LMO1 (LIM domain only 1 (rhombotin 1))

2011-08-01   Norihisa Saeki , Hiroki Sasaki 

Genetics Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan

Identity

HGNC
LOCATION
11p15.4
IMAGE
Atlas Image
LEGEND
LMO1 gene is located between RIC3 and STK33 genes in Chromosome 11p15. The arrow indicates the orientation of the genes.
LOCUSID
ALIAS
RBTN1,RHOM1,TTG1
FUSION GENES

DNA/RNA

Atlas Image
Structure of LMO1 gene. The gene consists of 5 exons and several splicing variants were reported.

Description

4,4 kb (from the beginning of the 1st exon to the end of the 5th exon) consisting of 5 exons.

Transcription

mRNA of approximately 700 - 1000 bp, depending on the splicing variants.

Pseudogene

Not reported.

Proteins

Description

The protein contains two highly conserved, cysteine-rich motifs known as LIM domains, which interact with other proteins. As LMO1 has no DNA-binding domain, its DNA binding ability is dependent on the other proteins with which it interacts. The proteins known for binding to LMO1 include TAL1/SCL and LDB1, and the molecules have an oncogenic function in T cell acute leukemia with the chromosomal translocation t(11;14)(p15;q11).

Expression

LMO1 expression is prominent in the central nervous system in both human and mouse. In mice it was observed by an in situ hybridization technique in the cerebral cortex, diencephalon, mesencephalon, cerebellum, myeloencephalon and spinal cord. Northern blot analysis revealed its expression in the thymus, kidney and placenta of adult mice.

Localisation

Nucleus.

Function

Transcription factor.

Mutations

Note

Not reported.

Implicated in

Entity name
Neuroblastoma
Disease
Genome-wide association studies revealed a corelation between neuroblastoma and a single nucleotide polymorphism in LMO1 gene, rs110419 (A/G), of which the A allele was shown to promote LMO1 expression and to corelate the cases. The DNA copy number gain of the LMO1 locus due to duplication was also demonstrated to associate with the cases. These findings suggest that the gene has a role in the development and/or progression of neuroblastoma. It was also reported that LMO3 is a neuroblastoma oncogene.
Entity name
Apoptosis of the gastric epithelial cells
Note
In some gastric-cancer derived cell lines, LMO1 is upregulated by TGFbeta signalling and induces their apoptosis through enhancing GSDMA expression. This TGFbeta-LMO1-GSDMA cascade is considered a mechanism for apoptosis induction in the gastric epithelial cells, and has a role in maintaining their homeostasis.
Atlas Image
LMO1 induces apoptosis of the pit cells in TGFbeta signalling. This function is assumed to have a role in homeostasis of the gastric epithelium.
Disease
Originally, the LMO1 gene was identified at a break point of the translocation t(11;14)(p15;q11), which was frequently observed in T-ALL. Using LMO1 as a probe, LMO2 and LMO3 were identified. LMO1 is expressed in inmature T cells but suppressed in the mature cells, and overexpression of the gene in thymocytes, hematopoeitic progeniter cells located in the thymus, resulted in developing T-ALL in mice. LMO1 acts cooperatively with SCL (Stem cell leukemia) as a transcriptional activator or represser, dependent on the genes and the cells, and enforced expression of LMO1 and SCL in the thymocytes inhibits T-cell differentiation and causes T-ALL. It is known that the LMO1-SCL complex regulates several genes, including suppression of NFKB1 (nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) and PTCRA (pre T-cell antigen receptor alpha), activation of NKX3.1 (NK3 homeobox 1).

Bibliography

Pubmed IDLast YearTitleAuthors
159302762005LMO3 interacts with neuronal transcription factor, HEN2, and acts as an oncogene in neuroblastoma.Aoyama M et al
20346761991The rhombotin family of cysteine-rich LIM-domain oncogenes: distinct members are involved in T-cell translocations to human chromosomes 11p15 and 11p13.Boehm T et al
20523541991Developmentally regulated and tissue specific expression of mRNAs encoding the two alternative forms of the LIM domain oncogene rhombotin: evidence for thymus expression.Boehm T et al
167781712006NFKB1 is a direct target of the TAL1 oncoprotein in human T leukemia cells.Chang PY et al
112488062000SCL and LMO1 alter thymocyte differentiation: inhibition of E2A-HEB function and pre-T alpha chain expression.Herblot S et al
208554952010NKX3.1 is a direct TAL1 target gene that mediates proliferation of TAL1-expressing human T cell acute lymphoblastic leukemia.Kusy S et al
15082131992Thymic overexpression of Ttg-1 in transgenic mice results in T-cell acute lymphoblastic leukemia/lymphoma.McGuire EA et al
98193821998TAL1 and LIM-only proteins synergistically induce retinaldehyde dehydrogenase 2 expression in T-cell acute lymphoblastic leukemia by acting as cofactors for GATA3.Ono Y et al
174712402007GASDERMIN, suppressed frequently in gastric cancer, is a target of LMO1 in TGF-beta-dependent apoptotic signalling.Saeki N et al
98723351998The LMO1 and LDB1 proteins interact in human T cell acute leukaemia with the chromosomal translocation t(11;14)(p15;q11).Valge-Archer V et al
211243172011Integrative genomics identifies LMO1 as a neuroblastoma oncogene.Wang K et al

Other Information

Locus ID:

NCBI: 4004
MIM: 186921
HGNC: 6641
Ensembl: ENSG00000166407

Variants:

dbSNP: 4004
ClinVar: 4004
TCGA: ENSG00000166407
COSMIC: LMO1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000166407ENST00000335790P25800
ENSG00000166407ENST00000428101P25800
ENSG00000166407ENST00000534484E9PK83

Expression (GTEx)

0
1
2
3
4
5
6
7
8
9

References

Pubmed IDYearTitleCitations
211243172011Integrative genomics identifies LMO1 as a neuroblastoma oncogene.134
265600272015Genetic predisposition to neuroblastoma mediated by a LMO1 super-enhancer polymorphism.104
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
270098392016LMO1 gene polymorphisms contribute to decreased neuroblastoma susceptibility in a Southern Chinese population.28
202009532010Genome-wide pleiotropy of osteoporosis-related phenotypes: the Framingham Study.27
288671472017LMO1 Synergizes with MYCN to Promote Neuroblastoma Initiation and Metastasis.26
174712402007GASDERMIN, suppressed frequently in gastric cancer, is a target of LMO1 in TGF-beta-dependent apoptotic signalling.22
260307542015Candidate Gene Association Analysis of Neuroblastoma in Chinese Children Strengthens the Role of LMO1.13
282607882017APOBEC signature mutation generates an oncogenic enhancer that drives LMO1 expression in T-ALL.13
161030652005OLIG2 (BHLHB1), a bHLH transcription factor, contributes to leukemogenesis in concert with LMO1.11

Citation

Norihisa Saeki ; Hiroki Sasaki

LMO1 (LIM domain only 1 (rhombotin 1))

Atlas Genet Cytogenet Oncol Haematol. 2011-08-01

Online version: http://atlasgeneticsoncology.org/gene/33/lmo1