PLN

phospholamban

Basic information

Region (hg38): 6:118548296-118561716

Previous symbols: [ "PLB" ]

Links

ENSG00000198523 ∙ NCBI:5350 ∙ OMIM:172405 ∙ HGNC:9080 ∙ Uniprot:P26678 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypertrophic cardiomyopathy 18 (Strong), mode of inheritance: AD
• dilated cardiomyopathy 1P (Strong), mode of inheritance: AD
• hypertrophic cardiomyopathy 18 (Limited), mode of inheritance: AD
• familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
• dilated cardiomyopathy 1P (Definitive), mode of inheritance: AD
• dilated cardiomyopathy 1P (Strong), mode of inheritance: AD
• hypertrophic cardiomyopathy 18 (Strong), mode of inheritance: AD
• arrhythmogenic right ventricular cardiomyopathy (Moderate), mode of inheritance: AD
• intrinsic cardiomyopathy (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, dilated, 1P; Cardiomyopathy, familial hypertrophic, 18	AD/AR	Cardiovascular	The conditions can involve cardiomyopathy, and surveillance and preventive measures, including medical management, may reduce morbidity and mortality	Cardiovascular	12639993; 12705874; 12610310; 16432188; 17655857; 18241046; 21167350
The severity may depend on inheritance (ie, heterozygosity vs. homozygosity/compound heterozygosity)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLN gene.

• Dilated cardiomyopathy 1P (5 variants)
• Cardiomyopathy (1 variants)
• not provided (1 variants)
• Primary dilated cardiomyopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLN 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				10		10
missense	1		38			39
nonsense		1				1
start loss			1			1
frameshift	4	1	3			8
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding			27	15	13	55
Total	5	2	70	25	13

Variants in PLN

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

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

Position	Type	Phenotype	Significance	ClinVar
6-118548340-G-A		Dilated cardiomyopathy 1P	Benign/Likely benign (Jan 13, 2018)
6-118548348-T-A		Dilated Cardiomyopathy, Dominant • Hypertrophic cardiomyopathy • Dilated cardiomyopathy 1P;Hypertrophic cardiomyopathy 18	Uncertain significance (Aug 27, 2021)
6-118548370-C-T		Dilated cardiomyopathy 1P • Dilated cardiomyopathy 1P;Hypertrophic cardiomyopathy 18	Uncertain significance (Jul 29, 2021)
6-118548407-T-A			Likely benign (Apr 25, 2018)
6-118548409-G-A		not specified	Likely benign (Mar 01, 2016)
6-118558532-T-C			Likely benign (Jun 30, 2018)
6-118558619-G-T			Benign (Aug 13, 2019)
6-118558624-CAT-C			Likely benign (Oct 21, 2019)
6-118558626-TACAC-T			Benign (Aug 21, 2019)
6-118558626-T-TAC			Benign (Aug 10, 2019)
6-118558626-T-TACAC			Benign (Aug 15, 2019)
6-118558626-T-TACACAC			Benign (Nov 14, 2019)
6-118558626-T-TACACACAC			Benign (Aug 21, 2019)
6-118558646-CACACACACACACACAG-C			Benign (Aug 13, 2019)
6-118558656-C-G			Benign (Aug 10, 2019)
6-118558658-C-G			Benign (Aug 10, 2019)
6-118558658-CACAGAG-C			Likely benign (Aug 13, 2019)
6-118558662-G-C			Benign (Aug 18, 2019)
6-118558664-G-C			Benign (Aug 18, 2019)
6-118558666-G-C			Benign (Aug 18, 2019)
6-118558720-A-G			Likely benign (Jun 19, 2018)
6-118558772-T-A			Likely benign (Jun 19, 2018)
6-118558816-A-G			Likely benign (Dec 27, 2019)
6-118558820-T-C		Dilated cardiomyopathy 1P	Uncertain significance (Mar 28, 2024)
6-118558825-G-A			Uncertain significance (Feb 09, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLN	protein_coding	protein_coding	ENST00000357525	1	12433

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.449	0.460	125630	0	3	125633	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.624	19	28.4	0.670	0.00000172	332
Missense in Polyphen		1	1.574	0.63532		30
Synonymous	1.14	5	9.46	0.529	4.80e-7	104
Loss of Function	1.13	0	1.49	0.00	6.47e-8	18

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.000109	0.000109
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Reversibly inhibits the activity of ATP2A2 in cardiac sarcoplasmic reticulum by decreasing the apparent affinity of the ATPase for Ca(2+). Modulates the contractility of the heart muscle in response to physiological stimuli via its effects on ATP2A2. Modulates calcium re-uptake during muscle relaxation and plays an important role in calcium homeostasis in the heart muscle. The degree of ATP2A2 inhibition depends on the oligomeric state of PLN. ATP2A2 inhibition is alleviated by PLN phosphorylation. {ECO:0000269|PubMed:22427649, ECO:0000269|PubMed:22707725}.
• Disease: DISEASE: Cardiomyopathy, dilated 1P (CMD1P) [MIM:609909]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:12610310, ECO:0000269|PubMed:16432188, ECO:0000269|PubMed:22137083, ECO:0000269|PubMed:22427649, ECO:0000269|PubMed:22707725}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, familial hypertrophic 18 (CMH18) [MIM:613874]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. {ECO:0000269|PubMed:12705874}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Dilated cardiomyopathy (DCM) - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Antiarrhythmic Pathway, Pharmacodynamics;Disopyramide Action Pathway;Procainamide (Antiarrhythmic) Action Pathway;Phenytoin (Antiarrhythmic) Action Pathway;Fosphenytoin (Antiarrhythmic) Action Pathway;Bopindolol Action Pathway;Timolol Action Pathway;Carteolol Action Pathway;Bevantolol Action Pathway;Practolol Action Pathway;Dobutamine Action Pathway;Isoprenaline Action Pathway;Arbutamine Action Pathway;Amiodarone Action Pathway;Levobunolol Action Pathway;Metipranolol Action Pathway;Mexiletine Action Pathway;Lidocaine (Antiarrhythmic) Action Pathway;Quinidine Action Pathway;Sotalol Action Pathway;Epinephrine Action Pathway;Betaxolol Action Pathway;Atenolol Action Pathway;Alprenolol Action Pathway;Acebutolol Action Pathway;Muscle/Heart Contraction;Diltiazem Action Pathway;Propranolol Action Pathway;Pindolol Action Pathway;Penbutolol Action Pathway;Oxprenolol Action Pathway;Metoprolol Action Pathway;Esmolol Action Pathway;Bisoprolol Action Pathway;Bupranolol Action Pathway;Nebivolol Action Pathway;Amlodipine Action Pathway;Verapamil Action Pathway;Nitrendipine Action Pathway;Nisoldipine Action Pathway;Nimodipine Action Pathway;Ibutilide Action Pathway;Tocainide Action Pathway;Flecainide Action Pathway;Isradipine Action Pathway;Nifedipine Action Pathway;Felodipine Action Pathway;Nadolol Action Pathway;Carvedilol Action Pathway;Labetalol Action Pathway;Calcium Regulation in the Cardiac Cell;Ion channel transport;Ion homeostasis;Transport of small molecules;actions of nitric oxide in the heart;Cardiac conduction;Muscle contraction;Ion transport by P-type ATPases (Consensus)

Intolerance Scores

• loftool: 0.676
• rvis_EVS: 0.12
• rvis_percentile_EVS: 62.38

Haploinsufficiency Scores

• pHI: 0.604
• hipred: Y
• hipred_score: 0.525
• ghis: 0.463

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Low	Low	Low

Mouse Genome Informatics

• Gene name: Pln
• Phenotype: muscle phenotype; homeostasis/metabolism 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); vision/eye phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: regulation of the force of heart contraction;calcium ion transport;Notch signaling pathway;blood circulation;regulation of heart contraction;response to zinc ion;negative regulation of heart rate;regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion;negative regulation of ATPase activity;response to insulin;response to testosterone;negative regulation of catalytic activity;cardiac muscle tissue development;protein homooligomerization;regulation of cytosolic calcium ion concentration;regulation of calcium ion transport;negative regulation of calcium ion transport;relaxation of cardiac muscle;regulation of ryanodine-sensitive calcium-release channel activity;regulation of cardiac muscle cell contraction;adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process;regulation of cardiac muscle cell membrane potential;regulation of the force of heart contraction by cardiac conduction;negative regulation of calcium ion import;negative regulation of calcium ion transmembrane transporter activity;negative regulation of calcium ion binding;regulation of calcium-transporting ATPase activity;negative regulation of calcium-transporting ATPase activity;regulation of relaxation of cardiac muscle;negative regulation of calcium ion import into sarcoplasmic reticulum
• Cellular component: mitochondrion;endoplasmic reticulum;membrane;mitochondrial membrane;vesicle;sarcoplasmic reticulum membrane;perinuclear region of cytoplasm;calcium ion-transporting ATPase complex
• Molecular function: enzyme inhibitor activity;calcium channel regulator activity;protein binding;ATPase inhibitor activity;identical protein binding;ATPase binding