEMBL3190895
5.53	IC50	2932	nM	CHEMBL3193946
5.47	IC50	3405	nM	CHEMBL1532953
5.43	IC50	3734	nM	CHEMBL1415156
5.43	IC50	3743	nM	CHEMBL2000670
5.41	IC50	3910	nM	CHEMBL1440277
5.40	IC50	3958	nM	CHEMBL1346753
5.39	IC50	4032	nM	CHEMBL1308195
5.38	IC50	4214	nM	CHEMBL1334670
5.37	IC50	4266	nM	CHEMBL1447803
5.36	IC50	4371	nM	CHEMBL1320537
5.36	IC50	4382	nM	CHEMBL1529584
5.34	IC50	4514	nM	CHEMBL1438567
5.34	IC50	4550	nM	CHEMBL1455832
5.33	IC50	4658	nM	CHEMBL1546183
5.30	IC50	5040	nM	CHEMBL1416302
5.30	IC50	4982	nM	CHEMBL3192206
5.29	IC50	5126	nM	CHEMBL2028186
5.29	IC50	5110	nM	CHEMBL1454269
5.27	IC50	5412	nM	CHEMBL1334670
5.27	IC50	5406	nM	CHEMBL1469444
5.25	IC50	5607	nM	CHEMBL1985649
5.25	IC50	5665	nM	CHEMBL1559707
5.24	IC50	5753	nM	CHEMBL88326
5.23	IC50	5940	nM	CHEMBL1370375
5.22	IC50	6051	nM	CHEMBL1302170
5.21	IC50	6217	nM	CHEMBL1603065
5.21	IC50	6228	nM	CHEMBL1334149
5.20	IC50	6359	nM	CHEMBL1478085
5.20	IC50	6305	nM	CHEMBL1351935
5.19	IC50	6448	nM	CHEMBL1380232
5.17	IC50	6694	nM	CHEMBL1545384
5.15	IC50	7099	nM	CHEMBL1411702
5.14	IC50	7292	nM	CHEMBL1548333
5.12	IC50	7654	nM	CHEMBL1351543

PubChem BioAssay actives

1 with measured affinity, of 12 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149023: Binding affinity to human PLEC incubated for 45 mins by Kinobead based pull down assay	kd	0.0110	uM

CTD chemical–gene interactions

91 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, decreases expression, increases abundance, affects expression, increases expression	5
bisphenol A	increases expression, decreases expression, affects expression, affects cotreatment, increases methylation	4
Tobacco Smoke Pollution	affects expression, decreases expression, decreases methylation, increases expression	4
Cadmium Chloride	decreases expression, increases abundance, increases expression	4
Particulate Matter	decreases expression, increases abundance, increases expression, affects cotreatment	4
sodium arsenite	affects binding, increases reaction, decreases expression, increases abundance, increases expression	3
Arsenic	affects methylation, increases expression, decreases expression, increases abundance	3
Benzo(a)pyrene	increases methylation, affects cotreatment, increases expression, decreases expression	3
Estradiol	affects expression, decreases expression	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
titanium dioxide	decreases expression, decreases methylation	2
Zoledronic Acid	decreases expression	2
Caffeine	affects phosphorylation, decreases expression	2
Cisplatin	affects expression, decreases expression	2
Doxorubicin	affects expression, decreases expression	2
Ozone	affects cotreatment, decreases expression, increases abundance, affects expression	2
Progesterone	decreases expression	2
Quercetin	increases expression, increases phosphorylation	2
Smoke	affects expression, increases abundance, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	decreases methylation, increases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
chloroacetaldehyde	affects expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
lead acetate	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, increases expression	1
beta-lapachone	decreases expression	1

ChEMBL screening assays

12 unique, capped per target: 12 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1614066	Binding	PUBCHEM_BIOASSAY: HTS fluorescence polarization-based dose response confirmatory screen for the Siah-1 primary assay utilizing an alternative fluorophore, fluorescein-labeled plectin. (Class of assay: confirmatory) [Related pubchem assays (	PubChem BioAssay data set

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1661	ZR-75-30	Cancer cell line	Female
CVCL_A4GM	U2OS PLEC KO	Cancer cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 410 trials:

