Incidental Mutation 'A4554:Rbck1'
ID 93
Institutional Source Beutler Lab
Gene Symbol Rbck1
Ensembl Gene ENSMUSG00000027466
Gene Name RanBP-type and C3HC4-type zinc finger containing 1
Synonyms Ubce7ip3, HOIL-1L, HOIL-1
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # A4554 of strain gemini
Quality Score
Status Validated
Chromosome 2
Chromosomal Location 152158254-152174573 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to T at 152161092 bp (GRCm39)
Zygosity Homozygous
Amino Acid Change Asparagine to Lysine at position 385 (N385K)
Ref Sequence ENSEMBL: ENSMUSP00000105473 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000028964] [ENSMUST00000109847]
AlphaFold Q9WUB0
Predicted Effect probably damaging
Transcript: ENSMUST00000028964
AA Change: N385K

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000028964
Gene: ENSMUSG00000027466
AA Change: N385K

DomainStartEndE-ValueType
PDB:4DBG|A 37 137 2e-60 PDB
Blast:UBQ 59 133 2e-15 BLAST
low complexity region 143 152 N/A INTRINSIC
ZnF_RBZ 193 217 5.25e-5 SMART
low complexity region 232 256 N/A INTRINSIC
RING 280 324 2.67e-5 SMART
Pfam:IBR 346 409 1.5e-9 PFAM
Pfam:IBR 422 483 2.5e-8 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000109847
AA Change: N385K

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000105473
Gene: ENSMUSG00000027466
AA Change: N385K

DomainStartEndE-ValueType
PDB:4DBG|A 37 137 2e-60 PDB
Blast:UBQ 59 133 2e-15 BLAST
low complexity region 143 152 N/A INTRINSIC
ZnF_RBZ 193 217 5.25e-5 SMART
low complexity region 232 256 N/A INTRINSIC
RING 280 324 2.67e-5 SMART
Blast:IBR 427 507 1e-18 BLAST
Predicted Effect noncoding transcript
Transcript: ENSMUST00000128645
Predicted Effect noncoding transcript
Transcript: ENSMUST00000130165
Predicted Effect unknown
Transcript: ENSMUST00000144865
AA Change: N206K
SMART Domains Protein: ENSMUSP00000118592
Gene: ENSMUSG00000027466
AA Change: N206K

DomainStartEndE-ValueType
coiled coil region 13 41 N/A INTRINSIC
RING 63 107 2.67e-5 SMART
low complexity region 142 153 N/A INTRINSIC
Predicted Effect noncoding transcript
Transcript: ENSMUST00000145889
Meta Mutation Damage Score 0.6467 question?
Coding Region Coverage
  • 1x: 85.5%
  • 3x: 63.0%
Validation Efficiency 84% (92/109)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is similar to mouse UIP28/UbcM4 interacting protein. Alternative splicing has been observed at this locus, resulting in distinct isoforms. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit increased TNF-induced hepatocyte apoptosis. [provided by MGI curators]
Allele List at MGI

All alleles(5) : Gene trapped(5)

Other mutations in this stock
Total: 18 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Asap1 T C 15: 63,996,560 (GRCm39) probably benign Het
Bpifb5 A T 2: 154,069,100 (GRCm39) Y139F possibly damaging Homo
Chd2 A C 7: 73,130,716 (GRCm39) V782G probably benign Homo
Chst4 G T 8: 110,756,520 (GRCm39) Q448K probably benign Homo
Dido1 T C 2: 180,317,164 (GRCm39) K8E probably damaging Homo
Evpl A G 11: 116,111,660 (GRCm39) L2010P probably damaging Homo
Fgl2 A G 5: 21,577,776 (GRCm39) E21G probably benign Homo
Greb1l A T 18: 10,532,862 (GRCm39) M919L possibly damaging Homo
Kel T A 6: 41,674,353 (GRCm39) D359V possibly damaging Homo
Lmtk2 A G 5: 144,103,135 (GRCm39) D298G possibly damaging Homo
Masp1 A T 16: 23,273,690 (GRCm39) probably null Homo
Mrgprb8 A T 7: 48,039,156 (GRCm39) I276F probably damaging Homo
Nde1 T C 16: 14,006,274 (GRCm39) probably benign Homo
Senp6 G T 9: 80,055,740 (GRCm39) probably benign Het
Tm4sf4 T A 3: 57,345,188 (GRCm39) probably null Homo
Ubn2 A T 6: 38,461,045 (GRCm39) H488L probably damaging Homo
Vmn2r120 A G 17: 57,832,715 (GRCm39) F155L probably benign Homo
Vmn2r65 T A 7: 84,595,791 (GRCm39) T298S probably damaging Homo
Other mutations in Rbck1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00518:Rbck1 APN 2 152,160,315 (GRCm39) missense probably damaging 0.98
IGL00765:Rbck1 APN 2 152,172,874 (GRCm39) splice site probably benign
IGL01647:Rbck1 APN 2 152,165,152 (GRCm39) missense probably damaging 1.00
IGL01945:Rbck1 APN 2 152,160,236 (GRCm39) missense probably damaging 1.00
IGL02141:Rbck1 APN 2 152,160,294 (GRCm39) missense possibly damaging 0.56
IGL02573:Rbck1 APN 2 152,164,087 (GRCm39) missense possibly damaging 0.90
IGL02950:Rbck1 APN 2 152,172,997 (GRCm39) missense possibly damaging 0.95
circei UTSW 2 152,161,145 (GRCm39) missense probably damaging 1.00
green_fire UTSW 2 152,165,094 (GRCm39) nonsense probably null
iron_throne UTSW 2 152,160,371 (GRCm39) missense probably benign 0.45
Viserion UTSW 2 152,172,886 (GRCm39) missense possibly damaging 0.87
westeros UTSW 2 152,160,653 (GRCm39) nonsense probably null
R0532:Rbck1 UTSW 2 152,166,250 (GRCm39) missense probably damaging 0.99
R1426:Rbck1 UTSW 2 152,169,161 (GRCm39) unclassified probably benign
R1598:Rbck1 UTSW 2 152,165,090 (GRCm39) critical splice donor site probably null
R1666:Rbck1 UTSW 2 152,158,819 (GRCm39) missense probably damaging 0.99
R1668:Rbck1 UTSW 2 152,158,819 (GRCm39) missense probably damaging 0.99
R1889:Rbck1 UTSW 2 152,160,276 (GRCm39) missense probably damaging 0.99
R4572:Rbck1 UTSW 2 152,160,653 (GRCm39) nonsense probably null
R4592:Rbck1 UTSW 2 152,160,653 (GRCm39) nonsense probably null
R5077:Rbck1 UTSW 2 152,160,371 (GRCm39) missense probably benign 0.45
R6049:Rbck1 UTSW 2 152,165,094 (GRCm39) nonsense probably null
R6494:Rbck1 UTSW 2 152,172,886 (GRCm39) missense possibly damaging 0.87
R7530:Rbck1 UTSW 2 152,166,212 (GRCm39) missense possibly damaging 0.54
R7878:Rbck1 UTSW 2 152,160,330 (GRCm39) missense probably damaging 0.97
R8346:Rbck1 UTSW 2 152,160,700 (GRCm39) missense probably damaging 1.00
R8871:Rbck1 UTSW 2 152,164,096 (GRCm39) missense possibly damaging 0.92
R9353:Rbck1 UTSW 2 152,161,145 (GRCm39) missense probably damaging 1.00
R9782:Rbck1 UTSW 2 152,165,113 (GRCm39) missense probably damaging 0.99
Z1177:Rbck1 UTSW 2 152,166,218 (GRCm39) missense probably benign 0.09
Nature of Mutation
DNA sequencing using the SOLiD technique identified a C to A transversion at position 1525 of the Rbck1 transcript in exon 10 of 13 total exons. Multiple transcripts of the Rbck1 gene are displayed on Ensembl.  The mutated nucleotide causes an asparagine to lysine substitution at amino acid 385 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function and Prediction
The Rbck1 gene encodes a 508 amino acid protein that may act as an E3 ubiquitin-protein ligase or as part of the E3 complex, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes like UBE2L3.  RBCK1 contains a RanBP2-type zinc finger at amino acids 188-220, a RING-type zinc finger at amino acids 280-325, a B box-type zinc finger at amino acids 374-409, and an ubiquitin-like domain at amino acids 55-119. It may interact with protein kinase C isoforms (PKCβ1 and PKCζ) (Uniprot Q9WUB0).
 
The N385K change occurs in the B boc-type zinc finger, and is predicted to be probably damaging by the PolyPhen program.
Posted On 2010-03-16