ALX1

Chr 12AR

ALX homeobox 1

Also known as: CART1, FND3, HEL23

NCBI Gene: 8092ENSG00000180318UniProt: Q15699

The specific function of this gene has yet to be determined in humans; however, in rodents, it is necessary for survival of the forebrain mesenchyme and may also be involved in development of the cervix. Mutations in the mouse gene lead to neural tube defects such as acrania and meroanencephaly. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Frontonasal dysplasia 3MIM #613456
AR
0
ClinVar variants
0
Pathogenic / LP
0.18
pLI score
0
Active trials
Clinical Summary— ALX1
🧬
Gene-Disease Validity (ClinGen)
frontonasal dysplasia - severe microphthalmia - severe facial clefting syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.61LOEUF
pLI 0.176
Z-score 2.64
OE 0.27 (0.13–0.61)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.10Z-score
OE missense 0.98 (0.87–1.11)
183 obs / 186.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.27 (0.13–0.61)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.87–1.11)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.04
0≤1.21.6
LoF obs/exp: 4 / 15.1Missense obs/exp: 183 / 186.7Syn Z: -0.25

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

ALX1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ALX1-related frontonasal dysplasia

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Frontonasal dysplasia 3

MIM #613456

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification of a DNA-methylome-based signature for prognosis prediction in driver gene-negative lung adenocarcinoma.
Shu M et al.·Cancer Lett
2024
ALX1-related frontonasal dysplasia results from defective neural crest cell development and migration.
Pini J et al.·EMBO Mol Med
2020
ALX-Related Frontonasal Dysplasias: Clinical Characteristics and Surgical Management.
Vargel I et al.·Cleft Palate Craniofac J
2022
Disruption of ALX1 causes extreme microphthalmia and severe facial clefting: expanding the spectrum of autosomal-recessive ALX-related frontonasal dysplasia.
Uz E et al.·Am J Hum Genet
2010
Exome sequencing revealed a novel splice site variant in the ALX1 gene underlying frontonasal dysplasia.
Ullah A et al.·Clin Genet
2017
The oculoauriculofrontonasal syndrome: Further clinical characterization and additional evidence suggesting a nontraditional mode of inheritance.
Lehalle D et al.·Am J Med Genet A
2018
Identification and validation of a novel autoantibody biomarker panel for differential diagnosis of pancreatic ductal adenocarcinoma.
Mowoe MO et al.·Front Immunol
2025
Clinical and molecular characterization of a transmitted reciprocal translocation t(1;12)(p32.1;q21.3) in a family co-segregating with mental retardation, language delay, and microcephaly.
Liao HM et al.·BMC Med Genet
2011
Novel Potential Biomarkers for Opisthorchis viverrini Infection and Associated Cholangiocarcinoma.
Aksorn N et al.·In Vivo
2018
Profiling of long non-coding RNAs identifies LINC00958 and LINC01296 as candidate oncogenes in bladder cancer.
Seitz AK et al.·Sci Rep
2017
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
lnc-ALX1-2:10 is a novel regulator that enhances proliferation, migration and invasion in prostate cancer cells.
Wang X et al.·Sci Rep
2026
The ALX1 transcription factor acts in the early cranial mesoderm to specify extraocular muscle formation.
Iyyanar PPR et al.·Dis Model Mech
2026🔓 Open Access
Retinoic Acid-Regulated Epigenetic Marks Identify Alx1 as a Direct Target Gene Required for Optic Cup Formation.
Berenguer M et al.·Genes (Basel)
2025🔓 Open Access
Correlation between CT spectral quantitative parameters and expression levels of HIF-1α and ALX1 in non-small cell lung cancer.
Jia Y et al.·Medicine (Baltimore)
2024🔓 Open Access
ALX1-transcribed LncRNA AC132217.4 promotes osteogenesis and bone healing via IGF-AKT signaling in mesenchymal stem cells.
Zhang C et al.·Cell Mol Life Sci
2022
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools