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27 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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AXIN1
axin 1
Chromosome 16 · 16p13.3
NCBI Gene: 8312Ensembl: ENSG00000103126.16HGNC: HGNC:903UniProt: A0A0S2Z4R0
321PubMed Papers
23Diseases
0Drugs
4Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneTumor Suppressor
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of protein catabolic processubiquitin protein ligase bindingcell peripheryprotein-containing complex assemblyhepatocellular carcinomacraniometadiaphyseal osteosclerosis with hip dysplasiacancercaudal duplication
✦AI Summary

AXIN1 is a critical scaffold protein that functions as a tumor suppressor through its central role in the β-catenin destruction complex, which regulates Wnt signaling 1. The protein facilitates the phosphorylation and ubiquitination of β-catenin (CTNNB1), thereby controlling its cellular levels and modulating Wnt pathway activity 2. Loss-of-function mutations in AXIN1 occur in approximately 35% of human hepatocellular carcinomas (HCCs), where they contribute to oncogenic Wnt/β-catenin pathway activation 13. AXIN1 mutations are associated with specific mutational signatures in HCC and represent one of the core deregulated pathways in liver cancer 4. Beyond Wnt signaling, AXIN1 regulates additional cellular processes including YAP/TAZ stability in the Hippo pathway, where AXIN1 binds to and stabilizes these transcriptional co-activators 5. Recent studies have also identified AXIN1's role in antiviral immunity, where it stabilizes IRF3 by preventing autophagic degradation and undergoes phase separation upon viral infection to boost interferon production 6. The protein's diverse functions make it an important therapeutic target, with AXIN1 agonists showing promise as both antiviral agents and potential cancer treatments 65.

Sources cited
1
AXIN1 loss-of-function mutations occur in ~35% of HCCs and contribute to Wnt/β-catenin pathway activation
PMID: 35166233
2
AXIN1 functions in the β-catenin destruction complex to regulate Wnt signaling through GSK3 sequestration
PMID: 34196570
3
AXIN1 is among the most frequently mutated genes in HCC and defines core deregulated pathways
PMID: 26099527
4
AXIN1 mutations are associated with specific mutational signatures and represent putative driver alterations in HCC
PMID: 25822088
5
AXIN1 binds to and regulates YAP/TAZ stability in the Hippo pathway
PMID: 35921500
6
AXIN1 stabilizes IRF3 to boost antiviral immunity and undergoes phase separation upon viral infection
PMID: 39384753
Disease Associationsⓘ23
hepatocellular carcinomaOpen Targets
0.79Strong
craniometadiaphyseal osteosclerosis with hip dysplasiaOpen Targets
0.63Moderate
cancerOpen Targets
0.56Moderate
caudal duplicationOpen Targets
0.37Weak
chronic myelogenous leukemiaOpen Targets
0.37Weak
Hepatobiliary NeoplasmOpen Targets
0.37Weak
lung carcinomaOpen Targets
0.37Weak
esophageal adenocarcinomaOpen Targets
0.37Weak
carcinoma of liver and intrahepatic biliary tractOpen Targets
0.37Weak
lymphoid neoplasmOpen Targets
0.37Weak
neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndromeOpen Targets
0.37Weak
nodular melanomaOpen Targets
0.37Weak
Ovarian Endometrioid Adenocarcinoma with Squamous DifferentiationOpen Targets
0.37Weak
prostate carcinomaOpen Targets
0.37Weak
skin basal cell carcinomaOpen Targets
0.37Weak
superficial spreading melanomaOpen Targets
0.37Weak
papillary thyroid carcinomaOpen Targets
0.30Weak
non-small cell lung carcinomaOpen Targets
0.29Weak
melanomaOpen Targets
0.29Weak
esophageal squamous cell carcinomaOpen Targets
0.29Weak
Caudal duplication anomalyUniProt
Craniometadiaphyseal osteosclerosis with hip dysplasiaUniProt
Hepatocellular carcinomaUniProt
Pathogenic Variants4
NM_003502.4(AXIN1):c.2194C>T (p.Gln732Ter)Pathogenic
Craniometadiaphyseal osteosclerosis with hip dysplasia
★☆☆☆2025→ Residue 732
NM_003502.4(AXIN1):c.2503dup (p.Val835fs)Pathogenic
Craniometadiaphyseal osteosclerosis with hip dysplasia
☆☆☆☆2023→ Residue 835
NM_003502.4(AXIN1):c.2521C>T (p.Arg841Ter)Pathogenic
Craniometadiaphyseal osteosclerosis with hip dysplasia
☆☆☆☆2023→ Residue 841
NM_003502.4(AXIN1):c.1085_1116del (p.Val362fs)Pathogenic
Hepatocellular carcinoma
☆☆☆☆2000→ Residue 362
View on ClinVar ↗
Related Genes
ADARProtein interaction100%CSNK1EProtein interaction100%CTNNA1Protein interaction100%CTNNB1Protein interaction100%DAB2Protein interaction100%DVL1Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
97%
Ovary
85%
Liver
61%
Brain
33%
Heart
33%
Gene Interaction Network
Click a node to explore
AXIN1ADARCSNK1ECTNNA1CTNNB1DAB2DVL1
PROTEIN STRUCTURE
Preparing viewer…
PDB1DK8 · 1.57 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.56Moderately Constrained
pLIⓘ
0.16Tolerant
Observed/Expected LoF0.42 [0.31–0.56]
RankingsWhere AXIN1 stands among ~20K protein-coding genes
  • #1,036of 20,598
    Most Researched321 · top 10%
  • #3,681of 5,498
    Most Pathogenic Variants4
  • #3,663of 17,882
    Most Constrained (LOEUF)0.56 · top quartile
Genes detectedAXIN1
Sources retrieved27 papers
Response time—
📄 Sources
27▼
1
β-Catenin signaling in hepatocellular carcinoma.
PMID: 35166233
J Clin Invest · 2022
1.00
2
Cell Biology of Canonical Wnt Signaling.
PMID: 34196570
Annu Rev Cell Dev Biol · 2021
0.90
3
Multi‑layered prevention and treatment of chronic inflammation, organ fibrosis and cancer associated with canonical WNT/β‑catenin signaling activation (Review).
PMID: 29786110
Int J Mol Med · 2018
0.80
4
Precision targeting of β-catenin induces tumor reprogramming and immunity in hepatocellular cancers.
PMID: 40442146
Nat Commun · 2025
0.72
5
Genetic Landscape and Biomarkers of Hepatocellular Carcinoma.
PMID: 26099527
Gastroenterology · 2015
0.70