Incidental Mutation 'R0056:Ncoa2'
| ID |
16850 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Ncoa2
|
| Ensembl Gene |
ENSMUSG00000005886 |
| Gene Name |
nuclear receptor coactivator 2 |
| Synonyms |
TIF2/GRIP-1, Grip1, KAT13C, SRC-2, TIF-2, glucocorticoid receptor-interacting protein 1, TIF2, bHLHe75, D1Ertd433e |
| MMRRC Submission |
038350-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably essential
(E-score: 0.965)
|
| Stock # |
R0056 (G1)
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
1 |
| Chromosomal Location |
13209329-13444307 bp(-) (GRCm39) |
| Type of Mutation |
critical splice donor site (1 bp from exon) |
| DNA Base Change (assembly) |
C to A
at 117516497 bp (GRCm38)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000123234
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000138410]
|
| AlphaFold |
Q61026 |
| PDB Structure |
Solution Structure of the PDZ Domain from Mouse Glutamate Receptor Interacting Protein 1A-L (GRIP1) Homolog [SOLUTION NMR]
|
| Predicted Effect |
probably null
Transcript: ENSMUST00000138410
|
| SMART Domains |
Protein: ENSMUSP00000123234
Gene: ENSMUSG00000034813
| Domain | Start | End | E-Value | Type |
|---|
|
PDZ
|
62 |
136 |
4.86e-13 |
SMART |
|
PDZ
|
160 |
238 |
6.4e-22 |
SMART |
|
PDZ
|
261 |
336 |
1.97e-13 |
SMART |
|
low complexity region
|
393 |
421 |
N/A |
INTRINSIC |
|
low complexity region
|
439 |
456 |
N/A |
INTRINSIC |
|
low complexity region
|
464 |
475 |
N/A |
INTRINSIC |
|
PDZ
|
480 |
560 |
6.36e-17 |
SMART |
|
PDZ
|
581 |
657 |
1.11e-16 |
SMART |
|
PDZ
|
680 |
754 |
1.73e-18 |
SMART |
|
PDZ
|
1013 |
1085 |
2.79e-13 |
SMART |
|
| Meta Mutation Damage Score |
0.9755 |
| Coding Region Coverage |
- 1x: 89.2%
- 3x: 86.3%
- 10x: 78.7%
- 20x: 65.9%
|
| Validation Efficiency |
89% (66/74) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene functions as a transcriptional coactivator for nuclear hormone receptors, including steroid, thyroid, retinoid, and vitamin D receptors. The encoded protein acts as an intermediary factor for the ligand-dependent activity of these nuclear receptors, which regulate their target genes upon binding of cognate response elements. This gene has been found to be involved in translocations that result in fusions with other genes in various cancers, including the lysine acetyltransferase 6A (KAT6A) gene in acute myeloid leukemia, the ETS variant 6 (ETV6) gene in acute lymphoblastic leukemia, and the hes related family bHLH transcription factor with YRPW motif 1 (HEY1) gene in mesenchymal chondrosarcoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]
PHENOTYPE: Homozygous null mice exhibit a transient postnatal growth deficiency and hypofertility. Male hypofertility is due to defects in spermiogenesis and an age-dependent testicular degeneration preceded by defective lipid metabolism in Sertoli cells. Female hypofertility is due to a placental hypoplasia. [provided by MGI curators]
|
| Allele List at MGI |
All alleles(43) : Targeted(4) Gene trapped(39)
|
| Other mutations in this stock |
Total: 48 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Adam34l |
A |
T |
8: 44,078,540 (GRCm39) |
C561* |
probably null |
Het |
| Ankfn1 |
A |
G |
11: 89,282,502 (GRCm39) |
S1061P |
possibly damaging |
