Incidental Mutation 'R9276:Dock4'
ID 703322
Institutional Source Beutler Lab
Gene Symbol Dock4
Ensembl Gene ENSMUSG00000035954
Gene Name dedicator of cytokinesis 4
Synonyms 6330411N01Rik, EST N28122
MMRRC Submission
Accession Numbers
Essential gene? Probably non essential (E-score: 0.181) question?
Stock # R9276 (G1)
Quality Score 225.009
Status Validated
Chromosome 12
Chromosomal Location 40495956-40896873 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to G at 40699404 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Methionine to Arginine at position 206 (M206R)
Ref Sequence ENSEMBL: ENSMUSP00000047387 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000037488] [ENSMUST00000220912]
AlphaFold P59764
Predicted Effect possibly damaging
Transcript: ENSMUST00000037488
AA Change: M206R

PolyPhen 2 Score 0.478 (Sensitivity: 0.89; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000047387
Gene: ENSMUSG00000035954
AA Change: M206R

DomainStartEndE-ValueType
SH3 9 66 7.29e-10 SMART
Pfam:DOCK_N 69 392 8.2e-110 PFAM
Pfam:DOCK-C2 397 583 1.9e-55 PFAM
low complexity region 829 842 N/A INTRINSIC
Pfam:DHR-2 1092 1596 5e-108 PFAM
low complexity region 1651 1664 N/A INTRINSIC
low complexity region 1681 1696 N/A INTRINSIC
low complexity region 1700 1713 N/A INTRINSIC
low complexity region 1842 1872 N/A INTRINSIC
low complexity region 1883 1896 N/A INTRINSIC
low complexity region 1940 1950 N/A INTRINSIC
low complexity region 1958 1973 N/A INTRINSIC
Predicted Effect possibly damaging
Transcript: ENSMUST00000220912
AA Change: M206R

PolyPhen 2 Score 0.852 (Sensitivity: 0.83; Specificity: 0.93)
Meta Mutation Damage Score 0.2339 question?
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.6%
  • 20x: 98.7%
Validation Efficiency 99% (83/84)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is a member of the dedicator of cytokinesis (DOCK) family and encodes a protein with a DHR-1 (CZH-1) domain, a DHR-2 (CZH-2) domain and an SH3 domain. This membrane-associated, cytoplasmic protein functions as a guanine nucleotide exchange factor and is involved in regulation of adherens junctions between cells. Mutations in this gene have been associated with ovarian, prostate, glioma, and colorectal cancers. Alternatively spliced variants which encode different protein isoforms have been described, but only one has been fully characterized. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous disruption of this gene leads to complete embryonic lethality. Heterozygotes display altered blood vessel lumen formation. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 84 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
9630041A04Rik A T 9: 101,819,887 (GRCm39) R102S probably benign Het
Abitram A T 4: 56,806,141 (GRCm39) K184N probably benign Het
Acvr2b C T 9: 119,231,616 (GRCm39) T2M probably benign Het
Adamtsl3 A G 7: 82,206,710 (GRCm39) probably benign Het
Adcy7 A G 8: 89,052,014 (GRCm39) Y894C probably damaging Het
Afdn T A 17: 14,024,270 (GRCm39) C59S probably damaging Het
Amt C A 9: 108,178,410 (GRCm39) T339K probably benign Het
Ankrd27 G T 7: 35,319,995 (GRCm39) V639L probably benign Het
Anxa10 G T 8: 62,549,753 (GRCm39) Q31K probably damaging Het
Ap1g2 T C 14: 55,339,818 (GRCm39) T454A probably benign Het
Boll A T 1: 55,399,812 (GRCm39) I43N possibly damaging Het
Cacna1c T C 6: 118,601,394 (GRCm39) D1472G Het
Calcrl T C 2: 84,205,643 (GRCm39) N16S probably benign Het
Ccdc191 C T 16: 43,764,041 (GRCm39) Q501* probably null Het
Cchcr1 T C 17: 35,841,105 (GRCm39) L658P probably damaging Het
Cfap46 A T 7: 139,201,207 (GRCm39) C1919S unknown Het
Col6a3 G A 1: 90,735,403 (GRCm39) L1356F possibly damaging Het
Dlc1 A G 8: 37,046,558 (GRCm39) S680P possibly damaging Het
Eml5 T C 12: 98,765,060 (GRCm39) K1630E probably damaging Het
Fat1 A G 8: 45,488,514 (GRCm39) T3432A probably damaging Het
Fcrl5 G T 3: 87,343,138 (GRCm39) probably benign Het
Fcrla A G 1: 170,755,135 (GRCm39) probably benign Het
Fut4 C A 9: 14,662,572 (GRCm39) D241Y probably benign Het
Fzd6 A G 15: 38,870,962 (GRCm39) probably benign Het
Gjc2 T C 11: 59,068,453 (GRCm39) T10A probably damaging Het
Gle1 C T 2: 29,829,514 (GRCm39) H203Y possibly damaging Het
Gm5565 A T 5: 146,096,917 (GRCm39) I74N probably damaging Het
Gnl2 T A 4: 124,947,250 (GRCm39) I624K possibly damaging Het
Gnpat C A 8: 125,614,524 (GRCm39) N653K probably benign Het
Gstcd A G 3: 132,777,665 (GRCm39) L382S probably damaging Het
Ipcef1 A G 10: 6,857,936 (GRCm39) probably benign Het
Jmjd7 T C 2: 119,860,895 (GRCm39) V115A possibly damaging Het
Ltbp2 G A 12: 84,837,864 (GRCm39) P1192L probably benign Het
Ltbp2 T G 12: 84,876,885 (GRCm39) D440A possibly damaging Het
Macf1 T G 4: 123,328,501 (GRCm39) D4744A probably damaging Het
Mapk11 T C 15: 89,029,372 (GRCm39) D230G probably damaging Het
Mfsd6 A C 1: 52,747,514 (GRCm39) Y450* probably null Het
Mtmr9 A G 14: 63,781,001 (GRCm39) C30R probably damaging Het
Ncf1 G A 5: 134,250,693 (GRCm39) Q376* probably null Het
Ncor2 C A 5: 125,113,150 (GRCm39) R296M Het
Or51ah3 A T 7: 103,210,004 (GRCm39) T107S probably damaging Het
Or5d37 A G 2: 87,923,806 (GRCm39) V158A probably benign Het
Or5k8 A G 16: 58,644,734 (GRCm39) F113L probably benign Het
Or8b57 A T 9: 40,003,632 (GRCm39) I210K possibly damaging Het
Or8b8 C A 9: 37,809,415 (GRCm39) S238R probably benign Het
Or8k31-ps1 A T 2: 86,356,392 (GRCm39) L43* probably null Het
Pate9 A T 9: 36,445,727 (GRCm39) C75S probably damaging Het
Pcsk6 A T 7: 65,559,950 (GRCm39) I92F probably damaging Het
Plec A G 15: 76,060,445 (GRCm39) V3164A probably benign Het
Prss16 A G 13: 22,190,175 (GRCm39) probably benign Het
Ptch2 T A 4: 116,967,505 (GRCm39) H724Q probably damaging Het
Pzp A T 6: 128,499,077 (GRCm39) F190Y probably damaging Het
Rab6a A G 7: 100,275,809 (GRCm39) T41A probably benign Het
Rbm6 A G 9: 107,660,926 (GRCm39) L879P probably damaging Het
Rem1 T A 2: 152,469,969 (GRCm39) probably benign Het
Rnf17 T C 14: 56,719,554 (GRCm39) S935P probably damaging Het
Ryr1 C A 7: 28,802,254 (GRCm39) V789L probably damaging Het
Scgb2b3 A T 7: 31,059,528 (GRCm39) M82K possibly damaging Het
Sgce T A 6: 4,674,585 (GRCm39) L451F probably damaging Het
Slc25a17 A C 15: 81,207,814 (GRCm39) V258G probably benign Het
Spidr G A 16: 15,784,712 (GRCm39) T452I probably benign Het
Tas2r129 A G 6: 132,928,576 (GRCm39) N171S probably benign Het
Tbc1d24 A T 17: 24,405,114 (GRCm39) V10E probably damaging Het
Tdo2 T G 3: 81,876,885 (GRCm39) M115L probably benign Het
Tdrd9 T C 12: 111,980,935 (GRCm39) probably null Het
Tead1 T A 7: 112,493,601 (GRCm39) I376N probably damaging Het
Tmem26 A G 10: 68,614,488 (GRCm39) H301R possibly damaging Het
Tnxb A G 17: 34,929,134 (GRCm39) T2726A possibly damaging Het
Trim43c T C 9: 88,723,966 (GRCm39) M164T probably benign Het
Trpc1 G A 9: 95,590,288 (GRCm39) S723L probably benign Het
Txndc15 A G 13: 55,865,914 (GRCm39) D126G probably benign Het
Urb1 C T 16: 90,569,463 (GRCm39) probably benign Het
Usp25 C T 16: 76,910,721 (GRCm39) H926Y probably benign Het
Uvssa T A 5: 33,572,180 (GRCm39) M700K possibly damaging Het
Vdac1 T A 11: 52,274,789 (GRCm39) Y146N probably damaging Het
Vmn1r231 A T 17: 21,110,560 (GRCm39) S118R probably benign Het
Vmn1r41 A G 6: 89,724,080 (GRCm39) Y207C probably damaging Het
Vmn2r79 A G 7: 86,687,045 (GRCm39) I809V probably damaging Het
Vnn1 G A 10: 23,776,794 (GRCm39) G382R probably damaging Het
Xcr1 A T 9: 123,685,680 (GRCm39) H27Q probably benign Het
Yeats2 T A 16: 19,975,786 (GRCm39) N94K probably benign Het
Zfp28 C T 7: 6,397,440 (GRCm39) T625M probably damaging Het
Zfp521 T C 18: 13,977,698 (GRCm39) Q905R probably benign Het
Zfp804b T C 5: 6,821,398 (GRCm39) D555G probably damaging Het
Other mutations in Dock4
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00427:Dock4 APN 12 40,882,305 (GRCm39) missense possibly damaging 0.48
IGL00726:Dock4 APN 12 40,840,067 (GRCm39) splice site probably benign
IGL00790:Dock4 APN 12 40,884,390 (GRCm39) missense probably damaging 1.00
IGL01061:Dock4 APN 12 40,752,968 (GRCm39) missense probably benign 0.01
IGL01083:Dock4 APN 12 40,838,380 (GRCm39) splice site probably benign
IGL01412:Dock4 APN 12 40,780,040 (GRCm39) splice site probably benign
IGL01583:Dock4 APN 12 40,860,466 (GRCm39) nonsense probably null
IGL01603:Dock4 APN 12 40,743,030 (GRCm39) missense probably damaging 1.00
IGL01766:Dock4 APN 12 40,496,378 (GRCm39) nonsense probably null
IGL02067:Dock4 APN 12 40,884,384 (GRCm39) missense probably damaging 1.00
IGL02302:Dock4 APN 12 40,775,776 (GRCm39) missense probably damaging 1.00
IGL02406:Dock4 APN 12 40,827,206 (GRCm39) missense probably benign 0.01
IGL02547:Dock4 APN 12 40,787,478 (GRCm39) missense probably benign
IGL02613:Dock4 APN 12 40,860,465 (GRCm39) missense probably damaging 1.00
IGL02643:Dock4 APN 12 40,718,429 (GRCm39) missense probably damaging 1.00
IGL02952:Dock4 APN 12 40,760,902 (GRCm39) critical splice donor site probably null
IGL02994:Dock4 APN 12 40,829,159 (GRCm39) missense probably damaging 0.99
IGL03096:Dock4 APN 12 40,798,000 (GRCm39) missense probably benign 0.00
IGL03144:Dock4 APN 12 40,742,906 (GRCm39) splice site probably benign
IGL03223:Dock4 APN 12 40,867,593 (GRCm39) missense probably damaging 1.00
IGL03296:Dock4 APN 12 40,783,256 (GRCm39) missense possibly damaging 0.84
IGL03349:Dock4 APN 12 40,783,309 (GRCm39) missense probably benign 0.42
IGL03353:Dock4 APN 12 40,867,757 (GRCm39) splice site probably null
BB005:Dock4 UTSW 12 40,838,302 (GRCm39) missense probably damaging 0.98
BB015:Dock4 UTSW 12 40,838,302 (GRCm39) missense probably damaging 0.98
R0046:Dock4 UTSW 12 40,787,359 (GRCm39) splice site probably benign
R0046:Dock4 UTSW 12 40,787,359 (GRCm39) splice site probably benign
R0110:Dock4 UTSW 12 40,671,311 (GRCm39) splice site probably benign
R0238:Dock4 UTSW 12 40,787,539 (GRCm39) missense probably damaging 0.98
R0238:Dock4 UTSW 12 40,787,539 (GRCm39) missense probably damaging 0.98
R0239:Dock4 UTSW 12 40,787,539 (GRCm39) missense probably damaging 0.98
R0239:Dock4 UTSW 12 40,787,539 (GRCm39) missense probably damaging 0.98
R0472:Dock4 UTSW 12 40,888,437 (GRCm39) intron probably benign
R0616:Dock4 UTSW 12 40,754,414 (GRCm39) missense probably benign 0.31
R0647:Dock4 UTSW 12 40,760,883 (GRCm39) missense probably damaging 1.00
R0706:Dock4 UTSW 12 40,752,922 (GRCm39) missense probably damaging 0.98
R0791:Dock4 UTSW 12 40,754,480 (GRCm39) missense probably damaging 1.00
R0940:Dock4 UTSW 12 40,681,626 (GRCm39) splice site probably benign
R1087:Dock4 UTSW 12 40,779,937 (GRCm39) missense probably benign 0.40
R1180:Dock4 UTSW 12 40,690,413 (GRCm39) missense possibly damaging 0.52
R1194:Dock4 UTSW 12 40,879,615 (GRCm39) missense probably damaging 1.00
R1463:Dock4 UTSW 12 40,866,324 (GRCm39) frame shift probably null
R1468:Dock4 UTSW 12 40,805,809 (GRCm39) missense probably benign 0.00
R1468:Dock4 UTSW 12 40,805,809 (GRCm39) missense probably benign 0.00
R1523:Dock4 UTSW 12 40,743,024 (GRCm39) missense possibly damaging 0.88
R1616:Dock4 UTSW 12 40,719,044 (GRCm39) missense probably damaging 0.99
R1682:Dock4 UTSW 12 40,775,779 (GRCm39) missense probably damaging 1.00
R1691:Dock4 UTSW 12 40,775,754 (GRCm39) missense probably benign 0.26
R1693:Dock4 UTSW 12 40,884,721 (GRCm39) missense probably benign 0.07
R1737:Dock4 UTSW 12 40,857,000 (GRCm39) splice site probably null
R1802:Dock4 UTSW 12 40,844,597 (GRCm39) missense possibly damaging 0.90
R1813:Dock4 UTSW 12 40,686,227 (GRCm39) missense probably damaging 1.00
R1846:Dock4 UTSW 12 40,783,267 (GRCm39) missense probably benign 0.00
R1959:Dock4 UTSW 12 40,760,797 (GRCm39) missense probably damaging 1.00
R1975:Dock4 UTSW 12 40,829,641 (GRCm39) splice site probably benign
R1986:Dock4 UTSW 12 40,780,062 (GRCm39) missense probably damaging 1.00
R2105:Dock4 UTSW 12 40,742,988 (GRCm39) missense probably benign 0.00
R2134:Dock4 UTSW 12 40,795,667 (GRCm39) missense probably benign
R2135:Dock4 UTSW 12 40,795,667 (GRCm39) missense probably benign
R2154:Dock4 UTSW 12 40,894,547 (GRCm39) small insertion probably benign
R2154:Dock4 UTSW 12 40,870,661 (GRCm39) missense probably damaging 1.00
R2864:Dock4 UTSW 12 40,780,072 (GRCm39) missense probably damaging 1.00
R2890:Dock4 UTSW 12 40,673,800 (GRCm39) critical splice acceptor site probably null
R3086:Dock4 UTSW 12 40,781,862 (GRCm39) missense probably benign 0.02
R3808:Dock4 UTSW 12 40,722,809 (GRCm39) missense probably damaging 0.99
R3811:Dock4 UTSW 12 40,829,123 (GRCm39) missense possibly damaging 0.87
R3836:Dock4 UTSW 12 40,844,623 (GRCm39) critical splice donor site probably null
R3838:Dock4 UTSW 12 40,844,623 (GRCm39) critical splice donor site probably null
R4091:Dock4 UTSW 12 40,894,266 (GRCm39) missense probably damaging 0.99
R4735:Dock4 UTSW 12 40,681,525 (GRCm39) missense probably benign 0.31
R4752:Dock4 UTSW 12 40,496,364 (GRCm39) missense probably benign 0.04
R4828:Dock4 UTSW 12 40,718,436 (GRCm39) missense probably damaging 1.00
R5039:Dock4 UTSW 12 40,867,745 (GRCm39) missense probably damaging 1.00
R5092:Dock4 UTSW 12 40,894,440 (GRCm39) missense probably benign
R5146:Dock4 UTSW 12 40,699,491 (GRCm39) splice site probably null
R5213:Dock4 UTSW 12 40,726,741 (GRCm39) missense probably damaging 1.00
R5214:Dock4 UTSW 12 40,754,465 (GRCm39) missense probably benign 0.00
R5270:Dock4 UTSW 12 40,783,270 (GRCm39) missense probably benign 0.02
R5426:Dock4 UTSW 12 40,795,744 (GRCm39) missense probably damaging 1.00
R5474:Dock4 UTSW 12 40,795,730 (GRCm39) missense probably benign
R5544:Dock4 UTSW 12 40,884,701 (GRCm39) missense possibly damaging 0.87
R5615:Dock4 UTSW 12 40,699,479 (GRCm39) missense probably benign 0.22
R5649:Dock4 UTSW 12 40,894,539 (GRCm39) missense probably benign 0.03
R5702:Dock4 UTSW 12 40,787,490 (GRCm39) missense probably benign 0.02
R5846:Dock4 UTSW 12 40,867,735 (GRCm39) missense probably damaging 1.00
R5847:Dock4 UTSW 12 40,671,250 (GRCm39) missense probably damaging 0.97
R5895:Dock4 UTSW 12 40,805,812 (GRCm39) missense probably damaging 1.00
R5997:Dock4 UTSW 12 40,805,833 (GRCm39) missense probably damaging 0.99
R6011:Dock4 UTSW 12 40,867,756 (GRCm39) critical splice donor site probably null
R6022:Dock4 UTSW 12 40,798,109 (GRCm39) missense probably benign 0.04
R6038:Dock4 UTSW 12 40,783,350 (GRCm39) splice site probably null
R6038:Dock4 UTSW 12 40,783,350 (GRCm39) splice site probably null
R6179:Dock4 UTSW 12 40,781,868 (GRCm39) missense probably benign 0.00
R6479:Dock4 UTSW 12 40,878,954 (GRCm39) missense probably damaging 1.00
R6516:Dock4 UTSW 12 40,781,898 (GRCm39) missense possibly damaging 0.94
R6748:Dock4 UTSW 12 40,754,465 (GRCm39) missense probably benign 0.44
R6752:Dock4 UTSW 12 40,870,616 (GRCm39) missense probably damaging 1.00
R6814:Dock4 UTSW 12 40,862,325 (GRCm39) critical splice donor site probably null
R6864:Dock4 UTSW 12 40,795,745 (GRCm39) missense probably damaging 1.00
R6872:Dock4 UTSW 12 40,862,325 (GRCm39) critical splice donor site probably null
R6891:Dock4 UTSW 12 40,829,135 (GRCm39) missense probably damaging 1.00
R6937:Dock4 UTSW 12 40,884,634 (GRCm39) missense probably benign 0.01
R6950:Dock4 UTSW 12 40,783,313 (GRCm39) missense possibly damaging 0.80
R7081:Dock4 UTSW 12 40,671,285 (GRCm39) missense probably damaging 1.00
R7129:Dock4 UTSW 12 40,878,878 (GRCm39) missense probably damaging 1.00
R7140:Dock4 UTSW 12 40,686,158 (GRCm39) missense probably benign 0.06
R7241:Dock4 UTSW 12 40,844,859 (GRCm39) missense probably damaging 1.00
R7378:Dock4 UTSW 12 40,838,243 (GRCm39) missense possibly damaging 0.94
R7714:Dock4 UTSW 12 40,775,648 (GRCm39) nonsense probably null
R7720:Dock4 UTSW 12 40,856,974 (GRCm39) missense probably damaging 0.99
R7756:Dock4 UTSW 12 40,760,878 (GRCm39) missense probably benign 0.02
R7758:Dock4 UTSW 12 40,760,878 (GRCm39) missense probably benign 0.02
R7759:Dock4 UTSW 12 40,867,735 (GRCm39) missense probably damaging 1.00
R7787:Dock4 UTSW 12 40,775,676 (GRCm39) missense probably benign
R7879:Dock4 UTSW 12 40,780,083 (GRCm39) missense possibly damaging 0.76
R7928:Dock4 UTSW 12 40,838,302 (GRCm39) missense probably damaging 0.98
R8000:Dock4 UTSW 12 40,883,118 (GRCm39) missense probably benign 0.05
R8042:Dock4 UTSW 12 40,795,759 (GRCm39) missense probably benign 0.01
R8231:Dock4 UTSW 12 40,752,950 (GRCm39) missense possibly damaging 0.88
R8234:Dock4 UTSW 12 40,884,837 (GRCm39) splice site probably null
R8758:Dock4 UTSW 12 40,838,231 (GRCm39) missense probably benign 0.12
R8871:Dock4 UTSW 12 40,795,730 (GRCm39) missense probably benign
R8873:Dock4 UTSW 12 40,726,767 (GRCm39) nonsense probably null
R8884:Dock4 UTSW 12 40,856,884 (GRCm39) missense probably damaging 1.00
R9164:Dock4 UTSW 12 40,754,337 (GRCm39) missense probably damaging 1.00
R9225:Dock4 UTSW 12 40,879,669 (GRCm39) missense probably benign 0.02
R9307:Dock4 UTSW 12 40,686,155 (GRCm39) missense probably damaging 1.00
R9675:Dock4 UTSW 12 40,894,393 (GRCm39) small insertion probably benign
R9675:Dock4 UTSW 12 40,894,379 (GRCm39) small insertion probably benign
R9676:Dock4 UTSW 12 40,894,397 (GRCm39) small insertion probably benign
R9676:Dock4 UTSW 12 40,894,387 (GRCm39) small insertion probably benign
R9676:Dock4 UTSW 12 40,894,379 (GRCm39) small insertion probably benign
R9676:Dock4 UTSW 12 40,894,401 (GRCm39) small insertion probably benign
R9678:Dock4 UTSW 12 40,894,396 (GRCm39) small insertion probably benign
R9678:Dock4 UTSW 12 40,894,387 (GRCm39) small insertion probably benign
R9678:Dock4 UTSW 12 40,894,379 (GRCm39) small insertion probably benign
R9691:Dock4 UTSW 12 40,686,097 (GRCm39) missense probably damaging 1.00
RF018:Dock4 UTSW 12 40,894,398 (GRCm39) frame shift probably null
RF025:Dock4 UTSW 12 40,894,392 (GRCm39) frame shift probably null
RF063:Dock4 UTSW 12 40,894,398 (GRCm39) frame shift probably null
X0028:Dock4 UTSW 12 40,719,046 (GRCm39) missense probably benign 0.25
Z1176:Dock4 UTSW 12 40,681,615 (GRCm39) missense probably benign 0.16
Z1176:Dock4 UTSW 12 40,681,613 (GRCm39) missense probably benign 0.01
Z1177:Dock4 UTSW 12 40,867,640 (GRCm39) missense possibly damaging 0.88
Predicted Primers PCR Primer
(F):5'- GCAATAGCCTTGATGAAGCTAG -3'
(R):5'- TTATACAATGAACTGAGGGTGGTAG -3'

Sequencing Primer
(F):5'- TTAGATACTGAATCTAGCCTGAGGG -3'
(R):5'- TCCACATGCCATTACCTG -3'
Posted On 2022-03-25