DFFA (DNA Fragmentation Factor Subunit Alpha)
Key regulator of apoptotic DNA fragmentation and chromatin condensation
Gene Information Card
| Symbol | DFFA |
|---|---|
| Full Name | DNA Fragmentation Factor Subunit Alpha |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.22 |
| NCBI Gene ID | 1676 ncbi.nlm.nih.gov/gene/1676 |
| Ensembl ID | ENSG00000160014 |
| UniProt ID | O00273 |
| OMIM ID | 601833 |
| HGNC ID | 2772 |
| Aliases | DFF45, ICAD, DFF-45, DNA fragmentation factor 45 kDa subunit |
Description
The DFFA gene encodes DNA fragmentation factor subunit alpha (DFF45/ICAD), a key inhibitor of caspase-activated DNase (CAD). During apoptosis, caspase-3 cleaves DFFA, releasing CAD to fragment nuclear DNA and condense chromatin. DFFA is essential for apoptotic DNA degradation and plays roles in development, immune regulation, and tumor suppression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal Cancer | Reduced DFFA expression correlates with impaired apoptosis and tumor progression | PMID: 15604213 |
| Breast Cancer | DFFA downregulation linked to chemoresistance and poor prognosis | PMID: 20629184 |
| Autoimmune Lymphoproliferative Syndrome (ALPS) | DFFA mutations impair apoptotic DNA fragmentation, leading to lymphocyte accumulation | PMID: 10581029 |
| Systemic Lupus Erythematosus (SLE) | Altered DFFA expression may contribute to defective clearance of apoptotic cells | PMID: 17632759 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 11.8 | Medium |
| Bone marrow | 10.2 | Medium |
| Testis | 9.1 | Medium |
| Brain | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.2 | Cervical cancer cell line |
| K562 | 13.5 | Leukemia cell line |
| MCF7 | 11.0 | Breast cancer cell line |
| HEK293 | 9.8 | Embryonic kidney cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.103C>T (p.Arg35Ter) | Nonsense | Rare | Loss of function; truncated protein |
| c.260G>A (p.Arg87Gln) | Missense | Rare | Impaired caspase-3 cleavage site |
| c.497_498del (p.Val166Alafs*12) | Frameshift | Rare | Loss of CAD binding |
| c.682C>T (p.Arg228Trp) | Missense | Rare | Reduced inhibitor activity |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate DFFA, preventing CAD inhibition and leading to premature DNA fragmentation.
Gain of Function (GOF)
Not reported for DFFA.
Dominant Negative (DN)
Missense mutations (e.g., p.Arg87Gln) that disrupt caspase cleavage but retain CAD binding, blocking normal DFFA processing.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Apoptosis (KEGG hsa04210)
• Caspase cascade in apoptosis (Reactome R-HSA-111471)
• DNA fragmentation during apoptosis (Reactome R-HSA-140342)
Protein Summary
DNA fragmentation factor subunit alpha (DFFA) is a 45 kDa protein that forms a heterodimer with CAD (caspase-activated DNase). In non-apoptotic cells, DFFA inhibits CAD nuclease activity. Upon apoptotic stimuli, caspase-3 cleaves DFFA at two sites (D117 and D224), releasing active CAD to fragment genomic DNA into nucleosomal units. DFFA also facilitates CAD folding and nuclear import. The protein contains an N-terminal CAD-binding domain and a C-terminal inhibitory domain. Dysregulation of DFFA contributes to cancer progression and autoimmune disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DFFA Knockout HEK293 Cell Line | EDJ-KQ4438 | Human | 1676 | Details Get a Quote |
| DFFA Knockout A-549 Cell Line | EDJ-KQ26986 | Human | 1676 | Details Get a Quote |
| DFFA Knockout HCT 116 Cell Line | EDJ-KQ26987 | Human | 1676 | Details Get a Quote |
| DFFA Knockout HeLa Cell Line | EDJ-KQ26988 | Human | 1676 | Details Get a Quote |
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