ALX4

Chr 11ADAR

ALX homeobox 4

Also known as: CRS5, FND2

NCBI Gene: 60529 ENSG00000052850 UniProt: Q9H161 OMIM: 605420

ALX4 encodes a paired-like homeodomain transcription factor involved in skull and limb development, playing an essential role in craniofacial development, skin and hair follicle development. Mutations cause autosomal dominant parietal foramina 2 (characterized by deficient ossification of the parietal bones), frontonasal dysplasia 2 with alopecia and hypogonadism, and craniosynostosis 5. Deletions involving ALX4 contribute to Potocki-Shaffer syndrome, which includes craniofacial anomalies, cognitive disability, multiple exostoses, and genital abnormalities in males.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Craniosynostosis 5, susceptibility to}MIM #615529

Frontonasal dysplasia 2MIM #613451

Parietal foramina 2MIM #609597

UniProtPotocki-Shaffer syndrome

Clinical highlights

Gene-disease validity (ClinGen)

frontonasal dysplasia with alopecia and genital anomaly · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.52

LOEUF

LOF

Mechanism· G2P

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GeneReview available — ALX4