Incidental Mutation 'D4186:Clp1'
ID139
Institutional Source Beutler Lab
Gene Symbol Clp1
Ensembl Gene ENSMUSG00000027079
Gene NameCLP1, cleavage and polyadenylation factor I subunit
Synonyms
Accession Numbers

Genbank: NM_133840; MGI: 2138968

Is this an essential gene? Essential (E-score: 1.000) question?
Stock #D4186 (G3) of strain 521
Quality Score
Status Validated
Chromosome2
Chromosomal Location84722104-84727350 bp(-) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) T to C at 84725635 bp
ZygosityHomozygous
Amino Acid Change Tyrosine to Cysteine at position 167 (Y167C)
Ref Sequence ENSEMBL: ENSMUSP00000129300 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000028475] [ENSMUST00000165219]
Predicted Effect probably benign
Transcript: ENSMUST00000028475
AA Change: Y167C

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)
SMART Domains Protein: ENSMUSP00000028475
Gene: ENSMUSG00000027079
AA Change: Y167C

DomainStartEndE-ValueType
Pfam:CLP1_N 15 107 1.7e-36 PFAM
Pfam:CLP1_P 121 307 2e-79 PFAM
Pfam:Clp1 312 423 1.3e-34 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000138231
Predicted Effect probably benign
Transcript: ENSMUST00000165219
AA Change: Y167C

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)
SMART Domains Protein: ENSMUSP00000129300
Gene: ENSMUSG00000027079
AA Change: Y167C

DomainStartEndE-ValueType
low complexity region 15 28 N/A INTRINSIC
Pfam:MobB 115 230 5.7e-24 PFAM
Pfam:Clp1 232 424 3e-62 PFAM
Meta Mutation Damage Score 0.0758 question?
Coding Region Coverage
  • 1x: 85.3%
  • 3x: 59.3%
Validation Efficiency 77% (85/111)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the Clp1 family. The encoded protein is a multifunctional kinase which is a component of the tRNA splicing endonuclease complex and a component of the pre-mRNA cleavage complex II. This protein is implicated in tRNA, mRNA, and siRNA maturation. Mutations in this gene are associated with pontocerebellar hypoplasia type 10 (PCH10). Alternatively splice transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]
PHENOTYPE: Mice homozygous for a kinase dead allele exhibit background sensitive lethality, motor neuron degeneration, defects in diaphragm innervation, progressive muscle weakness and impaired pre-tRNA processing. Mice homozygous for a globally targeted allele exhibit complete embryonic lethality. [provided by MGI curators]
Allele List at MGI

All alleles(6) : Gene trapped(6)

Other mutations in this stock
Total: 6 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Ampd2 C A 3: 108,081,111 A11S probably benign Het
Fsip2 T A 2: 82,988,412 S4830T probably benign Homo
Patj T A 4: 98,638,762 S181R probably benign Homo
Pde11a T C 2: 76,291,290 T316A probably damaging Het
Tango2 G A 16: 18,312,666 R80W possibly damaging Het
Ugt2a3 T C 5: 87,329,613 L309R probably damaging Het
Other mutations in Clp1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL02725:Clp1 APN 2 84723864 missense probably benign 0.36
R0540:Clp1 UTSW 2 84725591 missense possibly damaging 0.69
R0607:Clp1 UTSW 2 84725591 missense possibly damaging 0.69
R1954:Clp1 UTSW 2 84724051 missense probably damaging 1.00
R2908:Clp1 UTSW 2 84724144 missense possibly damaging 0.89
R4769:Clp1 UTSW 2 84725875 missense possibly damaging 0.53
R4949:Clp1 UTSW 2 84723742 missense possibly damaging 0.58
R5568:Clp1 UTSW 2 84725978 nonsense probably null
R7191:Clp1 UTSW 2 84724146 nonsense probably null
Z1177:Clp1 UTSW 2 84725963 missense probably benign 0.01
Nature of Mutation
DNA sequencing using the SOLiD technique identified an A to G transition at position 628 of the Clp1 transcript in exon 2 of 3 total exons.  Two transcripts of the Clp1 gene are displayed on Ensembl. The mutated nucleotide causes a tyrosine to cysteine substitution at amino acid 167 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function and Prediction
The Clp1 gene encodes a 425 amino acid polynucleotide kinase that can phosphorylate the 5'-hydroxyl groups of double-stranded RNA (dsRNA), single-stranded RNA (ssRNA), double stranded DNA (dsDNA) and double-stranded DNA:RNA hybrids. This kinase appears to have roles in both tRNA splicing and mRNA 3'-end formation, and is a component of the tRNA splicing endonuclease complex and of the pre-mRNA cleavage complex II (CF-II). CLP1 phosphorylates the 5'-terminus of the tRNA 3'-exon during tRNA splicing; this phosphorylation event is a prerequisite for the subsequent ligation of the two exon halves and the production of a mature tRNA. CLP1 can also phosphorylate the 5'-terminus of exogenously introduced short interfering RNAs (siRNAs), but is likely dispensable for normal RNA-mediated gene silencing. Nucleotide binding occurs at amino acids 121-128 (Uniprot Q99LI9). 
 
The Y167C change is predicted to be benign by the PolyPhen program.
Posted On2010-03-19