ALX4 information

ALX4
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2M0C
Identifiers
Aliases	ALX4, CRS5, FND2, ALX homeobox 4
External IDs	OMIM: 605420; MGI: 108359; HomoloGene: 7229; GeneCards: ALX4; OMA:ALX4 - orthologs
Gene location (Human)
Chr.	Chromosome 11 (human)
End	44,310,139 bp
Gene location (Mouse)
Chr.	Chromosome 2 (mouse)
End	93,511,684 bp
RNA expression pattern
	Top expressed in
	tendon; ; Achilles tendon; ; ganglionic eminence; ; skin of abdomen; ; skeletal muscle tissue; ; prefrontal cortex; ; gastrocnemius muscle; ; minor salivary glands; ; smooth muscle tissue; ; renal cortex;
	Top expressed in
	medial nasal prominence; ; urethra; ; male urethra; ; lateral nasal prominence; ; lip; ; human mandible; ; tongue; ; extraocular muscle; ; triceps brachii muscle; ; meninges;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	DNA binding; sequence-specific DNA binding; RNA polymerase II transcription regulatory region sequence-specific DNA binding; DNA-binding transcription factor activity; DNA-binding transcription activator activity, RNA polymerase II-specific; HMG box domain binding; protein heterodimerization activity; DNA-binding transcription factor activity, RNA polymerase II-specific;
Cellular component	transcription regulator complex; nucleus;
Biological process	regulation of apoptotic process; hair follicle development; embryonic skeletal system morphogenesis; pattern specification process; skeletal system development; roof of mouth development; regulation of transcription, DNA-templated; limb morphogenesis; regulation of transcription by RNA polymerase II; skeletal system morphogenesis; muscle organ development; embryonic digit morphogenesis; transcription by RNA polymerase II; post-embryonic development; transcription, DNA-templated; multicellular organism development; digestive tract development; embryonic forelimb morphogenesis; anterior/posterior pattern specification; positive regulation of transcription by RNA polymerase II; embryonic hindlimb morphogenesis;
	Sources:Amigo / QuickGO
Orthologs
	60529
	11695
	ENSG00000052850
	ENSMUSG00000040310
	Q9H161
	O35137
	NM_021926
	NM_007442
	NP_068745
	NP_031468
	Wikidata
View/Edit Human	View/Edit Mouse

Homeobox protein aristaless-like 4 is a protein that in humans is encoded by the ALX4 gene.^[5]^[6]^[7] Alx4 belongs to the group-1 aristaless-related genes, a majority of which are linked to the development of the craniofacial and/or appendicular skeleton, along with PRRX1, SHOX, ALX3, and CART1.^[8] The Alx4 protein acts as a transcriptional activator and is predominantly expressed in the mesenchyme of the developing embryonic limb buds.^[9]^[8]^[10] Transcripts of this gene are detectable in the lateral plate mesoderm just prior to limb induction. Alx4 expression plays a major role in the determination of spatial orientation of the growing limb bud by aiding in the establishment of anteroposterior polarity of the limb.^[9]^[10]^[11] It does this by working in conjunction with Gli3 and dHand to restrict the expression of Sonic Hedgehog (SHh) to the posterior mesenchyme, which will eventually give rise to the Zone of Polarizing Activity (ZPA).^[12] This gene has been proven to be allelic with mutations and deletions giving rise to a host of craniofacial dismorphologies and several forms of polydactyly in mammalian development.^[8]^[13] A mouse-model knockout of this gene, dubbed Strong's luxoid, was originally created by Forstheofel in the 1960s and has been extensively studied to understand the partial and complete loss-of-function properties of this gene.^[8]^[9]^[11]^[12]^[13]^[14]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000052850 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000040310 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Wu YQ, Badano JL, McCaskill C, Vogel H, Potocki L, Shaffer LG (November 2000). "Haploinsufficiency of ALX4 as a potential cause of parietal foramina in the 11p11.2 contiguous gene-deletion syndrome". American Journal of Human Genetics. 67 (5): 1327–32. doi:10.1016/S0002-9297(07)62963-2. PMC 1288575. PMID 11017806.
^ Bartsch O, Wuyts W, Van Hul W, Hecht JT, Meinecke P, Hogue D, Werner W, Zabel B, Hinkel GK, Powell CM, Shaffer LG, Willems PJ (April 1996). "Delineation of a contiguous gene syndrome with multiple exostoses, enlarged parietal foramina, craniofacial dysostosis, and mental retardation, caused by deletions in the short arm of chromosome 11". American Journal of Human Genetics. 58 (4): 734–42. PMC 1914683. PMID 8644736.
^ "Entrez Gene: ALX4 aristaless-like homeobox 4".
^ ^a ^b ^c ^d Meijlink F, Beverdam A, Brouwer A, Oosterveen TC, Berge DT (1999). "Vertebrate aristaless-related genes". The International Journal of Developmental Biology. 43 (7): 651–63. PMID 10668975.
^ ^a ^b ^c Takahashi M, Tamura K, Büscher D, Masuya H, Yonei-Tamura S, Matsumoto K, Naitoh-Matsuo M, Takeuchi J, Ogura K, Shiroishi T, Ogura T, Izpisúa Belmonte JC (November 1998). "The role of Alx-4 in the establishment of anteroposterior polarity during vertebrate limb development". Development. 125 (22): 4417–25. doi:10.1242/dev.125.22.4417. PMID 9778501.
^ ^a ^b Panman L, Drenth T, Tewelscher P, Zuniga A, Zeller R (2004-07-01). "Genetic interaction of Gli3 and Alx4 during limb development". The International Journal of Developmental Biology. 49 (4): 443–8. doi:10.1387/ijdb.051984lp. PMID 15968591.
^ ^a ^b Kuijper S, Feitsma H, Sheth R, Korving J, Reijnen M, Meijlink F (September 2005). "Function and regulation of Alx4 in limb development: complex genetic interactions with Gli3 and Shh". Developmental Biology. 285 (2): 533–44. doi:10.1016/j.ydbio.2005.06.017. PMID 16039644.
^ ^a ^b Niswander L (2002). "Interplay between the molecular signals that control vertebrate limb development". The International Journal of Developmental Biology. 46 (7): 877–81. PMID 12455624.
^ ^a ^b Kayserili H, Uz E, Niessen C, Vargel I, Alanay Y, Tuncbilek G, Yigit G, Uyguner O, Candan S, Okur H, Kaygin S, Balci S, Mavili E, Alikasifoglu M, Haase I, Wollnik B, Akarsu NA (November 2009). "ALX4 dysfunction disrupts craniofacial and epidermal development". Human Molecular Genetics. 18 (22): 4357–66. doi:10.1093/hmg/ddp391. PMID 19692347.
^ Forsthoefel PF (November 1963). "The embryological development of the effects of Strong's luxoid gene in the mouse". Journal of Morphology. 113 (3): 427–51. doi:10.1002/jmor.1051130307. PMID 14079603. S2CID 27145861.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000052850 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000040310 – 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.

