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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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ACTN1
actinin alpha 1
Chromosome 14 Β· 14q24.1|14q22-q24
NCBI Gene: 87Ensembl: ENSG00000072110.17HGNC: HGNC:163UniProt: A0A024R694
358PubMed Papers
21Diseases
0Drugs
21Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub Gene
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
glutamatergic synapseplatelet activationactin filamentZ discplatelet-type bleeding disorder 15MacrothrombocytopeniaThrombocytopeniatype 2 diabetes mellitus
✦AI Summary

ACTN1 (actinin alpha 1) is an F-actin cross-linking cytoskeletal protein that anchors actin filaments to intracellular structures and regulates actin filament organization and bundle assembly. Beyond its canonical cytoskeletal role, ACTN1 has emerged as a critical oncogenic driver across multiple cancer types. In head and neck squamous cell carcinoma, ACTN1 promotes tumorigenesis and cisplatin resistance by enhancing MYH9-dependent GSK-3Ξ² degradation and activating integrin Ξ²1-mediated FAK/PI3K/AKT signaling, with high expression correlating with poor chemotherapy response and reduced overall survival 1. In triple-negative breast cancer, elevated ACTN1 confers chemoresistance and survival advantages in basal epithelial subpopulations 2. Similarly, in thyroid carcinoma, ACTN1 overexpression promotes cell proliferation, migration, invasion, and epithelial-mesenchymal transition through PI3K/AKT/mTOR pathway activation, correlating with metastasis and poor prognosis 3. In glioblastoma, USP14-mediated stabilization of ACTN1 maintains mesenchymal characteristics and drives proneural-to-mesenchymal transition, with elevated expression predicting poor survival 4. Clinically, ACTN1 also serves as a serum extracellular vesicle biomarker for cholangiocarcinoma prognosis 5. Genetically, pathogenic ACTN1 variants cause autosomal dominant macrothrombocytopenia through actin network disorganization 6, and functional compensation by ACTN1 occurs in PLS3-related bone disorders 7.

Sources cited
1
ACTN1 promotes HNSCC tumorigenesis and cisplatin resistance via MYH9-GSK-3Ξ² and integrin Ξ²1-FAK signaling; high expression correlates with poor chemotherapy response and overall survival
PMID: 38057867
2
ACTN1 confers survival advantage and chemoresistance in basal epithelial subpopulations of triple-negative breast cancer
PMID: 38480932
3
ACTN1 promotes thyroid cancer cell proliferation, migration, invasion, and EMT through PI3K/AKT/mTOR pathway activation; associated with metastasis and poor prognosis
PMID: 39738470
4
USP14-mediated ACTN1 stabilization maintains mesenchymal characteristics in glioblastoma and drives proneural-to-mesenchymal transition; elevated expression predicts poor survival
PMID: 41291211
5
ACTN1 serves as a prognostic serum extracellular vesicle biomarker for cholangiocarcinoma
PMID: 36868481
6
Pathogenic ACTN1 variants cause autosomal dominant macrothrombocytopenia through actin network disorganization
PMID: 31237726
7
ACTN1 provides functional compensation in PLS3-related bone disorders
PMID: 39273077
Disease Associationsβ“˜21
platelet-type bleeding disorder 15Open Targets
0.79Strong
MacrothrombocytopeniaOpen Targets
0.62Moderate
ThrombocytopeniaOpen Targets
0.48Moderate
type 2 diabetes mellitusOpen Targets
0.44Moderate
restless legs syndromeOpen Targets
0.43Moderate
genetic disorderOpen Targets
0.38Weak
autosomal dominant macrothrombocytopeniaOpen Targets
0.37Weak
diabetes mellitusOpen Targets
0.36Weak
migraine disorderOpen Targets
0.34Weak
chronic obstructive pulmonary diseaseOpen Targets
0.33Weak
mixed connective tissue diseaseOpen Targets
0.32Weak
health study participationOpen Targets
0.31Weak
First degree atrioventricular blockOpen Targets
0.30Weak
major depressive disorderOpen Targets
0.29Weak
thyroid diseaseOpen Targets
0.27Weak
Urethral strictureOpen Targets
0.26Weak
Crohn's diseaseOpen Targets
0.22Weak
Abnormal bleedingOpen Targets
0.15Weak
smoking cessationOpen Targets
0.14Weak
Abnormal platelet functionOpen Targets
0.12Weak
Bleeding disorder, platelet-type, 15UniProt
Pathogenic Variants21
NM_001130004.2(ACTN1):c.137G>A (p.Arg46Gln)Pathogenic
