Mutagenetix > Incidental Mutations

Incidental Mutation 'R0047:Ppp2r1b'

15991

Institutional Source

Beutler Lab

Gene Symbol

Ppp2r1b

Ensembl Gene

ENSMUSG00000032058

Gene Name

protein phosphatase 2, regulatory subunit A, beta

Synonyms

2410091N08Rik

MMRRC Submission

038341-MU

Accession Numbers

Ncbi RefSeq: NM_001034085.1, NM_028614.2; MGI:1920949

Is this an essential gene?

Possibly essential (E-score: 0.644) question?

Stock #

R0047 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

50845301-50894229 bp(+) (GRCm38)

Type of Mutation

nonsense

DNA Base Change (assembly)

C to T at 50861573 bp

Zygosity

Heterozygous

Amino Acid Change

Arginine to Stop codon at position 117 (R117*)

Ref Sequence

ENSEMBL: ENSMUSP00000135525 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000034560] [ENSMUST00000114437] [ENSMUST00000174628] [ENSMUST00000175640] [ENSMUST00000175645] [ENSMUST00000175926] [ENSMUST00000176349] [ENSMUST00000176798]

Predicted Effect

probably null
Transcript: ENSMUST00000034560
AA Change: R117*

SMART Domains

Protein: ENSMUSP00000034560
Gene: ENSMUSG00000032058
AA Change: R117*

Domain	Start	End	E-Value	Type
low complexity region	2	21	N/A	INTRINSIC
Pfam:HEAT	178	208	2.2e-6	PFAM
Pfam:HEAT_EZ	182	243	9.9e-6	PFAM
Pfam:HEAT	295	325	5.9e-6	PFAM
Pfam:HEAT_2	378	479	1.1e-10	PFAM
Pfam:HEAT_2	495	596	5.1e-8	PFAM

Predicted Effect

probably null
Transcript: ENSMUST00000114437
AA Change: R117*

SMART Domains

Protein: ENSMUSP00000110080
Gene: ENSMUSG00000032058
AA Change: R117*

Domain	Start	End	E-Value	Type
low complexity region	2	21	N/A	INTRINSIC
Pfam:HEAT	178	208	1.6e-6	PFAM
Pfam:HEAT_EZ	180	243	7.3e-6	PFAM
Pfam:HEAT	217	247	4.3e-5	PFAM
Pfam:HEAT	295	325	4.2e-6	PFAM
Pfam:HEAT_2	378	479	9e-11	PFAM
Pfam:HEAT_2	494	597	4.2e-8	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000174555

Predicted Effect

probably null
Transcript: ENSMUST00000174628
AA Change: R117*

SMART Domains

Protein: ENSMUSP00000133404
Gene: ENSMUSG00000032058
AA Change: R117*

Domain	Start	End	E-Value	Type
low complexity region	2	21	N/A	INTRINSIC
Pfam:HEAT	178	208	4.6e-6	PFAM
Pfam:HEAT	217	247	4.5e-5	PFAM
Pfam:HEAT	295	325	4.3e-6	PFAM
Pfam:HEAT_2	378	479	1.7e-11	PFAM
low complexity region	643	655	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000175640

SMART Domains

Protein: ENSMUSP00000134740
Gene: ENSMUSG00000032058

Domain	Start	End	E-Value	Type
low complexity region	2	21	N/A	INTRINSIC
Pfam:HEAT	129	159	5.7e-5	PFAM
Pfam:HEAT	168	198	4e-6	PFAM
Pfam:HEAT_2	251	352	6.3e-11	PFAM
Pfam:HEAT_2	365	470	3e-8	PFAM

Predicted Effect

probably null
Transcript: ENSMUST00000175645
AA Change: R117*

SMART Domains

Protein: ENSMUSP00000135871
Gene: ENSMUSG00000032058
AA Change: R117*

Domain	Start	End	E-Value	Type
low complexity region	2	21	N/A	INTRINSIC
Pfam:HEAT_EZ	173	243	8e-6	PFAM
Pfam:HEAT	178	208	1.8e-6	PFAM
Pfam:HEAT	217	247	4.9e-5	PFAM
Pfam:HEAT	295	325	4.8e-6	PFAM
Pfam:HEAT_2	449	552	3.9e-8	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000175926

SMART Domains

Protein: ENSMUSP00000134886
Gene: ENSMUSG00000032058

Domain	Start	End	E-Value	Type
SCOP:d1b3ua_	14	104	4e-15	SMART
PDB:3DW8\|D	22	104	4e-45	PDB

Predicted Effect

probably null
Transcript: ENSMUST00000176349
AA Change: R53*

SMART Domains

Protein: ENSMUSP00000135758
Gene: ENSMUSG00000032058
AA Change: R53*

Domain	Start	End	E-Value	Type
low complexity region	2	21	N/A	INTRINSIC
Pfam:HEAT	114	144	2e-6	PFAM
Pfam:HEAT_EZ	116	179	8.7e-6	PFAM
Pfam:HEAT	153	183	5.5e-5	PFAM
Pfam:HEAT	231	261	5.3e-6	PFAM
Pfam:HEAT_2	314	415	9.3e-11	PFAM
Pfam:HEAT_2	430	532	4.4e-8	PFAM

Predicted Effect

probably null
Transcript: ENSMUST00000176798
AA Change: R117*

SMART Domains

Protein: ENSMUSP00000135525
Gene: ENSMUSG00000032058
AA Change: R117*

Domain	Start	End	E-Value	Type
low complexity region	2	21	N/A	INTRINSIC
Pfam:HEAT	178	208	2.3e-6	PFAM
Pfam:HEAT_EZ	182	243	1e-5	PFAM
Pfam:HEAT	295	325	6e-6	PFAM
Pfam:HEAT_2	378	479	1.1e-10	PFAM
Pfam:HEAT_2	495	596	5.2e-8	PFAM

Meta Mutation Damage Score

0.9755

Coding Region Coverage

1x: 89.2%
3x: 86.3%
10x: 78.8%
20x: 65.9%

Validation Efficiency

95% (110/116)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a constant regulatory subunit of protein phosphatase 2. Protein phosphatase 2 is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The constant regulatory subunit A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. This gene encodes a beta isoform of the constant regulatory subunit A. Mutations in this gene have been associated with some lung and colon cancers. Alternatively spliced transcript variants have been described. [provided by RefSeq, Apr 2010]

Allele List at MGI

All alleles(3) : Targeted(2) Gene trapped(1)

