Incidental Mutation 'R7090:Ncoa2'
ID 550123
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 045184-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.965) question?
Stock # R7090 (G1)
Quality Score 225.009
Status Validated
Chromosome 1
Chromosomal Location 13209329-13444307 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 13257062 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Tyrosine to Histidine at position 146 (Y146H)
Ref Sequence ENSEMBL: ENSMUSP00000006037 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000006037] [ENSMUST00000068304] [ENSMUST00000081713] [ENSMUST00000145280]
AlphaFold Q61026
PDB Structure Human Estrogen Receptor alpha Ligand-binding Domain in Complex with (R,R)-5,11-cis-diethyl-5,6,11,12-tetrahydrochrysene-2,8-diol and a Glucocorticoid Receptor Interacting Protein 1 NR box II Peptide [X-RAY DIFFRACTION]
STRUCTURAL BASIS FOR BILE ACID BINDING AND ACTIVATION OF THE NUCLEAR RECEPTOR FXR [X-RAY DIFFRACTION]
PPARgamma in complex with a 2-BABA compound [X-RAY DIFFRACTION]
Crystal Structure of Estrogen Receptor alpha Complexed to a B-N Substituted Ligand [X-RAY DIFFRACTION]
Crystal Structure of Estrogen Receptor Alpha mutant 537S Complexed with 4-(6-hydroxy-1H-indazol-3-yl)benzene-1,3-diol [X-RAY DIFFRACTION]
Crystal Structure of the Estrogen Receptor Alpha Ligand Binding Domain Mutant 537S Complexed with Genistein [X-RAY DIFFRACTION]
Crystal Structure of Estrogen Receptor Alpha Ligand Binding Domain Mutant 537S Complexed with an Ethyl Indazole Compound [X-RAY DIFFRACTION]
Crystal Structure of the Estrogen Receptor Alpha Ligand Binding Domain Complexed to an Ether Estradiol Compound [X-RAY DIFFRACTION]
Crystal Structure of the Estrogen Receptor Alpha Ligand Binding Domain Complexed with a Chloro-Indazole Compound [X-RAY DIFFRACTION]
Crystal Structure of the Estrogen Receptor Alpha Ligand Binding Domain Complexed with an Oxabicyclic diarylethylene Compound [X-RAY DIFFRACTION]
>> 8 additional structures at PDB <<
Predicted Effect probably damaging
Transcript: ENSMUST00000006037
AA Change: Y146H

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000006037
Gene: ENSMUSG00000005886
AA Change: Y146H

DomainStartEndE-ValueType
HLH 32 89 2.25e-8 SMART
PAS 114 181 4.52e-9 SMART
PAC 334 377 1.13e0 SMART
low complexity region 434 447 N/A INTRINSIC
Pfam:NCOA_u2 463 587 6.7e-39 PFAM
Pfam:SRC-1 636 709 5.8e-23 PFAM
Pfam:DUF4927 731 816 2.7e-33 PFAM
low complexity region 1021 1037 N/A INTRINSIC
Pfam:Nuc_rec_co-act 1071 1117 6.5e-27 PFAM
low complexity region 1183 1204 N/A INTRINSIC
low complexity region 1243 1264 N/A INTRINSIC
DUF1518 1279 1336 5.92e-28 SMART
low complexity region 1409 1420 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000068304
AA Change: Y146H

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000069509
Gene: ENSMUSG00000005886
AA Change: Y146H

DomainStartEndE-ValueType
HLH 32 89 2.25e-8 SMART
PAS 114 181 4.52e-9 SMART
PAC 334 377 1.13e0 SMART
low complexity region 434 447 N/A INTRINSIC
Pfam:SRC-1 636 709 2.2e-28 PFAM
low complexity region 802 813 N/A INTRINSIC
low complexity region 952 968 N/A INTRINSIC
Pfam:Nuc_rec_co-act 1002 1048 1.3e-25 PFAM
low complexity region 1114 1135 N/A INTRINSIC
low complexity region 1174 1195 N/A INTRINSIC
DUF1518 1210 1267 5.92e-28 SMART
low complexity region 1340 1351 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000081713
AA Change: Y146H

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000080413
Gene: ENSMUSG00000005886
AA Change: Y146H

DomainStartEndE-ValueType
HLH 32 89 2.25e-8 SMART
PAS 114 181 4.52e-9 SMART
PAC 334 377 1.13e0 SMART
low complexity region 434 447 N/A INTRINSIC
Pfam:SRC-1 636 709 2.2e-28 PFAM
low complexity region 802 813 N/A INTRINSIC
low complexity region 952 968 N/A INTRINSIC
Pfam:Nuc_rec_co-act 1002 1048 1.3e-25 PFAM
low complexity region 1114 1135 N/A INTRINSIC
low complexity region 1174 1195 N/A INTRINSIC
DUF1518 1210 1267 5.92e-28 SMART
low complexity region 1340 1351 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000145280
SMART Domains Protein: ENSMUSP00000116641
Gene: ENSMUSG00000005886

DomainStartEndE-ValueType
HLH 32 89 2.25e-8 SMART
Meta Mutation Damage Score 0.8257 question?
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 100.0%
  • 10x: 99.7%
  • 20x: 99.1%
Validation Efficiency 100% (66/66)
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: 65 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Calm3 A T 7: 16,651,004 (GRCm39) Y139* probably null Het
Ccdc27 T C 4: 154,112,523 (GRCm39) N584S probably benign Het
Cdh24 C G 14: 54,876,964 (GRCm39) G13A probably damaging Het
Chd8 T C 14: 52,452,677 (GRCm39) K1281E probably damaging Het
Clasp1 G T 1: 118,409,816 (GRCm39) G4C probably benign Het
Cul9 G T 17: 46,811,765 (GRCm39) P2488T probably damaging Het
Daam2 A G 17: 49,789,973 (GRCm39) V428A probably damaging Het
Dcaf8 A G 1: 172,016,535 (GRCm39) S441G probably damaging Het
Dchs2 A G 3: 83,255,581 (GRCm39) T2426A probably benign Het
Dnai3 C A 3: 145,746,582 (GRCm39) K881N possibly damaging Het
Dpys A G 15: 39,690,279 (GRCm39) V358A probably damaging Het
Efhd1 A G 1: 87,217,219 (GRCm39) D112G probably damaging Het
Exoc1 T C 5: 76,714,800 (GRCm39) S120P unknown Het
Fyco1 A G 9: 123,626,784 (GRCm39) L1309S probably damaging Het
Gm14403 A G 2: 177,201,114 (GRCm39) N111S possibly damaging Het
Gm5901 A G 7: 105,026,555 (GRCm39) T108A probably benign Het
Idh2 TCCCAGG T 7: 79,748,079 (GRCm39) probably benign Het
Itgb5 T G 16: 33,705,464 (GRCm39) D251E probably damaging Het
Kcnk15 T C 2: 163,700,637 (GRCm39) V292A probably benign Het
Kdm2a A T 19: 4,369,169 (GRCm39) Y1149N probably damaging Het
Kdm3a T C 6: 71,572,529 (GRCm39) T1011A possibly damaging Het
Krt35 A T 11: 99,986,498 (GRCm39) probably null Het
Lipn T A 19: 34,049,180 (GRCm39) D115E possibly damaging Het
Lpin3 T G 2: 160,738,672 (GRCm39) L208R probably damaging Het
Ltf C A 9: 110,855,048 (GRCm39) Q354K probably benign Het
Marf1 C A 16: 13,929,566 (GRCm39) C1680F possibly damaging Het
Mtss2 T A 8: 111,456,656 (GRCm39) V242E probably damaging Het
Myo7b T C 18: 32,131,765 (GRCm39) Y477C probably damaging Het
Nbn T A 4: 15,981,350 (GRCm39) S481T probably benign Het
Ntng1 A T 3: 109,842,496 (GRCm39) C92* probably null Het
Or10ad1b C T 15: 98,125,083 (GRCm39) V150I probably benign Het
Or2n1b G A 17: 38,460,385 (GRCm39) G302D probably benign Het
Or8k18 T A 2: 86,085,420 (GRCm39) N206Y probably damaging Het
Or8k31-ps1 T C 2: 86,356,471 (GRCm39) I17V probably benign Het
Os9 A T 10: 126,935,547 (GRCm39) S308T probably benign Het
Otx2 T A 14: 48,896,192 (GRCm39) T289S probably benign Het
Pakap C T 4: 57,648,042 (GRCm39) A60V probably benign Het
Pigg A G 5: 108,484,378 (GRCm39) T675A possibly damaging Het
Pink1 C T 4: 138,042,912 (GRCm39) E461K probably damaging Het
Pip5k1a A G 3: 94,967,809 (GRCm39) S543P possibly damaging Het
Prkaa1 A G 15: 5,206,611 (GRCm39) T454A probably benign Het
Ptk2 G A 15: 73,093,658 (GRCm39) P854S possibly damaging Het
Rab31 C T 17: 66,005,012 (GRCm39) V83I possibly damaging Het
Rabggtb G T 3: 153,615,986 (GRCm39) D117E probably benign Het
Rbl1 T C 2: 156,994,820 (GRCm39) H951R probably benign Het
Sapcd2 A G 2: 25,266,091 (GRCm39) S314G probably benign Het
Septin4 T C 11: 87,475,264 (GRCm39) L164P probably damaging Het
Shroom1 A G 11: 53,356,760 (GRCm39) E541G probably damaging Het
Slc26a7 C A 4: 14,565,460 (GRCm39) G208* probably null Het
Smco2 A G 6: 146,772,711 (GRCm39) I304M probably damaging Het
Spg7 T C 8: 123,818,491 (GRCm39) probably null Het
Spocd1 T C 4: 129,847,691 (GRCm39) F552L Het
St6galnac2 T C 11: 116,568,461 (GRCm39) D334G probably damaging Het
Sub1 A G 15: 11,986,572 (GRCm39) S92P probably benign Het
Syne2 T C 12: 75,989,125 (GRCm39) F1829L probably benign Het
Tdrd1 T C 19: 56,839,833 (GRCm39) V631A probably benign Het
Tdrd9 T C 12: 111,958,904 (GRCm39) S113P probably benign Het
Tgfbrap1 A C 1: 43,110,725 (GRCm39) V260G probably damaging Het
Tyw3 G C 3: 154,299,426 (GRCm39) S94R probably benign Het
Urb2 T C 8: 124,757,338 (GRCm39) V1015A probably benign Het
Usp5 A G 6: 124,806,357 (GRCm39) M1T probably null Het
Utrn T C 10: 12,560,260 (GRCm39) D1343G possibly damaging Het
Vmn2r56 T C 7: 12,449,254 (GRCm39) Y328C probably damaging Het
Vmn2r99 A T 17: 19,613,972 (GRCm39) E564V possibly damaging Het
Zc3h8 T C 2: 128,777,241 (GRCm39) T133A possibly damaging Het
Other mutations in Ncoa2
AlleleSourceChrCoordTypePredicted EffectPPH 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
R0056:Ncoa2 UTSW 1 117,516,497 (GRCm38) critical splice donor site probably null
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
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
Predicted Primers PCR Primer
(F):5'- GGTTGCTGACATGCCTATGAC -3'
(R):5'- ACTTCTATTTCCCCAGAGAACATG -3'

Sequencing Primer
(F):5'- TATGACAGACACAACAGGCTTTACTG -3'
(R):5'- AACATGTGTTCATTGTTTCTGAAGG -3'
Posted On 2019-05-15