LMO7

Chr 13

LIM domain 7

Also known as: FBX20, FBXO20, LMO7b, LOMP

NCBI Gene: 4008 ENSG00000136153 UniProt: Q8WWI1

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.

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]

ResearchGenerating clinical summary…

Clinical highlights

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.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.41

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

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

Background carrier burden — how many people carry a rare variant somewhere in LMO7?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 20

2,352 rare PASS variants

Rare truncating (LoF)

1 in 240

345 rare PASS variants

Rare synonymous (reference)

1 in 55

828 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LMO7. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 29	1 in 180
South Asian	~43k	1 in 23	1 in 200
Remaining (unassigned)	~30k	1 in 18	1 in 200
European (Finnish)	~27k	1 in 71	1 in 730
Admixed American	~22k	1 in 21	1 in 240
African / African American	~21k	1 in 23	1 in 310
East Asian	~20k	1 in 26	1 in 350
Ashkenazi Jewish	~13k	1 in 160	1 in 700
Middle Eastern	~2,884	1 in 20	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 20 of 31 coding exons well covered in gnomAD exomes; exons 2, 3, 5, 6, 16 and 6 more marginal. Genomes: all 31.? see exons ↓