Het |
| Atp9b |
A |
G |
18: 80,809,018 (GRCm39) |
S634P |
probably damaging |
Het |
| Bche |
A |
T |
3: 73,608,654 (GRCm39) |
N257K |
possibly damaging |
Het |
| Bms1 |
A |
T |
6: 118,382,190 (GRCm39) |
D449E |
probably benign |
Het |
| C630050I24Rik |
G |
T |
8: 107,846,026 (GRCm39) |
V59F |
unknown |
Het |
| Camkk2 |
C |
T |
5: 122,880,261 (GRCm39) |
E452K |
probably damaging |
Het |
| Ccdc121rt1 |
T |
C |
1: 181,338,118 (GRCm39) |
Y278C |
probably damaging |
Het |
| Chd9 |
A |
G |
8: 91,660,165 (GRCm39) |
H375R |
possibly damaging |
Het |
| Entpd7 |
T |
A |
19: 43,713,733 (GRCm39) |
V364E |
probably benign |
Het |
| Epb41l3 |
A |
T |
17: 69,560,392 (GRCm39) |
D313V |
probably damaging |
Het |
| Etv6 |
G |
T |
6: 134,225,497 (GRCm39) |
E154* |
probably null |
Het |
| Fshr |
T |
G |
17: 89,295,885 (GRCm39) |
H274P |
probably damaging |
Het |
| G3bp1 |
A |
G |
11: 55,388,867 (GRCm39) |
N360D |
probably benign |
Het |
| Gdf11 |
C |
T |
10: 128,722,294 (GRCm39) |
R187H |
probably benign |
Het |
| Gpihbp1 |
T |
A |
15: 75,468,982 (GRCm39) |
I52N |
probably damaging |
Het |
| H1f8 |
G |
T |
6: 115,923,934 (GRCm39) |
|
probably benign |
Het |
| Htt |
T |
C |
5: 34,983,422 (GRCm39) |
|
probably benign |
Het |
| Iqcm |
A |
G |
8: 76,480,014 (GRCm39) |
Q324R |
probably benign |
Het |
| Kcng3 |
A |
G |
17: 83,895,185 (GRCm39) |
L427P |
probably damaging |
Het |
| Klk7 |
T |
C |
7: 43,461,434 (GRCm39) |
L17P |
possibly damaging |
Het |
| Klrd1 |
G |
A |
6: 129,570,738 (GRCm39) |
V50I |
probably benign |
Het |
| Lama5 |
A |
T |
2: 179,828,899 (GRCm39) |
|
probably benign |
Het |
| Lamtor3 |
T |
A |
3: 137,632,711 (GRCm39) |
|
probably benign |
Het |
| Lyplal1 |
G |
A |
1: 185,820,763 (GRCm39) |
T228I |
probably benign |
Het |
| Mapk6 |
A |
G |
9: 75,296,098 (GRCm39) |
Y467H |
possibly damaging |
Het |
| Marchf6 |
T |
C |
15: 31,467,880 (GRCm39) |
T776A |
possibly damaging |
Het |
| Mogat1 |
T |
G |
1: 78,500,407 (GRCm39) |
M157R |
probably damaging |
Het |
| Morc2b |
T |
A |
17: 33,357,733 (GRCm39) |
Q13L |
possibly damaging |
Het |
| Myo1h |
C |
T |
5: 114,468,273 (GRCm39) |
T356I |
probably damaging |
Het |
| Nobox |
A |
G |
6: 43,281,853 (GRCm39) |
C407R |
probably benign |
Het |
| Nup58 |
A |
G |
14: 60,476,924 (GRCm39) |
|
probably null |
Het |
| Or56a4 |
A |
G |
7: 104,806,329 (GRCm39) |
S187P |
probably benign |
Het |
| Otoa |
A |
G |
7: 120,730,570 (GRCm39) |
Y590C |
probably benign |
Het |
| Pelp1 |
A |
T |
11: 70,284,658 (GRCm39) |
V1070E |
unknown |
Het |
| Pglyrp3 |
G |
T |
3: 91,933,111 (GRCm39) |
|
probably benign |
Het |
| Plpp2 |
A |
G |
10: 79,363,063 (GRCm39) |
F189S |
probably damaging |
Het |
| Polr2b |
T |
C |
5: 77,482,382 (GRCm39) |
I640T |
possibly damaging |
Het |
| Ryr2 |
T |
A |
13: 11,683,924 (GRCm39) |
T3047S |
probably damaging |
Het |
| Snx25 |
A |
T |
8: 46,491,550 (GRCm39) |
W847R |
probably damaging |
Het |
| Son |
T |
C |
16: 91,475,043 (GRCm39) |
Y454H |
possibly damaging |
Het |
| Sos1 |
A |
T |
17: 80,721,050 (GRCm39) |
N923K |
probably damaging |
Het |
| Tex15 |
A |
G |
8: 34,072,055 (GRCm39) |
H2534R |
probably benign |
Het |
| Ticam2 |
G |
T |
18: 46,693,401 (GRCm39) |
Q229K |
possibly damaging |
Het |
| Tnfaip3 |
A |
T |
10: 18,881,041 (GRCm39) |
V342E |
