LMO1 (LIM domain only 1 (rhombotin 1))

2011-08-01 Norihisa Saeki , Hiroki Sasaki Affiliation

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

Identity

HGNC

LMO1

LOCATION

11p15.4

IMAGE

LEGEND

LMO1 gene is located between RIC3 and STK33 genes in Chromosome 11p15. The arrow indicates the orientation of the genes.

LOCUSID

4004

ALIAS

RBTN1,RHOM1,TTG1

FUSION GENES

Show Gene Fusions

DNA/RNA

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.

LMO1 induces apoptosis of the pit cells in TGFbeta signalling. This function is assumed to have a role in homeostasis of the gastric epithelium.

Entity name

T-cell acute lymphoblastic leukemia (T-ALL)

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).

Article Bibliography

Pubmed ID	Last Year	Title	Authors
15930276	2005	LMO3 interacts with neuronal transcription factor, HEN2, and acts as an oncogene in neuroblastoma.	Aoyama M et al
2034676	1991	The 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
2052354	1991	Developmentally 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
16778171	2006	NFKB1 is a direct target of the TAL1 oncoprotein in human T leukemia cells.	Chang PY et al
11248806	2000	SCL and LMO1 alter thymocyte differentiation: inhibition of E2A-HEB function and pre-T alpha chain expression.	Herblot S et al
20855495	2010	NKX3.1 is a direct TAL1 target gene that mediates proliferation of TAL1-expressing human T cell acute lymphoblastic leukemia.	Kusy S et al
1508213	1992	Thymic overexpression of Ttg-1 in transgenic mice results in T-cell acute lymphoblastic leukemia/lymphoma.	McGuire EA et al
9819382	1998	TAL1 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
17471240	2007	GASDERMIN, suppressed frequently in gastric cancer, is a target of LMO1 in TGF-beta-dependent apoptotic signalling.	Saeki N et al
9872335	1998	The 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
21124317	2011	Integrative 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 ID	Transcript ID	Uniprot
ENSG00000166407	ENST00000335790	P25800
ENSG00000166407	ENST00000428101	P25800
ENSG00000166407	ENST00000534484	E9PK83

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

References

Pubmed ID	Year	Title	Citations
34076278	2021	Circ_0021087 acts as a miR-184 sponge and represses gastric cancer progression by adsorbing miR-184 and elevating FOSB expression.	7
34076278	2021	Circ_0021087 acts as a miR-184 sponge and represses gastric cancer progression by adsorbing miR-184 and elevating FOSB expression.	7
31830377	2020	LMO1 polymorphisms and the risk of neuroblastoma: Assessment of meta-analysis of case-control studies.	7
31830377	2020	LMO1 polymorphisms and the risk of neuroblastoma: Assessment of meta-analysis of case-control studies.	7
31819055	2019	ASCL1 is a MYCN- and LMO1-dependent member of the adrenergic neuroblastoma core regulatory circuitry.	45
31819055	2019	ASCL1 is a MYCN- and LMO1-dependent member of the adrenergic neuroblastoma core regulatory circuitry.	45
30194082	2018	Indirect Down-regulation of Tumor-suppressive let-7 Family MicroRNAs by LMO1 in Neuroblastoma.	6
30194082	2018	Indirect Down-regulation of Tumor-suppressive let-7 Family MicroRNAs by LMO1 in Neuroblastoma.	6
28260788	2017	APOBEC signature mutation generates an oncogenic enhancer that drives LMO1 expression in T-ALL.	38
28768142	2017	Contributions of IKZF1, DDC, CDKN2A, CEBPE, and LMO1 Gene Polymorphisms to Acute Lymphoblastic Leukemia in a Yemeni Population.	8
28867147	2017	LMO1 Synergizes with MYCN to Promote Neuroblastoma Initiation and Metastasis.	53
28260788	2017	APOBEC signature mutation generates an oncogenic enhancer that drives LMO1 expression in T-ALL.	38
28768142	2017	Contributions of IKZF1, DDC, CDKN2A, CEBPE, and LMO1 Gene Polymorphisms to Acute Lymphoblastic Leukemia in a Yemeni Population.	8
28867147	2017	LMO1 Synergizes with MYCN to Promote Neuroblastoma Initiation and Metastasis.	53
27009839	2016	LMO1 gene polymorphisms contribute to decreased neuroblastoma susceptibility in a Southern Chinese population.	29

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-(lim-domain-only-1-(rhombotin-1))