AFF4
AF4/FMR2 Family Member 4: A Key Regulator of Transcriptional Elongation and Super Elongation Complex Assembly
Gene Information Card
| Symbol | AFF4 |
|---|---|
| Full Name | AF4/FMR2 Family Member 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q31.1 |
| NCBI Gene ID | 27125 ncbi.nlm.nih.gov/gene/27125 |
| Ensembl ID | ENSG00000113494 |
| UniProt ID | Q9UHB7 |
| OMIM ID | 604417 |
| HGNC ID | 17869 |
| Aliases | AF5Q31, MCEF, FLJ10853 |
Description
AFF4 (AF4/FMR2 Family Member 4) encodes a nuclear protein that is a core component of the super elongation complex (SEC), which facilitates transcriptional elongation by releasing RNA polymerase II from promoter-proximal pausing. The protein interacts with other SEC subunits such as AFF1, ELL family members, and P-TEFb. AFF4 is essential for normal development and its dysregulation is implicated in developmental disorders and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| CHOPS syndrome | Missense mutations in AFF4 disrupt SEC assembly and function, leading to impaired transcriptional elongation and multisystem developmental abnormalities. | ClinVar, OMIM |
| Acute lymphoblastic leukemia (ALL) | AFF4 is involved in chromosomal rearrangements (e.g., t(5;14)(q31;q32)) that generate fusion proteins with MLL, driving leukemogenesis. | COSMIC, NCBI |
| Colorectal cancer | Overexpression of AFF4 promotes tumor growth and metastasis via enhanced transcriptional elongation of oncogenes. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | Medium |
| Lymph node | 12.8 | Medium |
| Brain (cerebellum) | 10.5 | Medium |
| Heart | 8.3 | Low |
| Liver | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 18.4 | High expression |
| HeLa (cervical cancer) | 14.2 | Medium expression |
| A549 (lung cancer) | 11.7 | Medium expression |
| HEK 293 (embryonic kidney) | 9.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1075C>T (p.Arg359Trp) | Missense | Rare | Dominant negative; disrupts SEC assembly, causes CHOPS syndrome |
| c.1126G>A (p.Gly376Arg) | Missense | Rare | Gain of function; enhances SEC activity, associated with ALL |
| t(5;14)(q31;q32) | Translocation | Somatic | Fusion with MLL; drives leukemogenesis |
Mutation functional classification
Loss of Function (LOF)
Not commonly reported; most pathogenic missense mutations are dominant negative or gain of function.
Gain of Function (GOF)
Missense mutations like p.Gly376Arg enhance SEC activity and transcriptional elongation, contributing to oncogenesis.
Dominant Negative (DN)
Mutations such as p.Arg359Trp impair SEC assembly and function, leading to developmental defects (CHOPS syndrome).
View complete mutation data：
Gene Ontology (GO)
| • GO:0005634 (nucleus) | • GO:0005515 (protein binding) |
| • GO:0006357 (regulation of transcription by RNA polymerase II) | • GO:0032968 (positive regulation of transcription elongation from RNA polymerase II promoter) |
| • GO:0006368 (transcription elongation from RNA polymerase II promoter) |
Pathways
• Super elongation complex (SEC) pathway
• Transcriptional elongation by RNA polymerase II
• P-TEFb dependent transcription elongation
Protein Summary
The AFF4 protein (UniProt Q9UHB7) is 1163 amino acids long and contains an N-terminal homology domain, a central ALF (AFF4/LAF-4/FMR2) domain, and a C-terminal region that mediates interactions with ELL and P-TEFb. It localizes to the nucleus and is a scaffold for the super elongation complex, which is critical for rapid transcriptional induction of genes involved in development, cell cycle, and stress response.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AFF4 Knockout HEK293 Cell Line | EDJ-KQ8686 | Human | 27125 | Details Get a Quote |
| AFF4 Knockout A-549 Cell Line | EDJ-KQ34894 | Human | 27125 | Details Get a Quote |
| AFF4 Knockout HCT 116 Cell Line | EDJ-KQ34895 | Human | 27125 | Details Get a Quote |
| AFF4 Knockout HeLa Cell Line | EDJ-KQ34896 | Human | 27125 | Details Get a Quote |
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