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.
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. 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. 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).
Chariot A, Moreau L, Senterre G, Sobel ME, Castronovo V (Oct 1995). "Retinoic acid induces three newly cloned HOXA1 transcripts in MCF7 breast cancer cells". Biochemical and Biophysical Research Communications215 (2): 713–20. doi:10.1006/bbrc.1995.2522. PMID7488013.
Studer M, Gavalas A, Marshall H, Ariza-McNaughton L, Rijli FM, Chambon P, Krumlauf R (Mar 1998). "Genetic interactions between Hoxa1 and Hoxb1 reveal new roles in regulation of early hindbrain patterning". Development125 (6): 1025–36. PMID9463349.
Green NC, Rambaldi I, Teakles J, Featherstone MS (May 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". The Journal of Biological Chemistry273 (21): 13273–9. doi:10.1074/jbc.273.21.13273. PMID9582372.
Barrow JR, Capecchi MR (Nov 1999). "Compensatory defects associated with mutations in Hoxa1 restore normal palatogenesis to Hoxa2 mutants". Development126 (22): 5011–26. PMID10529419.
Li J, Tabor HK, Nguyen L, Gleason C, Lotspeich LJ, Spiker D, Risch N, Myers RM (Jan 2002). "Lack of association between HoxA1 and HoxB1 gene variants and autism in 110 multiplex families". American Journal of Medical Genetics114 (1): 24–30. doi:10.1002/ajmg.1618. PMID11840501.
Kosaki K, Kosaki R, Suzuki T, Yoshihashi H, Takahashi T, Sasaki K, Tomita M, McGinnis W, Matsuo N (Feb 2002). "Complete mutation analysis panel of the 39 human HOX genes". Teratology65 (2): 50–62. doi:10.1002/tera.10009. PMID11857506.
Devlin B, Bennett P, Cook EH, Dawson G, Gonen D, Grigorenko EL, McMahon W, Pauls D, Smith M, Spence MA, Schellenberg GD (Aug 2002). "No evidence for linkage of liability to autism to HOXA1 in a sample from the CPEA network". American Journal of Medical Genetics114 (6): 667–72. doi:10.1002/ajmg.10603. PMID12210285.
Zhang X, Zhu T, Chen Y, Mertani HC, Lee KO, Lobie PE (Feb 2003). "Human growth hormone-regulated HOXA1 is a human mammary epithelial oncogene". The Journal of Biological Chemistry278 (9): 7580–90. doi:10.1074/jbc.M212050200. PMID12482855.
Conciatori M, Stodgell CJ, Hyman SL, O'Bara M, Militerni R, Bravaccio C, Trillo S, Montecchi F, Schneider C, Melmed R, Elia M, Crawford L, Spence SJ, Muscarella L, Guarnieri V, D'Agruma L, Quattrone A, Zelante L, Rabinowitz D, Pascucci T, Puglisi-Allegra S, Reichelt KL, Rodier PM, Persico AM (Feb 2004). "Association between the HOXA1 A218G polymorphism and increased head circumference in patients with autism". Biological Psychiatry55 (4): 413–9. doi:10.1016/j.biopsych.2003.10.005. PMID14960295.