Human Gene ALX4 (ENST00000652299.1) from GENCODE V43
  Description: Homo sapiens ALX homeobox 4 (ALX4), mRNA. (from RefSeq NM_021926)
RefSeq Summary (NM_021926): This gene encodes a paired-like homeodomain transcription factor expressed in the mesenchyme of developing bones, limbs, hair, teeth, and mammary tissue. Mutations in this gene cause parietal foramina 2 (PFM2); an autosomal dominant disease characterized by deficient ossification of the parietal bones. Mutations in this gene also cause a form of frontonasal dysplasia with alopecia and hypogonadism; suggesting a role for this gene in craniofacial development, mesenchymal-epithelial communication, and hair follicle development. Deletion of a segment of chromosome 11 containing this gene, del(11)(p11p12), causes Potocki-Shaffer syndrome (PSS); a syndrome characterized by craniofacial anomalies, cognitive disability, multiple exostoses, and genital abnormalities in males. In mouse, this gene has been shown to use dual translation initiation sites located 16 codons apart. [provided by RefSeq, Oct 2009]. Sequence Note: The RefSeq transcript and protein were derived from transcript and genomic sequence to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on alignments.
Gencode Transcript: ENST00000652299.1
Gencode Gene: ENSG00000052850.8
Transcript (Including UTRs)
   Position: hg38 chr11:44,260,440-44,310,139 Size: 49,700 Total Exon Count: 4 Strand: -
Coding Region
   Position: hg38 chr11:44,264,854-44,310,062 Size: 45,209 Coding Exon Count: 4 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsOther NamesGeneReviewsMethods
Data last updated at UCSC: 2023-02-17 22:02:02

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr11:44,260,440-44,310,139)mRNA (may differ from genome)Protein (411 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSCGAPEnsemblEntrez GeneExonPrimerGencode

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Homeobox protein aristaless-like 4;
FUNCTION: Transcription factor involved in skull and limb development. Plays an essential role in craniofacial development, skin and hair follicle development.
SUBUNIT: Binds DNA (By similarity).
TISSUE SPECIFICITY: Expression is likely to be restricted to bone. Found in parietal bone.
DISEASE: Defects in ALX4 are the cause of parietal foramina 2 (PFM2) [MIM:609597]; also known as foramina parietalia permagna (FPP). PFM2 is an autosomal dominant disease characterized by oval defects of the parietal bones caused by deficient ossification around the parietal notch, which is normally obliterated during the fifth fetal month. PFM2 is also a clinical feature of Potocki- Shaffer syndrome.
DISEASE: Defects in ALX4 are the cause of frontonasal dysplasia type 2 (FND2) [MIM:613451]. The term frontonasal dysplasia describes an array of abnormalities affecting the eyes, forehead and nose and linked to midfacial dysraphia. The clinical picture is highly variable. Major findings include true ocular hypertelorism; broadening of the nasal root; median facial cleft affecting the nose and/or upper lip and palate; unilateral or bilateral clefting of the alae nasi; lack of formation of the nasal tip; anterior cranium bifidum occultum; a V-shaped or widow's peak frontal hairline.
DISEASE: Defects in ALX4 are a cause of Potocki-Shaffer syndrome (POSHS) [MIM:601224]. A contiguous gene syndrome caused by deletion of the 11p11.2 region.
SIMILARITY: Belongs to the paired homeobox family.
SIMILARITY: Contains 1 homeobox DNA-binding domain.
SEQUENCE CAUTION: Sequence=AAG23961.1; Type=Frameshift; Positions=314, 323, 340; Sequence=BAB47417.1; Type=Erroneous initiation;
WEB RESOURCE: Name=GeneReviews; URL="";

-  Primer design for this transcript

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3

-  MalaCards Disease Associations
  MalaCards Gene Search: ALX4
Diseases sorted by gene-association score: frontonasal dysplasia 2* (1369), parietal foramina 2* (1351), craniosynostosis 5* (903), parietal foramina* (306), potocki-shaffer syndrome* (55), autosomal dominant disease (28), craniosynostosis (15), isolated scaphocephaly* (14), basal encephalocele (13), wagr syndrome (11), omphalocele (10), dysostosis (9), encephalocele (4)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 1.16 RPKM in Breast - Mammary Tissue
Total median expression: 5.33 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -31.9077-0.414 Picture PostScript Text
3' UTR -1803.804414-0.409 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR017970 - Homeobox_CS
IPR001356 - Homeodomain
IPR009057 - Homeodomain-like
IPR003654 - OAR_dom

Pfam Domains:
PF00046 - Homeobox domain
PF03826 - OAR domain

ModBase Predicted Comparative 3D Structure on Q9H161
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
Protein SequenceProtein SequenceProtein Sequence   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding
GO:0003677 DNA binding
GO:0003700 transcription factor activity, sequence-specific DNA binding
GO:0043565 sequence-specific DNA binding
GO:0046982 protein heterodimerization activity
GO:0071837 HMG box domain binding

Biological Process:
GO:0001501 skeletal system development
GO:0001942 hair follicle development
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006357 regulation of transcription from RNA polymerase II promoter
GO:0006366 transcription from RNA polymerase II promoter
GO:0007275 multicellular organism development
GO:0007389 pattern specification process
GO:0007517 muscle organ development
GO:0009791 post-embryonic development
GO:0009952 anterior/posterior pattern specification
GO:0035108 limb morphogenesis
GO:0035115 embryonic forelimb morphogenesis
GO:0035116 embryonic hindlimb morphogenesis
GO:0042733 embryonic digit morphogenesis
GO:0042981 regulation of apoptotic process
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0048565 digestive tract development
GO:0048704 embryonic skeletal system morphogenesis
GO:0048705 skeletal system morphogenesis
GO:0060021 palate development

Cellular Component:
GO:0005634 nucleus
GO:0005667 transcription factor complex

-  Descriptions from all associated GenBank mRNAs
  AB058691 - Homo sapiens KIAA1788 mRNA for KIAA1788 protein.
AK092346 - Homo sapiens cDNA FLJ35027 fis, clone OCBBF2015599, highly similar to Homo sapiens partial ALX4 gene for homeodomain transcription factor ALX4.
AF294629 - Homo sapiens aristaless-like 4 (ALX4) mRNA, complete cds.
AJ404888 - Homo sapiens mRNA for homeodomain transcription factor ALX4.
BC166622 - Synthetic construct Homo sapiens clone IMAGE:100066348, MGC:195485 ALX homeobox 4 (ALX4) mRNA, encodes complete protein.
AB385504 - Synthetic construct DNA, clone: pF1KA1788, Homo sapiens ALX4 gene for aristaless-like homeobox 4, complete cds, without stop codon, in Flexi system.
JD400799 - Sequence 381823 from Patent EP1572962.
JD540019 - Sequence 521043 from Patent EP1572962.
JD209577 - Sequence 190601 from Patent EP1572962.
JD327545 - Sequence 308569 from Patent EP1572962.
JD366995 - Sequence 348019 from Patent EP1572962.
JD387601 - Sequence 368625 from Patent EP1572962.
JD190959 - Sequence 171983 from Patent EP1572962.
JD387569 - Sequence 368593 from Patent EP1572962.

-  Other Names for This Gene
  Alternate Gene Symbols: ALX4_HUMAN, KIAA1788, NM_021926, Q96JN7, Q9H161, Q9H198, Q9HAY9, uc287ipy.1
UCSC ID: ENST00000652299.1
RefSeq Accession: NM_021926
Protein: Q9H161 (aka ALX4_HUMAN)
CCDS: CCDS31468.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene ALX4:
msx2 (Enlarged Parietal Foramina)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.