RAD9A
protein-codingRAD9 checkpoint clamp component A, the group of Checkpoint clamp complex
Gene summary
This gene product is highly similar to Schizosaccharomyces pombe rad9, a cell cycle checkpoint protein required for cell cycle arrest and DNA damage repair. This protein possesses 3' to 5' exonuclease activity, which may contribute to its role in sensing and repairing DNA damage. It forms a checkpoint protein complex with RAD1 and HUS1. This complex is recruited by checkpoint protein RAD17 to the sites of DNA damage, which is thought to be important for triggering the checkpoint-signaling cascade. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]
- RAD9
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~80.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to RAD9A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004584.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 56 | 2 | 58 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 59 | 3 | 0 | 62 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004575.1 | 11 | MANE Select | |
| Ensembl | ENSP00000311360.2 | 11 | MANE Select | |
| RefSeq | NP_001230153.1 | 8 | Standard | |
| Ensembl | ENSP00000442064.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cellular senescence - Homo sapiens (human)
- Androgen receptor signaling pathway
- miRNA Regulation of DNA Damage Response
- ATM Signaling Pathway
- ATR Signaling
Biological Process
- DNA replication checkpoint
- DNA damage checkpoint
- DNA repair
- cellular response to DNA damage stimulus
- intra-S DNA damage checkpoint
Molecular Function
- protein binding
- 3'-5' exonuclease activity
- exodeoxyribonuclease III activity
- SH3 domain binding
- enzyme binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- checkpoint clamp complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000307980
- Coding exons
- 11
- Length
- 6706
- Individuals with no LoFs
- 125717
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 30
- Defined
- 125747
- p
- 0.000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.00665 | 246 | 246 | 1.00 | 0.0000153 | 2512 |
| Missense (PolyPhen) | 77 | 91.028 | 0.84589 | 990 | ||
| Synonymous | -1.96 | 127 | 102 | 1.25 | 0.00000622 | 809 |
| Loss of Function | 1.41 | 11 | 17.3 | 0.635 | 7.35e-7 | 211 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00042 | 0.00037 | rare |
| Latino/Admixed American | 0.000059 | 0.000058 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00013 | 0.00013 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the 9-1-1 cell-cycle checkpoint response complex that plays a major role in DNA repair. The 9-1-1 complex is recruited to DNA lesion upon damage by the RAD17-replication factor C (RFC) clamp loader complex. Acts then as a sliding clamp platform on DNA for several proteins involved in long-patch base excision repair (LP-BER). The 9-1-1 complex stimulates DNA polymerase beta (POLB) activity by increasing its affinity for the 3'-OH end of the primer-template and stabilizes POLB to those sites where LP-BER proceeds; endonuclease FEN1 cleavage activity on substrates with double, nick, or gap flaps of distinct sequences and lengths; and DNA ligase I (LIG1) on long-patch base excision repair substrates. The 9-1-1 complex is necessary for the recruitment of RHNO1 to sites of double-stranded breaks (DSB) occurring during the S phase. RAD9A possesses 3'->5' double stranded DNA exonuclease activity. Its phosphorylation by PRKCD may be required for the formation of the 9-1-1 complex. {ECO:0000269|PubMed:10713044, ECO:0000269|PubMed:21659603}.;
Recessive Scores
- pRec
- 0.197
Intolerance Scores
- LoFtool
- 0.588
- RVIS EVS
- -0.33
- RVIS percentile EVS
- 30.7
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.972
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |