DFFB (DNA Fragmentation Factor Subunit Beta)
A key endonuclease in caspase-activated DNase (CAD) pathway for apoptotic DNA fragmentation
Gene Information Card
| Symbol | DFFB |
|---|---|
| Full Name | DNA fragmentation factor subunit beta |
| Gene Type | protein-coding |
| Chromosomal Location | 1p36.3 |
| NCBI Gene ID | 1677 ncbi.nlm.nih.gov/gene/1677 |
| Ensembl ID | ENSG00000169598 |
| UniProt ID | O76075 |
| OMIM ID | 601875 |
| HGNC ID | 2775 |
| Aliases | CAD, CPAN, DFF-40, DFF2, DFF40, ICAD |
Description
DFFB encodes the 40 kDa caspase-activated DNase (CAD), also known as DNA fragmentation factor subunit beta. In non-apoptotic cells, CAD is inhibited by binding to its chaperone/inhibitor DFFA (ICAD). Upon apoptotic stimuli, caspase-3 cleaves DFFA, releasing active CAD which translocates to the nucleus and cleaves chromosomal DNA into internucleosomal fragments, a hallmark of apoptosis. DFFB is essential for DNA fragmentation during programmed cell death.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autoimmune lymphoproliferative syndrome (ALPS) type III | Defective DFFB leads to impaired apoptotic DNA fragmentation and accumulation of lymphocytes | PMID: 16973135 |
| Colorectal cancer | Reduced DFFB expression correlates with resistance to apoptosis and poor prognosis | PMID: 19160496 |
| Breast cancer | DFFB downregulation associated with chemoresistance and metastasis | PMID: 22006535 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 12.3 | Medium |
| Lymph node | 10.8 | Medium |
| Bone marrow | 9.5 | Medium |
| Thymus | 8.7 | Medium |
| Testis | 7.2 | Low |
| Colon | 6.1 | Low |
| Breast | 4.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical cancer cell line; high expression |
| K562 | 12.8 | Leukemia cell line; moderate expression |
| MCF7 | 8.3 | Breast cancer cell line; reduced expression |
| HCT116 | 7.9 | Colorectal cancer cell line; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.985C>T (p.Arg329*) | Nonsense | Rare | Loss of function; truncation of CAD endonuclease domain |
| c.682G>A (p.Glu228Lys) | Missense | Rare | Impaired caspase-3 cleavage site; reduced DNase activity |
| c.1A>G (p.Met1Val) | Start loss | Rare | Loss of translation initiation; complete loss of protein |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg329*) abolish CAD endonuclease activity, preventing DNA fragmentation and promoting cell survival.
Gain of Function (GOF)
No gain-of-function mutations reported in DFFB.
Dominant Negative (DN)
Missense mutations in the active site (e.g., p.His242Gln) can act as dominant-negative by forming inactive heterodimers with wild-type CAD.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Apoptosis – DNA fragmentation (KEGG: hsa04210)
• Caspase cascade in apoptosis (Reactome: R-HSA-111471)
Protein Summary
DFFB encodes the 40 kDa caspase-activated DNase (CAD), a magnesium-dependent endonuclease that cleaves double-stranded DNA at internucleosomal sites during apoptosis. The protein contains an N-terminal regulatory domain that binds DFFA (ICAD) and a C-terminal catalytic domain with a conserved HNH endonuclease motif. Upon caspase-3 cleavage of DFFA, CAD is released, dimerizes, and translocates to the nucleus to execute DNA fragmentation. DFFB is widely expressed in lymphoid tissues and is critical for immune homeostasis and tumor suppression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DFFB Knockout HEK293 Cell Line | EDJ-KQ1302 | Human | 1677 | Details Get a Quote |
| DFFB Knockout A-549 Cell Line | EDJ-KQ22016 | Human | 1677 | Details Get a Quote |
| DFFB Knockout HCT 116 Cell Line | EDJ-KQ22018 | Human | 1677 | Details Get a Quote |
| DFFB Knockout HeLa Cell Line | EDJ-KQ22019 | Human | 1677 | Details Get a Quote |
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