PLN phospholamban [Homo sapiens (human)] - Gene

Summary

Official Symbol: PLNprovided by HGNC
Official Full Name: phospholambanprovided by HGNC
Primary source: HGNC:HGNC:9080
See related: Ensembl:ENSG00000198523 MIM:172405; AllianceGenome:HGNC:9080
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PLB; CMD1P; CMH18
Summary: The protein encoded by this gene is found as a pentamer and is a major substrate for the cAMP-dependent protein kinase in cardiac muscle. The encoded protein is an inhibitor of cardiac muscle sarcoplasmic reticulum Ca(2+)-ATPase in the unphosphorylated state, but inhibition is relieved upon phosphorylation of the protein. The subsequent activation of the Ca(2+) pump leads to enhanced muscle relaxation rates, thereby contributing to the inotropic response elicited in heart by beta-agonists. The encoded protein is a key regulator of cardiac diastolic function. Mutations in this gene are a cause of inherited human dilated cardiomyopathy with refractory congestive heart failure, and also familial hypertrophic cardiomyopathy. [provided by RefSeq, Apr 2016]
Expression: Biased expression in heart (RPKM 615.2), gall bladder (RPKM 62.5) and 1 other tissue See more
Orthologs: mouse all
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Genomic context

Location:: 6q22.31

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (118548296..118561716)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (119733450..119746868)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (118869459..118882879)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Missense variants in phospholamban and cardiac myosin binding protein identified in patients with a family history and clinical diagnosis of dilated cardiomyopathy.
Title: Missense variants in phospholamban and cardiac myosin binding protein identified in patients with a family history and clinical diagnosis of dilated cardiomyopathy.
Phenotypic and Genetic Factors Associated with Absence of Cardiomyopathy Symptoms in PLN:c.40_42delAGA Carriers.
Title: Phenotypic and Genetic Factors Associated with Absence of Cardiomyopathy Symptoms in PLN:c.40_42delAGA Carriers.
Generation of two induced pluripotent stem cell lines carrying the phospholamban R14del mutation for modeling ARVD/C.
Title: Generation of two induced pluripotent stem cell lines carrying the phospholamban R14del mutation for modeling ARVD/C.
Inhibitory and stimulatory micropeptides preferentially bind to different conformations of the cardiac calcium pump.
Title: Inhibitory and stimulatory micropeptides preferentially bind to different conformations of the cardiac calcium pump.
Aberrant PLN-R14del Protein Interactions Intensify SERCA2a Inhibition, Driving Impaired Ca(2+) Handling and Arrhythmogenesis.
Title: Aberrant PLN-R14del Protein Interactions Intensify SERCA2a Inhibition, Driving Impaired Ca(2+) Handling and Arrhythmogenesis.
When is an obscurin variant pathogenic? The impact of Arg4344Gln and Arg4444Trp variants on protein-protein interactions and protein stability.
Title: When is an obscurin variant pathogenic? The impact of Arg4344Gln and Arg4444Trp variants on protein-protein interactions and protein stability.
Molecular noise filtering in the beta-adrenergic signaling network by phospholamban pentamers.
Title: Molecular noise filtering in the β-adrenergic signaling network by phospholamban pentamers.
An mRNA assay system demonstrates proteasomal-specific degradation contributes to cardiomyopathic phospholamban null mutation.
Title: An mRNA assay system demonstrates proteasomal-specific degradation contributes to cardiomyopathic phospholamban null mutation.
Istaroxime treatment ameliorates calcium dysregulation in a zebrafish model of phospholamban R14del cardiomyopathy.
Title: Istaroxime treatment ameliorates calcium dysregulation in a zebrafish model of phospholamban R14del cardiomyopathy.
Characterization of the PLN p.Arg14del Mutation in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.
Title: Characterization of the PLN p.Arg14del Mutation in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Submit: New GeneRIF Correction See all GeneRIFs (95)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Dilated cardiomyopathy 1P MedGen: C1835928 OMIM: 609909 GeneReviews: Dilated Cardiomyopathy Overview	not available
Hypertrophic cardiomyopathy 18 MedGen: C3151265 OMIM: 613874 GeneReviews: Hypertrophic Cardiomyopathy Overview	not available
Primary dilated cardiomyopathy MedGen: C0007193 GeneReviews: Dilated Cardiomyopathy Overview	not available

