Biology:Homeobox A1
 Generic protein structure example |
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
- ↑ "Structure and function of the HOX A1 human homeobox gene cDNA". Gene 159 (2): 209–14. July 1995. doi:10.1016/0378-1119(95)92712-G. PMID 7622051.
- ↑ "Fine mapping of human HOX gene clusters". Cytogenetics and Cell Genetics 73 (1–2): 114–5. 1996. doi:10.1159/000134320. PMID 8646877.
- ↑ "Nomenclature for human homeobox genes". Genomics 7 (3): 460. July 1990. doi:10.1016/0888-7543(90)90186-X. PMID 1973146.
- ↑ 4.0 4.1 "Entrez Gene: HOXA1 homeobox A1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3198.
- ↑ "Discovery of allelic variants of HOXA1 and HOXB1: genetic susceptibility to autism spectrum disorders". Teratology 62 (6): 393–405. December 2000. 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 282 (2): 56–63. doi:10.1038/scientificamerican0200-56. PMID 10710787. Bibcode: 2000SciAm.282b..56R.
- ↑ "The clinical spectrum of homozygous HOXA1 mutations". American Journal of Medical Genetics Part A 146A (10): 1235–40. May 2008. doi:10.1002/ajmg.a.32262. PMID 18412118.
- ↑ "MicroRNA fingerprints during human megakaryocytopoiesis". Proceedings of the National Academy of Sciences of the United States of America 103 (13): 5078–83. March 2006. doi:10.1073/pnas.0600587103. PMID 16549775. Bibcode: 2006PNAS..103.5078G.
Further reading
- "Retinoic acid induces three newly cloned HOXA1 transcripts in MCF7 breast cancer cells". Biochemical and Biophysical Research Communications 215 (2): 713–20. October 1995. doi:10.1006/bbrc.1995.2522. PMID 7488013. http://orbi.ulg.ac.be/handle/2268/3751.
- "Genetic interactions between Hoxa1 and Hoxb1 reveal new roles in regulation of early hindbrain patterning". Development 125 (6): 1025–36. March 1998. doi:10.1242/dev.125.6.1025. PMID 9463349.
- "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". The Journal of Biological Chemistry 273 (21): 13273–9. May 1998. doi:10.1074/jbc.273.21.13273. PMID 9582372.
- "Compensatory defects associated with mutations in Hoxa1 restore normal palatogenesis to Hoxa2 mutants". Development 126 (22): 5011–26. November 1999. doi:10.1242/dev.126.22.5011. PMID 10529419.
- "Altered HOX and WNT7A expression in human lung cancer". Proceedings of the National Academy of Sciences of the United States of America 97 (23): 12776–81. November 2000. doi:10.1073/pnas.97.23.12776. PMID 11070089. Bibcode: 2000PNAS...9712776C.
- "Lack of association between HoxA1 and HoxB1 gene variants and autism in 110 multiplex families". American Journal of Medical Genetics 114 (1): 24–30. Jan 2002. doi:10.1002/ajmg.1618. PMID 11840501.
- "Complete mutation analysis panel of the 39 human HOX genes". Teratology 65 (2): 50–62. February 2002. doi:10.1002/tera.10009. PMID 11857506.
- "No evidence for linkage of liability to autism to HOXA1 in a sample from the CPEA network". American Journal of Medical Genetics 114 (6): 667–72. August 2002. doi:10.1002/ajmg.10603. PMID 12210285.
- "Converging evidence for brain stem injury in autism". Development and Psychopathology 14 (3): 537–57. 2003. doi:10.1017/s0954579402003085. PMID 12349873.
- "Human growth hormone-regulated HOXA1 is a human mammary epithelial oncogene". The Journal of Biological Chemistry 278 (9): 7580–90. February 2003. doi:10.1074/jbc.M212050200. PMID 12482855.
- "Association between the HOXA1 A218G polymorphism and increased head circumference in patients with autism". Biological Psychiatry 55 (4): 413–9. February 2004. doi:10.1016/j.biopsych.2003.10.005. PMID 14960295.
- "Homozygous HOXA1 mutations disrupt human brainstem, inner ear, cardiovascular and cognitive development". Nature Genetics 37 (10): 1035–7. October 2005. 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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