MYOCD

Chr 17AD

myocardin

Also known as: MGBL, MYCD

NCBI Gene: 93649 ENSG00000141052 UniProt: Q8IZQ8 OMIM: 606127

This gene encodes a transcriptional co-activator of serum response factor that regulates cardiac and smooth muscle-specific gene expression, playing a crucial role in cardiogenesis and smooth muscle cell differentiation. Mutations cause congenital megabladder, a condition affecting urinary bladder development and smooth muscle function. Inheritance is autosomal dominant.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a nuclear protein, which is expressed in heart, aorta, and in smooth muscle cell-containing tissues. It functions as a transcriptional co-activator of serum response factor (SRF) and modulates expression of cardiac and smooth muscle-specific SRF-target genes, and thus may play a crucial role in cardiogenesis and differentiation of the smooth muscle cell lineage. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.391 OMIM phenotype

Clinical Summary— MYOCD

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.

📋

ClinVar Variants

11 unique Pathogenic / Likely Pathogenic· 136 VUS of 211 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.39LOEUF

pLI 0.334

Z-score 4.73

OE 0.23 (0.14–0.39)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.34Z-score

OE missense 0.96 (0.89–1.03)

517 obs / 539.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.23 (0.14–0.39)

0≤0.351.4

Missense OE?0.96 (0.89–1.03)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 10 / 43.8Missense obs/exp: 517 / 539.0Syn Z: -1.28

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongMYOCD-related congenital megabladderLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.5477th %ile

GOF

0.3292th %ile

LOF

0.61top 25%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

DNTogether, these data suggest that MYOCD ÃâExon 11 may participate in modulating SMC phenotype, potentially acting as a dominant-negative repressor of contraction-related genes.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

1.PMID 21792927 ↗

ClinVar Variant Classifications

211 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7

Likely Pathogenic4

VUS136

Likely Benign11

Benign40

Conflicting4

Pathogenic

Likely Pathogenic

136

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	7	0	0	0	7
Likely Pathogenic	3	1	0	0	4
VUS	3	132	0	1	136
Likely Benign	0	6	1	4	11
Benign	0	8	26	6	40
Conflicting	—				4
Total	13	147	27	11	202

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap MYOCD — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →