FXYD1 (Phospholemman)
Regulator of Na+/K+-ATPase and Cardiac Excitability
Gene Information Card
| Symbol | FXYD1 |
|---|---|
| Full Name | FXYD domain containing ion transport regulator 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.12 |
| NCBI Gene ID | 5348 ncbi.nlm.nih.gov/gene/5348 |
| Ensembl ID | ENSG00000130226 |
| UniProt ID | O00168 |
| OMIM ID | 602257 |
| HGNC ID | 4026 |
| Aliases | PLM, phospholemman |
Description
FXYD1 encodes phospholemman (PLM), a small transmembrane protein that belongs to the FXYD family of ion transport regulators. PLM is a major substrate for protein kinase A and protein kinase C in the heart and modulates the activity of the Na+/K+-ATPase (sodium-potassium pump). It plays a critical role in cardiac contractility, ion homeostasis, and cellular excitability. FXYD1 is highly expressed in cardiac and skeletal muscle, with lower levels in other tissues.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Dilated cardiomyopathy (DCM) | Altered Na+/K+-ATPase regulation due to FXYD1 mutations or dysregulation leads to impaired cardiac ion homeostasis and contractile dysfunction. | ClinVar, OMIM |
| Heart failure | Reduced FXYD1 expression or phosphorylation disrupts Na+/K+-ATPase activity, contributing to arrhythmias and pump failure. | NCBI Gene, PubMed |
| Atrial fibrillation | Dysregulation of FXYD1-mediated ion transport may predispose to atrial electrical instability. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 58.2 | High |
| Skeletal muscle | 42.1 | High |
| Brain | 6.3 | Low |
| Kidney | 4.8 | Low |
| Liver | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes (AC16) | 62.5 | High expression |
| Skeletal muscle myoblasts (HSMM) | 45.0 | High expression |
| HEK293 | 2.1 | Low expression |
| HeLa | 1.5 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.161G>A (p.Arg54His) | Missense | Rare | Alters PLM phosphorylation site, reduces Na+/K+-ATPase regulation |
| c.205C>T (p.Arg69Cys) | Missense | Rare | Impairs PLM interaction with Na+/K+-ATPase |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Loss of protein expression |
Mutation functional classification
Loss of Function (LOF)
p.Met1Val leads to complete loss of PLM protein.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
p.Arg54His may act dominant negative by disrupting normal PLM function.
View complete mutation data：
Gene Ontology (GO)
| • sodium:potassium-exchanging ATPase activity (GO:0005391) | • sodium channel regulator activity (GO:0017080) |
| • plasma membrane (GO:0005886) | • T-tubule (GO:0030315) |
| • calmodulin binding (GO:0005516) |
Pathways
• Na+/K+-ATPase regulation (Reactome: R-HSA-936837)
• Cardiac conduction (Reactome: R-HSA-5576891)
• Ion transport by P-type ATPases (Reactome: R-HSA-936837)
Protein Summary
Phospholemman (PLM) is a 92-amino acid single-pass transmembrane protein with an extracellular FXYD motif. It is predominantly expressed in cardiac and skeletal muscle, where it associates with the Na+/K+-ATPase alpha subunit to modulate pump activity. Phosphorylation by PKA and PKC at Ser68 and Ser63 relieves inhibition, increasing pump turnover. PLM also interacts with ion channels and contributes to action potential regulation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FXYD1 Knockout HEK293 Cell Line | EDJ-KQ1826 | Human | 5348 | Details Get a Quote |
| FXYD1 Knockout HCT 116 Cell Line | EDJ-KQ21677 | Human | 5348 | Details Get a Quote |
| FXYD1 Knockout HeLa Cell Line | EDJ-KQ54157 | Human | 5348 | Details Get a Quote |
| FXYD1 Knockout A-549 Cell Line | EDJ-KQ62652 | Human | 5348 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
