ALX3

The ALX3 gene, also known as aristaless-like homeobox 3, is a protein coding gene that provides instructions to build a protein which is a member of the homeobox protein family.[5][6][7] This grouping regulates patterns of anatomical development. The gene encodes a nuclear protein that functions as a transcription regulator involved in cell-type differentiation and development.

ALX3
Identifiers
Aliases	ALX3, FND, FND1, ALX homeobox 3
External IDs	OMIM: 606014 MGI: 1277097 HomoloGene: 4737 GeneCards: ALX3
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p13.3 Start 110,059,870 bp[1] End 110,070,672 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3 F2.3|3 46.83 cM Start 107,502,347 bp[2] End 107,513,092 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in anterior pituitary muscle tissue superior frontal gyrus left uterine tube mammary gland lymph node embryo myometrium temporal lobe hippocampal formation Top expressed in abdominal wall primitive streak medial nasal prominence female urethra lateral nasal prominence olfactory bulb pineal gland posterior horn of spinal cord maxillary prominence allantois More reference expression data BioGPS n/a
Gene ontology Molecular function sequence-specific DNA binding DNA binding DNA-binding transcription factor activity, RNA polymerase II-specific RNA polymerase II transcription regulatory region sequence-specific DNA binding Cellular component nucleus Biological process regulation of apoptotic process pattern specification process embryonic skeletal system morphogenesis multicellular organism development regulation of transcription, DNA-templated embryonic forelimb morphogenesis transcription, DNA-templated embryonic hindlimb morphogenesis embryonic cranial skeleton morphogenesis regulation of transcription by RNA polymerase II Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 257 11694 Ensembl ENSG00000156150 ENSMUSG00000014603 UniProt O95076 O70137 RefSeq (mRNA) NM_006492 NM_007441 RefSeq (protein) NP_006483 NP_031467 Location (UCSC) Chr 1: 110.06 – 110.07 Mb Chr 3: 107.5 – 107.51 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

The ALX3 protein, encoded by the gene, is a transcription factor, meaning that it binds to DNA and obtains control over the action of other genes. The ALX3 protein specifically controls genes that regulate cell growth, proliferation, and migration. This protein is essential for the development of the head and face, specifically the nose. This event begins around the fourth week of development.

At least 7 mutations in the ALX3 gene are known to cause frontonasal dysplasia. The mutations eliminate the function of the ALX3 protein, resulting in decreased ability to bind to DNA. The loss of regulatory function results in uncontrolled cell proliferation and migration during fetal development. One particular form of the disorder, called frontonasal dysplasia type 1, presents with abnormal development of structures in the middle of the face. The most common malformation of this defect is a cleft in the nose, lip, and palate.[8]

ALX3 was first discovered by a group of scientists, led by Hopi Hoekstra, a biologist from Harvard University, that investigated how stripe patterns form in animals. They investigated the Rhabdomys pumiliom, commonly known as the African striped mouse because of the alternating colored stripes observed on its back. One of the members of the team, Ricardo Mallarino, discovered that the stripes were formed during embryogenesis in the mice. Melanocytes, the specialized cells that produce the pigments in the skin, were not active in areas where the lighter stripes were observed. They then researched the genes active in those areas using RNA sequencing. They discovered that ALX3 was expressed in the light hair areas but not in the dark hair areas. They found that all mice expressed the gene on their abdomen but only the African striped mouse expressed it on its back, hence why the strips appear. Protein-DNA binding was then performed to determine where the ALX3 protein binds on the DNA. ALX3 binds to the promoter and represses MITF, which allows transcription to take place when making melanocytes. More tests were performed to confirm the function of ALX3 within the African striped mice. The gene was observed in other rodents such as the North American chipmunks and deemed responsible for the similar outcomes. The differences in evolution amongst the species did not hinder the similarities in the expression of the gene. This led the team to believe that ALX3 may have the same effect in mammals. However, further studies must be completed to confirm that ALX3 is responsible for the same in other mammals.