LMOD2

Chr 7AR

leiomodin 2

Also known as: C-LMOD, CLMOD, CMD2G

NCBI Gene: 442721 ENSG00000170807 UniProt: Q6P5Q4 OMIM: 608006

The LMOD2 protein mediates nucleation of actin filaments and promotes actin polymerization, and is required for normal sarcomere organization and heart function. Mutations cause autosomal recessive dilated cardiomyopathy 2G, a form of heart muscle disease where the heart becomes enlarged and weakened. The gene shows tolerance to loss-of-function variants in the general population (pLI 0.0006), consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables actin monomer binding activity and tropomyosin binding activity. Involved in actin nucleation; positive regulation of actin filament polymerization; and sarcomere organization. Located in M band and actin filament. Implicated in dilated cardiomyopathy 2G. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 0.861 OMIM phenotype

Clinical Summary— LMOD2

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Gene-Disease Validity (ClinGen)

cardiomyopathy, dilated, 2G · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

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

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ClinVar Variants

7 unique Pathogenic / Likely Pathogenic· 83 VUS of 101 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.86LOEUF

pLI 0.001

Z-score 2.00

OE 0.48 (0.28–0.86)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.27Z-score

OE missense 0.96 (0.87–1.05)

282 obs / 295.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.48 (0.28–0.86)

0≤0.351.4

Missense OE?0.96 (0.87–1.05)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 8 / 16.8Missense obs/exp: 282 / 295.1Syn Z: 0.12

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveLMOD2-related infantile dilated cardiomyopathyOTHERAR

This gene — mechanism propensity

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

0.7132th %ile

GOF

0.6639th %ile

LOF

0.3259th %ile

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.

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

ClinVar Variant Classifications

101 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic3

VUS83

Likely Benign4

Benign6

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	4	0	0	0	4
Likely Pathogenic	3	0	0	0	3
VUS	0	83	0	0	83
Likely Benign	0	4	0	0	4
Benign	0	0	4	2	6
Total	7	87	4	2	100

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap LMOD2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →