Incidental Mutation 'G5538:Polr3b'
ID 531
Institutional Source Beutler Lab
Gene Symbol Polr3b
Ensembl Gene ENSMUSG00000034453
Gene Name polymerase (RNA) III (DNA directed) polypeptide B
Synonyms 2700078H01Rik, RPC2, A330032P03Rik
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # G5538 (G3) of strain frizz
Quality Score
Status Validated
Chromosome 10
Chromosomal Location 84458156-84563042 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 84467658 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Asparagine to Lysine at position 79 (N79K)
Ref Sequence ENSEMBL: ENSMUSP00000076418 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000077175]
AlphaFold P59470
Predicted Effect probably benign
Transcript: ENSMUST00000077175
AA Change: N79K

PolyPhen 2 Score 0.206 (Sensitivity: 0.92; Specificity: 0.88)
SMART Domains Protein: ENSMUSP00000076418
Gene: ENSMUSG00000034453
AA Change: N79K

DomainStartEndE-ValueType
Pfam:RNA_pol_Rpb2_1 38 413 2e-55 PFAM
Pfam:RNA_pol_Rpb2_2 185 363 8.4e-29 PFAM
Pfam:RNA_pol_Rpb2_3 438 502 2.6e-22 PFAM
Pfam:RNA_pol_Rpb2_4 539 600 1e-29 PFAM
Pfam:RNA_pol_Rpb2_5 621 661 6.5e-14 PFAM
Pfam:RNA_pol_Rpb2_6 668 1041 5.8e-129 PFAM
Pfam:RNA_pol_Rpb2_7 1043 1129 7.6e-36 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000213263
Meta Mutation Damage Score 0.1407 question?
Coding Region Coverage
  • 1x: 75.9%
  • 3x: 46.5%
Het Detection Efficiency 20.9%
Validation Efficiency 82% (69/84)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes the second largest subunit of RNA polymerase III, the polymerase responsible for synthesizing transfer and small ribosomal RNAs in eukaryotes. The largest subunit and the encoded protein form the catalytic center of RNA polymerase III. Mutations in this gene are a cause of hypomyelinating leukodystrophy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]
Allele List at MGI

All alleles(48) : Targeted, other(2) Gene trapped(46)
Other mutations in this stock
Total: 2 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Eif3a A T 19: 60,770,340 (GRCm39) N120K probably damaging Het
Pikfyve T C 1: 65,242,075 (GRCm39) W272R probably damaging Homo
Other mutations in Polr3b
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00787:Polr3b APN 10 84,512,854 (GRCm39) missense probably benign
IGL00848:Polr3b APN 10 84,516,241 (GRCm39) missense probably damaging 1.00
IGL00901:Polr3b APN 10 84,467,660 (GRCm39) missense possibly damaging 0.94
IGL01313:Polr3b APN 10 84,561,607 (GRCm39) missense probably damaging 1.00
IGL01364:Polr3b APN 10 84,531,533 (GRCm39) missense probably benign 0.00
IGL01731:Polr3b APN 10 84,467,704 (GRCm39) nonsense probably null
IGL03326:Polr3b APN 10 84,503,259 (GRCm39) missense probably benign 0.43
IGL03369:Polr3b APN 10 84,512,816 (GRCm39) missense probably damaging 1.00
etruscan UTSW 10 84,468,402 (GRCm39) missense probably benign 0.00
pennyweight UTSW 10 84,549,496 (GRCm39) missense probably damaging 1.00
pinhead UTSW 10 84,491,855 (GRCm39) missense probably damaging 1.00
PIT4382001:Polr3b UTSW 10 84,520,049 (GRCm39) missense probably damaging 1.00
R0180:Polr3b UTSW 10 84,458,379 (GRCm39) missense probably benign
R0270:Polr3b UTSW 10 84,554,339 (GRCm39) missense probably benign 0.02
R0541:Polr3b UTSW 10 84,473,928 (GRCm39) missense probably damaging 1.00
R0890:Polr3b UTSW 10 84,550,200 (GRCm39) missense probably benign 0.01
R1302:Polr3b UTSW 10 84,468,350 (GRCm39) missense probably damaging 0.97
R1511:Polr3b UTSW 10 84,516,249 (GRCm39) missense probably benign
R1561:Polr3b UTSW 10 84,470,776 (GRCm39) missense probably damaging 1.00
R1607:Polr3b UTSW 10 84,488,647 (GRCm39) missense probably benign 0.00
R1624:Polr3b UTSW 10 84,515,669 (GRCm39) missense probably damaging 0.98
R1809:Polr3b UTSW 10 84,528,865 (GRCm39) missense probably damaging 1.00
R1830:Polr3b UTSW 10 84,528,786 (GRCm39) nonsense probably null
R2973:Polr3b UTSW 10 84,464,144 (GRCm39) missense probably benign 0.00
R3401:Polr3b UTSW 10 84,535,355 (GRCm39) missense probably damaging 0.96
R3876:Polr3b UTSW 10 84,556,382 (GRCm39) critical splice donor site probably null
R3961:Polr3b UTSW 10 84,520,166 (GRCm39) missense possibly damaging 0.89
R4664:Polr3b UTSW 10 84,550,233 (GRCm39) missense probably damaging 1.00
R4721:Polr3b UTSW 10 84,491,867 (GRCm39) missense possibly damaging 0.56
R4972:Polr3b UTSW 10 84,473,988 (GRCm39) missense probably damaging 1.00
R5065:Polr3b UTSW 10 84,468,402 (GRCm39) missense probably benign 0.00
R5264:Polr3b UTSW 10 84,503,280 (GRCm39) missense probably benign 0.02
R5302:Polr3b UTSW 10 84,535,264 (GRCm39) missense possibly damaging 0.59
R5795:Polr3b UTSW 10 84,464,116 (GRCm39) missense probably benign
R5795:Polr3b UTSW 10 84,512,875 (GRCm39) missense probably damaging 0.97
R5838:Polr3b UTSW 10 84,510,454 (GRCm39) missense probably benign 0.09
R6419:Polr3b UTSW 10 84,473,975 (GRCm39) missense possibly damaging 0.78
R6568:Polr3b UTSW 10 84,470,767 (GRCm39) missense probably damaging 1.00
R6787:Polr3b UTSW 10 84,464,489 (GRCm39) critical splice acceptor site probably null
R6913:Polr3b UTSW 10 84,549,496 (GRCm39) missense probably damaging 1.00
R7405:Polr3b UTSW 10 84,520,043 (GRCm39) missense probably benign
R7456:Polr3b UTSW 10 84,458,355 (GRCm39) missense probably benign
R7657:Polr3b UTSW 10 84,491,855 (GRCm39) missense probably damaging 1.00
R8074:Polr3b UTSW 10 84,549,523 (GRCm39) missense probably damaging 1.00
R8082:Polr3b UTSW 10 84,491,927 (GRCm39) missense probably damaging 1.00
R8127:Polr3b UTSW 10 84,515,653 (GRCm39) missense probably benign
R8676:Polr3b UTSW 10 84,516,251 (GRCm39) missense probably benign 0.00
R8744:Polr3b UTSW 10 84,464,488 (GRCm39) splice site probably benign
R8797:Polr3b UTSW 10 84,532,879 (GRCm39) nonsense probably null
R8866:Polr3b UTSW 10 84,531,555 (GRCm39) missense probably benign 0.14
R9006:Polr3b UTSW 10 84,467,697 (GRCm39) missense probably benign 0.05
R9397:Polr3b UTSW 10 84,467,653 (GRCm39) missense possibly damaging 0.93
R9509:Polr3b UTSW 10 84,467,650 (GRCm39) missense probably damaging 1.00
X0066:Polr3b UTSW 10 84,549,559 (GRCm39) missense probably damaging 0.97
Z1177:Polr3b UTSW 10 84,550,157 (GRCm39) missense probably damaging 1.00
Nature of Mutation

DNA sequencing using the SOLiD technique identified a T to A transversion at position 267 of the Polr3b transcript in exon 5 of 28 total exons. The mutated nucleotide causes an asparagine to lysine substitution at amino acid 79 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function and Prediction

The Polr3b gene encodes the 1133 amino acid C2 subunit of RNA polymerase III (Pol III). This is a DNA-dependent RNA polymerase that catalyzes the transcription of DNA into RNA. Pol III transcribes significantly shorter genes than those transcribed by Pol I and Pol II. Pol III also synthesizes small RNAs, such as 5S rRNA and tRNAs. The C2 subunit is the second largest core component of the polymerase and is proposed to contribute to the polymerase catalytic activity and form the polymerase active center together with the largest subunit. Pol III plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses by sensing non-self dsDNA that serves as template for transcription into dsRNA. The non-self RNA polymerase III transcripts induce type I interferon and NF- Kappa-B through the RIG-I pathway. Zinc binding occurs at residues 1080, 1083, 1092 and 1095 (Uniprot P59470).

The N79K change is predicted to be benign by the PolyPhen program. 
Posted On 2010-11-10