PLN

Chr 6

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCardiomyopathy, dilated, 1P
UniProtCardiomyopathy, familial hypertrophic, 18

Clinical highlights

Gene-disease validity (ClinGen)
arrhythmogenic right ventricular cardiomyopathy · ADModerateconsider for supplementary testing2 gene-disease associations curated in total
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
209
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
1.56
LOEUF
Multiple*
Mechanism· predicted
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
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?
0.62Z-score
OE missense 0.67 (0.47–0.98)
19 obs / 28.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.00 (0.00–1.56)
0≤0.351.4
Missense OE?0.67 (0.47–0.98)
0≤0.61.4
Synonymous OE?0.53
0≤1.21.6
LoF obs/exp: 0 / 1.5Missense obs/exp: 19 / 28.4Syn Z: 1.14

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients