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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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AHNAK
AHNAK nucleoprotein
Chromosome 11 · 11q12.3
NCBI Gene: 79026Ensembl: ENSG00000124942.14HGNC: HGNC:347UniProt: B4DTV0
281PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
membrane raftRNA bindingprotein bindingS100 protein bindingAganglionic megacolonhypertrophic cardiomyopathyneoplasmhepatocellular carcinoma
✦AI Summary

AHNAK is a large (~700 kDa) ubiquitously expressed scaffolding nucleoprotein involved in diverse cellular processes through extensive protein-protein interactions 1. Primary functions include calcium homeostasis regulation via interaction with L-type voltage-gated calcium channels in excitable cells 2, membrane repair, and cell architecture maintenance 1. AHNAK mediates DNA damage repair (DDR) pathways critical for cellular stress responses; its mRNA is stabilized by NAT10-mediated ac4C modification, and this stabilization is essential for cisplatin resistance in bladder cancer 3. The protein acts as a scaffolding component in TGF-β/Smad signaling, where it regulates epithelial-mesenchymal transition in cancer progression 4. In disease contexts, AHNAK emerges as a key driver protein in Alzheimer's disease pathogenesis within glia-neuron interaction networks 5, and its dysregulation is implicated in multiple cancer types through MAPK, ERK, Wnt, and MEK pathway activation 6. AHNAK is essential for productive infection by both influenza A and SARS-CoV-2 viruses 7, and somatic AHNAK mutations contribute to intracranial aneurysm pathogenesis via NF-κB signaling dysregulation 8. These diverse roles establish AHNAK as a multifunctional therapeutic target across neurodegeneration, oncology, and infectious disease contexts.

Sources cited
1
AHNAK is a ~700 kDa scaffolding protein with roles in blood-brain barrier formation, cell architecture, migration, calcium channel regulation, and tumor metastasis
PMID: 25172424
2
AHNAK regulates calcium homeostasis through interaction with L-type voltage-gated calcium channels in excitable cells
PMID: 33813182
3
NAT10 stabilizes AHNAK mRNA through ac4C modification, and AHNAK-mediated DNA damage repair is required for cisplatin resistance in bladder cancer
PMID: 36939377
4
AHNAK is a key regulator of TGF-β/Smad signaling that promotes epithelial-mesenchymal transition in non-small cell lung cancer
PMID: 38890620
5
AHNAK is a top key driver protein in an AD-associated glia-neuron interaction network identified through proteomic network modeling
PMID: 41005309
6
AHNAK dysregulation in cancers activates ERK, MAPK, Wnt, and MEK signaling pathways and promotes tumor progression
PMID: 38033502
7
AHNAK is essential for productive infection by both influenza A virus and SARS-CoV-2
PMID: 37758692
8
Somatic AHNAK mutations are present in 43% of intracranial aneurysm cases and are linked to NF-κB signaling dysregulation
PMID: 37315111
Disease Associationsⓘ20
Aganglionic megacolonOpen Targets
0.27Weak
hypertrophic cardiomyopathyOpen Targets
0.12Weak
neoplasmOpen Targets
0.11Weak
hepatocellular carcinomaOpen Targets
0.09Suggestive
cancerOpen Targets
0.09Suggestive
ovarian cancerOpen Targets
0.08Suggestive
systemic lupus erythematosusOpen Targets
0.08Suggestive
triple-negative breast cancerOpen Targets
0.08Suggestive
gliomaOpen Targets
0.08Suggestive
melanomaOpen Targets
0.07Suggestive
esophageal squamous cell carcinomaOpen Targets
0.07Suggestive
ThymomaOpen Targets
0.07Suggestive
lung adenocarcinomaOpen Targets
0.06Suggestive
Hepatic steatosisOpen Targets
0.06Suggestive
Chronic mucocutaneous candidosisOpen Targets
0.06Suggestive
breast cancerOpen Targets
0.05Suggestive
liver diseaseOpen Targets
0.05Suggestive
Autosomal recessive hyper-IgE syndromeOpen Targets
0.05Suggestive
Autosomal recessive hyper-IgE syndrome due to TYK2 deficiencyOpen Targets
0.05Suggestive
immunodeficiency 35Open Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CLK1Shared pathway100%HNRNPH2Shared pathway100%RBM12Shared pathway100%MBNL2Shared pathway100%ESRP1Shared pathway100%RBM38Shared pathway100%
Tissue Expression6 tissues
Lung
100%
Ovary
77%
Heart
65%
Bone Marrow
23%
Liver
20%
Brain
16%
Gene Interaction Network
Click a node to explore
AHNAKCLK1HNRNPH2RBM12MBNL2ESRP1RBM38
PROTEIN STRUCTURE
Preparing viewer…
PDB4HRG · 2.00 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.79LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.56 [0.40–0.79]
RankingsWhere AHNAK stands among ~20K protein-coding genes
  • #1,283of 20,598
    Most Researched281 · top 10%
  • #6,553of 17,882
    Most Constrained (LOEUF)0.79
Genes detectedAHNAK
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
NAT10 Drives Cisplatin Chemoresistance by Enhancing ac4C-Associated DNA Repair in Bladder Cancer.
PMID: 36939377
Cancer Res · 2023
1.00
2
Multiscale proteomic modeling reveals protein networks driving Alzheimer's disease pathogenesis.
PMID: 41005309
Cell · 2025
0.90
3
Proteomic and genetic analyses of influenza A viruses identify pan-viral host targets.
PMID: 37758692
Nat Commun · 2023
0.80
4
AHNAKs roles in physiology and malignant tumors.
PMID: 38033502
Front Oncol · 2023
0.70
5
PRMT5-mediated arginine methylation of FXR1 is essential for RNA binding in cancer cells.
PMID: 38709899
Nucleic Acids Res · 2024
0.64