NCT	Phase	Status	Title
NCT01373918	Phase 4	TERMINATED	Low Dose Fat for the Prevention of Liver Disease in Babies With Gastrointestinal Disorders
NCT01585935	Phase 4	COMPLETED	Preventing Cholestasis Using SMOFLipid®
NCT01998620	Phase 4	UNKNOWN	Efficacy and Safety of S-adenosyl-L-methionine in Treatment of Chronic Hepatitis B Patients With Cholestasis
NCT07290257	Phase 4	RECRUITING	Long-Term Low-Intervention SafEty and Clinical Outcomes Clinical Study of LivmArli® in Patients With Alagille Syndrome or Progressive Familial Intrahepatic Cholestasis in the European Union (LEAP-EU)
NCT00120055	Phase 4	COMPLETED	Association Between Systemic Exposure of Atorvastatin and Metabolites and Atorvastatin-induced Myotoxicity
NCT03633565	Phase 4	UNKNOWN	Comparative Study of Strategies for Management of Duchenne Myopathy (DM)
NCT00037102	Phase 4	COMPLETED	Combination Therapy With Avonex and BiMonthly High Dose Intravenous Methotrexate in Multiple Sclerosis
NCT00037115	Phase 4	WITHDRAWN	Induction Therapy With a Single High Dose Bolus of Intravenous Methotrexate With Leucovorin Rescue, Prior to Initiation of AVONEX® Treatment, in Patients Presenting With a First Acute Demyelinating Event.
NCT00146068	Phase 4	COMPLETED	EARLY IFNB-1a and Simvastatin Combination Therapy in Clinically Isolated Syndrome Suggestive of Multiple Sclerosis
NCT00151294	Phase 4	TERMINATED	The Efficacy and Safety of Escitalopram for Depression in Multiple Sclerosis
NCT00176592	Phase 4	COMPLETED	Phase IV Study, Betaseron Versus Copaxone for Relapsing Remitting or CIS Forms of MS Using Triple Dose Gad 3 T MRI
NCT00179478	Phase 4	COMPLETED	Long Term Study of Avonex Therapy Following a First Attack of Multiple Sclerosis
NCT00220922	Phase 4	COMPLETED	A Study to Evaluate the Impact on Skin (Injection Site) Reactions of Using Alcohol Wipes Prior to Daily Injections of Copaxone®.
NCT00239993	Phase 4	COMPLETED	A Study to Evaluate the Impact of Using Warm Compress Prior to Daily Injections of Copaxone®
NCT00240006	Phase 4	COMPLETED	A Study Comparing Shared Solutions® Plus MS Center Support Versus Shared Solutions® Alone
NCT00240032	Phase 4	COMPLETED	A Study to Evaluate the Impact on Skin (Injection Site) Reactions of Taking an Antihistamine (Zyrtec®) or Placebo Prior to Daily Injections of Copaxone®.
NCT00246324	Phase 4	COMPLETED	Safety and Efficacy Study of Doxycycline in Combination With Interferon-B-1a to Treat Multiple Sclerosis
NCT00267319	Phase 4	COMPLETED	FOCUS Fatigue Outcome in Copaxone USers
NCT00381264	Phase 4	COMPLETED	Evaluation of the Efficacy of Cesamet™ for the Treatment of Pain in Patients With Multiple Sclerosis
NCT00414453	Phase 4	TERMINATED	Trial of Analgesia With Lidocaine or Extended-release Oxycodone for Neuropathic Pain Treatment in Multiple Sclerosis
NCT00423527	Phase 4	COMPLETED	Levetiracetam in Central Pain in Multiple Sclerosis(MS)
NCT00480181	Phase 4	COMPLETED	Efficacy and Safety Evaluation of Nabilone as Adjunctive Therapy to Gabapentin for the Management of Neuropathic Pain in Multiple Sclerosis
NCT00492765	Phase 4	COMPLETED	Simvastatin as an Add-on Treatment to Interferon-beta-1a for the Treatment of Relapsing-Remitting Multiple Sclerosis
NCT00493077	Phase 4	COMPLETED	Safety of Avonex Treatment in Multiple Sclerosis Patients With Neutralizing Antibodies to Interferon Beta Therapy
NCT00536120	Phase 4	COMPLETED	The Effects of Tysabri Treatment on Vaccination Response and Lymphocyte Subsets in Subjects With Relapsing Forms of Multiple Sclerosis
NCT00629642	Phase 4	COMPLETED	Clinical Study of Solifenacin Succinate in Patients With Bladder Symptoms Due to Spinal Cord Injury or Multiple Sclerosis
NCT00638027	Phase 4	COMPLETED	Memantine for Spasticity in MS Patients
NCT00744679	Phase 4	COMPLETED	A Pharmacokinetic (PK) Study of Natalizumab (Tysabri) at Steady State
NCT00752778	Phase 4	TERMINATED	Magnetic Resonance Imaging (MRI) Follow-up of Macrophagic Infiltration in MS Patients Treated With Tysabri
NCT00753792	Phase 4	COMPLETED	Oral Corticotherapy in Megadoses to Treat Multiple Sclerosis During Relapse
NCT00854750	Phase 4	TERMINATED	Modeling and Treating the Pathophysiology of Demyelination in Multiple Sclerosis
NCT00881205	Phase 4	TERMINATED	Rivastigmine in Multiple Sclerosis Patients With Cognitive Impairment
NCT00910598	Phase 4	UNKNOWN	Optical Coherence Tomography: Glatiramer in Clinically Isolated Syndrome or Early Relapsing Remitting Multiple Sclerosis (MS)
NCT00913666	Phase 4	COMPLETED	Pharmacodynamic Study to Better Understand the Therapeutic Response and Immunomodulatory Effects of Avonex in Multiple Sclerosis (MS) Patients and Healthy Volunteers
NCT00915460	Phase 4	COMPLETED	Open-Label Safety Extension Study of Avonex
NCT00942214	Phase 4	COMPLETED	Biomarkers and Response to Natalizumab for Multiple Sclerosis Treatment
NCT00988988	Phase 4	WITHDRAWN	The Effects of Ethyl-Alpha-Guanido-Methyl Ethanoate on Skin Reactions From Glatiramer Acetate Injections
NCT01005095	Phase 4	TERMINATED	The Effects of Interferon Beta Combined With Vitamin D on Relapsing Remitting Multiple Sclerosis Patients
NCT01034579	Phase 4	COMPLETED	The REbif® vs Glatiramer Acetate in Relapsing Multiple Sclerosis Pharmacogenetics Trial
NCT01085318	Phase 4	COMPLETED	Rebif Advanced Magnetic Resonance Imaging (MRI) and Immunology Pilot Trial
NCT01236534	Phase 4	COMPLETED	Lubiprostone in Patients With Multiple Sclerosis Associated Constipation
NCT01333501	Phase 4	COMPLETED	Fingolimod Versus Interferon Beta 1b in Cognitive Symptoms
NCT01339676	Phase 4	UNKNOWN	Colecalciferol as an Add-on Treatment to Interferon-beta-1b for Treatment of Multiple Sclerosis (MS)
NCT01356940	Phase 4	COMPLETED	A Placebo Controlled Trial of Dalfampridine ER for Ambulatory Activity in People With Multiple Sclerosis
NCT01395316	Phase 4	COMPLETED	Alemtuzumab on Surrogate Markers of Disease Activity and Repair Using Advanced MRI Measures in Subjects With Relapsing Remitting Multiple Sclerosis
NCT01411514	Phase 4	TERMINATED	Oral Prednisone Taper Versus Placebo for the Treatment of Acute Relapses in Multiple Sclerosis
NCT01454791	Phase 4	COMPLETED	Diclofenac Sodium Topical Gel to Reduce Injection Site Discomfort in Patients Taking Glatiramer Acetate
NCT01480076	Phase 4	COMPLETED	Open-Label Study to Assess the Effect of Long-Term Prolonged-Release Fampridine (BIIB041) on Quality of Life as Reported by Participants With Multiple Sclerosis
NCT01556685	Phase 4	COMPLETED	MATRIX: Measuring Neutralizing Antibodies in the Patients Treated With Interferon Beta 1a IM, in Mexico and Colombia
NCT01578330	Phase 4	COMPLETED	A 12 -Month, Open-label, Multi-center Study to Explore the Health Outcomes of FTY720
NCT01585298	Phase 4	COMPLETED	STudy to vAlidate telemetRic ECG Systems for firsT Dose Administration of Fingolimod (START)
NCT01621269	Phase 4	WITHDRAWN	ENGYNE Exploring Gilenya in Patients With Neutralizing Antibodies Against Interferon
NCT01656148	Phase 4	COMPLETED	FAME - Fampyra Outcome Measures Study: a Study of Different Outcome Measures on the Effect of Fampyra
NCT01767493	Phase 4	COMPLETED	Study to Evaluate the Feasibility of [18F]Florbetapir PET for Assessment in MS Patients
NCT01791244	Phase 4	COMPLETED	A Phase 4 Study to Assess the Impact of Patient Support Program on Health Related Quality of Life and Adherence in Subjects With Relapsing-Remitting Multiple Sclerosis Administered Rebif® With the RebiSmart™ Device
NCT01795872	Phase 4	COMPLETED	Follow-up Study After 11 Years of Patients Who Were Included in the BENEFIT Trial (304747) With a First Demyelinating Event Suggestive of Multiple Sclerosis
NCT01834586	Phase 4	COMPLETED	Anesthetic Topical Adhesive (Synera™) to Reduce Injection Pain With Subcutaneous Multiple Sclerosis Medications
NCT01838174	Phase 4	TERMINATED	A Trial of Neuroprotection With ACTH in Acute Optic Neuritis
NCT01888354	Phase 4	COMPLETED	Pilot Clinical Trial of ACTHar Gel 14 Days Subcutaneous (SQ)Versus ACTHar Gel Five Days SQ for the Treatment of MS Exacerbations
NCT01895335	Phase 4	COMPLETED	Using Patient Reported Outcomes (PROs) to Evaluate Teriflunomide Treatment in Relapsing Multiple Sclerosis (RMS) Patients

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PLEC across ~30M SureChEMBL compounds — explore on Sugi Predict.