Retinal homeobox protein Rx

Retinal homeobox protein Rx also known as retina and anterior neural fold homeobox is a protein that in humans is encoded by the RAX gene.[5] The RAX gene is located on chromosome 18 in humans, mice, and rats.[6]

RAX
Identifiers
Aliases	RAX, MCOP3, RX, retina and anterior neural fold homeobox
External IDs	OMIM: 601881 MGI: 109632 HomoloGene: 8383 GeneCards: RAX
Gene location (Human) Chr. Chromosome 18 (human)[1] Band 18q21.32 Start 59,267,035 bp[1] End 59,274,086 bp[1]
Gene location (Mouse) Chr. Chromosome 18 (mouse)[2] Band 18 E1|18 39.03 cM Start 65,928,277 bp[2] End 65,939,787 bp[2]
Gene ontology Molecular function • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding • DNA binding • sequence-specific DNA binding • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component • cell nucleus Biological process • pattern specification process • multicellular organism development • camera-type eye development • brain development • regulation of transcription, DNA-templated • transcription from RNA polymerase II promoter • transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • hypothalamus development • limb development • visual perception Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	30062	19434
Ensembl	ENSG00000134438	ENSMUSG00000024518
UniProt	Q9Y2V3	O35602
RefSeq (mRNA)	NM_013435	NM_013833
RefSeq (protein)	NP_038463	NP_038861
Location (UCSC)	Chr 18: 59.27 – 59.27 Mb	Chr 18: 65.93 – 65.94 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

This gene encodes a homeobox-containing transcription factor that functions in eye development. The gene is expressed early in the eye primordia, and is required for retinal cell fate determination and also regulates stem cell proliferation.[5]

Towards the end of late gastrulation a single eye field has formed and splits into bilateral fields via action by the signaling molecule, sonic hedgehog (Shh) secreted from the forebrain. Rax and Six-3 (also a transcription factor) maintain the forebrain's ability to secrete Shh by inhibiting activity of the signaling molecule Wnt.[7]

Rax (Retina and Anterior Neural Fold Homeobox) is a gene in the OAR (Otx, Arx,& Rax) subgroup of the paired-like homeodomain family of transcription factors. Discovered in 1997,[8] the Rax gene is known to contribute to the development of the retina, hypothalamus, pineal gland and pituitary gland.[9]

Clinical significance

Mutations in this gene have been reported in patients with defects in ocular development, including microphthalmia, anophthalmia, and coloboma.[5]

Mutations to the Rax gene cause malformation of the retinal field, including anophthalmia and micropthalmai.[10]

Individuals who have a mutation in the RAX gene fail to develop ocular structures, referred to as anophthalmia.[7] RAX mutant individuals can also have micropthalmia, where one or both of the eyes is smaller than normal.[6]

Animal studies

Rax genes are conserved among vertebrates. RAX knockout mice have no eyes and abnormal forebrain formation. In the frog Xenopus tropicalis, Rax mutants are eyeless; the future retinal tissue instead has diencephalon and telencephalon features.[11] Due to a genome duplication at the basis of the teleost fish lineage, fishes contain three Rax genes: Rx1, Rx2, and Rx3.[12] Zebrafish and medaka mutants in Rx3 are eyeless.[12][13]

References

1. GRCh38: Ensembl release 89: ENSG00000134438 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000024518 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: Retina and anterior neural fold homeobox".
6. Muranishi Y, Terada K, Furukawa T (Apr 2012). "An essential role for Rax in retina and neuroendocrine system development". Development, Growth & Differentiation. 54 (3): 341–8. doi:10.1111/j.1440-169X.2012.01337.x. PMID 22524605. S2CID 20066919.
7. Carlson BM (2014). "Sense Organs". Human Embryology and Developmental Biology (5th ed.). Elsevier/Saunders. pp. 270–71. ISBN 978-1-4557-2794-0.
8. Furukawa T, Kozak CA, Cepko CL (Apr 1997). "rax, a novel paired-type homeobox gene, shows expression in the anterior neural fold and developing retina". Proceedings of the National Academy of Sciences of the United States of America. 94 (7): 3088–93. Bibcode:1997PNAS...94.3088F. doi:10.1073/pnas.94.7.3088. PMC 20326. PMID 9096350.
9. Mathers PH, Grinberg A, Mahon KA, Jamrich M (Jun 1997). "The Rx homeobox gene is essential for vertebrate eye development". Nature. 387 (6633): 603–7. Bibcode:1997Natur.387..603M. doi:10.1038/42475. PMID 9177348. S2CID 4284692.
10. Voronina VA, Kozhemyakina EA, O'Kernick CM, Kahn ND, Wenger SL, Linberg JV, Schneider AS, Mathers PH (Feb 2004). "Mutations in the human RAX homeobox gene in a patient with anophthalmia and sclerocornea". Human Molecular Genetics. 13 (3): 315–22. doi:10.1093/hmg/ddh025. PMID 14662654.
11. Fish MB, Nakayama T, Fisher M, Hirsch N, Cox A, Reeder R, Carruthers S, Hall A, Stemple DL, Grainger RM (Nov 2014). "Xenopus mutant reveals necessity of rax for specifying the eye field which otherwise forms tissue with telencephalic and diencephalic character". Developmental Biology. 395 (2): 317–330. doi:10.1016/j.ydbio.2014.09.004. PMC 4267880. PMID 25224223.
12. Furutani-Seiki, Makoto; Wittbrodt, Joachim (2004-07-01). "Medaka and zebrafish, an evolutionary twin study". Mechanisms of Development. Medaka. 121 (7): 629–637. doi:10.1016/j.mod.2004.05.010. ISSN 0925-4773. PMID 15210172. S2CID 1798545.
13. Loosli, Felix; Staub, Wendy; Finger-Baier, Karin C; Ober, Elke A; Verkade, Heather; Wittbrodt, Joachim; Baier, Herwig (2003-09-01). "Loss of eyes in zebrafish caused by mutation of chokh/rx3". EMBO Reports. 4 (9): 894–899. doi:10.1038/sj.embor.embor919. ISSN 1469-221X. PMC 1326357. PMID 12947416.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.