Homeobox A1
Homeobox protein Hox-A1 is a protein that in humans is encoded by the HOXA1 gene.[1][2][3]
Gene
Two transcript variants encoding two different isoforms have been found for this gene, with only one of the isoforms containing the homeodomain region.[4]
Function
In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and cellular differentiation. The homeobox protein Hox-A1 may be involved in the placement of hindbrain segments in the proper location along the anterior-posterior axis during development.[4]
Clinical significance
A common polymorphism in the HOXA1 gene is associated with a susceptibility to autism spectrum disorder, with individuals possessing these gene variant have an approximately doubled risk of developing the disorder. [5] Studies on knockout mice have indicated that the gene can alter embryological development of the brain stem (specifically the facial and superior olivary nuclei), as well as induce several other physical changes such as in ear shape. [6] Both of these sets of changes can also be seen in patients with autism.
Other HOXA1 mutations are associated with Bosley-Salih-Alorainy syndrome (BSAS) or the Athabascan brainstem dysgenesis syndrome (ABDS).[7]
Regulation
The HOXA1 gene is repressed by the microRNA miR-10a.[8]
See also
References
- ↑ Hong YS, Kim SY, Bhattacharya A, Pratt DR, Hong WK, Tainsky MA (July 1995). "Structure and function of the HOX A1 human homeobox gene cDNA". Gene 159 (2): 209–14. doi:10.1016/0378-1119(95)92712-G. PMID 7622051.
- ↑ Apiou F, Flagiello D, Cillo C, Malfoy B, Poupon MF, Dutrillaux B (1996). "Fine mapping of human HOX gene clusters". Cytogenet. Cell Genet. 73 (1-2): 114–5. doi:10.1159/000134320. PMID 8646877.
- ↑ McAlpine PJ, Shows TB (Aug 1990). "Nomenclature for human homeobox genes". Genomics 7 (3): 460. doi:10.1016/0888-7543(90)90186-X. PMID 1973146.
- ↑ 4.0 4.1 "Entrez Gene: HOXA1 homeobox A1".
- ↑ Ingram JL, Stodgell CJ, Hyman SL, Figlewicz DA, Weitkamp LR, Rodier PM (December 2000). "Discovery of allelic variants of HOXA1 and HOXB1: genetic susceptibility to autism spectrum disorders". Teratology 62 (6): 393–405. doi:10.1002/1096-9926(200012)62:6<393::AID-TERA6>3.0.CO;2-V. PMID 11091361.
- ↑ Rodier, Patricia (February 2000). "The Early Origins of Autism". Scientific American.
- ↑ Bosley TM, Alorainy IA, Salih MA, Aldhalaan HM, Abu-Amero KK, Oystreck DT, Tischfield MA, Engle EC, Erickson RP (May 2008). "The clinical spectrum of homozygous HOXA1 mutations". Am. J. Med. Genet. A 146A (10): 1235–40. doi:10.1002/ajmg.a.32262. PMC 3517166. PMID 18412118.
- ↑ Garzon R, Pichiorri F, Palumbo T, Iuliano R, Cimmino A, Aqeilan R et al. (2006). "MicroRNA fingerprints during human megakaryocytopoiesis.". Proc Natl Acad Sci U S A 103 (13): 5078–83. doi:10.1073/pnas.0600587103. PMC 1458797. PMID 16549775.
Further reading
- Chariot A, Moreau L, Senterre G et al. (1995). "Retinoic acid induces three newly cloned HOXA1 transcripts in MCF7 breast cancer cells.". Biochem. Biophys. Res. Commun. 215 (2): 713–20. doi:10.1006/bbrc.1995.2522. PMID 7488013.
- Studer M, Gavalas A, Marshall H et al. (1998). "Genetic interactions between Hoxa1 and Hoxb1 reveal new roles in regulation of early hindbrain patterning.". Development 125 (6): 1025–36. PMID 9463349.
- Green NC, Rambaldi I, Teakles J, Featherstone MS (1998). "A conserved C-terminal domain in PBX increases DNA binding by the PBX homeodomain and is not a primary site of contact for the YPWM motif of HOXA1.". J. Biol. Chem. 273 (21): 13273–9. doi:10.1074/jbc.273.21.13273. PMID 9582372.
- Barrow JR, Capecchi MR (1999). "Compensatory defects associated with mutations in Hoxa1 restore normal palatogenesis to Hoxa2 mutants.". Development 126 (22): 5011–26. PMID 10529419.
- Calvo R, West J, Franklin W et al. (2001). "Altered HOX and WNT7A expression in human lung cancer.". Proc. Natl. Acad. Sci. U.S.A. 97 (23): 12776–81. doi:10.1073/pnas.97.23.12776. PMC 18840. PMID 11070089.
- Li J, Tabor HK, Nguyen L et al. (2002). "Lack of association between HoxA1 and HoxB1 gene variants and autism in 110 multiplex families.". Am. J. Med. Genet. 114 (1): 24–30. doi:10.1002/ajmg.1618. PMID 11840501.
- Kosaki K, Kosaki R, Suzuki T et al. (2002). "Complete mutation analysis panel of the 39 human HOX genes.". Teratology 65 (2): 50–62. doi:10.1002/tera.10009. PMID 11857506.
- Devlin B, Bennett P, Cook EH et al. (2003). "No evidence for linkage of liability to autism to HOXA1 in a sample from the CPEA network.". Am. J. Med. Genet. 114 (6): 667–72. doi:10.1002/ajmg.10603. PMID 12210285.
- Rodier PM (2003). "Converging evidence for brain stem injury in autism.". Dev. Psychopathol. 14 (3): 537–57. doi:10.1017/s0954579402003085. PMID 12349873.
- Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Zhang X, Zhu T, Chen Y et al. (2003). "Human growth hormone-regulated HOXA1 is a human mammary epithelial oncogene.". J. Biol. Chem. 278 (9): 7580–90. doi:10.1074/jbc.M212050200. PMID 12482855.
- Scherer SW, Cheung J, MacDonald JR et al. (2003). "Human chromosome 7: DNA sequence and biology.". Science 300 (5620): 767–72. doi:10.1126/science.1083423. PMC 2882961. PMID 12690205.
- Hillier LW, Fulton RS, Fulton LA et al. (2003). "The DNA sequence of human chromosome 7.". Nature 424 (6945): 157–64. doi:10.1038/nature01782. PMID 12853948.
- Conciatori M, Stodgell CJ, Hyman SL et al. (2004). "Association between the HOXA1 A218G polymorphism and increased head circumference in patients with autism.". Biol. Psychiatry 55 (4): 413–9. doi:10.1016/j.biopsych.2003.10.005. PMID 14960295.
- Gerhard DS, Wagner L, Feingold EA et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Tischfield MA, Bosley TM, Salih MA et al. (2005). "Homozygous HOXA1 mutations disrupt human brainstem, inner ear, cardiovascular and cognitive development.". Nat. Genet. 37 (10): 1035–7. doi:10.1038/ng1636. PMID 16155570.
External links
- HOXA1 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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