Platelet-type bleeding disorder 15|Macrothrombocytopenia|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 46
NM_001130004.2(ACTN1):c.313G>A (p.Val105Ile)Pathogenic
Platelet-type bleeding disorder 15|Macrothrombocytopenia|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 105
NM_001130004.2(ACTN1):c.136C>T (p.Arg46Trp)Pathogenic
Thrombocytopenia|Macrothrombocytopenia|Inborn genetic diseases|Platelet-type bleeding disorder 15|not provided|ACTN1-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 46
NM_001130004.2(ACTN1):c.673G>A (p.Glu225Lys)Pathogenic
Platelet-type bleeding disorder 15|Macrothrombocytopenia|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 225
NM_001130004.2(ACTN1):c.1348C>T (p.Arg450Cys)Pathogenic
Platelet-type bleeding disorder 15
β˜…β˜…β˜†β˜†β†’ Residue 450
NM_001130004.2(ACTN1):c.2225G>T (p.Gly742Val)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 742
NM_001130004.2(ACTN1):c.388A>G (p.Ile130Val)Likely pathogenic
Platelet-type bleeding disorder 15
β˜…β˜†β˜†β˜†2024β†’ Residue 130
NM_001130004.2(ACTN1):c.2728G>C (p.Gly910Arg)Likely pathogenic
Abnormal bleeding;Thrombocytopenia|Platelet-type bleeding disorder 15
β˜…β˜†β˜†β˜†2022β†’ Residue 910
NM_001130004.2(ACTN1):c.1592A>T (p.Asp531Val)Likely pathogenic
Thrombocytopenia
β˜…β˜†β˜†β˜†2019β†’ Residue 531
NM_001130004.2(ACTN1):c.1592_1593insGGGGCCATGGAG (p.Asp531delinsGluGlyProTrpSer)Likely pathogenic
Thrombocytopenia
β˜…β˜†β˜†β˜†2019β†’ Residue 531
NM_001130004.2(ACTN1):c.2551G>A (p.Val851Ile)Likely pathogenic
Platelet-type bleeding disorder 15
β˜…β˜†β˜†β˜†β†’ Residue 851
NM_001130004.2(ACTN1):c.1864C>T (p.His622Tyr)Likely pathogenic
Platelet-type bleeding disorder 15
β˜…β˜†β˜†β˜†β†’ Residue 622
NM_001130004.2(ACTN1):c.1295C>T (p.Ala432Val)Likely pathogenic
Platelet-type bleeding disorder 15
β˜…β˜†β˜†β˜†β†’ Residue 432
NM_001130004.2(ACTN1):c.1193A>C (p.Lys398Thr)Likely pathogenic
Platelet-type bleeding disorder 15
β˜…β˜†β˜†β˜†β†’ Residue 398
NM_001130004.2(ACTN1):c.986A>G (p.Gln329Arg)Likely pathogenic
Platelet-type bleeding disorder 15
β˜…β˜†β˜†β˜†β†’ Residue 329
NM_001130004.2(ACTN1):c.970A>G (p.Lys324Glu)Likely pathogenic
Platelet-type bleeding disorder 15
β˜…β˜†β˜†β˜†β†’ Residue 324
NM_001130004.2(ACTN1):c.1184T>A (p.Leu395Gln)Likely pathogenic
ACTN1-related disorder
β˜†β˜†β˜†β˜†2024β†’ Residue 395
NM_001130004.2(ACTN1):c.342A>C (p.Glu114Asp)Likely pathogenic
Platelet-type bleeding disorder 15
β˜†β˜†β˜†β˜†2022β†’ Residue 114
NM_001130004.2(ACTN1):c.94C>A (p.Gln32Lys)Pathogenic
Platelet-type bleeding disorder 15
β˜†β˜†β˜†β˜†2013β†’ Residue 32
NM_001130004.2(ACTN1):c.127T>A (p.Ser43Thr)Likely pathogenic
Platelet-type bleeding disorder 15
β˜†β˜†β˜†β˜†β†’ Residue 43
View on ClinVar β†—
Related Genes
ACTBProtein interaction100%ACTG1Protein interaction100%ITGA6Protein interaction100%CTNNA1Protein interaction100%ZYXProtein interaction100%VCLProtein interaction100%
Tissue Expression6 tissues
Lung
100%
Bone Marrow
99%
Heart
85%
Liver
61%
Ovary
50%
Brain
35%
Gene Interaction Network
Click a node to explore
ACTN1ACTBACTG1ITGA6CTNNA1ZYXVCL
PROTEIN STRUCTURE
Preparing viewer…
PDB2EYI Β· 1.70 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.33Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.24 [0.18–0.33]
RankingsWhere ACTN1 stands among ~20K protein-coding genes
  • #863of 20,598
    Most Researched358 Β· top 5%
  • #2,126of 5,498
    Most Pathogenic Variants21
  • #1,388of 17,882
    Most Constrained (LOEUF)0.33 Β· top 10%
Genes detectedACTN1
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Liquid biopsy-based protein biomarkers for risk prediction, early diagnosis, and prognostication of cholangiocarcinoma.
PMID: 36868481
J Hepatol Β· 2023
1.00
2
ACTN1 promotes HNSCC tumorigenesis and cisplatin resistance by enhancing MYH9-dependent degradation of GSK-3Ξ² and integrin Ξ²1-mediated phosphorylation of FAK.
PMID: 38057867
J Exp Clin Cancer Res Β· 2023
0.90
3
Exploring CD26
PMID: 39319599
Allergy Β· 2024
0.80
4
Basal-epithelial subpopulations underlie and predict chemotherapy resistance in triple-negative breast cancer.
PMID: 38480932
EMBO Mol Med Β· 2024
0.80
5
ACTN1 promotes cell invasion, migration, and EMT in thyroid cancer and is associated with immune infiltration.
PMID: 39738470
Sci Rep Β· 2024
0.70