RNF169
protein-codingring finger protein 169, the group of Ring finger proteins
Gene summary
Enables K63-linked polyubiquitin modification-dependent protein binding activity; nucleosome binding activity; and ubiquitin-modified histone reader activity. Involved in double-strand break repair via homologous recombination and negative regulation of double-strand break repair. Located in cytosol; nuclear lumen; and site of double-strand break. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~93.6 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 RNF169 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001098638.2. 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 | 0 | |||||
| missense | 105 | 5 | 110 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 106 | 5 | 0 | 111 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001092108.1 | 6 | MANE Select | |
| Ensembl | ENSP00000299563.4 | 6 | MANE Select | |
| Ensembl | ENSP00000436339.1 | 1 | Standard | |
| Ensembl | ENSP00000581326.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- cellular response to DNA damage stimulus
- protein ubiquitination
- negative regulation of double-strand break repair
Molecular Function
- transferase activity
- nucleosome binding
- metal ion binding
- K63-linked polyubiquitin modification-dependent protein binding
Cellular Component
- nucleus
- nucleoplasm
- nuclear speck
- site of double-strand break
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000299563
- Coding exons
- 6
- Length
- 93546
- Individuals with no LoFs
- 124768
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 35
- Defined
- 124803
- p
- 0.000140
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.358 | 303 | 321 | 0.944 | 0.0000183 | 4499 |
| Missense (PolyPhen) | 104 | 126.73 | 0.82067 | 1659 | ||
| Synonymous | -1.89 | 149 | 122 | 1.22 | 0.00000612 | 1508 |
| Loss of Function | 3.20 | 7 | 23.9 | 0.293 | 0.00000150 | 321 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00046 | 0.00046 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Probable E3 ubiquitin-protein ligase that acts as a negative regulator of double-strand breaks (DSBs) repair following DNA damage. Recruited to DSB repair sites by recognizing and binding ubiquitin catalyzed by RNF168 and competes with TP53BP1 and BRCA1 for association with RNF168-modified chromatin, thereby acting as a negative regulator of DSBs repair. E3 ubiquitin- protein ligase activity is not required for regulation of DSBs repair. {ECO:0000269|PubMed:22492721, ECO:0000269|PubMed:22733822, ECO:0000269|PubMed:22742833}.;
Intolerance Scores
- LoFtool
- 0.577
- RVIS EVS
- -0.56
- RVIS percentile EVS
- 19.73
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.134
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |