RAD18
protein-codingRAD18 E3 ubiquitin protein ligase, the group of Ring finger proteins
Gene summary
The protein encoded by this gene is highly similar to S. cerevisiae DNA damage repair protein Rad18. Yeast Rad18 functions through its interaction with Rad6, which is an ubiquitin-conjugating enzyme required for post-replication repair of damaged DNA. Similar to its yeast counterpart, this protein is able to interact with the human homolog of yeast Rad6 protein through a conserved ring-finger motif. Mutation of this motif results in defective replication of UV-damaged DNA and hypersensitivity to multiple mutagens. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~188.4 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 RAD18 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020165.4. 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 | 2 | 1 | 3 | |||
| missense | 89 | 2 | 91 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 92 | 3 | 0 | 95 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_064550.3 | 13 | MANE Select | |
| Ensembl | ENSP00000264926.2 | 13 | MANE Select | |
| Ensembl | ENSP00000412261.1 | 5 | Standard | |
| Ensembl | ENSP00000402049.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- DNA Repair
- Post-translational protein modification
- Metabolism of proteins
- Recognition of DNA damage by PCNA-containing replication complex
- Protein ubiquitination
Biological Process
- DNA repair
- postreplication repair
- protein monoubiquitination
- cellular response to DNA damage stimulus
- response to UV
Molecular Function
- Y-form DNA binding
- damaged DNA binding
- single-stranded DNA binding
- protein binding
- polyubiquitin modification-dependent protein binding
Cellular Component
- nucleus
- nucleoplasm
- replication fork
- cytoplasm
- centrosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000264926
- Coding exons
- 13
- Length
- 188370
- Individuals with no LoFs
- 125662
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 86
- Defined
- 125748
- p
- 0.000342
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.135 | 267 | 261 | 1.02 | 0.0000139 | 3261 |
| Missense (PolyPhen) | 56 | 68.562 | 0.81678 | 864 | ||
| Synonymous | -0.394 | 93 | 88.3 | 1.05 | 0.00000464 | 878 |
| Loss of Function | 1.60 | 16 | 24.5 | 0.652 | 0.00000112 | 350 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00015 | 0.00012 | rare |
| Latino/Admixed American | 0.000088 | 0.000087 | rare |
| Ashkenazi Jewish | 0.00050 | 0.00050 | rare |
| East Asian | 0.00038 | 0.00033 | rare |
| Finnish | 0.00061 | 0.00060 | rare |
| European (Non-Finnish) | 0.00033 | 0.00032 | rare |
| South Asian | 0.00077 | 0.00062 | rare |
| Other | 0.00034 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: E3 ubiquitin-protein ligase involved in postreplication repair of UV-damaged DNA. Postreplication repair functions in gap- filling of a daughter strand on replication of damaged DNA. Associates to the E2 ubiquitin conjugating enzyme UBE2B to form the UBE2B-RAD18 ubiquitin ligase complex involved in mono- ubiquitination of DNA-associated PCNA on 'Lys-164'. Has ssDNA binding activity. {ECO:0000269|PubMed:17108083, ECO:0000269|PubMed:21659603}.;
Recessive Scores
- pRec
- 0.0799
Intolerance Scores
- LoFtool
- 0.634
- RVIS EVS
- 0.04
- RVIS percentile EVS
- 57.31
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.957
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |