Mutagenetix > Incidental Mutation

Incidental Mutation 'R0067:Gps2'

16554

Institutional Source

Beutler Lab

Gene Symbol

Gps2

Ensembl Gene

ENSMUSG00000023170

Gene Name

G protein pathway suppressor 2

Synonyms

MMRRC Submission

038358-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.899) question?

Stock #

R0067 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

69804714-69807417 bp(+) (GRCm39)

Type of Mutation

nonsense

DNA Base Change (assembly)

C to T at 69805607 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glutamine to Stop codon at position 42 (Q42*)

Ref Sequence

ENSEMBL: ENSMUSP00000112062 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000043419] [ENSMUST00000057884] [ENSMUST00000061837] [ENSMUST00000070996] [ENSMUST00000071026] [ENSMUST00000072581] [ENSMUST00000108607] [ENSMUST00000116358] [ENSMUST00000134581] [ENSMUST00000108608] [ENSMUST00000108611] [ENSMUST00000108617] [ENSMUST00000108609] [ENSMUST00000108610] [ENSMUST00000133203] [ENSMUST00000108612] [ENSMUST00000152589] [ENSMUST00000108613] [ENSMUST00000177476] [ENSMUST00000177138] [ENSMUST00000153652] [ENSMUST00000164359]

AlphaFold

Q921N8

Predicted Effect

probably benign
Transcript: ENSMUST00000043419

SMART Domains

Protein: ENSMUSP00000047008
Gene: ENSMUSG00000078812

Domain	Start	End	E-Value	Type
SCOP:d1bkb_1	16	82	4e-39	SMART
eIF-5a	83	150	2.43e-29	SMART

Predicted Effect

probably null
Transcript: ENSMUST00000057884
AA Change: Q42*

SMART Domains

Protein: ENSMUSP00000054072
Gene: ENSMUSG00000023170
AA Change: Q42*

Domain	Start	End	E-Value	Type
Pfam:G_path_suppress	5	294	6.1e-93	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000061837

SMART Domains

Protein: ENSMUSP00000053235
Gene: ENSMUSG00000047284

Domain	Start	End	E-Value	Type
low complexity region	3	44	N/A	INTRINSIC
NEUZ	47	165	1.02e-28	SMART
low complexity region	207	237	N/A	INTRINSIC
NEUZ	317	442	7.22e-52	SMART
low complexity region	492	503	N/A	INTRINSIC
NEUZ	520	644	6.15e-46	SMART
low complexity region	686	700	N/A	INTRINSIC
NEUZ	716	840	7.81e-39	SMART
NEUZ	913	1043	2.27e-17	SMART
low complexity region	1108	1117	N/A	INTRINSIC
NEUZ	1130	1250	4.93e-6	SMART
low complexity region	1453	1464	N/A	INTRINSIC
low complexity region	1474	1483	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000070996

SMART Domains

Protein: ENSMUSP00000067077
Gene: ENSMUSG00000078812

Domain	Start	End	E-Value	Type
SCOP:d1bkb_1	16	82	4e-39	SMART
Pfam:eIF-5a	83	150	4.8e-27	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000071026

SMART Domains

Protein: ENSMUSP00000068651
Gene: ENSMUSG00000078812

Domain	Start	End	E-Value	Type
SCOP:d1bkb_1	16	82	4e-39	SMART
Pfam:eIF-5a	83	150	4.8e-27	PFAM

Predicted Effect

probably null
Transcript: ENSMUST00000072581
AA Change: Q42*

SMART Domains

Protein: ENSMUSP00000072389
Gene: ENSMUSG00000023170
AA Change: Q42*

Domain	Start	End	E-Value	Type
SCOP:d1jjva_	22	83	9e-3	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000108607

SMART Domains

Protein: ENSMUSP00000104247
Gene: ENSMUSG00000078812

Domain	Start	End	E-Value	Type
SCOP:d1bkb_1	16	82	4e-39	SMART
Pfam:eIF-5a	83	150	4.8e-27	PFAM

Predicted Effect

probably null
Transcript: ENSMUST00000116358
AA Change: Q42*

SMART Domains

Protein: ENSMUSP00000112062
Gene: ENSMUSG00000023170
AA Change: Q42*

Domain	Start	End	E-Value	Type
SCOP:d1jjva_	22	83	9e-3	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000143861

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000124596

Predicted Effect

probably benign
Transcript: ENSMUST00000134581

Predicted Effect

probably benign
Transcript: ENSMUST00000108608

SMART Domains

Protein: ENSMUSP00000104248
Gene: ENSMUSG00000078812

Domain	Start	End	E-Value	Type
SCOP:d1bkb_1	16	82	4e-39	SMART
Pfam:eIF-5a	83	150	4.8e-27	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000108611

SMART Domains

Protein: ENSMUSP00000104251
Gene: ENSMUSG00000078812

Domain	Start	End	E-Value	Type
SCOP:d1bkb_1	16	82	4e-39	SMART
Pfam:eIF-5a	83	150	4.8e-27	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000108617

SMART Domains

Protein: ENSMUSP00000104257
Gene: ENSMUSG00000047284

Domain	Start	End	E-Value	Type
low complexity region	3	44	N/A	INTRINSIC
NEUZ	47	165	3.5e-31	SMART
low complexity region	207	237	N/A	INTRINSIC
NEUZ	295	420	2.5e-54	SMART
low complexity region	470	481	N/A	INTRINSIC
NEUZ	498	622	2e-48	SMART
low complexity region	664	678	N/A	INTRINSIC
NEUZ	694	818	2.6e-41	SMART
NEUZ	891	1021	7.6e-20	SMART
low complexity region	1086	1095	N/A	INTRINSIC
NEUZ	1108	1228	1.7e-8	SMART
low complexity region	1431	1442	N/A	INTRINSIC
low complexity region	1452	1461	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000108609

SMART Domains

Protein: ENSMUSP00000104249
Gene: ENSMUSG00000078812

Domain	Start	End	E-Value	Type
SCOP:d1bkb_1	16	82	4e-39	SMART
Pfam:eIF-5a	83	150	4.8e-27	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000108610

SMART Domains

Protein: ENSMUSP00000104250
Gene: ENSMUSG00000078812

Domain	Start	End	E-Value	Type
SCOP:d1bkb_1	16	82	4e-39	SMART
Pfam:eIF-5a	83	150	4.8e-27	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000133203

SMART Domains

Protein: ENSMUSP00000117917
Gene: ENSMUSG00000047284

Domain	Start	End	E-Value	Type
NEUZ	60	185	7.22e-52	SMART
low complexity region	235	246	N/A	INTRINSIC
NEUZ	263	387	6.15e-46	SMART
low complexity region	429	443	N/A	INTRINSIC
NEUZ	459	583	7.81e-39	SMART
NEUZ	656	786	2.27e-17	SMART
low complexity region	851	860	N/A	INTRINSIC
Pfam:Neuralized	875	942	6.5e-10	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000108612

SMART Domains

Protein: ENSMUSP00000104252
Gene: ENSMUSG00000078812

Domain	Start	End	E-Value	Type
SCOP:d1bkb_1	16	82	4e-39	SMART
Pfam:eIF-5a	83	150	4.8e-27	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000132183

SMART Domains

Protein: ENSMUSP00000118868
Gene: ENSMUSG00000047284

Domain	Start	End	E-Value	Type
low complexity region	161	172	N/A	INTRINSIC
low complexity region	182	191	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000152589

SMART Domains

Protein: ENSMUSP00000123402
Gene: ENSMUSG00000078812

Domain	Start	End	E-Value	Type
SCOP:d1bkb_1	16	82	2e-39	SMART
Pfam:eIF-5a	83	149	6.9e-26	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000108613

SMART Domains

Protein: ENSMUSP00000104253
Gene: ENSMUSG00000078812

Domain	Start	End	E-Value	Type
SCOP:d1bkb_1	16	82	4e-39	SMART
Pfam:eIF-5a	83	150	4.8e-27	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000175761

Predicted Effect

probably benign
Transcript: ENSMUST00000177476

SMART Domains

Protein: ENSMUSP00000135185
Gene: ENSMUSG00000047284

Domain	Start	End	E-Value	Type
low complexity region	3	44	N/A	INTRINSIC
NEUZ	47	165	1.02e-28	SMART
low complexity region	207	237	N/A	INTRINSIC
NEUZ	317	442	7.22e-52	SMART
low complexity region	492	503	N/A	INTRINSIC
NEUZ	520	644	6.15e-46	SMART
low complexity region	686	700	N/A	INTRINSIC
NEUZ	716	840	7.81e-39	SMART
NEUZ	911	1041	2.27e-17	SMART
low complexity region	1106	1115	N/A	INTRINSIC
NEUZ	1128	1248	4.93e-6	SMART
low complexity region	1451	1462	N/A	INTRINSIC
low complexity region	1472	1481	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000177138

SMART Domains

Protein: ENSMUSP00000135277
Gene: ENSMUSG00000047284

Domain	Start	End	E-Value	Type
low complexity region	3	44	N/A	INTRINSIC
NEUZ	47	165	1.02e-28	SMART
low complexity region	207	237	N/A	INTRINSIC
NEUZ	295	420	7.22e-52	SMART
low complexity region	470	481	N/A	INTRINSIC
NEUZ	498	622	6.15e-46	SMART
low complexity region	664	678	N/A	INTRINSIC
NEUZ	694	818	7.81e-39	SMART
NEUZ	889	1019	2.27e-17	SMART
low complexity region	1084	1093	N/A	INTRINSIC
NEUZ	1106	1226	4.93e-6	SMART
low complexity region	1429	1440	N/A	INTRINSIC
low complexity region	1450	1459	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000153652

SMART Domains

Protein: ENSMUSP00000137459
Gene: ENSMUSG00000078812

Domain	Start	End	E-Value	Type
Pfam:eIF-5a	5	72	1.7e-27	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000164359

SMART Domains

Protein: ENSMUSP00000132717
Gene: ENSMUSG00000078812

Domain	Start	End	E-Value	Type
SCOP:d1bkb_1	16	82	4e-39	SMART
Pfam:eIF-5a	83	150	4.8e-27	PFAM

Meta Mutation Damage Score

0.9712

Coding Region Coverage

1x: 87.3%
3x: 82.3%
10x: 64.1%
20x: 35.8%

Validation Efficiency

96% (73/76)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a protein involved in G protein-mitogen-activated protein kinase (MAPK) signaling cascades. When overexpressed in mammalian cells, this gene could potently suppress a RAS- and MAPK-mediated signal and interfere with JNK activity, suggesting that the function of this gene may be signal repression. The encoded protein is an integral subunit of the NCOR1-HDAC3 (nuclear receptor corepressor 1-histone deacetylase 3) complex, and it was shown that the complex inhibits JNK activation through this subunit and thus could potentially provide an alternative mechanism for hormone-mediated antagonism of AP1 (activator protein 1) function. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit embryonic lethality during organogenesis. [provided by MGI curators]

Allele List at MGI

All alleles(1) : Gene trapped(1)

