Incidental Mutation 'P0021:Rnf168'
| ID |
7664 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Rnf168
|
| Ensembl Gene |
ENSMUSG00000014074 |
| Gene Name |
ring finger protein 168 |
| Synonyms |
3110001H15Rik |
| MMRRC Submission |
038274-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably essential
(E-score: 0.921)
|
| Stock # |
P0021 (G1)
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
16 |
| Chromosomal Location |
32096277-32120252 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
C to T
at 32117705 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Threonine to Isoleucine
at position 422
(T422I)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000126484
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000014218]
[ENSMUST00000171474]
|
| AlphaFold |
Q80XJ2 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000014218
AA Change: T420I
PolyPhen 2
Score 0.960 (Sensitivity: 0.78; Specificity: 0.95)
|
| SMART Domains |
Protein: ENSMUSP00000014218
Gene: ENSMUSG00000014074
AA Change: T420I
| Domain | Start | End | E-Value | Type |
|---|
|
RING
|
16 |
54 |
8.23e-6 |
SMART |
|
coiled coil region
|
114 |
184 |
N/A |
INTRINSIC |
|
low complexity region
|
208 |
221 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000171474
AA Change: T422I
PolyPhen 2
Score 0.963 (Sensitivity: 0.78; Specificity: 0.95)
|
| SMART Domains |
Protein: ENSMUSP00000126484
Gene: ENSMUSG00000014074
AA Change: T422I
| Domain | Start | End | E-Value | Type |
|---|
|
RING
|
18 |
56 |
8.23e-6 |
SMART |
|
coiled coil region
|
116 |
186 |
N/A |
INTRINSIC |
|
low complexity region
|
210 |
223 |
N/A |
INTRINSIC |
|
| Meta Mutation Damage Score |
0.0933 |
| Coding Region Coverage |
- 1x: 73.1%
- 3x: 63.5%
- 10x: 31.6%
- 20x: 17.3%
|
| Validation Efficiency |
79% (146/184) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes an E3 ubiquitin ligase protein that contains a RING finger, a motif present in a variety of functionally distinct proteins and known to be involved in protein-DNA and protein-protein interactions. The protein is involved in DNA double-strand break (DSB) repair. Mutations in this gene result in Riddle syndrome. [provided by RefSeq, Sep 2011]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit immunodeficient, increased radiosensitivity and age-dependent reduction in male infertility. [provided by MGI curators]
|
| Allele List at MGI |
All alleles(56) : Gene trapped(56)
|
| Other mutations in this stock |
Total: 7 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Fas |
A |
G |
19: 34,284,610 (GRCm39) |
E39G |
probably damaging |
Het |
| Fig4 |
A |
G |
10: 41,127,821 (GRCm39) |
S548P |
probably damaging |
Het |
| Msh4 |
T |
A |
3: 153,594,455 (GRCm39) |
E115D |
probably damaging |
Het |
| Ptpn13 |
A |
G |
5: 103,676,686 (GRCm39) |
E683G |
probably benign |
Het |
| Rasgrp3 |
G |
T |
17: 75,807,708 (GRCm39) |
R255L |
probably damaging |
Het |
| Smarcd1 |
T |
C |
15: 99,610,242 (GRCm39) |
|
probably benign |
Het |
| Stxbp1 |
T |
C |
2: 32,713,550 (GRCm39) |
K29E |
probably damaging |
Het |
|
| Other mutations in Rnf168 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL02997:Rnf168
|
APN |
16 |
32,104,239 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL03108:Rnf168
|
APN |
16 |
32,097,099 (GRCm39) |
missense |
possibly damaging |
0.79 |
|
R0038:Rnf168
|
UTSW |
16 |
32,117,813 (GRCm39) |
missense |
probably benign |
0.05 |
|
R0038:Rnf168
|
UTSW |
16 |
32,117,813 (GRCm39) |
missense |
probably benign |
0.05 |
|
R0040:Rnf168
|
UTSW |
16 |
32,096,991 (GRCm39) |
splice site |
probably null |
|
|
R0049:Rnf168
|
UTSW |
16 |
32,117,287 (GRCm39) |
missense |
possibly damaging |
0.56 |
|
R0049:Rnf168
|
UTSW |
16 |
32,117,287 (GRCm39) |
missense |