Other mutations in this stock

Total: 71 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1110002E22Rik	A	G	3: 138,066,264	T405A	probably damaging	Het
4932438A13Rik	T	A	3: 36,908,192	L481M	possibly damaging	Het
Acer1	A	T	17: 56,955,624	D175E	possibly damaging	Het
Adamts9	G	A	6: 92,905,306		probably benign	Het
Amigo3	T	C	9: 108,054,658	S427P	probably benign	Het
Arid4a	T	G	12: 71,075,419	L858W	probably damaging	Het
Bbox1	A	G	2: 110,268,302	F310S	probably damaging	Het
Bmper	T	A	9: 23,406,686	C534S	probably damaging	Het
Cacna1d	T	G	14: 30,346,790		probably benign	Het
Capn12	G	A	7: 28,890,387		probably null	Het
Chchd1	T	C	14: 20,704,163	S48P	possibly damaging	Het
Cnot7	A	G	8: 40,495,921		probably benign	Het
Cux1	T	C	5: 136,363,253		probably benign	Het
Cyp2b19	T	A	7: 26,766,826	D351E	probably benign	Het
Dctn1	G	T	6: 83,182,632	G31*	probably null	Het
Duox1	T	A	2: 122,346,641		probably benign	Het
Egflam	T	G	15: 7,253,430	E382A	possibly damaging	Het
Ext1	T	C	15: 53,345,146	N73S	probably benign	Het
Glg1	A	T	8: 111,165,582	M866K	probably damaging	Het
Gm3333	A	G	13: 62,274,471		noncoding transcript	Het
Golm1	T	A	13: 59,645,100	H197L	probably benign	Het
Gtse1	A	G	15: 85,862,378	K132E	probably damaging	Het
Gxylt2	A	T	6: 100,733,378		probably benign	Het
Hrc	T	A	7: 45,336,689	S421R	probably benign	Het
Ighg2c	T	A	12: 113,288,168		probably benign	Het
Ihh	A	G	1: 74,946,591	I245T	probably benign	Het
Ilf3	T	A	9: 21,388,714	M65K	possibly damaging	Het
Kif9	A	G	9: 110,485,038	I33V	probably benign	Het
Lama1	A	T	17: 67,795,186		probably benign	Het
Lamb1	T	C	12: 31,278,601	I188T	possibly damaging	Het
Lpp	T	A	16: 24,661,800		probably benign	Het
Mark2	A	C	19: 7,283,577		probably benign	Het
Mmp3	T	C	9: 7,451,910		probably benign	Het
Mthfd1l	T	A	10: 3,978,727		probably benign	Het
Mtr	A	T	13: 12,222,226	S569T	probably damaging	Het
Myh13	T	A	11: 67,367,237	S1752T	probably benign	Het
Myo5a	T	A	9: 75,156,207	L565H	probably damaging	Het
Numa1	A	G	7: 102,009,453	K296E	probably damaging	Het
Olfr1477	A	G	19: 13,502,589	E82G	probably benign	Het
Olfr201	C	T	16: 59,269,211	G152D	probably damaging	Het
Olfr613	A	T	7: 103,552,322	Y179F	probably damaging	Het
Pla2g2c	T	C	4: 138,743,590		probably benign	Het
Pnpla7	A	T	2: 25,011,606	E548V	probably damaging	Het
Ppm1m	C	A	9: 106,196,696	E273*	probably null	Het
Psg-ps1	A	G	7: 17,677,881		noncoding transcript	Het
Rabgap1l	G	A	1: 160,231,789		probably benign	Het
Rapgef6	T	A	11: 54,546,378	M49K	possibly damaging	Het
Rnf219	T	A	14: 104,503,344		probably null	Het
Rtel1	T	G	2: 181,323,405	I146M	probably damaging	Het
Sdr9c7	A	T	10: 127,903,672	M219L	probably benign	Het
Serpinb1a	A	T	13: 32,850,276	L44Q	probably damaging	Het
Slc13a4	A	G	6: 35,287,362	I190T	possibly damaging	Het
Slc46a2	A	G	4: 59,914,392	L177P	probably damaging	Het
Slc47a2	C	T	11: 61,336,242	V167M	possibly damaging	Het
Snrnp200	C	T	2: 127,234,954		probably benign	Het
Snx13	C	A	12: 35,101,124		probably benign	Het
Snx25	C	T	8: 46,041,365	A828T	probably damaging	Het
Spic	A	G	10: 88,675,941	L151P	probably damaging	Het
Sptb	G	T	12: 76,622,950	Q535K	probably damaging	Het
Ssu2	G	A	6: 112,374,820	H315Y	probably damaging	Het
Stk32a	T	C	18: 43,313,378		probably benign	Het
Tcaf2	A	G	6: 42,629,613	I469T	probably benign	Het
Tln2	A	G	9: 67,240,672		probably benign	Het
Top2a	T	A	11: 98,997,856	I1260L	probably benign	Het
Treml1	C	A	17: 48,364,980	S91*	probably null	Het
Trmt11	T	C	10: 30,535,243	N418S	probably benign	Het
Ttf1	A	G	2: 29,084,655	Y801C	probably damaging	Het
Usp34	C	T	11: 23,464,403	A2782V	probably benign	Het
Vps4a	T	C	8: 107,036,701	L29P	probably damaging	Het
Wdfy3	A	G	5: 101,944,033	I480T	probably damaging	Het
Ywhag	A	T	5: 135,911,299	V147E	probably damaging	Het

