Phenotypic Mutation 'rio' (pdf version)
Allelerio
Mutation Type critical splice acceptor site (2 bp from exon)
Chromosome13
Coordinate59,673,055 bp (GRCm39)
Base Change T ⇒ C (forward strand)
Gene Agtpbp1
Gene Name ATP/GTP binding protein 1
Synonym(s) 2310001G17Rik, Ccp1, Nna1, 4930445M19Rik, 1700020N17Rik, 2900054O13Rik, 5730402G09Rik, atms
Chromosomal Location 59,597,348-59,705,184 bp (-) (GRCm39)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] NNA1 is a zinc carboxypeptidase that contains nuclear localization signals and an ATP/GTP-binding motif that was initially cloned from regenerating spinal cord neurons of the mouse.[supplied by OMIM, Jul 2002]
PHENOTYPE: Homozygotes show moderate ataxia due to degeneration of Purkinje cells of the cerebellum. Also, there is gradual degeneration of retina photoreceptor cells, olfactory bulb mitral cells and some thalamic neurons. Males have abnormal sperm and are sterile. [provided by MGI curators]
Accession Number

NCBI RefSeq: NM_023328; MGI: 2159437

MappedYes 
Limits of the Critical Region 45159272 - 86068736 bp
Amino Acid Change
Institutional SourceBeutler Lab
Gene Model not available
AlphaFold Q641K1
SMART Domains Protein: ENSMUSP00000022040
Gene: ENSMUSG00000021557

DomainStartEndE-ValueType
low complexity region 362 391 N/A INTRINSIC
low complexity region 589 603 N/A INTRINSIC
Pfam:Peptidase_M14 851 1099 1.7e-13 PFAM
Predicted Effect probably benign
SMART Domains Protein: ENSMUSP00000105456
Gene: ENSMUSG00000021557

DomainStartEndE-ValueType
Pfam:V-ATPase_H_N 34 309 2.3e-7 PFAM
low complexity region 362 391 N/A INTRINSIC
low complexity region 589 603 N/A INTRINSIC
Predicted Effect probably benign
SMART Domains Protein: ENSMUSP00000126238
Gene: ENSMUSG00000021557

DomainStartEndE-ValueType
low complexity region 250 279 N/A INTRINSIC
low complexity region 477 491 N/A INTRINSIC
Predicted Effect probably benign
SMART Domains Protein: ENSMUSP00000130939
Gene: ENSMUSG00000021557

DomainStartEndE-ValueType
low complexity region 362 391 N/A INTRINSIC
low complexity region 589 603 N/A INTRINSIC
Pfam:Peptidase_M14 847 1123 1.2e-26 PFAM
Predicted Effect probably benign
Predicted Effect probably benign
Predicted Effect probably benign
Predicted Effect probably benign
Predicted Effect probably benign
Predicted Effect probably benign
Predicted Effect probably benign
SMART Domains Protein: ENSMUSP00000128589
Gene: ENSMUSG00000021557

DomainStartEndE-ValueType
Pfam:V-ATPase_H_N 34 309 2.4e-7 PFAM
low complexity region 362 391 N/A INTRINSIC
low complexity region 589 603 N/A INTRINSIC
low complexity region 787 795 N/A INTRINSIC
Predicted Effect probably benign
SMART Domains Protein: ENSMUSP00000132697
Gene: ENSMUSG00000021557

DomainStartEndE-ValueType
Pfam:V-ATPase_H_N 34 309 2.3e-7 PFAM
low complexity region 362 391 N/A INTRINSIC
low complexity region 589 603 N/A INTRINSIC
Predicted Effect probably benign
Meta Mutation Damage Score Not available question?
Is this an essential gene? Probably essential (E-score: 0.815) question?
Phenotypic Category Autosomal Recessive
Candidate Explorer Status loading ...
Single pedigree
Linkage Analysis Data
Penetrance 100% 
Alleles Listed at MGI

All alleles(17) : Gene trapped(6) Transgenic(1) Spontaneous(6) Chemically induced(4)

Lab Alleles
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00544:Agtpbp1 APN 13 59597986 missense probably damaging 1.00
IGL00808:Agtpbp1 APN 13 59609908 missense possibly damaging 0.84
IGL01298:Agtpbp1 APN 13 59652040 missense possibly damaging 0.77
IGL01628:Agtpbp1 APN 13 59655877 splice site probably benign
IGL01921:Agtpbp1 APN 13 59660297 missense possibly damaging 0.71
IGL02189:Agtpbp1 APN 13 59648275 missense probably benign 0.01
IGL02325:Agtpbp1 APN 13 59648303 missense probably benign 0.01
IGL02700:Agtpbp1 APN 13 59676233 missense probably damaging 1.00
IGL02821:Agtpbp1 APN 13 59630415 missense possibly damaging 0.69
IGL03130:Agtpbp1 APN 13 59622403 missense possibly damaging 0.73
IGL03167:Agtpbp1 APN 13 59679894 splice site probably benign
IGL03218:Agtpbp1 APN 13 59648021 missense possibly damaging 0.94
bobs UTSW 13 59630385 missense possibly damaging 0.53
drunk UTSW 13 59660136 critical splice donor site probably benign
gru UTSW 13 59621560 missense probably damaging 1.00
shreds UTSW 13 59609902 missense probably damaging 1.00
Unfocused UTSW 13 59609884 nonsense probably null
wobble UTSW 13 59622364 missense probably damaging 1.00
R0025:Agtpbp1 UTSW 13 59648014 missense probably benign 0.00
R0025:Agtpbp1 UTSW 13 59648014 missense probably benign 0.00
R0276:Agtpbp1 UTSW 13 59609845 missense possibly damaging 0.93
R0413:Agtpbp1 UTSW 13 59661966 missense probably damaging 0.99
R0559:Agtpbp1 UTSW 13 59644814 missense probably benign 0.32
R0848:Agtpbp1 UTSW 13 59681753 intron probably benign
R0943:Agtpbp1 UTSW 13 59648416 missense probably benign
R1196:Agtpbp1 UTSW 13 59598132 unclassified probably benign
R1421:Agtpbp1 UTSW 13 59643389 missense possibly damaging 0.86
R1531:Agtpbp1 UTSW 13 59648448 splice site probably null
R1833:Agtpbp1 UTSW 13 59613797 critical splice donor site probably null
R1864:Agtpbp1 UTSW 13 59598016 missense possibly damaging 0.92
R1994:Agtpbp1 UTSW 13 59678872 missense probably damaging 1.00
R1995:Agtpbp1 UTSW 13 59678872 missense probably damaging 1.00
R2001:Agtpbp1 UTSW 13 59623617 frame shift probably null
R2006:Agtpbp1 UTSW 13 59648135 missense probably benign 0.00
R2397:Agtpbp1 UTSW 13 59622383 missense probably benign 0.10
R2918:Agtpbp1 UTSW 13 59644829 missense possibly damaging 0.90
R3873:Agtpbp1 UTSW 13 59608410 missense possibly damaging 0.88
R3924:Agtpbp1 UTSW 13 59648221 missense probably benign 0.01
R4649:Agtpbp1 UTSW 13 59676213 missense possibly damaging 0.89
R4913:Agtpbp1 UTSW 13 59647886 missense probably damaging 1.00
R4933:Agtpbp1 UTSW 13 59648386 missense probably benign
R4969:Agtpbp1 UTSW 13 59648392 missense probably benign
R5066:Agtpbp1 UTSW 13 59622364 missense probably damaging 1.00
R5139:Agtpbp1 UTSW 13 59648027 missense probably damaging 0.99
R5194:Agtpbp1 UTSW 13 59648453 missense probably benign 0.19
R5269:Agtpbp1 UTSW 13 59621557 missense probably damaging 1.00
R5352:Agtpbp1 UTSW 13 59621560 missense probably damaging 1.00
R5558:Agtpbp1 UTSW 13 59630394 missense probably benign 0.05
R5687:Agtpbp1 UTSW 13 59648329 missense probably benign
R5824:Agtpbp1 UTSW 13 59613913 missense probably damaging 1.00
R5979:Agtpbp1 UTSW 13 59681860 nonsense probably null
R6109:Agtpbp1 UTSW 13 59621560 missense probably damaging 1.00
R6264:Agtpbp1 UTSW 13 59598114 missense possibly damaging 0.89
R6413:Agtpbp1 UTSW 13 59647834 missense possibly damaging 0.90
R6498:Agtpbp1 UTSW 13 59624854 missense possibly damaging 0.71
R6747:Agtpbp1 UTSW 13 59692167 splice site probably null
R6950:Agtpbp1 UTSW 13 59598080 missense probably benign 0.32
R7030:Agtpbp1 UTSW 13 59652108 missense probably damaging 1.00
R7180:Agtpbp1 UTSW 13 59613852 missense probably benign 0.11
R7196:Agtpbp1 UTSW 13 59680994 missense possibly damaging 0.83
R7535:Agtpbp1 UTSW 13 59652067 missense probably benign
R7683:Agtpbp1 UTSW 13 59660312 missense probably damaging 1.00
R7713:Agtpbp1 UTSW 13 59661966 missense probably damaging 0.99
R8081:Agtpbp1 UTSW 13 59676221 nonsense probably null
R8210:Agtpbp1 UTSW 13 59630385 missense possibly damaging 0.53
R8861:Agtpbp1 UTSW 13 59643287 missense probably damaging 1.00
R9163:Agtpbp1 UTSW 13 59609884 nonsense probably null
R9199:Agtpbp1 UTSW 13 59613808 missense probably benign 0.00
R9389:Agtpbp1 UTSW 13 59613884 missense probably damaging 1.00
R9414:Agtpbp1 UTSW 13 59609902 missense probably damaging 1.00
R9435:Agtpbp1 UTSW 13 59622429 missense probably benign 0.35
Mode of Inheritance Autosomal Recessive
Local Stock Sperm
Repository

none

Last Updated 2018-05-22 9:37 AM by Anne Murray
Record Created unknown
Record Posted 2010-04-14
Phenotypic Description
The rio phenotype was first observed in G3 mice homozygous for mutations induced by N-ethyl-N-nitrosourea (ENU). Homozygous rio mice display tremor and a slightly reduced size. Sperm from homozygous males are only 50% motile.  Intracytoplasmic sperm injection (ICSI) in C57BL/6J oocytes successfully generated progeny.
 
Nature of Mutation
The rio mutation was mapped to Chromosome 13, and the candidate gene Agtpbp1 located in the critical region was subsequently sequenced. The rio mutation corresponds to an A to G transition at base pair 59,626,602 in the Genbank genomic region NC_000079 (Build 37.1) for the Agtpbp1 gene (TTTCTCAG ->TTTCTCGG). The mutation is located within intron 7 from the ATG start exon, two nucleotides to the next exon (Figure 1). The Agtpbp1 transcript contains 27 total exons. Three transcripts of the Agtpbp1 gene are displayed on Ensembl. Currently, it is unknown how the rio mutation affects splicing of the gene. Possibly, the acceptor splice site from intron 8 is utilized, resulting in skipping of exon 8 and causing a frame shift beginning with the first nucleotide of exon 9 (depicted below).  In this case, three aberrant amino acids encoded by exon 9 will be inserted before a premature stop codon. 
 
       <--exon 7  <--intron 7 exon 8-->  exon 9-->
    TCTACCAACT……CTTGTTTCTCAGCTGTGAACT……GGTTGCTTTAG
187 -S--T--N--              S--V--N-   W--L--L--*  192
     correct                deleted     aberrant
 
The mutated nucleotide is indicated in red lettering; the acceptor splice site of intron 7 is indicated in blue lettering.
Illustration of Mutations in
Gene & Protein
Protein Prediction
Figure 2. Domain structure of NNA1. The rio mutation corresponds to an A to G transition within intron 7 in the Agtpbp1 gene. It is unknown how the rio mutation affects splicing of the gene. Click on each mututation in red for more specific information.
The rio mutation located in the acceptor splice site of intron 7 in the Agtpbp1 gene likely affects normal splicing and probably results in severe truncation of the normally 1218 amino acid protein. Truncation is likely to occur prior to the zinc carboxypeptidase domain located near the C-terminus of the protein, rendering any expressed protein nonfunctional. It is likely that the rio mutation renders the protein unstable, leading to its rapid degeneration.  
 
Please see the record for drunk for more information about the Agtpbp1 gene.
Primers Primers cannot be located by automatic search.
Genotyping
Rio genotyping is performed by amplifying the region containing the mutation using PCR, followed by sequencing of the amplified region to detect the single nucleotide transition.
 
Primers
Rio(F): 5’- CTGCCATGCTCACTACTCAGGTTG -3’
Rio(R): 5’- TCTGGACAAAACAGGCGTGTGTAAC-3’
 
PCR program
1) 94°C             2:00
2) 94°C             0:30
3) 62°C             0:30
4) 72°C             1:00
5) repeat steps (2-4) 35X
6) 72°C             5:00
7) 4°C               ∞
 
Sequencing Primers
Rio_seq(F): 5’- GCTTAGAGCAGAGCCTGTATACTTC -3’
Rio_seq(R): 5’- CTTTCAGACAGTCCATAATGGTGAG-3’
 
The following sequence of 806 nucleotides (NCBI Mouse Genome Build 37.1, Chromosome 13, bases 59,626,079 to 59,626,884) is amplified:
 
ctgccatgct cactactcag gttgcttaga gcagagcctg tatacttctt gtctttgatt
cccaacactc actttcctgg tgtcatctga tagcaactgt ttttggaatg ctagttgctc
ccaacttctc ataaaaacaa agcaaaatac gtccccctcc caacccctac agcccagctt
tacagggcct gggagcttgc atttatattg actaaatact ttggggtaat tttagattca
tcactaagat ttaaatcact ttgtgtcttt ttcttgtttc tcagctgtga actcagtatc
tttaggtaaa aatggagttg tggagttgat gtttaaaatc attgggccat tcagtaagaa
gaattcgggt ctcatgaagt aagtaaatgt tgtgatgcga gtggaagttt atccttaggc
attctgagct tcactgccct gacatgtacc tgagcaggtg aggtcagcta tagctagagt
ctctagttct taaatagtca tttcttttaa taaagatgtt cttaattcaa agcttaatgt
ttaagttaga gcatttcaat ttgttaagta cactgtttta agggcgatga ctgaagctgg
tggccctgtg cgaggggctg ggctgtgtcc agcaccatcc cctgaagcct ttgttgagtg
cccactctaa tgctcgccca ttgtgcttag ctctcgatga ccattcgtcc tcttcaccat
tatggactgt ctgaaagtta cacacgcctg ttttgtcctc accattatgg actgtctgaa
agttacacac gcctgttttg tccaga
 
Primer binding sites are underlined; the mutated A is highlighted in red.
 
Science Writers Nora G. Smart
Illustrators Diantha La Vine
AuthorsPhilippe Krebs, Bruce Beutler
Edit History
2010-11-02 8:53 AM (current)
2010-06-22 9:04 AM
2010-04-27 1:46 PM
2010-04-14 2:47 PM
2010-04-14 2:46 PM