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28 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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GADD45A
growth arrest and DNA damage inducible alpha
Chromosome 1 · 1p31.3
NCBI Gene: 1647Ensembl: ENSG00000116717.13HGNC: HGNC:4095UniProt: A5JUZ3
212PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingkinase bindingprotein homodimerization activityprotein heterodimerization activitycataractgastroenteritisglaucomaspermatocele
✦AI Summary

GADD45A (Growth Arrest and DNA Damage Inducible Alpha) is a stress-responsive protein that functions as a critical regulator of cellular responses to genotoxic and non-genotoxic stressors 1. The protein acts as a recognized tumor suppressor, regulating cell cycle progression, DNA repair, and apoptosis through multiple mechanisms 1. GADD45A controls cell cycle by inhibiting entry into S phase and promoting G2/M phase arrest, partly through modulating translation of cell cycle regulators like RB1 2. In cancer contexts, loss of GADD45A promotes leukemia stem cell activity and confers resistance to ferroptosis by activating antioxidant pathways including FTH1 and PRDX1 3. The protein also regulates muscle repair and metabolism by targeting ATP synthase F1 subunit alpha (ATP5A1) for ubiquitination degradation via recruitment of E3 ligase TRIM25, thereby decreasing ATP synthesis and inactivating cAMP/PKA/LKB1 signaling 4. In reproductive biology, GADD45A dysregulation contributes to diminished ovarian reserve by disrupting granulosa cell differentiation and proliferation 5. Additionally, GADD45A serves as a stress sensor in preeclampsia, activating MKK3-p38 and JNK signaling pathways in response to hypoxia and inflammatory stimuli 6.

Sources cited
1
GADD45A regulates cellular responses to stressors and functions as a tumor suppressor controlling cell cycle, DNA repair, and apoptosis
PMID: 38264852
2
GADD45A modulates translation of cell cycle regulators like RB1 and promotes G2/M phase arrest
PMID: 38822363
3
Loss of GADD45A promotes leukemia stem cell activity and ferroptosis resistance through antioxidant pathway activation
PMID: 38579286
4
GADD45A regulates muscle repair by targeting ATP5A1 for degradation via TRIM25, affecting ATP synthesis and cAMP/PKA/LKB1 signaling
PMID: 36511343
5
GADD45A dysregulation contributes to diminished ovarian reserve by disrupting granulosa cell function
PMID: 40916072
6
GADD45A acts as a stress sensor in preeclampsia, activating MKK3-p38 and JNK signaling pathways
PMID: 35505165
Disease Associationsⓘ20
cataractOpen Targets
0.34Weak
gastroenteritisOpen Targets
0.26Weak
glaucomaOpen Targets
0.26Weak
spermatoceleOpen Targets
0.25Weak
cartilage diseaseOpen Targets
0.24Weak
rectosigmoid junction neoplasmOpen Targets
0.24Weak
open-angle glaucomaOpen Targets
0.19Weak
trauma complicationOpen Targets
0.18Weak
Abnormality of the skeletal systemOpen Targets
0.11Weak
breast cancerOpen Targets
0.10Weak
hepatocellular carcinomaOpen Targets
0.10Suggestive
acute myeloid leukemiaOpen Targets
0.09Suggestive
glioblastoma multiformeOpen Targets
0.09Suggestive
cancerOpen Targets
0.09Suggestive
chronic myelogenous leukemiaOpen Targets
0.08Suggestive
melanomaOpen Targets
0.08Suggestive
esophageal squamous cell carcinomaOpen Targets
0.08Suggestive
squamous cell carcinomaOpen Targets
0.08Suggestive
gliomaOpen Targets
0.08Suggestive
glioblastomaOpen Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MAP3K4Protein interaction100%CARM1Protein interaction100%FOXO3Protein interaction100%PRMT1Protein interaction99%CDKN1AProtein interaction98%CCNB1Protein interaction97%
Tissue Expression6 tissues
Brain
100%
Liver
76%
Lung
56%
Bone Marrow
55%
Ovary
37%
Heart
36%
Gene Interaction Network
Click a node to explore
GADD45AMAP3K4CARM1FOXO3PRMT1CDKN1ACCNB1
PROTEIN STRUCTURE
Preparing viewer…
PDB2KG4 · NMR
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.78LoF Tolerant
pLIⓘ
0.47Tolerant
Observed/Expected LoF0.37 [0.19–0.78]
RankingsWhere GADD45A stands among ~20K protein-coding genes
  • #1,961of 20,598
    Most Researched212 · top 10%
  • #6,391of 17,882
    Most Constrained (LOEUF)0.78
Genes detectedGADD45A
Sources retrieved28 papers
Response time—
📄 Sources
28▼
1
GADD45A: With or without you.
PMID: 38264852
Med Res Rev · 2024
1.00
2
Cell type mapping of inflammatory muscle diseases highlights selective myofiber vulnerability in inclusion body myositis.
PMID: 38834884
Nat Aging · 2024
0.90
3
Loss of the stress sensor GADD45A promotes stem cell activity and ferroptosis resistance in LGR4/HOXA9-dependent AML.
PMID: 38579286
Blood · 2024
0.80
4
HDAC inhibitors modulate Hippo pathway signaling in hormone positive breast cancer.
PMID: 40012020
Clin Epigenetics · 2025
0.76
5
Gadd45 in Normal Hematopoiesis and Leukemia.
PMID: 35505161
Adv Exp Med Biol · 2022
0.72