probably damaging |
Het |
| Traf6 |
A |
G |
2: 101,527,496 (GRCm39) |
I415M |
possibly damaging |
Het |
| Trpm1 |
A |
G |
7: 63,893,334 (GRCm39) |
D1062G |
probably damaging |
Het |
| Wdr59 |
C |
T |
8: 112,207,239 (GRCm39) |
|
probably benign |
Het |
|
| Other mutations in Ncoa2 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL01085:Ncoa2
|
APN |
1 |
13,219,303 (GRCm39) |
missense |
possibly damaging |
0.91 |
|
IGL01469:Ncoa2
|
APN |
1 |
13,257,093 (GRCm39) |
missense |
probably benign |
0.02 |
|
IGL01735:Ncoa2
|
APN |
1 |
13,235,127 (GRCm39) |
missense |
probably benign |
0.01 |
|
IGL01799:Ncoa2
|
APN |
1 |
13,222,599 (GRCm39) |
splice site |
probably benign |
|
|
IGL02023:Ncoa2
|
APN |
1 |
13,245,078 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02115:Ncoa2
|
APN |
1 |
13,223,041 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02263:Ncoa2
|
APN |
1 |
13,244,987 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL03131:Ncoa2
|
APN |
1 |
13,247,398 (GRCm39) |
missense |
probably damaging |
0.98 |
|
IGL03189:Ncoa2
|
APN |
1 |
13,260,360 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL03240:Ncoa2
|
APN |
1 |
13,247,316 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Swatch
|
UTSW |
1 |
13,251,521 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R0017:Ncoa2
|
UTSW |
1 |
13,244,976 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0158:Ncoa2
|
UTSW |
1 |
13,222,608 (GRCm39) |
missense |
probably benign |
0.05 |
|
R0164:Ncoa2
|
UTSW |
1 |
13,256,955 (GRCm39) |
critical splice donor site |
probably null |
|
|
R0164:Ncoa2
|
UTSW |
1 |
13,256,955 (GRCm39) |
critical splice donor site |
probably null |
|
|
R0684:Ncoa2
|
UTSW |
1 |
13,294,875 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R0788:Ncoa2
|
UTSW |
1 |
13,237,113 (GRCm39) |
splice site |
probably benign |
|
|
R1433:Ncoa2
|
UTSW |
1 |
13,218,602 (GRCm39) |
missense |
probably benign |
0.01 |
|
R1517:Ncoa2
|
UTSW |
1 |
13,235,281 (GRCm39) |
missense |
probably benign |
0.33 |
|
R1799:Ncoa2
|
UTSW |
1 |
13,232,517 (GRCm39) |
splice site |
probably null |
|
|
R1959:Ncoa2
|
UTSW |
1 |
13,230,476 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2034:Ncoa2
|
UTSW |
1 |
13,235,207 (GRCm39) |
missense |
probably benign |
0.00 |
|
R2175:Ncoa2
|
UTSW |
1 |
13,294,837 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R2437:Ncoa2
|
UTSW |
1 |
13,218,584 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R2851:Ncoa2
|
UTSW |
1 |
13,257,113 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2853:Ncoa2
|
UTSW |
1 |
13,257,113 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4334:Ncoa2
|
UTSW |
1 |
13,245,187 (GRCm39) |
missense |
possibly damaging |
0.77 |
|
R4365:Ncoa2
|
UTSW |
1 |
13,250,771 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R4386:Ncoa2
|
UTSW |
1 |
13,247,389 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R4516:Ncoa2
|
UTSW |
1 |
13,217,130 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R5109:Ncoa2
|
UTSW |
1 |
13,257,070 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5162:Ncoa2
|
UTSW |
1 |
13,245,396 (GRCm39) |
missense |
possibly damaging |
0.79 |
|
R5183:Ncoa2
|
UTSW |
1 |
13,244,590 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5250:Ncoa2
|
UTSW |
1 |
