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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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DFFA
DNA fragmentation factor subunit alpha
Chromosome 1 · 1p36.22
NCBI Gene: 1676Ensembl: ENSG00000160049.13HGNC: HGNC:2772UniProt: O00273
94PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Apoptosis
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
negative regulation of apoptotic DNA fragmentationprotein bindingdeoxyribonuclease inhibitor activitynegative regulation of execution phase of apoptosisatrial fibrillationneurodegenerative diseaseandrogenetic alopeciaAbnormality of the skeletal system
✦AI Summary

DFFA (DNA fragmentation factor subunit alpha), also known as DFF45, is a nuclear and cytoplasmic protein that functions as an inhibitor of the caspase-activated DNase DFF40, thereby negatively regulating apoptotic DNA fragmentation and the execution phase of apoptosis 1. Beyond its classical apoptotic role, DFFA is part of the CIDE protein family, which has been redefined as regulators of lipid droplet dynamics and fat metabolism rather than purely apoptotic factors 1. DFFA-like effector proteins (particularly CIDEA, CIDEB, and CIDEC/FSP27) associate with lipid droplets and regulate their fusion and expansion, thereby controlling substrate utilization in adipocytes 2. In metabolic contexts, CIDEA expression is decreased in obese humans and increased following weight loss, suggesting a role in metabolic homeostasis and obesity-related complications 3, 4. Dysregulation of DFFA-related proteins contributes to multiple diseases: CIDEC elevation is associated with diabetic cardiomyopathy through metabolic disturbance and insulin resistance 5, while aberrant DFFA expression patterns correlate with gastrointestinal cancer progression 6. Additionally, DFFA has been identified in the neuroblastoma tumor suppressor region 1p36.2, with rare variants detected in some tumors 7. These findings establish DFFA as a multifunctional protein regulating both apoptosis and metabolic lipid dynamics.

Sources cited
1
CIDE proteins including DFFA-like effectors are lipid droplet-associated regulators of fat metabolism, redefining them from apoptotic proteins to metabolic regulators
PMID: 30871156
2
DFFA-like effector proteins associate with lipid droplets and regulate lipid droplet fusion and expansion in adipocytes
PMID: 36477540
3
CIDEA (DFFA-like effector) expression is decreased in obese humans, normalized after weight loss, and regulates lipolysis
PMID: 15919794
4
CIDEA expression increases in adipose tissue following extensive weight loss from bariatric surgery
PMID: 26434764
5
CIDEC (DFFA-like effector C) elevation causes metabolic disturbance and insulin resistance contributing to diabetic cardiomyopathy
PMID: 33913563
6
DFFA aberrant expression patterns are associated with gastrointestinal cancer development and progression
PMID: 29091952
7
DFFA is located in neuroblastoma tumor suppressor region 1p36.2 with rare variants detected in tumor samples
PMID: 11870543
Disease Associationsⓘ20
atrial fibrillationOpen Targets
0.36Weak
neurodegenerative diseaseOpen Targets
0.30Weak
androgenetic alopeciaOpen Targets
0.10Weak
Abnormality of the skeletal systemOpen Targets
0.09Suggestive
alcohol drinkingOpen Targets
0.08Suggestive
prostate carcinomaOpen Targets
0.08Suggestive
benign prostatic hyperplasiaOpen Targets
0.08Suggestive
adverse effectOpen Targets
0.07Suggestive
response to stimulusOpen Targets
0.07Suggestive
breast carcinomaOpen Targets
0.07Suggestive
ankylosing spondylitisOpen Targets
0.07Suggestive
asthmaOpen Targets
0.07Suggestive
Abnormality of refractionOpen Targets
0.06Suggestive
estrogen-receptor negative breast cancerOpen Targets
0.05Suggestive
breast cancerOpen Targets
0.05Suggestive
oral mucosa leukoplakiaOpen Targets
0.05Suggestive
alopeciaOpen Targets
0.05Suggestive
luminal B breast carcinomaOpen Targets
0.04Suggestive
diabetic ketoacidosisOpen Targets
0.04Suggestive
respiratory system diseaseOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CASP3Protein interaction97%CASP7Protein interaction97%GZMBProtein interaction97%CIDEBProtein interaction95%CIDECProtein interaction92%DNASE2Protein interaction80%
Tissue Expression6 tissues
Brain
100%
Heart
70%
Ovary
57%
Liver
53%
Lung
41%
Bone Marrow
24%
Gene Interaction Network
Click a node to explore
DFFACASP3CASP7GZMBCIDEBCIDECDNASE2
PROTEIN STRUCTURE
Preparing viewer…
PDB1IBX · NMR
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.78LoF Tolerant
pLIⓘ
0.01Tolerant
Observed/Expected LoF0.52 [0.35–0.78]
RankingsWhere DFFA stands among ~20K protein-coding genes
  • #5,078of 20,598
    Most Researched94 · top quartile
  • #6,433of 17,882
    Most Constrained (LOEUF)0.78
Genes detectedDFFA
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
CLSTN3β enforces adipocyte multilocularity to facilitate lipid utilization.
PMID: 36477540
Nature · 2023
1.00
2
The rhythmic coupling of Egr-1 and Cidea regulates age-related metabolic dysfunction in the liver of male mice.
PMID: 36964140
Nat Commun · 2023
0.90
3
A human-specific role of cell death-inducing DFFA (DNA fragmentation factor-alpha)-like effector A (CIDEA) in adipocyte lipolysis and obesity.
PMID: 15919794
Diabetes · 2005
0.80
4
CIDE Proteins in Human Health and Disease.
PMID: 30871156
Cells · 2019
0.70
5
Analyses of apoptotic regulators CASP9 and DFFA at 1P36.2, reveal rare allele variants in human neuroblastoma tumours.
PMID: 11870543
Br J Cancer · 2002
0.60