ACTN4 Gene - Alpha-Actinin-4
Actinin Alpha 4: A key player in podocyte function, cell motility, and cancer progression
Gene Information Card
| Symbol | ACTN4 |
|---|---|
| Full Name | Actinin Alpha 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.2 |
| NCBI Gene ID | 81 ncbi.nlm.nih.gov/gene/81 |
| Ensembl ID | ENSG00000130402 |
| UniProt ID | O43707 |
| OMIM ID | 604638 |
| HGNC ID | 166 |
| Aliases | FSGS1, ACTININ-4, alpha-actinin-4 |
Description
ACTN4 encodes alpha-actinin-4, an actin-binding protein that crosslinks actin filaments and anchors them to the cell membrane. It is essential for podocyte foot process integrity in the kidney glomerulus and plays roles in cell adhesion, migration, and transcriptional regulation. Mutations in ACTN4 cause autosomal dominant focal segmental glomerulosclerosis (FSGS1). Overexpression and mutations are linked to cancer invasion and metastasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Focal segmental glomerulosclerosis 1 (FSGS1) | Missense mutations in the actin-binding domain disrupt podocyte cytoskeleton, leading to foot process effacement and proteinuria. | OMIM #603278; multiple familial FSGS pedigrees |
| Breast cancer | ACTN4 overexpression enhances cell motility and invasion via increased actin dynamics and focal adhesion turnover. | ClinVar; COSMIC; PMID: 20526336 |
| Colorectal cancer | Amplification and overexpression of ACTN4 correlate with poor prognosis and metastatic potential. | COSMIC; PMID: 24576830 |
| Ovarian cancer | ACTN4 upregulation promotes peritoneal dissemination and chemoresistance. | PMID: 21804532 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 28.5 | High |
| Heart | 22.1 | High |
| Skeletal muscle | 18.7 | Medium |
| Liver | 12.3 | Medium |
| Lung | 9.8 | Low |
| Brain | 6.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 32.1 | High expression; used in functional studies |
| HeLa | 18.5 | Moderate; involved in cell adhesion |
| MCF7 | 14.2 | Moderate; linked to invasion |
| A549 | 11.0 | Low; lung adenocarcinoma line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Thr259Ile | Missense | <0.01% | Disrupts actin binding; causes FSGS1 |
| p.Arg310Gln | Missense | <0.01% | Reduces actin crosslinking; FSGS1 |
| p.Lys255Glu | Missense | <0.01% | Alters podocyte cytoskeleton; FSGS1 |
| p.Ser262Pro | Missense | <0.01% | Dominant negative effect; FSGS1 |
| p.Glu407Lys | Missense | 0.02% | Gain of function in cancer cell migration |
Mutation functional classification
Loss of Function (LOF)
Rare truncating or missense mutations that impair actin binding or crosslinking, leading to podocyte cytoskeletal instability.
Gain of Function (GOF)
Overexpression or specific missense variants (e.g., p.Glu407Lys) that enhance cell motility and invasion in cancer.
Dominant Negative (DN)
FSGS1-associated mutations (e.g., p.Thr259Ile) that disrupt normal actin filament organization in the presence of wild-type protein.
View complete mutation data：
Gene Ontology (GO)
| • GO:0003779 - actin binding | • GO:0005515 - protein binding |
| • GO:0005856 - cytoskeleton | • GO:0030027 - lamellipodium |
| • GO:0030054 - cell junction | • GO:0042802 - identical protein binding |
| • GO:0051015 - actin filament binding | • GO:0098978 - glutamatergic synapse |
Pathways
• Regulation of actin cytoskeleton (KEGG: hsa04810)
• Focal adhesion (KEGG: hsa04510)
• Adherens junction (KEGG: hsa04520)
• Leukocyte transendothelial migration (KEGG: hsa04670)
Protein Summary
Alpha-actinin-4 (UniProt O43707) is a 911-amino acid protein that forms antiparallel homodimers, crosslinking actin filaments. It contains an N-terminal actin-binding domain, a central rod domain with four spectrin repeats, and a C-terminal calmodulin-like domain. It localizes to focal adhesions, lamellipodia, and podocyte foot processes. Post-translational modifications include phosphorylation and ubiquitination, regulating its stability and function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ACTN4 Knockout HEK293 Cell Line | EDJ-KQ4003 | Human | 81 | Details Get a Quote |
| ACTN4 Knockout A-549 Cell Line | EDJ-KQ26324 | Human | 81 | Details Get a Quote |
| ACTN4 Knockout HCT 116 Cell Line | EDJ-KQ26325 | Human | 81 | Details Get a Quote |
| ACTN4 Knockout HeLa Cell Line | EDJ-KQ26326 | Human | 81 | Details Get a Quote |
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