[pmid11017806-5] Wu YQ, Badano JL, McCaskill C, Vogel H, Potocki L, Shaffer LG (November 2000). "Haploinsufficiency of ALX4 as a potential cause of parietal foramina in the 11p11.2 contiguous gene-deletion syndrome". American Journal of Human Genetics. 67 (5): 1327–32. doi:10.1016/S0002-9297(07)62963-2. PMC 1288575. PMID 11017806.

[pmid8644736-6] Bartsch O, Wuyts W, Van Hul W, Hecht JT, Meinecke P, Hogue D, Werner W, Zabel B, Hinkel GK, Powell CM, Shaffer LG, Willems PJ (April 1996). "Delineation of a contiguous gene syndrome with multiple exostoses, enlarged parietal foramina, craniofacial dysostosis, and mental retardation, caused by deletions in the short arm of chromosome 11". American Journal of Human Genetics. 58 (4): 734–42. PMC 1914683. PMID 8644736.

[entrez-7] "Entrez Gene: ALX4 aristaless-like homeobox 4".

[Meijlink_1999-8] Meijlink F, Beverdam A, Brouwer A, Oosterveen TC, Berge DT (1999). "Vertebrate aristaless-related genes". The International Journal of Developmental Biology. 43 (7): 651–63. PMID 10668975.

[Takahashi_1998-9] Takahashi M, Tamura K, Büscher D, Masuya H, Yonei-Tamura S, Matsumoto K, Naitoh-Matsuo M, Takeuchi J, Ogura K, Shiroishi T, Ogura T, Izpisúa Belmonte JC (November 1998). "The role of Alx-4 in the establishment of anteroposterior polarity during vertebrate limb development". Development. 125 (22): 4417–25. doi:10.1242/dev.125.22.4417. PMID 9778501.

[Panman_2004-10] Panman L, Drenth T, Tewelscher P, Zuniga A, Zeller R (2004-07-01). "Genetic interaction of Gli3 and Alx4 during limb development". The International Journal of Developmental Biology. 49 (4): 443–8. doi:10.1387/ijdb.051984lp. PMID 15968591.

[Kuijper_2005-11] Kuijper S, Feitsma H, Sheth R, Korving J, Reijnen M, Meijlink F (September 2005). "Function and regulation of Alx4 in limb development: complex genetic interactions with Gli3 and Shh". Developmental Biology. 285 (2): 533–44. doi:10.1016/j.ydbio.2005.06.017. PMID 16039644.

[Niswander_2002-12] Niswander L (2002). "Interplay between the molecular signals that control vertebrate limb development". The International Journal of Developmental Biology. 46 (7): 877–81. PMID 12455624.

[Kayserili_2009-13] Kayserili H, Uz E, Niessen C, Vargel I, Alanay Y, Tuncbilek G, Yigit G, Uyguner O, Candan S, Okur H, Kaygin S, Balci S, Mavili E, Alikasifoglu M, Haase I, Wollnik B, Akarsu NA (November 2009). "ALX4 dysfunction disrupts craniofacial and epidermal development". Human Molecular Genetics. 18 (22): 4357–66. doi:10.1093/hmg/ddp391. PMID 19692347.

[14] Forsthoefel PF (November 1963). "The embryological development of the effects of Strong's luxoid gene in the mouse". Journal of Morphology. 113 (3): 427–51. doi:10.1002/jmor.1051130307. PMID 14079603. S2CID 27145861.

ALX4 information

and 12 Related for: ALX4 information

ALX4

Omphalocele

Homeobox

List of human transcription factors

Dun gene

Ciliopathy

Zone of polarizing activity

List of conditions with craniosynostosis

TBX15

ALX1

List of OMIM disorder codes

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