PLN (Phospholamban) Gene
Key regulator of cardiac calcium homeostasis and sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) activity
Gene Information Card
| Symbol | PLN |
|---|---|
| Full Name | Phospholamban |
| Gene Type | Protein coding |
| Chromosomal Location | 6q22.31 |
| NCBI Gene ID | 5350 ncbi.nlm.nih.gov/gene/5350 |
| Ensembl ID | ENSG00000198576 |
| UniProt ID | P26678 |
| OMIM ID | 172405 |
| HGNC ID | 9080 |
| Aliases | PLB, CMD1P, CMH18 |
Description
The PLN gene encodes phospholamban, a 52-amino acid transmembrane protein that regulates the activity of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a) in cardiac muscle. Phospholamban inhibits SERCA2a under basal conditions; phosphorylation by protein kinase A or Ca2+/calmodulin-dependent protein kinase relieves this inhibition, enhancing calcium uptake into the sarcoplasmic reticulum and promoting cardiac relaxation. Mutations in PLN are associated with dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Dilated Cardiomyopathy 1P (CMD1P) | Loss-of-function or dominant-negative mutations impair SERCA regulation, leading to calcium handling defects and contractile dysfunction. | OMIM #609909; ClinVar |
| Hypertrophic Cardiomyopathy 18 (CMH18) | Gain-of-function or altered phosphorylation sites disrupt calcium cycling, promoting hypertrophy. | OMIM #613874; ClinVar |
| Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) | PLN mutations (e.g., p.Arg14del) cause mislocalization and altered calcium homeostasis, contributing to fibrofatty replacement. | ClinVar; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 1234.5 | High |
| Skeletal Muscle | 56.7 | Low |
| Brain | 12.3 | Not detected |
| Liver | 5.6 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes (iPSC-derived) | 1500.0 | High expression |
| HEK293 | 2.1 | Very low |
| HeLa | 1.0 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.40_42delAGA (p.Arg14del) | Deletion | Founder mutation in Europe; ~0.5% in general population | Dominant-negative; causes ARVC and DCM |
| c.25C>T (p.Arg9Cys) | Missense | Rare | Loss of function; associated with DCM |
| c.116A>G (p.Asn39Ser) | Missense | Rare | Gain of function; associated with HCM |
Mutation functional classification
Loss of Function (LOF)
p.Arg9Cys reduces SERCA inhibition, impairing calcium reuptake and contractility.
Gain of Function (GOF)
p.Asn39Ser enhances SERCA inhibition, leading to increased calcium transient amplitude and hypertrophy.
Dominant Negative (DN)
p.Arg14del produces a truncated protein that disrupts wild-type phospholamban function, causing severe cardiomyopathy.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Adrenergic signaling in cardiomyocytes (KEGG: hsa04261)
• Calcium signaling pathway (KEGG: hsa04020)
• cGMP-PKG signaling pathway (KEGG: hsa04022)
Protein Summary
Phospholamban is a small transmembrane protein (52 aa) predominantly expressed in cardiac muscle. It exists as a pentamer and interacts with SERCA2a to regulate calcium uptake into the sarcoplasmic reticulum. Phosphorylation at Ser16 (PKA) and Thr17 (CaMKII) relieves its inhibitory effect, playing a critical role in the cardiac relaxation phase (lusitropy). Mutations in PLN disrupt calcium homeostasis, leading to various cardiomyopathies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PLN Knockout HEK293 Cell Line | EDJ-KQ1561 | Human | 5350 | Details Get a Quote |
| PLN Knockout HeLa Cell Line | EDJ-KQ54159 | Human | 5350 | Details Get a Quote |
| PLN Knockout A-549 Cell Line | EDJ-KQ62654 | Human | 5350 | Details Get a Quote |
| PLN Knockout HCT 116 Cell Line | EDJ-KQ71121 | Human | 5350 | Details Get a Quote |