13,294,913 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5514:Ncoa2
|
UTSW |
1 |
13,251,445 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5691:Ncoa2
|
UTSW |
1 |
13,250,774 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R5837:Ncoa2
|
UTSW |
1 |
13,294,930 (GRCm39) |
utr 5 prime |
probably benign |
|
|
R6003:Ncoa2
|
UTSW |
1 |
13,237,254 (GRCm39) |
missense |
possibly damaging |
0.81 |
|
R6134:Ncoa2
|
UTSW |
1 |
13,244,595 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6559:Ncoa2
|
UTSW |
1 |
13,220,841 (GRCm39) |
splice site |
probably null |
|
|
R6623:Ncoa2
|
UTSW |
1 |
13,251,521 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R6949:Ncoa2
|
UTSW |
1 |
13,226,725 (GRCm39) |
missense |
possibly damaging |
0.92 |
|
R7090:Ncoa2
|
UTSW |
1 |
13,257,062 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7251:Ncoa2
|
UTSW |
1 |
13,218,599 (GRCm39) |
missense |
probably benign |
0.01 |
|
R7389:Ncoa2
|
UTSW |
1 |
13,257,049 (GRCm39) |
missense |
possibly damaging |
0.62 |
|
R7565:Ncoa2
|
UTSW |
1 |
13,218,600 (GRCm39) |
missense |
probably benign |
0.03 |
|
R7602:Ncoa2
|
UTSW |
1 |
13,247,350 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
R7661:Ncoa2
|
UTSW |
1 |
13,244,761 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7735:Ncoa2
|
UTSW |
1 |
13,218,661 (GRCm39) |
missense |
probably benign |
0.31 |
|
R8366:Ncoa2
|
UTSW |
1 |
13,250,830 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8824:Ncoa2
|
UTSW |
1 |
13,247,409 (GRCm39) |
missense |
probably benign |
0.34 |
|
R9028:Ncoa2
|
UTSW |
1 |
13,223,079 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9084:Ncoa2
|
UTSW |
1 |
13,244,653 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9745:Ncoa2
|
UTSW |
1 |
13,245,192 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9792:Ncoa2
|
UTSW |
1 |
13,260,355 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
R9793:Ncoa2
|
UTSW |
1 |
13,260,355 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
RF021:Ncoa2
|
UTSW |
1 |
13,219,333 (GRCm39) |
critical splice acceptor site |
probably benign |
|
|
X0063:Ncoa2
|
UTSW |
1 |
13,245,462 (GRCm39) |
missense |
possibly damaging |
0.82 |
|
X0066:Ncoa2
|
UTSW |
1 |
13,218,673 (GRCm39) |
missense |
possibly damaging |
0.91 |
|
| Protein Function and Prediction |
Ncoa2 encodes GRIP1/TIF2/SRC2, is a member of the p160 family of transcriptional coactivators that act as binding platforms to modulate the function of nuclear hormone receptors and cofactors with chromatin-modifying and remodeling activities (1;2). In primary macrophages, GRIP1 mediates the glucocorticoid repression of cytokine genes, subsequently facilitating the anti-inflammatory effects of glucocorticoids (2). Additional functions for GRIP1 include reproduction, mammary morphogenesis, uterine function, and energy metabolism in adipose tissue (3-5).
|
| Background |
Ncoa2tm1.2Ipc/tm1.2Ipc; MGI: 2183803
involves: 129S2/SvPas * C57BL/6
Homozygous null mice exhibit a transient postnatal growth deficiency and hypofertility (6;7). Male hypofertility is due to defects in spermiogenesis and an age-dependent testicular degeneration preceded by defective lipid metabolism in Sertoli cells (6;7). Female hypofertility is due to a placental hypoplasia (6;7).
Ncoa2tm1.2Ipc/tm1.2Ipc; MGI: 2183803
involves: 129S2/SvPas * C57BL/6J
In this genetic background, homozygotes exhibit normal white blood cell numbers (8).
Ncoa2tm1.2Ipc/tm1.2Ipc; MGI: 2183803
involves: 129S2/SvPas ?
Homozygotes have increased bone mass (due to enhanced osteoblastogenesis) as well as decreased adipocyte volume and adipocyte number (due to decreased adipogenesis) (9).
|
| References |
1. Hong, H., Kohli, K., Trivedi, A., Johnson, D. L., and Stallcup, M. R. (1996) GRIP1, a Novel Mouse Protein that Serves as a Transcriptional Coactivator in Yeast for the Hormone Binding Domains of Steroid Receptors. Proc Natl Acad Sci U S A. 93, 4948-4952.
2. Chinenov, Y., Gupte, R., Dobrovolna, J., Flammer, J. R., Liu, B., Michelassi, F. E., and Rogatsky, I. (2012) Role of Transcriptional Coregulator GRIP1 in the Anti-Inflammatory Actions of Glucocorticoids. Proc Natl Acad Sci U S A. 109, 11776-11781.
3. Mukherjee, A., Amato, P., Craig-Allred, D., DeMayo, F. J., O'Malley, B. W., and Lydon, J. P. (2007) Steroid Receptor Coactivator 2: An Essential Coregulator of Progestin-Induced Uterine and Mammary Morphogenesis. Ernst Schering Found Symp Proc. (1), 55-76.
4. Jeong, J. W., Lee, K. Y., Han, S. J., Aronow, B. J., Lydon, J. P., O'Malley, B. W., and DeMayo, F. J. (2007) The p160 Steroid Receptor Coactivator 2, SRC-2, Regulates Murine Endometrial Function and Regulates Progesterone-Independent and -Dependent Gene Expression. Endocrinology. 148, 4238-4250.
5. Picard, F., Gehin, M., Annicotte, J., Rocchi, S., Champy, M. F., O'Malley, B. W., Chambon, P., and Auwerx, J. (2002) SRC-1 and TIF2 Control Energy Balance between White and Brown Adipose Tissues. Cell. 111, 931-941.
6. Gehin, M., Mark, M., Dennefeld, C., Dierich, A., Gronemeyer, H., and Chambon, P. (2002) The Function of TIF2/GRIP1 in Mouse Reproduction is Distinct from those of SRC-1 and p/CIP. Mol Cell Biol. 22, 5923-5937.
7. Mascrez, B., Ghyselinck, N. B., Watanabe, M., Annicotte, J. S., Chambon, P., Auwerx, J., and Mark, M. (2004) Ligand-Dependent Contribution of RXRbeta to Cholesterol Homeostasis in Sertoli Cells. EMBO Rep. 5, 285-290.
8. Coste, A., Antal, M. C., Chan, S., Kastner, P., Mark, M., O'Malley, B. W., and Auwerx, J. (2006) Absence of the Steroid Receptor Coactivator-3 Induces B-Cell Lymphoma. EMBO J. 25, 2453-2464.
9. Modder, U. I., Monroe, D. G., Fraser, D. G., Spelsberg, T. C., Rosen, C. J., Gehin, M., Chambon, P., O'Malley, B. W., and Khosla, S. (2009) Skeletal Consequences of Deletion of Steroid Receptor Coactivator-2/transcription Intermediary Factor-2. J Biol Chem. 284, 18767-18777. |
| Posted On |
2013-01-20 |
| Science Writer |
Anne Murray |
Incidental Mutation