ALX1: ALX Homeobox 1 Gene
Key regulator of craniofacial development and associated with frontonasal dysplasia
Gene Information Card
| Symbol | ALX1 |
|---|---|
| Full Name | ALX homeobox 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 12q21.31 |
| NCBI Gene ID | 8092 ncbi.nlm.nih.gov/gene/8092 |
| Ensembl ID | ENSG00000135446 |
| UniProt ID | Q15699 |
| OMIM ID | 601526 |
| HGNC ID | 449 |
| Aliases | CART1, ALX1 homeobox, ALX1 transcription factor |
Description
ALX1 (ALX homeobox 1) encodes a homeobox-containing transcription factor essential for craniofacial development. It regulates the expression of genes involved in neural crest cell migration and differentiation. Mutations in ALX1 cause autosomal recessive frontonasal dysplasia type 3 (FND3), characterized by severe craniofacial malformations including hypertelorism, cleft lip/palate, and nasal defects.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Frontonasal dysplasia type 3 (FND3) | Loss-of-function mutations in ALX1 disrupt homeodomain DNA binding, impairing transcriptional regulation of craniofacial development genes. | OMIM #613451; multiple homozygous mutations reported in affected families |
| Craniofacial abnormalities (non-syndromic) | ALX1 variants may contribute to isolated cleft lip/palate via altered neural crest gene expression. | ClinVar; limited case-control studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 0.2 | Low |
| Heart | 0.1 | Low |
| Kidney | 0.1 | Low |
| Liver | 0.1 | Low |
| Lung | 0.1 | Low |
| Muscle | 0.1 | Low |
| Spleen | 0.1 | Low |
| Testis | 0.1 | Low |
| Thyroid | 0.1 | Low |
| Skin | 0.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 0.1 | Low expression; not a primary site |
| HeLa | 0.1 | Low expression |
| K562 | 0.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.64C>T (p.Arg22Ter) | Nonsense | Rare | Premature stop; loss of homeodomain; associated with FND3 |
| c.226C>T (p.Arg76Trp) | Missense | Rare | Disrupts DNA binding; loss of function; FND3 |
| c.331C>T (p.Arg111Ter) | Nonsense | Rare | Truncated protein; loss of function; FND3 |
| c.449G>A (p.Arg150Gln) | Missense | Rare | Reduced transcriptional activity; FND3 |
Mutation functional classification
Loss of Function (LOF)
Most reported ALX1 mutations are loss-of-function (nonsense, frameshift, missense in homeodomain), leading to haploinsufficiency or non-functional protein, causing frontonasal dysplasia type 3.
Gain of Function (GOF)
No gain-of-function mutations reported for ALX1.
Dominant Negative (DN)
No dominant-negative mutations reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity (GO:0003700) | • RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978) |
| • sequence-specific double-stranded DNA binding (GO:1990837) | • regulation of transcription by RNA polymerase II (GO:0006357) |
| • anterior/posterior pattern specification (GO:0009952) | • neural crest cell migration (GO:0001755) |
| • craniofacial development (GO:0060322) |
Pathways
• Craniofacial development (Reactome: R-HSA-5617472)
• Neural crest differentiation (Reactome: R-HSA-375276)
Protein Summary
ALX1 is a 326-amino acid homeobox transcription factor (UniProt Q15699) containing a conserved homeodomain that binds DNA sequences to regulate gene expression during embryonic development. It is critical for neural crest cell migration and patterning of the frontonasal region. The protein localizes to the nucleus and interacts with other transcription factors to modulate craniofacial morphogenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ALX1 Knockout HEK293 Cell Line | EDJ-KQ6172 | Human | 8092 | Details Get a Quote |
| ALX1 Knockout A-549 Cell Line | EDJ-KQ29993 | Human | 8092 | Details Get a Quote |
| ALX1 Knockout HeLa Cell Line | EDJ-KQ29994 | Human | 8092 | Details Get a Quote |
| ALX1 Knockout HCT 116 Cell Line | EDJ-KQ71782 | Human | 8092 | Details Get a Quote |
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