RNF8
ring finger protein 8, the group of Ring finger proteins
Basic information
Region (hg38): 6:37353978-37394734
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (8 variants)
- not provided (3 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the RNF8 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | |||||
| missense | 8 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 1 | 1 | ||||
| non coding ? | 0 | |||||
| Total | 0 | 0 | 8 | 2 | 0 |
Variants in RNF8
This is a list of pathogenic ClinVar variants found in the RNF8 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 6-37354251-G-C | not specified | Uncertain significance (Jan 29, 2024) | ||
| 6-37360454-A-G | Likely benign (Dec 01, 2022) | |||
| 6-37360553-A-G | Likely benign (Dec 01, 2022) | |||
| 6-37360582-A-G | Benign (Jul 10, 2018) | |||
| 6-37368515-G-A | not specified | Uncertain significance (Aug 04, 2021) | ||
| 6-37368637-A-G | not specified | Uncertain significance (Dec 06, 2022) | ||
| 6-37368649-C-G | not specified | Uncertain significance (Apr 18, 2023) | ||
| 6-37368713-G-A | not specified | Uncertain significance (Feb 06, 2024) | ||
| 6-37368836-C-T | not specified | Uncertain significance (Jan 02, 2024) | ||
| 6-37368848-A-G | not specified | Uncertain significance (Mar 14, 2023) | ||
| 6-37368892-G-A | not specified | Uncertain significance (Dec 12, 2023) | ||
| 6-37369151-A-G | not specified | Uncertain significance (Dec 15, 2023) | ||
| 6-37374632-A-G | not specified | Uncertain significance (Sep 26, 2022) | ||
| 6-37374652-C-A | not specified | Uncertain significance (Jan 17, 2024) | ||
| 6-37377008-T-C | not specified | Uncertain significance (Jan 11, 2023) | ||
| 6-37381235-G-A | not specified | Uncertain significance (Mar 16, 2022) | ||
| 6-37381241-A-T | not specified | Uncertain significance (Dec 03, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| RNF8 | protein_coding | protein_coding | ENST00000373479 | 8 | 40767 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.999 | 0.000567 | 125736 | 0 | 2 | 125738 | 0.00000795 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.16 | 156 | 252 | 0.618 | 0.0000121 | 3201 |
| Missense in Polyphen | 51 | 95.586 | 0.53355 | 1170 | ||
| Synonymous | 2.05 | 65 | 89.6 | 0.725 | 0.00000416 | 874 |
| Loss of Function | 4.54 | 1 | 25.9 | 0.0385 | 0.00000127 | 313 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000884 | 0.00000879 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: E3 ubiquitin-protein ligase that plays a key role in DNA damage signaling via 2 distinct roles: by mediating the 'Lys-63'- linked ubiquitination of histones H2A and H2AX and promoting the recruitment of DNA repair proteins at double-strand breaks (DSBs) sites, and by catalyzing 'Lys-48'-linked ubiquitination to remove target proteins from DNA damage sites. Following DNA DSBs, it is recruited to the sites of damage by ATM-phosphorylated MDC1 and catalyzes the 'Lys-63'-linked ubiquitination of histones H2A and H2AX, thereby promoting the formation of TP53BP1 and BRCA1 ionizing radiation-induced foci (IRIF). Also controls the recruitment of UIMC1-BRCC3 (RAP80-BRCC36) and PAXIP1/PTIP to DNA damage sites. Also recruited at DNA interstrand cross-links (ICLs) sites and catalyzes 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20/C1orf86 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Promotes the formation of 'Lys-63'-linked polyubiquitin chains via interactions with the specific ubiquitin-conjugating UBE2N/UBC13 and ubiquitinates non-histone substrates such as PCNA. Substrates that are polyubiquitinated at 'Lys-63' are usually not targeted for degradation. Also catalyzes the formation of 'Lys-48'-linked polyubiquitin chains via interaction with the ubiquitin- conjugating UBE2L6/UBCH8, leading to degradation of substrate proteins such as CHEK2, JMJD2A/KDM4A and KU80/XRCC5: it is still unclear how the preference toward 'Lys-48'- versus 'Lys-63'-linked ubiquitination is regulated but it could be due to RNF8 ability to interact with specific E2 specific ligases. For instance, interaction with phosphorylated HERC2 promotes the association between RNF8 and UBE2N/UBC13 and favors the specific formation of 'Lys-63'-linked ubiquitin chains. Promotes non-homologous end joining (NHEJ) by promoting the 'Lys-48'-linked ubiquitination and degradation the of KU80/XRCC5. Following DNA damage, mediates the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF168, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites (PubMed:11322894, PubMed:14981089, PubMed:17724460, PubMed:18001824, PubMed:18001825, PubMed:18006705, PubMed:18077395, PubMed:18337245, PubMed:18948756, PubMed:19015238, PubMed:19124460, PubMed:19202061, PubMed:19203578, PubMed:19203579, PubMed:20550933, PubMed:21558560, PubMed:21857671, PubMed:21911360, PubMed:22266820, PubMed:22373579, PubMed:22531782, PubMed:22705371, PubMed:22865450, PubMed:22980979). Following DNA damage, mediates the ubiquitination and degradation of POLD4/p12, a subunit of DNA polymerase delta. In the absence of POLD4, DNA polymerase delta complex exhibits higher proofreading activity (PubMed:23233665). In addition to its function in damage signaling, also plays a role in higher-order chromatin structure by mediating extensive chromatin decondensation. Involved in the activation of ATM by promoting histone H2B ubiquitination, which indirectly triggers histone H4 'Lys-16' acetylation (H4K16ac), establishing a chromatin environment that promotes efficient activation of ATM kinase. Required in the testis, where it plays a role in the replacement of histones during spermatogenesis. At uncapped telomeres, promotes the joining of deprotected chromosome ends by inducing H2A ubiquitination and TP53BP1 recruitment, suggesting that it may enhance cancer development by aggravating telomere- induced genome instability in case of telomeric crisis. Promotes the assembly of RAD51 at DNA DSBs in the absence of BRCA1 and TP53BP1 Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. May be required for proper exit from mitosis after spindle checkpoint activation and may regulate cytokinesis. May play a role in the regulation of RXRA-mediated transcriptional activity. Not involved in RXRA ubiquitination by UBE2E2 (PubMed:11322894, PubMed:14981089, PubMed:17724460, PubMed:18001824, PubMed:18001825, PubMed:18006705, PubMed:18077395, PubMed:18337245, PubMed:18948756, PubMed:19015238, PubMed:19124460, PubMed:19202061, PubMed:19203578, PubMed:19203579, PubMed:20550933, PubMed:21558560, PubMed:21857671, PubMed:21911360, PubMed:22266820, PubMed:22373579, PubMed:22531782, PubMed:22705371, PubMed:22865450, PubMed:22980979). {ECO:0000269|PubMed:11322894, ECO:0000269|PubMed:14981089, ECO:0000269|PubMed:17724460, ECO:0000269|PubMed:18001824, ECO:0000269|PubMed:18001825, ECO:0000269|PubMed:18006705, ECO:0000269|PubMed:18077395, ECO:0000269|PubMed:18337245, ECO:0000269|PubMed:18948756, ECO:0000269|PubMed:19015238, ECO:0000269|PubMed:19124460, ECO:0000269|PubMed:19202061, ECO:0000269|PubMed:19203578, ECO:0000269|PubMed:19203579, ECO:0000269|PubMed:20550933, ECO:0000269|PubMed:21558560, ECO:0000269|PubMed:21857671, ECO:0000269|PubMed:21911360, ECO:0000269|PubMed:22266820, ECO:0000269|PubMed:22373579, ECO:0000269|PubMed:22531782, ECO:0000269|PubMed:22705371, ECO:0000269|PubMed:22865450, ECO:0000269|PubMed:22980979, ECO:0000269|PubMed:23233665}.;
- Pathway
- ATM Signaling Network in Development and Disease;HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;Nonhomologous End-Joining (NHEJ);DNA Double-Strand Break Repair;Homology Directed Repair;G2/M DNA damage checkpoint;G2/M Checkpoints;Cell Cycle Checkpoints;Cell Cycle;Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks;DNA Double Strand Break Response;Processing of DNA double-strand break ends;ATM pathway
(Consensus)
Recessive Scores
- pRec
- 0.109
Intolerance Scores
- loftool
- 0.0442
- rvis_EVS
- -0.54
- rvis_percentile_EVS
- 20.26
Haploinsufficiency Scores
- pHI
- 0.105
- hipred
- Y
- hipred_score
- 0.809
- ghis
- 0.599
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.699
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Rnf8
- Phenotype
- integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; hematopoietic system phenotype; neoplasm; immune system phenotype;
Gene ontology
- Biological process
- double-strand break repair;double-strand break repair via nonhomologous end joining;ubiquitin-dependent protein catabolic process;cellular response to DNA damage stimulus;cell cycle;spermatid development;response to ionizing radiation;histone H2A ubiquitination;histone H2B ubiquitination;negative regulation of transcription elongation from RNA polymerase II promoter;spermatogenesis, exchange of chromosomal proteins;interstrand cross-link repair;histone exchange;isotype switching;positive regulation of DNA repair;cell division;protein autoubiquitination;protein K63-linked ubiquitination;histone H2A K63-linked ubiquitination;protein K48-linked ubiquitination
- Cellular component
- ubiquitin ligase complex;chromosome, telomeric region;nucleus;nucleoplasm;cytosol;midbody;site of double-strand break
- Molecular function
- chromatin binding;ubiquitin-protein transferase activity;protein binding;zinc ion binding;ubiquitin protein ligase binding;histone binding;identical protein binding;protein homodimerization activity;ubiquitin binding