MYPN

Chr 10ADAR

myopalladin

Also known as: CMD1DD, CMH22, CMYO24, CMYP24, MYOP, NEM11, RCM4

Myopalladin is a sarcomere component that tethers nebulin (in skeletal muscle) and nebulette (in cardiac muscle) to alpha-actinin at the Z-lines. Mutations cause various cardiomyopathies (dilated, restrictive, and hypertrophic) and congenital myopathy, with both autosomal dominant and autosomal recessive inheritance patterns. The gene is highly constrained against loss-of-function variants, indicating that complete loss of function is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/ARLOEUF 0.514 OMIM phenotypes
Clinical SummaryMYPN
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Gene-Disease Validity (ClinGen)
MYPN-related myopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

3 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.51LOEUF
pLI 0.000
Z-score 4.65
OE 0.35 (0.250.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.13Z-score
OE missense 0.99 (0.931.05)
716 obs / 725.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.35 (0.250.51)
00.351.4
Missense OE0.99 (0.931.05)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 21 / 59.8Missense obs/exp: 716 / 725.8Syn Z: -0.80
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedMYPN-related hypertrophic cardiomyopathyOTHERAD
limitedMYPN-related dilated cardiomyopathyOTHERAD
strongMYPN-related childhood-onset, slowly progressive nemaline myopathyLOFAR
DN
0.7034th %ile
GOF
0.6736th %ile
LOF
0.4234th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MYPN · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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