ALX4 ALX homeobox 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ALX4provided by HGNC
Official Full Name: ALX homeobox 4provided by HGNC
Primary source: HGNC:HGNC:450
See related: Ensembl:ENSG00000052850 MIM:605420; AllianceGenome:HGNC:450
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CRS5; FND2
Summary: 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]
Expression: Low expression observed in reference dataset See more
Orthologs: mouse all
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Genomic context

Location:: 11p11.2

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (44260440..44310139, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (44415783..44465465, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (44281990..44331689, complement)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Dominant frontonasal dysplasia with ectodermal defects results from increased activity of ALX4.
Title: Dominant frontonasal dysplasia with ectodermal defects results from increased activity of ALX4.
De novo ALX4 variant detected in child with non-syndromic craniosynostosis.
Title: De novo ALX4 variant detected in child with non-syndromic craniosynostosis.
Variants in ALX4 and their association with genitourinary defects.
Title: Variants in ALX4 and their association with genitourinary defects.
Overexpression of circ_0001445 decelerates hepatocellular carcinoma progression by regulating miR-942-5p/ALX4 axis.
Title: Overexpression of circ_0001445 decelerates hepatocellular carcinoma progression by regulating miR-942-5p/ALX4 axis.
Vertical transmission of a large calvarial ossification defect due to heterozygous variants of ALX4 and TWIST1.
Title: Vertical transmission of a large calvarial ossification defect due to heterozygous variants of ALX4 and TWIST1.
miR-1470 regulates cell proliferation and apoptosis by targeting ALX4 in hepatocellular carcinoma.
Title: miR-1470 regulates cell proliferation and apoptosis by targeting ALX4 in hepatocellular carcinoma.
We reveal for the first time that ALX4 acts as a novel functional tumor suppressor inactivated by DNA methylation and is an independent prognostic factor in breast cancer
Title: ALX4, an epigenetically down regulated tumor suppressor, inhibits breast cancer progression by interfering Wnt/β-catenin pathway.
overexpression of ALX4 inhibited the proliferation, invasion, and epithelial-mesenchymal transition (EMT) in HCC cells. ALX4 had an inhibitory effect on the sonic hedgehog (Shh) signaling pathway.
Title: Overexpression of Aristaless-Like Homeobox-4 Inhibits Proliferation, Invasion, and EMT in Hepatocellular Carcinoma Cells.
mother of Case 2 also had a mutation in the ALX4 gene, but no enlarged parietal foramina
Title: [Mother and son with enlarged parietal foramina, persistent fetal vein, and ALX4 mutation].
Our results show that HOXB13/SLUG and ALX4/SLUG axes are novel pathways that promote EMT and invasion of ovarian cancer cells.
Title: HOXB13 and ALX4 induce SLUG expression for the promotion of EMT and cell invasion in ovarian cancer cells.

Submit: New GeneRIF Correction See all GeneRIFs (25)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Craniosynostosis 5, susceptibility to MedGen: C3809819 OMIM: 615529 GeneReviews: Not available	Compare labs
Frontonasal dysplasia with alopecia and genital anomaly MedGen: C3150703 OMIM: 613451 GeneReviews: Not available	Compare labs
Parietal foramina 2 MedGen: C1865044 OMIM: 609597 GeneReviews: Enlarged Parietal Foramina	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2020-07-22) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2020-07-22) ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
Genome-wide association study identifies 8 novel loci associated with blood pressure responses to interventions in Han Chinese. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:482838

NoName (e-PCR)
- UniSTS:480627

D11S2375 (e-PCR)
- UniSTS:59301

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA binding	NAS Non-traceable Author Statement more info	PubMed
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
enables HMG box domain binding	IEA Inferred from Electronic Annotation more info
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sequence-specific double-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in anterior/posterior pattern specification	IEA Inferred from Electronic Annotation more info
involved_in digestive tract development	IEA Inferred from Electronic Annotation more info
involved_in embryonic digit morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in embryonic forelimb morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in embryonic hindlimb morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in embryonic skeletal system morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in hair follicle development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in muscle organ development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in post-embryonic development	IEA Inferred from Electronic Annotation more info
involved_in regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in roof of mouth development	IEA Inferred from Electronic Annotation more info
involved_in skeletal system development	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in chromatin	ISA Inferred from Sequence Alignment more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	NAS Non-traceable Author Statement more info	PubMed
part_of transcription regulator complex	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: homeobox protein aristaless-like 4

Names: aristaless-like homeobox 4; homeodomain transcription factor ALX4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.