Other mutations in Ppp2r1b

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01622:Ppp2r1b	APN	9	50878122	missense	probably damaging	0.99
IGL01623:Ppp2r1b	APN	9	50878122	missense	probably damaging	0.99
IGL02120:Ppp2r1b	APN	9	50861769	splice site	probably benign
IGL02158:Ppp2r1b	APN	9	50861609	missense	probably benign	0.02
IGL02706:Ppp2r1b	APN	9	50878834	missense	possibly damaging	0.83
IGL02801:Ppp2r1b	APN	9	50878827	missense	probably benign	0.00
IGL02943:Ppp2r1b	APN	9	50883585	missense	probably damaging	1.00
R0047:Ppp2r1b	UTSW	9	50861573	nonsense	probably null
R0211:Ppp2r1b	UTSW	9	50861625	missense	probably benign	0.00
R0603:Ppp2r1b	UTSW	9	50861685	missense	probably damaging	1.00
R1219:Ppp2r1b	UTSW	9	50867321	splice site	probably benign
R1513:Ppp2r1b	UTSW	9	50870145	missense	probably damaging	1.00
R1545:Ppp2r1b	UTSW	9	50862425	missense	possibly damaging	0.68
R1997:Ppp2r1b	UTSW	9	50867371	missense	possibly damaging	0.71
R1998:Ppp2r1b	UTSW	9	50883585	missense	probably damaging	1.00
R2153:Ppp2r1b	UTSW	9	50866554	missense	probably damaging	1.00
R3829:Ppp2r1b	UTSW	9	50862494	missense	probably benign	0.02
R4672:Ppp2r1b	UTSW	9	50867719	missense	probably damaging	0.99
R5299:Ppp2r1b	UTSW	9	50857040	missense	probably benign	0.04
R5376:Ppp2r1b	UTSW	9	50866928	missense	possibly damaging	0.78
R5504:Ppp2r1b	UTSW	9	50858887	missense	probably damaging	1.00
R5700:Ppp2r1b	UTSW	9	50878157	missense	probably damaging	1.00
R5771:Ppp2r1b	UTSW	9	50866832	missense	probably damaging	0.98
R7547:Ppp2r1b	UTSW	9	50862462	missense	probably benign	0.06
R7626:Ppp2r1b	UTSW	9	50878176	missense	possibly damaging	0.91
Z1088:Ppp2r1b	UTSW	9	50866911	missense	probably damaging	1.00

Protein Function and Prediction

Ppp2r1b encodes PP2AA-beta, the beta isoform of the structural regulatory A subunit (PP2AA) of the trimeric serine/threonine protein phosphatase-2A (PP2A), a phosphatase that downregulates the mitogen-activated protein kinase (MAPK) cascade, relays signals for cell proliferation, and may be linked to carcinogenesis. PP2AA-beta interacts with the catalytic PP2AC subunit and variable PP2AB regulatory subunits to facilitate phosphatase activity (1;2). In immortalized human cells, the suppression of PP2AA-beta exrpression resulted in a conversion of the cells to a tumorigenic state through an interaction with, and a modulation of activity of, the small GTPase, RalA; this study proposed that PP2AA-beta is a tumor suppressor (3).

References

1. Walter, G., and Mumby, M. (1993) Protein serine/threonine Phosphatases and Cell Transformation. Biochim Biophys Acta. 1155, 207-226.

2. Wang, S. S., Esplin, E. D., Li, J. L., Huang, L., Gazdar, A., Minna, J., and Evans, G. A. (1998) Alterations of the PPP2R1B Gene in Human Lung and Colon Cancer. Science. 282, 284-287.

3. Sablina, A. A., Chen, W., Arroyo, J. D., Corral, L., Hector, M., Bulmer, S. E., DeCaprio, J. A., and Hahn, W. C. (2007) The Tumor Suppressor PP2A Abeta Regulates the RalA GTPase. Cell. 129, 969-982.

Posted On

2013-01-08

Science Writer

Anne Murray