LMO7

Chr 13

LIM domain 7

Also known as: FBX20, FBXO20, LMO7b, LOMP

NCBI Gene: 4008 ENSG00000136153 UniProt: Q8WWI1 OMIM: 604362

The LMO7 protein contains calponin homology, PDZ, and LIM domains that mediate protein-protein interactions. Mutations cause autosomal dominant Emery-Dreifuss muscular dystrophy and dilated cardiomyopathy, affecting both skeletal and cardiac muscle. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

OMIM ResearchSummary from RefSeq

This gene encodes a protein containing a calponin homology (CH) domain, a PDZ domain, and a LIM domain, and may be involved in protein-protein interactions. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene, however, the full-length nature of some variants is not known. [provided by RefSeq, Jan 2009]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.41

Clinical Summary— LMO7

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.

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ClinVar Variants

242 VUS of 334 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?

0.41LOEUF

pLI 0.000

Z-score 5.76

OE 0.29 (0.20–0.41)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

-0.17Z-score

OE missense 1.02 (0.96–1.08)

752 obs / 739.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.29 (0.20–0.41)

0≤0.351.4

Missense OE?1.02 (0.96–1.08)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 22 / 76.3Missense obs/exp: 752 / 739.1Syn Z: -0.32

This gene — mechanism propensity

0.6842th %ile

GOF

0.6443th %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

334 submitted variants in ClinVar

ClinVar

Classification Summary

VUS242

Likely Benign29

Benign5

Conflicting1

242

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	240	1	0	242
Likely Benign	0	21	3	5	29
Benign	0	2	1	2	5
Conflicting	—				1
Total	1	263	5	7	277

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

View in ClinVar →

69 pathogenic / likely-pathogenic (of 78) ClinVar copy-number / structural variants overlap LMO7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →