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Aliases for ALX4 Gene

Aliases for ALX4 Gene

  • ALX Homeobox 4 2 3 5
  • Homeobox Protein Aristaless-Like 4 3 4
  • Aristaless-Like Homeobox 4 2 3
  • Homeodomain Transcription Factor ALX4 3
  • Parietal Foramina 2 2
  • KIAA1788 4
  • CRS5 3
  • FND2 3

External Ids for ALX4 Gene

Previous HGNC Symbols for ALX4 Gene

  • PFM2

Previous GeneCards Identifiers for ALX4 Gene

  • GC11P045601
  • GC11M044967
  • GC11M044321
  • GC11M044246
  • GC11M043991

Summaries for ALX4 Gene

Entrez Gene Summary for ALX4 Gene

  • 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]

GeneCards Summary for ALX4 Gene

ALX4 (ALX Homeobox 4) is a Protein Coding gene. Diseases associated with ALX4 include Frontonasal Dysplasia 2 and Parietal Foramina 2. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and protein heterodimerization activity. An important paralog of this gene is ALX3.

UniProtKB/Swiss-Prot for ALX4 Gene

  • Transcription factor involved in skull and limb development. Plays an essential role in craniofacial development, skin and hair follicle development.

Gene Wiki entry for ALX4 Gene

Additional gene information for ALX4 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for ALX4 Gene

Genomics for ALX4 Gene

GeneHancer (GH) Regulatory Elements for ALX4 Gene

Promoters and enhancers for ALX4 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH11J044308 Promoter/Enhancer 1.8 EPDnew Ensembl ENCODE 615.7 +9.8 9819 2 ZFX SP1 NCOA6 EGR1 GMEB1 ZBTB8A ZNF512 ATF1 REST GTF2E2 ALX4 PIR47853
GH11J044319 Enhancer 0.7 FANTOM5 603.5 -0.8 -784 0.3 SP1 ZFX ZNF148 MLLT1 ZNF639 ATF1 REST NRF1 EZH2 MGA ALX4 ENSG00000255451
GH11J044320 Enhancer 0.5 FANTOM5 601.9 -0.1 -76 0.2 ZNF639 EZH2 E2F5 ZKSCAN1 ALX4 ENSG00000255451
GH11J044299 Enhancer 0.8 Ensembl 12.9 +17.8 17819 4 NCOA3 MAFK ZNF639 EGR1 ZIC2 CTBP1 SMARCC1 CEBPB SP1 EZH2 ALX4 PIR47853
GH11J044305 Enhancer 0.5 FANTOM5 10.3 +13.6 13616 0.3 POLR2A EZH2 RNF2 BMI1 CEBPB ALX4 PIR47853
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ALX4 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the ALX4 gene promoter:
  • FOXC1
  • GATA-1
  • Lhx3a
  • LHX3b
  • MyoD
  • MZF-1
  • NF-kappaB
  • NF-kappaB1
  • Pax-3
  • POU6F1 (c2)

Genomic Locations for ALX4 Gene

Genomic Locations for ALX4 Gene
58,783 bases
Minus strand
49,723 bases
Minus strand

Genomic View for ALX4 Gene

Genes around ALX4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ALX4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ALX4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ALX4 Gene

Proteins for ALX4 Gene

  • Protein details for ALX4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Homeobox protein aristaless-like 4
    Protein Accession:
    Secondary Accessions:
    • Q96JN7
    • Q9H198
    • Q9HAY9

    Protein attributes for ALX4 Gene

    411 amino acids
    Molecular mass:
    44241 Da
    Quaternary structure:
    • Binds DNA.
    • Sequence=AAG23961.1; Type=Frameshift; Positions=314, 323, 340; Evidence={ECO:0000305}; Sequence=BAB47417.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for ALX4 Gene

neXtProt entry for ALX4 Gene

Post-translational modifications for ALX4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for ALX4 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for ALX4 Gene

Domains & Families for ALX4 Gene

Gene Families for ALX4 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for ALX4 Gene

Suggested Antigen Peptide Sequences for ALX4 Gene

GenScript: Design optimal peptide antigens:
  • Homeobox protein aristaless-like 4 (ALX4_HUMAN)

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the paired homeobox family.
  • Belongs to the paired homeobox family.
genes like me logo Genes that share domains with ALX4: view

Function for ALX4 Gene

Molecular function for ALX4 Gene

UniProtKB/Swiss-Prot Function:
Transcription factor involved in skull and limb development. Plays an essential role in craniofacial development, skin and hair follicle development.

Phenotypes From GWAS Catalog for ALX4 Gene

Gene Ontology (GO) - Molecular Function for ALX4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding IBA 21873635
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific NAS 19274049
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific IEA,IBA 21873635
GO:0003677 DNA binding NAS 11137991
GO:0003700 DNA-binding transcription factor activity IEA --
genes like me logo Genes that share ontologies with ALX4: view
genes like me logo Genes that share phenotypes with ALX4: view

Human Phenotype Ontology for ALX4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for ALX4 Gene

MGI Knock Outs for ALX4:

Animal Model Products

CRISPR Products

miRNA for ALX4 Gene

miRTarBase miRNAs that target ALX4

Clone Products

  • Applied Biological Materials (abm): Clones for ALX4 - Now 50% OFF >
  • * ALX4 as ready-to-use vector or virus: ORF | Lenti- | Retro- | Adeno- | AAV- | Protein Vector - Browse All
  • * ALX4 tags and reporters available: His, HA, Myc, Flag, GFP, RFP, Luciferase - Browse All

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for ALX4 Gene

Localization for ALX4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ALX4 Gene

Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ALX4 gene
Compartment Confidence
nucleus 5

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for ALX4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus NAS,IBA 11137991
GO:0005667 transcription factor complex IEA --
genes like me logo Genes that share ontologies with ALX4: view

Pathways & Interactions for ALX4 Gene

PathCards logo

SuperPathways for ALX4 Gene

No Data Available

SIGNOR curated interactions for ALX4 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for ALX4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001501 skeletal system development NAS 11106354
GO:0001942 hair follicle development IMP 19692347
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006357 regulation of transcription by RNA polymerase II IEA --
GO:0007275 multicellular organism development IEA --
genes like me logo Genes that share ontologies with ALX4: view

No data available for Pathways by source for ALX4 Gene

Drugs & Compounds for ALX4 Gene

No Compound Related Data Available

Transcripts for ALX4 Gene

mRNA/cDNA for ALX4 Gene

(1) REFSEQ mRNAs :
(4) Additional mRNA sequences :
(11) Selected AceView cDNA sequences:
(2) Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Unigene Clusters for ALX4 Gene

ALX homeobox 4:
Representative Sequences:

CRISPR Products

Clone Products

  • Applied Biological Materials (abm): Clones for ALX4 - Now 50% OFF >
  • * ALX4 as ready-to-use vector or virus: ORF | Lenti- | Retro- | Adeno- | AAV- | Protein Vector - Browse All
  • * ALX4 tags and reporters available: His, HA, Myc, Flag, GFP, RFP, Luciferase - Browse All

Alternative Splicing Database (ASD) splice patterns (SP) for ALX4 Gene

No ASD Table

Relevant External Links for ALX4 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for ALX4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for ALX4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ALX4 Gene

This gene is overexpressed in Breast - Mammary Tissue (x10.9), Skin - Not Sun Exposed (Suprapubic) (x6.5), and Skin - Sun Exposed (Lower leg) (x4.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for ALX4 Gene

NURSA nuclear receptor signaling pathways regulating expression of ALX4 Gene:


SOURCE GeneReport for Unigene cluster for ALX4 Gene:


mRNA Expression by UniProt/SwissProt for ALX4 Gene:

Tissue specificity: Expression is likely to be restricted to bone. Found in parietal bone.

Evidence on tissue expression from TISSUES for ALX4 Gene

  • Nervous system(4.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for ALX4 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
  • cardiovascular
  • digestive
  • integumentary
  • nervous
  • reproductive
  • skeletal muscle
  • skeleton
Head and neck:
  • brain
  • cerebellum
  • cheek
  • cranial nerve
  • ear
  • eye
  • eyelid
  • face
  • forehead
  • head
  • jaw
  • lip
  • mandible
  • maxilla
  • meninges
  • mouth
  • neck
  • nose
  • outer ear
  • scalp
  • skull
  • tooth
  • chest wall
  • clavicle
  • rib
  • rib cage
  • scapula
  • sternum
  • pelvis
  • penis
  • placenta
  • testicle
  • uterus
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
  • blood vessel
  • hair
  • peripheral nervous system
  • skin
  • spinal column
  • vertebrae
genes like me logo Genes that share expression patterns with ALX4: view

No data available for Protein differential expression in normal tissues and Protein tissue co-expression partners for ALX4 Gene

Orthologs for ALX4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for ALX4 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia ALX4 35 34
  • 94.12 (n)
(Bos Taurus)
Mammalia ALX4 35 34
  • 91.1 (n)
(Canis familiaris)
Mammalia ALX4 35 34
  • 90.35 (n)
(Rattus norvegicus)
Mammalia Alx4 34
  • 88.47 (n)
(Mus musculus)
Mammalia Alx4 17 35 34
  • 88.39 (n)
(Monodelphis domestica)
Mammalia ALX4 35
  • 79 (a)
(Ornithorhynchus anatinus)
Mammalia ALX4 35
  • 58 (a)
(Gallus gallus)
Aves ALX4 34
  • 79.37 (n)
ALX-4 35
  • 77 (a)
(Anolis carolinensis)
Reptilia ALX4 35
  • 84 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia alx4 34
  • 72.1 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.16593 34
(Danio rerio)
Actinopterygii alx4a 35 34
  • 70.33 (n)
alx4b 35
  • 63 (a)
Species where no ortholog for ALX4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for ALX4 Gene

Gene Tree for ALX4 (if available)
Gene Tree for ALX4 (if available)
Evolutionary constrained regions (ECRs) for ALX4: view image

Paralogs for ALX4 Gene

(6) SIMAP similar genes for ALX4 Gene using alignment to 1 proteins:

genes like me logo Genes that share paralogs with ALX4: view

Variants for ALX4 Gene

Sequence variations from dbSNP and Humsavar for ALX4 Gene

SNP ID Clin Chr 11 pos Variation AA Info Type
rs10458913 likely-benign, Enlarged parietal foramina 44,263,723(-) A/G 3_prime_UTR_variant
rs104894191 pathogenic, Parietal foramina 2 44,309,645(-) G/A coding_sequence_variant, stop_gained
rs104894192 pathogenic, Parietal foramina 2 44,275,389(-) G/A coding_sequence_variant, stop_gained
rs104894193 pathogenic, Parietal foramina 2, Parietal foramina 2 (PFM2) [MIM:609597] 44,275,472(-) C/T coding_sequence_variant, missense_variant
rs104894196 pathogenic, Parietal foramina 2, Parietal foramina 2 (PFM2) [MIM:609597] 44,267,585(-) C/G/T coding_sequence_variant, missense_variant

Structural Variations from Database of Genomic Variants (DGV) for ALX4 Gene

Variant ID Type Subtype PubMed ID
dgv344e212 CNV loss 25503493
dgv67n21 CNV loss 19592680
esv2761670 CNV loss 21179565
esv3547679 CNV deletion 23714750
esv3579500 CNV loss 25503493
esv3626160 CNV loss 21293372
nsv832139 CNV loss 17160897

Variation tolerance for ALX4 Gene

Residual Variation Intolerance Score: 46.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 17.33; 98.15% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ALX4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
Human Gene Mutation Database (HGMD)

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ALX4 Gene

Disorders for ALX4 Gene

MalaCards: The human disease database

(12) MalaCards diseases for ALX4 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
frontonasal dysplasia 2
  • fnd2
parietal foramina 2
  • foramina parietalia permagna
craniosynostosis 5
  • craniosynostosis 5, susceptibility to
parietal foramina
  • pfm
potocki-shaffer syndrome
  • pss
- elite association - COSMIC cancer census association via MalaCards
Search ALX4 in MalaCards View complete list of genes associated with diseases


  • Parietal foramina 2 (PFM2) [MIM:609597]: 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. {ECO:0000269 PubMed:11106354, ECO:0000269 PubMed:11137991}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Frontonasal dysplasia 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. {ECO:0000269 PubMed:19692347}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Potocki-Shaffer syndrome (POSHS) [MIM:601224]: A syndrome characterized by foramina parietalia permagna, multiple exostoses, and craniofacial dysostosis and mental retardation in some cases. {ECO:0000305 PubMed:11017806, ECO:0000305 PubMed:11903336}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Craniosynostosis 5 (CRS5) [MIM:615529]: A primary abnormality of skull growth involving premature fusion of one or more cranial sutures. The growth velocity of the skull often cannot match that of the developing brain resulting in an abnormal head shape and, in some cases, increased intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability. {ECO:0000269 PubMed:22829454}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Additional Disease Information for ALX4

Genetic Association Database
Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with ALX4: view

No data available for Genatlas for ALX4 Gene

Publications for ALX4 Gene

  1. Haploinsufficiency of ALX4 as a potential cause of parietal foramina in the 11p11.2 contiguous gene-deletion syndrome. (PMID: 11017806) Wu YQ … Shaffer LG (American journal of human genetics 2000) 2 3 4 23 58
  2. ALX4 dysfunction disrupts craniofacial and epidermal development. (PMID: 19692347) Kayserili H … Akarsu NA (Human molecular genetics 2009) 3 4 23 58
  3. The ALX4 homeobox gene is mutated in patients with ossification defects of the skull (foramina parietalia permagna, OMIM 168500). (PMID: 11106354) Wuyts W … Van Hul W (Journal of medical genetics 2000) 3 4 23 58
  4. ALX4 gain-of-function mutations in nonsyndromic craniosynostosis. (PMID: 22829454) Yagnik G … Boyadjiev SA (Human mutation 2012) 3 4 58
  5. Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia. (PMID: 20634891) Jugessur A … Murray JC (PloS one 2010) 3 45 58

Products for ALX4 Gene

Sources for ALX4 Gene

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