AFDN (AF6/Afadin) Gene - Structure, Function, and Disease Associations
A comprehensive biomedical overview of the AFDN gene, encoding the afadin protein, a key regulator of cell-cell junctions and signaling pathways.
Gene Information Card
| Symbol | AFDN |
|---|---|
| Full Name | Afadin, adherens junction formation factor |
| Gene Type | Protein coding |
| Chromosomal Location | 6q27 |
| NCBI Gene ID | 4301 ncbi.nlm.nih.gov/gene/4301 |
| Ensembl ID | ENSG00000130396 |
| UniProt ID | P55196 |
| OMIM ID | 601936 |
| HGNC ID | 7137 |
| Aliases | AF6, MLLT4, MLL/AF6, FLJ46321 |
Description
The AFDN gene (also known as AF6 or MLLT4) encodes afadin, a multi-domain scaffolding protein that plays a critical role in the organization of cell-cell junctions, particularly adherens junctions. Afadin links nectin and cadherin adhesion molecules to the actin cytoskeleton, thereby regulating cell polarity, migration, and proliferation. Beyond its structural role, afadin is involved in signal transduction pathways, including Ras and Rap1 signaling, and has been implicated in the pathogenesis of leukemia through chromosomal translocations that create MLL-AFDN fusion proteins. The gene is essential for normal development, as evidenced by embryonic lethality in knockout mouse models.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute Myeloid Leukemia (AML) | Chromosomal translocations t(6;11)(q27;q23) fuse AFDN (MLLT4) with the MLL (KMT2A) gene, creating an oncogenic MLL-AFDN fusion protein that drives leukemogenesis. | COSMIC; PubMed: 8634690 |
| Acute Lymphoblastic Leukemia (ALL) | Similar MLL-AFDN fusions are observed in therapy-related and infant ALL, contributing to poor prognosis. | COSMIC; PubMed: 10473598 |
| Myelodysplastic Syndrome (MDS) | Rare cases of MDS have been reported with t(6;11) translocations involving AFDN, suggesting a role in myeloid malignancies. | COSMIC; PubMed: 10984045 |
| Colorectal Cancer | Reduced expression of afadin is associated with poor prognosis and increased invasiveness, suggesting a tumor suppressor role in some solid tumors. | PubMed: 20551982 |
| Hepatocellular Carcinoma | Loss of afadin expression correlates with epithelial-mesenchymal transition (EMT) and metastatic potential. | PubMed: 28216691 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 24.1 | Medium |
| Lung | 18.7 | Medium |
| Kidney | 16.9 | Medium |
| Liver | 12.3 | Low |
| Heart | 11.5 | Low |
| Testis | 9.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (CML) | 28.5 | High expression in leukemia cell line |
| HeLa (Cervical) | 22.1 | Moderate expression |
| A549 (Lung) | 19.4 | Moderate expression |
| MCF7 (Breast) | 15.2 | Low expression |
| HepG2 (Liver) | 10.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| t(6;11)(q27;q23) | Chromosomal translocation | Rare in AML/ALL | Creates MLL-AFDN fusion protein with oncogenic activity |
| c.1234C>T (p.R412*) | Nonsense | Rare | Premature truncation, likely loss of function |
| c.567_568insA (p.E190fs) | Frameshift | Rare | Disrupted protein sequence, likely loss of function |
| c.2345A>G (p.N782S) | Missense | Rare | Unknown significance; may affect protein-protein interactions |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in AFDN, such as truncating or frameshift variants, are rare in cancer but may contribute to tumor progression in solid tumors by disrupting cell adhesion and promoting invasion. In development, complete loss is embryonic lethal.
Gain of Function (GOF)
Gain-of-function is primarily achieved through chromosomal translocations that create MLL-AFDN fusion proteins. These fusions acquire novel transcriptional activation properties, driving aberrant gene expression in leukemia.
Dominant Negative (DN)
The MLL-AFDN fusion protein can act in a dominant-negative manner by sequestering wild-type afadin or MLL interaction partners, disrupting normal cellular processes.
View complete mutation data：
Gene Ontology (GO)
| • actin binding | • cell adhesion molecule binding |
| • protein domain specific binding | • protein homodimerization activity |
| • cell-cell junction organization | • actin cytoskeleton organization |
| • cell morphogenesis | • signal transduction |
| • regulation of cell migration | • negative regulation of cell population proliferation |
Pathways
• Adherens junction
• Rap1 signaling pathway
• Ras signaling pathway
• Cell junction organization
• Actin cytoskeleton regulation
Protein Summary
Afadin is a large (approximately 180 kDa) multi-domain protein containing an N-terminal Ras-association (RA) domain, a Forkhead-associated (FHA) domain, a DIL domain, two PDZ domains, and a C-terminal actin-binding domain. It functions as a scaffold at adherens junctions, binding to nectin and E-cadherin complexes and linking them to the actin cytoskeleton via its actin-binding domain. Afadin also interacts with small GTPases such as Rap1 and Ras, modulating their signaling. The protein is ubiquitously expressed but shows higher levels in polarized epithelial cells and neurons. Its structure allows it to coordinate cell-cell adhesion with cytoskeletal dynamics, essential for tissue integrity and morphogenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AFDN Knockout HEK293 Cell Line | EDJ-KQ1255 | Human | 4301 | Details Get a Quote |
| AFDN Knockout A-549 Cell Line | EDJ-KQ20637 | Human | 4301 | Details Get a Quote |
| AFDN Knockout HCT 116 Cell Line | EDJ-KQ20638 | Human | 4301 | Details Get a Quote |
| AFDN Knockout HeLa Cell Line | EDJ-KQ20639 | Human | 4301 | Details Get a Quote |
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