Other mutations in this stock

Total: 40 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Actn4	C	T	7: 28,610,995 (GRCm39)	V248M	possibly damaging	Het
AW209491	A	T	13: 14,812,328 (GRCm39)	I394F	probably benign	Het
Cacna1d	A	T	14: 29,796,967 (GRCm39)		probably benign	Het
Cacna1i	A	T	15: 80,265,373 (GRCm39)	I1542F	probably damaging	Het
Cep97	A	T	16: 55,735,924 (GRCm39)	N291K	possibly damaging	Het
Clasp2	A	T	9: 113,689,209 (GRCm39)		probably benign	Het
Dennd1c	T	C	17: 57,382,465 (GRCm39)	Q67R	probably damaging	Het
Eva1c	A	T	16: 90,663,305 (GRCm39)	D13V	possibly damaging	Het
Fam151b	T	C	13: 92,610,504 (GRCm39)	K95R	probably benign	Het
Gm13941	T	C	2: 110,889,761 (GRCm39)		noncoding transcript	Het
Hivep1	T	A	13: 42,312,132 (GRCm39)	D1457E	probably benign	Het
L3mbtl1	A	G	2: 162,790,748 (GRCm39)	K225E	probably damaging	Het
Limch1	A	G	5: 67,131,965 (GRCm39)	S143G	probably damaging	Het
Macf1	T	C	4: 123,369,041 (GRCm39)	K342E	possibly damaging	Het
Mc5r	T	G	18: 68,472,637 (GRCm39)	M332R	probably damaging	Het
Mcf2l	A	G	8: 13,063,060 (GRCm39)	T882A	probably benign	Het
Mtrex	C	T	13: 113,023,396 (GRCm39)	V727I	probably benign	Het
Myf6	A	T	10: 107,329,340 (GRCm39)		probably null	Het
Plekha5	C	T	6: 140,470,629 (GRCm39)	T90I	probably damaging	Het
Ptbp2	T	C	3: 119,514,290 (GRCm39)	T478A	probably benign	Het
Rasgrp1	C	A	2: 117,125,301 (GRCm39)	R246S	probably damaging	Het
Rflnb	A	T	11: 75,912,987 (GRCm39)	S134T	possibly damaging	Het
Rnf214	A	G	9: 45,778,796 (GRCm39)		probably null	Het
Satb1	T	C	17: 52,111,364 (GRCm39)	T165A	probably damaging	Het
Scamp1	T	C	13: 94,340,658 (GRCm39)	Y237C	probably damaging	Het
Skint10	A	T	4: 112,568,753 (GRCm39)	F321L	probably benign	Het
Slc8a1	A	G	17: 81,745,188 (GRCm39)	V672A	probably benign	Het
Spats2	C	A	15: 99,110,168 (GRCm39)	P522T	possibly damaging	Het
Stkld1	A	T	2: 26,839,352 (GRCm39)	E339D	probably benign	Het
Tbc1d9	A	G	8: 83,960,872 (GRCm39)	T241A	probably damaging	Het
Ticrr	A	T	7: 79,327,158 (GRCm39)	D622V	probably damaging	Het
Trmt1l	T	C	1: 151,324,131 (GRCm39)	V326A	probably benign	Het
Ube3c	A	G	5: 29,803,936 (GRCm39)	T180A	possibly damaging	Het
Unc13a	A	C	8: 72,087,302 (GRCm39)	F1482V	probably damaging	Het
Unc79	A	G	12: 103,025,777 (GRCm39)	E388G	probably damaging	Het
Ush2a	A	T	1: 188,697,043 (GRCm39)	D5167V	probably damaging	Het
Vmn2r93	A	T	17: 18,546,672 (GRCm39)	H848L	probably benign	Het
Zcchc9	T	C	13: 91,945,368 (GRCm39)	I72V	probably benign	Het
Zfc3h1	G	T	10: 115,259,379 (GRCm39)	L1650F	possibly damaging	Het
Zzz3	A	G	3: 152,134,040 (GRCm39)	D366G	possibly damaging	Het

Other mutations in Gps2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
R0067:Gps2	UTSW	11	69,805,607 (GRCm39)	nonsense	probably null
R1086:Gps2	UTSW	11	69,806,050 (GRCm39)	unclassified	probably benign
R1109:Gps2	UTSW	11	69,806,507 (GRCm39)	missense	possibly damaging	0.94
R1938:Gps2	UTSW	11	69,806,195 (GRCm39)	missense	probably benign
R1964:Gps2	UTSW	11	69,807,246 (GRCm39)	missense	probably benign	0.03
R2355:Gps2	UTSW	11	69,806,207 (GRCm39)	frame shift	probably null
R3773:Gps2	UTSW	11	69,806,927 (GRCm39)	missense	probably damaging	0.99
R4765:Gps2	UTSW	11	69,807,187 (GRCm39)	unclassified	probably benign
R4811:Gps2	UTSW	11	69,806,754 (GRCm39)	missense	probably damaging	0.99
R5119:Gps2	UTSW	11	69,805,617 (GRCm39)	missense	probably benign	0.00
R5183:Gps2	UTSW	11	69,806,023 (GRCm39)	missense	probably benign	0.00
R5218:Gps2	UTSW	11	69,807,121 (GRCm39)	critical splice donor site	probably null
R5965:Gps2	UTSW	11	69,805,620 (GRCm39)	missense	possibly damaging	0.60
R7172:Gps2	UTSW	11	69,807,262 (GRCm39)	missense	probably benign	0.40
R7562:Gps2	UTSW	11	69,807,308 (GRCm39)	missense	probably benign	0.40
R7854:Gps2	UTSW	11	69,806,030 (GRCm39)	missense	probably damaging	1.00
R8524:Gps2	UTSW	11	69,805,832 (GRCm39)	missense	probably damaging	0.99
R8713:Gps2	UTSW	11	69,806,180 (GRCm39)	missense	probably benign	0.01
Z1186:Gps2	UTSW	11	69,807,130 (GRCm39)	missense	probably benign	0.26
Z1187:Gps2	UTSW	11	69,807,130 (GRCm39)	missense	probably benign	0.26
Z1188:Gps2	UTSW	11	69,807,130 (GRCm39)	missense	probably benign	0.26
Z1189:Gps2	UTSW	11	69,807,130 (GRCm39)	missense	probably benign	0.26
Z1190:Gps2	UTSW	11	69,807,130 (GRCm39)	missense	probably benign	0.26
Z1191:Gps2	UTSW	11	69,807,130 (GRCm39)	missense	probably benign	0.26
Z1192:Gps2	UTSW	11	69,807,130 (GRCm39)	missense	probably benign	0.26

