Disease relevance of HOXA13

• Exclusion of WTAP and HOXA13 as candidate genes for isolated hypospadias [1].
• In humans, mutations in HOXD13 have been associated with type II syndactyly or synpolydactyly, and, in HOXA13, with hand-foot-genital syndrome [2].
• We report a novel chromosomal translocation in a T-ALL patient that maps upstream of the HOXA13 gene and downstream of the BCL11B/CTIP2 locus [3].
• Expression of the Hoxa-13 gene correlates to hepatitis B and C virus associated HCC [4].
• To study the Hoxa-13 gene in the liver, we examined its expression by RT-PCR in various liver cell lines, rat livers under different conditions, and human primary hepatocellular carcinomas (HCCs) [4].

High impact information on HOXA13

• A nonsense mutation in the homeobox of HOXA13 has been identified in one affected family, making HFGS the second human syndrome shown to be caused by a HOX gene mutation [5].
• Polyalanine expansion in HOXA13: three new affected families and the molecular consequences in a mouse model [6].
• Polyalanine expansions in two of three large imperfect trinucleotide repeats encoded by the first exon of HOXA13 have been reported in hand-foot-genital syndrome (HFGS) [6].
• The chromosomal breakpoints on 7p15 were located within introns of HOXA11 or HOXA13 genes [7].
• We now report that six different genes of the cluster HOX 1 are sequentially induced by RA in a similar temporal pattern, beginning with genes at the 3' end of the cluster [8].

Biological context of HOXA13

• The HOXA13 gene is part of the HOXA cluster genes and contains 2 exons, encoding a protein of 338 amino acids with a homeodomain [9].
• Thus far, however, mutations have been documented in only three of the 39 human HOX genes (HOXD13, HOXA13, and HOXA11) partly because current knowledge on the complete coding sequence and genome structure is limited to only 20 of the 39 human HOX genes [10].
• Finally, using mammalian one-hybrid assay, we show that transcriptional activation by a GAL4/Smad3-C-terminus fusion protein is specifically inhibited by HOXA13 [11].
• A HOXA13 allele with a missense mutation in the homeobox and a dinucleotide deletion in the promoter underlies Guttmacher syndrome [12].
• We have therefore re-investigated the original Guttmacher syndrome family, and have found that affected individuals are heterozygous for a novel missense mutation in the HOXA13 homeobox (c.1112A>T; homeodomain residue Q50L), which arose on an allele already carrying a novel 2-bp deletion (-78-79delGC) in the gene's highly conserved promoter region [12].

Anatomical context of HOXA13

• Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis in various leukemic cell lines showed that the HOXA13 gene was expressed significantly more frequently in acute monocytic leukemic cell lines than in other leukemic cell lines (P = 0.039) [9].
• To identify candidate protein interactors of HOXA13, we created and screened an E11.5-E12.5, distal limb bud yeast two-hybrid prey library [11].
• Role of HOXA7 to HOXA13 and PBX1 genes in various forms of MRKH syndrome (congenital absence of uterus and vagina) [13].
• Tail gut endoderm and gut/genitourinary/tail development: a new tissue-specific role for Hoxa13 [14].
• These results suggest that Hoxa-11 and Hoxa-13 expression in the migrating premyoblasts is under the control of the limb mesenchyme and the polarizing signal(s) [15].

Associations of HOXA13 with chemical compounds

• A novel stable polyalanine [poly(A)] expansion in the HOXA13 gene associated with hand-foot-genital syndrome: proper function of poly(A)-harbouring transcription factors depends on a critical repeat length [16]?
• HOX-1 mRNA levels were found to be maximally induced after 6h of treatment with 200muM H(2)O(2) and remained elevated for at least 24h [17].

Other interactions of HOXA13

• We report here a novel NUP98 partner gene, HOXA13, in a patient with de novo AML having t(7;11)(p15;p15) [9].
• In this report we discuss what is known about HOXA13 and HOXD13 function during GU development, highlighting some of the cellular and molecular mechanisms controlled by these proteins during the GU formation [18].
• Cells transduced with TLX3 or HOXA13 could not be detected in the peripheral blood of mice post-transplantation and none of the mice developed malignancies [3].
• Molecular characterization of the 7p15 breakpoint showed that this was localized within a fully sequenced PAC clone RP1-170O19 containing the HOXA4 to HOXA13 genes and the EVX1 gene [19].
• RESULTS: shh, BMP4, Hoxa13, and Hoxd13 transcripts were detected in all samples, confirming that shh cascade is active during the process of hindgut development in fetal rats [20].

Analytical, diagnostic and therapeutic context of HOXA13

• In affected individuals from both families, sequence analysis of candidate gene HOXA13 did not identify a mutation, and there was no evidence of a microdeletion involving either HOXA13 or the HOXA cluster as a whole [21].
• Using whole-mount in situ hybridization, we localized Hoxa13 expression to the cervical and vaginal tissues, consistent with the observed defects [22].

References