MIM.142994 7q36 HGNC:4979 Entrez:3110
Wednesday 8 December 2004
Definition: The MNX1 (or HLXB9) gene is located at 7q36 and is a disease-causing gene (Currarino syndrome). MNX1 encodes the HB9 transcription factor and interacts with DNA through a highly evolutionarily conserved homeodomain early in embryological development.
This gene encodes a nuclear protein, which contains a homeobox domain and is a transcription factor. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.
Mutations in this gene result in Currarino syndrome, an autosomic dominant congenital malformation.
2 human homeobox genes, HLXB9 and HLX1 (MIM.142995), are highly expressed in CD34-positive (MIM.142230) marrow cells but not in CD34-depleted marrow cells. (CD34 is a cell surface antigen that is selectively expressed on human hematopoietic progenitor cells.)
Their expression was readily down-regulated during the differentiation of hematopoietic progenitors to specific cell lineages. Proteins encoded by homeobox-containing genes (Homeobox genes) are sequence-specific DNA binding proteins implicated in the control of gene expression in both developing and adult tissues.
germline mutations in the MNX1 (HLXB9) gene
- in type IV form of caudal regression syndromes (CRS) characterized by hemisacrum (some cases of Currarino syndrome)
- In 2008, 43 different heterozygous mutations have been reported in patients fulfilling CS criteria. Mutation detection rate is about 50%, and reaches 90% in familial cases.
Crétolle C, Pelet A, Sanlaville D, Zérah M, Amiel J, Jaubert F, Révillon Y, Baala L, Munnich A, Nihoul-Fékété C, Lyonnet S. Spectrum of HLXB9 gene mutations in Currarino syndrome and genotype-phenotype correlation. Hum Mutat. 2008 Apr 30. PMID: 18449898
von Bergh AR, van Drunen E, van Wering ER, van Zutven LJ, Hainmann I, Lonnerholm G, Meijerink JP, Pieters R, Beverloo HB. 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. Genes Chromosomes Cancer. 2006 Aug;45(8):731-9. PMID: 16646086