GADD45A
Growth Arrest and DNA Damage Inducible Alpha
Gene Information Card
| Symbol | GADD45A |
|---|---|
| Full Name | Growth Arrest and DNA Damage Inducible Alpha |
| Gene Type | Protein coding |
| Chromosomal Location | 1p31.3 |
| NCBI Gene ID | 1647 ncbi.nlm.nih.gov/gene/1647 |
| Ensembl ID | ENSG00000116717 |
| UniProt ID | P24522 |
| OMIM ID | 126335 |
| HGNC ID | 4095 |
| Aliases | GADD45, DDIT1 |
Description
GADD45A (Growth Arrest and DNA Damage Inducible Alpha) is a protein-coding gene that plays a critical role in cellular stress responses, including DNA repair, cell cycle arrest, apoptosis, and genomic stability. It is induced by various stressors such as ionizing radiation, UV light, and genotoxic agents. The encoded protein interacts with multiple partners including PCNA, p21, and MTK1/MEKK4 to mediate its functions. GADD45A is considered a tumor suppressor and is frequently downregulated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast Cancer | Reduced expression of GADD45A leads to impaired DNA damage response and increased genomic instability, promoting tumorigenesis. | ClinVar, COSMIC |
| Colorectal Cancer | Hypermethylation of the GADD45A promoter results in transcriptional silencing, contributing to cancer progression. | NCBI Gene, COSMIC |
| Hepatocellular Carcinoma | Downregulation of GADD45A correlates with poor prognosis and resistance to chemotherapy-induced apoptosis. | OMIM, ClinVar |
| Lung Cancer | Loss of GADD45A expression is associated with increased cell proliferation and reduced apoptosis in response to DNA damage. | COSMIC, NCBI Gene |
| Melanoma | GADD45A mutations and reduced expression are linked to defective DNA repair and increased susceptibility to UV-induced damage. | ClinVar, COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Lymph node | 10.2 | Medium |
| Spleen | 8.9 | Medium |
| Thymus | 7.6 | Low |
| Testis | 6.3 | Low |
| Colon | 5.1 | Low |
| Breast | 4.8 | Low |
| Liver | 3.2 | Low |
| Lung | 2.9 | Low |
| Skin | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.3 | High expression in embryonic kidney cells |
| HeLa | 12.7 | High expression in cervical cancer cells |
| MCF7 | 8.4 | Moderate expression in breast cancer cells |
| A549 | 6.1 | Low expression in lung cancer cells |
| HepG2 | 4.5 | Low expression in liver cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon, likely loss of function |
| c.205C>T (p.Arg69Trp) | Missense | 0.01% | Alters protein interaction with PCNA, reduced DNA repair |
| c.310G>A (p.Glu104Lys) | Missense | 0.005% | Impaired G2/M checkpoint activation |
| c.412_413insA (p.Thr138Asnfs*2) | Frameshift | Rare | Premature truncation, loss of function |
Mutation functional classification
Loss of Function (LOF)
Mutations leading to truncated or unstable protein, or impaired interaction with PCNA and MTK1, reduce DNA repair and cell cycle arrest capabilities.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in GADD45A.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg69Trp) may interfere with wild-type GADD45A function by disrupting protein-protein interactions, acting in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
| • DNA damage response | • signal transduction by p53 class mediator |
| • cell cycle arrest | • apoptotic process |
| • negative regulation of cell population proliferation | • protein binding |
| • chromatin binding | • nucleus |
| • cytoplasm |
Pathways
• p53 signaling pathway (KEGG: hsa04115)
• MAPK signaling pathway (KEGG: hsa04010)
• Cell cycle (KEGG: hsa04110)
• Apoptosis (KEGG: hsa04210)
• FoxO signaling pathway (KEGG: hsa04068)
Protein Summary
The GADD45A protein is a 165-amino acid, 18 kDa nuclear and cytoplasmic protein. It contains a conserved GADD45 domain and interacts with PCNA, p21, and MTK1/MEKK4. It functions as a stress sensor, promoting DNA repair by binding to PCNA, inducing G2/M cell cycle arrest via p21, and activating the JNK/p38 MAPK pathway through MTK1. GADD45A is also involved in base excision repair and nucleotide excision repair. Its expression is tightly regulated by p53 and BRCA1.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GADD45A Knockout HEK293 Cell Line | EDJ-KQ563 | Human | 1647 | Details Get a Quote |
| GADD45A Knockout A-549 Cell Line | EDJ-KQ18947 | Human | 1647 | Details Get a Quote |
| GADD45A Knockout HCT 116 Cell Line | EDJ-KQ18948 | Human | 1647 | Details Get a Quote |
| GADD45A Knockout HeLa Cell Line | EDJ-KQ18949 | Human | 1647 | Details Get a Quote |
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