RAD9A: A Key Checkpoint Protein in DNA Damage Response
Comprehensive gene card for RAD9A, including function, expression, mutations, and associated diseases.
Gene Information Card
| Symbol | RAD9A |
|---|---|
| Full Name | RAD9 checkpoint clamp component A |
| Gene Type | protein-coding |
| Chromosomal Location | 11q13.2 |
| NCBI Gene ID | 5883 ncbi.nlm.nih.gov/gene/5883 |
| Ensembl ID | ENSG00000137776 |
| UniProt ID | Q99638 |
| OMIM ID | 603761 |
| HGNC ID | 9822 |
| Aliases | RAD9, hRAD9 |
Description
RAD9A encodes a protein that is a component of the 9-1-1 cell-cycle checkpoint response complex (RAD9-HUS1-RAD1). This complex is loaded onto DNA in response to DNA damage and activates the checkpoint kinase CHK1, leading to cell cycle arrest and DNA repair. RAD9A is essential for maintaining genomic stability and is involved in the cellular response to replication stress and double-strand breaks.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lung Cancer | RAD9A overexpression may promote tumorigenesis by impairing checkpoint control and enhancing cell survival under genotoxic stress. | PMID: 19029980; COSMIC |
| Breast Cancer | Altered RAD9A expression and phosphorylation status are associated with poor prognosis and resistance to DNA-damaging chemotherapy. | PMID: 21784103; ClinVar |
| Colorectal Cancer | RAD9A mutations and copy number alterations contribute to genomic instability and tumor progression. | PMID: 22955915; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | High |
| Bone Marrow | 8.2 | Medium |
| Lymph Node | 6.7 | Medium |
| Brain | 3.1 | Low |
| Liver | 2.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 10.1 | Cervical cancer cell line |
| A549 | 9.4 | Lung cancer cell line |
| MCF7 | 7.8 | Breast cancer cell line |
| HEK293 | 6.5 | Embryonic kidney cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.1% | Likely loss of start codon; predicted loss of function |
| c.335C>T (p.Pro112Leu) | Missense | 0.2% | May affect protein stability; reported in COSMIC |
| c.682G>A (p.Glu228Lys) | Missense | 0.1% | Located in PCNA-binding domain; potential impact on checkpoint signaling |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in RAD9A impair the 9-1-1 complex assembly and checkpoint activation, leading to increased genomic instability and sensitivity to DNA damage.
Gain of Function (GOF)
Gain-of-function mutations are rare; overexpression of wild-type RAD9A has been observed in cancers, potentially conferring resistance to DNA-damaging agents.
Dominant Negative (DN)
Dominant-negative mutants of RAD9A can disrupt 9-1-1 complex function, abrogating the G2/M checkpoint and promoting chromosomal aberrations.
View complete mutation data：
Gene Ontology (GO)
| • DNA damage checkpoint | • cell cycle arrest |
| • protein binding | • damaged DNA binding |
| • chromatin binding | • nucleus |
Pathways
• ATM signaling pathway
• ATR signaling pathway
• Cell cycle: G2/M checkpoint
• DNA damage response (DDR)
Protein Summary
RAD9A is a 391-amino acid protein that contains a PCNA-like domain and a C-terminal tail involved in interactions with HUS1 and RAD1. It is phosphorylated in response to DNA damage and is required for the activation of CHK1. The protein localizes to sites of DNA damage and is essential for the intra-S and G2/M checkpoints.
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