EBI GWAS Catalog

Description
Common genetic variation near the phospholamban gene is associated with cardiac repolarisation: meta-analysis of three genome-wide association studies. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common variants at ten loci influence QT interval duration in the QTGEN Study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common variants at ten loci modulate the QT interval duration in the QTSCD Study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data. EBI GWAS Catalog EBI GWAS CatalogPubMed
Impact of ancestry and common genetic variants on QT interval in African Americans. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D12S1940 (e-PCR)
- UniSTS:14873

D6S1147E (e-PCR)
- UniSTS:151090

SHGC-107437 (e-PCR)
- UniSTS:170338

D6S1145E (e-PCR)
- UniSTS:56543

SHGC-77838 (e-PCR)
- UniSTS:95972

RH44514 (e-PCR)
- UniSTS:29435

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATPase binding	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables ATPase inhibitor activity	IBA Inferred from Biological aspect of Ancestor more info
enables ATPase inhibitor activity	IDA Inferred from Direct Assay more info	PubMed
enables ATPase inhibitor activity	ISS Inferred from Sequence or Structural Similarity more info
enables enzyme inhibitor activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables identical protein binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in Notch signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in acrosome assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process	IEA Inferred from Electronic Annotation more info
involved_in blood circulation	NAS Non-traceable Author Statement more info	PubMed
involved_in cardiac muscle tissue development	IEA Inferred from Electronic Annotation more info
involved_in circadian sleep/wake cycle, sleep	ISS Inferred from Sequence or Structural Similarity more info
involved_in intracellular calcium ion homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in locomotor rhythm	ISS Inferred from Sequence or Structural Similarity more info
involved_in muscle cell cellular homeostasis	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of ATP-dependent activity	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of ATP-dependent activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of ATPase-coupled calcium transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of calcium ion binding	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of calcium ion binding	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in negative regulation of calcium ion import	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in negative regulation of calcium ion import into sarcoplasmic reticulum	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of calcium ion import into sarcoplasmic reticulum	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of calcium ion transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of calcium ion transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in negative regulation of calcium ion transport	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of catalytic activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in negative regulation of heart rate	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of heart rate	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of ATPase-coupled calcium transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of calcium ion transport	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of calcium ion transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of cardiac muscle cell contraction	IC Inferred by Curator more info	PubMed
involved_in regulation of cardiac muscle cell membrane potential	IC Inferred by Curator more info	PubMed
involved_in regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	IEA Inferred from Electronic Annotation more info
involved_in regulation of cytosolic calcium ion concentration	IC Inferred by Curator more info	PubMed
involved_in regulation of heart contraction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of relaxation of cardiac muscle	IC Inferred by Curator more info	PubMed
involved_in regulation of the force of heart contraction	IC Inferred by Curator more info	PubMed
involved_in regulation of the force of heart contraction by cardiac conduction	IEA Inferred from Electronic Annotation more info
involved_in relaxation of cardiac muscle	TAS Traceable Author Statement more info	PubMed
involved_in visual learning	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
part_of calcium ion-transporting ATPase complex	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	ISS Inferred from Sequence or Structural Similarity more info
located_in endoplasmic reticulum membrane	ISS Inferred from Sequence or Structural Similarity more info
is_active_in membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial membrane	IEA Inferred from Electronic Annotation more info
located_in mitochondrion	HDA more info	PubMed
located_in perinuclear region of cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
is_active_in sarcoplasmic reticulum	IBA Inferred from Biological aspect of Ancestor more info
located_in sarcoplasmic reticulum membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in sarcoplasmic reticulum membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: phospholamban

Names: cardiac phospholamban

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.