Protein Function and Prediction

Gps2 encodes the ubiquitously expressed G protein suppressor 2 (GPS2); it is alternatively referred to as activation-domain modulating factor 1 (AMF-1). AMF-1 has been shown to bind p300, subsequently enhancing the interaction of p300 with papillomavirus E2 proteins (1). AMF-1 also exhibits transcriptional activation activity and was identified as a binding partner for papillomavirus E6 proteins (2). In addition, studies have shown that AMF-1 is a coregulatory of cholesterol homeostasis that affects bile acid biosynthesis in the liver and also functions in cholesterol transport and efflux in macrophages (3;4). Further studies identified AMF-1 as a binding partner of p53 and augments p53-dependent transcription (5). Overexpression of Gps2 in U2OS cells increases p21 expression and causes G1 arrest (5). In addition, following UV irradiation, U2OS cells overexpressing Gps2 exhibit increased apoptosis (5) AMF-1 is a subunit of the N-CoR-HDAC3 complex (6). AMF-1 was identified as a member of the SMRT corepressor complex and represses basal treanscription (7). In addition to its role in transcription regulation, AMF-1 is involved in cell cycle regulation, DNA repair, cytoskeleton architecture, brain development, and metabolism (7). One of these non-transcriptional roles is to guard against hyperstimulation of TNFα-induced signaling via the inhibition of TRAF2/Ubc13 enzymatic activity and subsequent RIP1 ubiquitylation and JNK activation (8).

References

1. Peng, Y. C., Breiding, D. E., Sverdrup, F., Richard, J., and Androphy, E. J. (2000) AMF-1/Gps2 Binds p300 and Enhances its Interaction with Papillomavirus E2 Proteins. J Virol. 74, 5872-5879.

2. Degenhardt, Y. Y., and Silverstein, S. J. (2001) Gps2, a Protein Partner for Human Papillomavirus E6 Proteins. J Virol. 75, 151-160.

3. Jakobsson, T., Venteclef, N., Toresson, G., Damdimopoulos, A. E., Ehrlund, A., Lou, X., Sanyal, S., Steffensen, K. R., Gustafsson, J. A., and Treuter, E. (2009) GPS2 is Required for Cholesterol Efflux by Triggering Histone Demethylation, LXR Recruitment, and Coregulator Assembly at the ABCG1 Locus. Mol Cell. 34, 510-518.

4. Sanyal, S., Bavner, A., Haroniti, A., Nilsson, L. M., Lundasen, T., Rehnmark, S., Witt, M. R., Einarsson, C., Talianidis, I., Gustafsson, J. A., and Treuter, E. (2007) Involvement of Corepressor Complex Subunit GPS2 in Transcriptional Pathways Governing Human Bile Acid Biosynthesis. Proc Natl Acad Sci U S A. 104, 15665-15670.

5. Peng, Y. C., Kuo, F., Breiding, D. E., Wang, Y. F., Mansur, C. P., and Androphy, E. J. (2001) AMF1 (GPS2) Modulates p53 Transactivation. Mol Cell Biol. 21, 5913-5924.

6. Zhang, J., Kalkum, M., Chait, B. T., and Roeder, R. G. (2002) The N-CoR-HDAC3 Nuclear Receptor Corepressor Complex Inhibits the JNK Pathway through the Integral Subunit GPS2. Mol Cell. 9, 611-623.

7. Cheng, X., and Kao, H. Y. (2009) G Protein Pathway Suppressor 2 (GPS2) is a Transcriptional Corepressor Important for Estrogen Receptor Alpha-Mediated Transcriptional Regulation. J Biol Chem. 284, 36395-36404.

8. Cardamone, M. D., Krones, A., Tanasa, B., Taylor, H., Ricci, L., Ohgi, K. A., Glass, C. K., Rosenfeld, M. G., and Perissi, V. (2012) A Protective Strategy Against Hyperinflammatory Responses Requiring the Nontranscriptional Actions of GPS2. Mol Cell. 46, 91-104.

Posted On

2013-01-20

Science Writer

Anne Murray