PLN

Chr 6AD

phospholamban

Also known as: CMD1P, CMH18, PLB

NCBI Gene: 5350ENSG00000198523UniProt: P26678

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]

Primary Disease Associations & Inheritance

Cardiomyopathy, dilated, 1PMIM #609909
Cardiomyopathy, hypertrophic, 18MIM #613874
AD
UniProtCardiomyopathy, familial hypertrophic, 18
208
ClinVar variants
41
Pathogenic / LP
0.45
pLI score
2
Active trials
Clinical Summary— PLN
🧬
Gene-Disease Validity (ClinGen)
arrhythmogenic right ventricular cardiomyopathy · ADModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.
📋
ClinVar Variants
41 Pathogenic / Likely Pathogenic· 111 VUS of 208 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.56LOEUF
pLI 0.449
Z-score 1.13
OE 0.00 (0.00–1.56)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.62Z-score
OE missense 0.67 (0.47–0.98)
19 obs / 28.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–1.56)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.67 (0.47–0.98)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.53
0≤1.21.6
LoF obs/exp: 0 / 1.5Missense obs/exp: 19 / 28.4Syn Z: 1.14

ClinVar Variant Classifications

208 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic8
VUS111
Likely Benign31
Benign15
Conflicting10
33
Pathogenic
8
Likely Pathogenic
111
VUS
31
Likely Benign
15
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
2
27
0
33
Likely Pathogenic
1
1
6
0
8
VUS
8
44
59
0
111
Likely Benign
0
1
15
15
31
Benign
0
0
15
0
15
Conflicting
—10
Total134812215208

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PLN · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

PLN-related intrinsic cardiomyopathy

definitive
ADUndeterminedAltered Gene Product Structure, Decreased Gene Product Level
Cardiac
G2P ↗
frameshift variantstop gainedmissense variantinframe deletion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
PHOSPHOLAMBAN; PLN
MIM #172405 · *

Cardiomyopathy, dilated, 1P

MIM #609909

Molecular basis of disorder known

Cardiomyopathy, hypertrophic, 18

MIM #613874

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — PLN
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Reevaluating the Genetic Contribution of Monogenic Dilated Cardiomyopathy.
Mazzarotto F et al.·Circulation
2020
Evidence-Based Assessment of Genes in Dilated Cardiomyopathy.
Jordan E et al.·Circulation
2021
Minor hypertrophic cardiomyopathy genes, major insights into the genetics of cardiomyopathies.
Walsh R et al.·Nat Rev Cardiol
2022Review
Bexotegrast in Patients with Idiopathic Pulmonary Fibrosis: The INTEGRIS-IPF Clinical Trial.
Lancaster L et al.·Am J Respir Crit Care Med
2024Clinical trial
Dilated cardiomyopathy in the era of precision medicine: latest concepts and developments.
Orphanou N et al.·Heart Fail Rev
2022Review
Excessive autophagic degradation of MYLK3 causes sunitinib-induced cardiotoxicity.
Pan Z et al.·Autophagy
2025
Additional value of screening for minor genes and copy number variants in hypertrophic cardiomyopathy.
Mademont-Soler I et al.·PLoS One
2017
Serine biosynthesis as a novel therapeutic target for dilated cardiomyopathy.
Perea-Gil I et al.·Eur Heart J
2022
The SERCA-PLN-DWORF axis in cardiometabolic disease: mechanisms and therapeutic perspectives.
Kim OH et al.·Cardiovasc Diabetol
2025Review
DWORF Extends Life Span in a PLN-R14del Cardiomyopathy Mouse Model by Reducing Abnormal Sarcoplasmic Reticulum Clusters.
Stege NM et al.·Circ Res
2023Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Congestive Heart FailureHeart FailureHeart Disease, Ischemic

AB-1002 in Patients With Class III Heart Failure

ACTIVE NOT RECRUITING
NCT04179643Phase PHASE1AskBio IncStarted 2019-11-20
3 x 10e13vg AB-1002
Arrhythmogenic Cardiomyopathies

Tissue and Metabolic Characterization of Arrhythmogenic Cardiomyopathies by Hybrid PET-MRI Imaging, Impact of the Observed Profiles on the Phenotype and on the Evolution of Cardiomyopathy

RECRUITING
NCT05450783Nantes University HospitalStarted 2022-09-01
Biocollection

External Resources

Links to major genomics databases and tools