LMO4

Chr 1

LIM domain only 4

NCBI Gene: 8543 ENSG00000143013 UniProt: P61968

LMO4 encodes a transcription cofactor that contains two LIM domains and functions in establishing motor neuron identity by disrupting LDB1-LHX3 complexes to negatively regulate interneuron genes in motor neurons. Mutations cause autosomal dominant developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, seizures, and motor dysfunction. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.595), consistent with its essential role in neurodevelopment.

ResearchSummary from RefSeq, UniProt

This gene encodes a cysteine-rich protein that contains two LIM domains but lacks a DNA-binding homeodomain. The encoded protein may play a role as a transcriptional regulator or as an oncogene. [provided by RefSeq, Aug 2008]

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

0.59

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?

0.59LOEUF

pLI 0.677

Z-score 2.29

OE 0.13 (0.04–0.59)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.10Z-score

OE missense 0.42 (0.33–0.54)

43 obs / 103.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.13 (0.04–0.59)

0≤0.351.4

Missense OE?0.42 (0.33–0.54)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 1 / 8.0Missense obs/exp: 43 / 103.0Syn Z: -0.90

Background carrier burden — how many people carry a rare variant somewhere in LMO4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 400

130 rare PASS variants

Rare truncating (LoF)

1 in 120,000

5 rare PASS variants

Rare synonymous (reference)

1 in 580

104 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LMO4. 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 1,300	≈ 1 in 190,000
South Asian	~43k	1 in 1,100	none seen
Remaining (unassigned)	~30k	1 in 430	none seen
European (Finnish)	~27k	1 in 920	≈ 1 in 27,000
Admixed American	~22k	1 in 480	none seen
African / African American	~21k	1 in 760	≈ 1 in 8,200
East Asian	~20k	1 in 1,200	none seen
Ashkenazi Jewish	~13k	1 in 1,700	none seen
Middle Eastern	~2,884	1 in 480	none seen

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): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