possibly damaging |
0.56 |
|
R0760:Rnf168
|
UTSW |
16 |
32,117,204 (GRCm39) |
critical splice acceptor site |
probably null |
|
|
R1188:Rnf168
|
UTSW |
16 |
32,117,477 (GRCm39) |
missense |
probably benign |
0.00 |
|
R1386:Rnf168
|
UTSW |
16 |
32,117,781 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1754:Rnf168
|
UTSW |
16 |
32,117,942 (GRCm39) |
missense |
probably benign |
|
|
R2118:Rnf168
|
UTSW |
16 |
32,097,036 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2122:Rnf168
|
UTSW |
16 |
32,097,036 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2124:Rnf168
|
UTSW |
16 |
32,097,036 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2520:Rnf168
|
UTSW |
16 |
32,097,221 (GRCm39) |
missense |
probably benign |
0.17 |
|
R2852:Rnf168
|
UTSW |
16 |
32,101,192 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R3418:Rnf168
|
UTSW |
16 |
32,118,010 (GRCm39) |
missense |
probably benign |
0.00 |
|
R3419:Rnf168
|
UTSW |
16 |
32,118,010 (GRCm39) |
missense |
probably benign |
0.00 |
|
R4886:Rnf168
|
UTSW |
16 |
32,118,014 (GRCm39) |
missense |
probably benign |
0.00 |
|
R5335:Rnf168
|
UTSW |
16 |
32,117,402 (GRCm39) |
missense |
possibly damaging |
0.78 |
|
R5738:Rnf168
|
UTSW |
16 |
32,101,192 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R6570:Rnf168
|
UTSW |
16 |
32,108,028 (GRCm39) |
missense |
probably benign |
0.00 |
|
R7165:Rnf168
|
UTSW |
16 |
32,101,179 (GRCm39) |
missense |
probably benign |
0.38 |
|
R7529:Rnf168
|
UTSW |
16 |
32,117,732 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R7556:Rnf168
|
UTSW |
16 |
32,117,863 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9338:Rnf168
|
UTSW |
16 |
32,110,801 (GRCm39) |
critical splice donor site |
probably null |
|
|
R9796:Rnf168
|
UTSW |
16 |
32,117,872 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9800:Rnf168
|
UTSW |
16 |
32,117,386 (GRCm39) |
missense |
probably benign |
0.43 |
|
| Protein Function and Prediction |
RNF168 is an E3 ubiquitin ligase that promotes the ubiquitinylation of H2A-type histones surrounding double strand DNA breaks (1-4). RNF168-dependent ubiqutylation promotes DSB repair, DNA damage checkpoints, and survival following exposure to ionizing radiation (1;2). Mutations in RNF168 are associated with RIDDLE syndrome [OMIM: #611943; (1)], a condition characterized by increased radiosensitivity, immunodeficiency, mild motor control and learning difficulties, facial dysmorphism, and short stature.
|
| References |
1. Stewart, G. S., Panier, S., Townsend, K., Al-Hakim, A. K., Kolas, N. K., Miller, E. S., Nakada, S., Ylanko, J., Olivarius, S., Mendez, M., Oldreive, C., Wildenhain, J., Tagliaferro, A., Pelletier, L., Taubenheim, N., Durandy, A., Byrd, P. J., Stankovic, T., Taylor, A. M., and Durocher, D. (2009) The RIDDLE Syndrome Protein Mediates a Ubiquitin-Dependent Signaling Cascade at Sites of DNA Damage. Cell. 136, 420-434.
2. Doil, C., Mailand, N., Bekker-Jensen, S., Menard, P., Larsen, D. H., Pepperkok, R., Ellenberg, J., Panier, S., Durocher, D., Bartek, J., Lukas, J., and Lukas, C. (2009) RNF168 Binds and Amplifies Ubiquitin Conjugates on Damaged Chromosomes to Allow Accumulation of Repair Proteins. Cell. 136, 435-446.
3. Mattiroli, F., Vissers, J. H., van Dijk, W. J., Ikpa, P., Citterio, E., Vermeulen, W., Marteijn, J. A., and Sixma, T. K. (2012) RNF168 Ubiquitinates K13-15 on H2A/H2AX to Drive DNA Damage Signaling. Cell. 150, 1182-1195.
4. Pinato, S., Scandiuzzi, C., Arnaudo, N., Citterio, E., Gaudino, G., and Penengo, L. (2009) RNF168, a New RING Finger, MIU-Containing Protein that Modifies Chromatin by Ubiquitination of Histones H2A and H2AX. BMC Mol Biol. 10, 55-2199-10-55. |
| Posted On |
2012-10-29 |
| Science Writer |
Anne Murray |
Incidental Mutation