MNX1 (homeo box HB9)

2003-12-01 Anne RM von Bergh , H Berna Beverloo Affiliation

Afdeling Klinische Genetica, Erasmus MC, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands

Identity

HGNC

MNX1

LOCATION

7q36.3

LOCUSID

3110

ALIAS

HB9,HLXB9,HOXHB9,SCRA1

FUSION GENES

Show Gene Fusions

DNA/RNA

Description

3 exons stretched over an area of 5-6 kb.

Transcription

In a telomere to centromere direction; 2061 bp mRNA, 1206 bp open reading frame.

Proteins

Description

The homeobox gene HLXB9 encodes the nuclear protein HB9. The protein contains a polyalanine repeat region and a homeobox domain.

Expression

Expressed in lymphoid and pancreatic tissues. Highly expressed in CD34+ bone marrow cells, down regulated upon differentiation.

Localisation

Nuclear

Function

Putative transcription factor.

Homology

Related to Mnr2.

Mutations

Note

Mutations in HLXB9 cause an autosomal dominant form of sacral agenesis, known as Currarino syndrome.

Implicated in

Entity name

t(7;12)(q36;p13) - associated infant acute myeloid leukemia (AML)

Prognosis

Prognosis probably poor: median survival is 13 months.

Cytogenetics

t(7;12)(q36;p13), but not always visible by chromosome banding; may also be misdiagnosed as del(12)(p13).

Hybrid gene

5 HLXB9 _ 3 ETV6

Fig. 3. Schematic representation of the HLXB9 and ETV6 proteins and the putative HLXB9-ETV6 chimeric protein resulting from the t(7;12)(q36;p13). Arrow, the observed breakpoints. nt numbers (cDNA level) are given above each protein, and amino acid numbers are given in bold type below each protein.

Fusion protein

N-term HLXB9, including its polyalanine repeat, is fused to a large C-term part of the ETV6 protein including its HLH domain and ETS domain; the homeobox domain of HLXB9 is not retained in the fusion protein; the reciprocal transcript is not expressed.

Bibliography

Pubmed ID	Last Year	Title	Authors
11454678	2001	Fusion of the homeobox gene HLXB9 and the ETV6 gene in infant acute myeloid leukemias with the t(7;12)(q36;p13).	Beverloo HB et al
7914194	1994	A novel human homeobox gene distantly related to proboscipedia is expressed in lymphoid and pancreatic tissues.	Harrison KA et al
9843207	1998	A homeobox gene, HLXB9, is the major locus for dominantly inherited sacral agenesis.	Ross AJ et al

Other Information

Locus ID:

NCBI: 3110
MIM: 142994
HGNC: 4979
Ensembl: ENSG00000130675

Variants:

dbSNP: 3110
ClinVar: 3110
TCGA: ENSG00000130675
COSMIC: MNX1

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000130675	ENST00000252971	P50219
ENSG00000130675	ENST00000425745	C9JFT4
ENSG00000130675	ENST00000428439	C9K088
ENSG00000130675	ENST00000469500	S4R464
ENSG00000130675	ENST00000474448	S4R364
ENSG00000130675	ENST00000479817	S4R3G1
ENSG00000130675	ENST00000543409	P50219

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

Pathways

Pathway	Source	External ID
Maturity onset diabetes of the young	KEGG	ko04950
Maturity onset diabetes of the young	KEGG	hsa04950

References

Pubmed ID	Year	Title	Citations
24411943	2014	Analysis of transcription factors key for mouse pancreatic development establishes NKX2-2 and MNX1 mutations as causes of neonatal diabetes in man.	37
27578002	2016	MNX1 Is Oncogenically Upregulated in African-American Prostate Cancer.	19
16646086	2006	High incidence of t(7;12)(q36;p13) in infant AML but not in infant ALL, with a dismal outcome and ectopic expression of HLXB9.	18
18449898	2008	Spectrum of HLXB9 gene mutations in Currarino syndrome and genotype-phenotype correlation.	16
15772702	2005	HLXB9 activates IL6 in Hodgkin lymphoma cell lines and is regulated by PI3K signalling involving E2F3.	14
24095820	2013	Novel MNX1 mutations and clinical analysis of familial and sporadic Currarino cases.	11
24425879	2014	GSK-3β protein phosphorylates and stabilizes HLXB9 protein in insulinoma cells to form a targetable mechanism of controlling insulinoma cell proliferation.	11
11940082	2002	Genetic control of caudal development.	9
28414551	2017	Long Noncoding RNA MNX1-AS1 Knockdown Inhibits Cell Proliferation and Migration in Ovarian Cancer.	9
28611045	2017	RGS12 Is a Novel Tumor-Suppressor Gene in African American Prostate Cancer That Represses AKT and MNX1 Expression.	9

Citation

Anne RM von Bergh ; H Berna Beverloo

MNX1 (homeo box HB9)

Atlas Genet Cytogenet Oncol Haematol. 2003-12-01

Online version: http://atlasgeneticsoncology.org/gene/393/mnx1-(homeo-box-hb9)