LMO2

Chr 11

LIM domain only 2

Also known as: LMO-2, RBTN2, RBTNL1, RHOM2, TTG2

NCBI Gene: 4005 ENSG00000135363 UniProt: P25791

LMO2 encodes a cysteine-rich LIM domain protein that acts with TAL1/SCL to regulate red blood cell development and maintains erythroid precursors in an immature state. Mutations cause acute T-cell leukemia, typically presenting in childhood. The gene shows autosomal inheritance patterns and has reduced constraint to loss-of-function variants.

ResearchSummary from RefSeq, OMIM, UniProt

LMO2 encodes a cysteine-rich, two LIM-domain protein that is required for yolk sac erythropoiesis. The LMO2 protein has a central and crucial role in hematopoietic development and is highly conserved. The LMO2 transcription start site is located approximately 25 kb downstream from the 11p13 T-cell translocation cluster (11p13 ttc), where a number T-cell acute lymphoblastic leukemia-specific translocations occur. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Nov 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

1.03

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

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.03LOEUF

pLI 0.159

Z-score 1.54

OE 0.33 (0.13–1.03)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.34Z-score

OE missense 0.62 (0.50–0.76)

60 obs / 97.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.33 (0.13–1.03)

0≤0.351.4

Missense OE?0.62 (0.50–0.76)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 2 / 6.1Missense obs/exp: 60 / 97.3Syn Z: 0.37

Background carrier burden — how many people carry a rare variant somewhere in LMO2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 240

301 rare PASS variants

Rare truncating (LoF)

1 in 2,300

55 rare PASS variants

Rare synonymous (reference)

1 in 420

133 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LMO2. 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 270	1 in 2,800
South Asian	~43k	1 in 160	1 in 1,500
Remaining (unassigned)	~30k	1 in 190	1 in 4,400
European (Finnish)	~27k	1 in 370	≈ 1 in 8,000
Admixed American	~22k	1 in 210	≈ 1 in 7,600
African / African American	~21k	1 in 140	1 in 2,200
East Asian	~20k	1 in 240	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 660	1 in 1,600
Middle Eastern	~2,884	1 in 230	≈ 1 in 1,300

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): 2 of 4 coding exons well covered in gnomAD exomes; exons 3, 4 marginal. Genomes: all 4.? see exons ↓