Incidental Mutation 'R7054:Dot1l'
ID 547788
Institutional Source Beutler Lab
Gene Symbol Dot1l
Ensembl Gene ENSMUSG00000061589
Gene Name DOT1 like histone lysine methyltransferase
Synonyms KMT4, mDot1
MMRRC Submission 045151-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R7054 (G1)
Quality Score 225.009
Status Validated
Chromosome 10
Chromosomal Location 80591040-80631295 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 80622857 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Tyrosine to Cysteine at position 636 (Y636C)
Ref Sequence ENSEMBL: ENSMUSP00000116581 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000105336] [ENSMUST00000127740] [ENSMUST00000149394] [ENSMUST00000150338]
AlphaFold Q6XZL8
Predicted Effect probably damaging
Transcript: ENSMUST00000105336
AA Change: Y853C

PolyPhen 2 Score 0.989 (Sensitivity: 0.72; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000100973
Gene: ENSMUSG00000061589
AA Change: Y853C

DomainStartEndE-ValueType
Pfam:DOT1 115 317 9.4e-86 PFAM
low complexity region 335 348 N/A INTRINSIC
AT_hook 407 419 4.64e-1 SMART
low complexity region 437 447 N/A INTRINSIC
coiled coil region 558 647 N/A INTRINSIC
low complexity region 917 936 N/A INTRINSIC
low complexity region 948 961 N/A INTRINSIC
low complexity region 1084 1095 N/A INTRINSIC
low complexity region 1145 1157 N/A INTRINSIC
low complexity region 1186 1198 N/A INTRINSIC
low complexity region 1436 1446 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000127740
Predicted Effect probably benign
Transcript: ENSMUST00000138505
SMART Domains Protein: ENSMUSP00000119492
Gene: ENSMUSG00000061589

DomainStartEndE-ValueType
low complexity region 24 43 N/A INTRINSIC
low complexity region 52 64 N/A INTRINSIC
low complexity region 73 87 N/A INTRINSIC
low complexity region 92 137 N/A INTRINSIC
low complexity region 189 206 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000149394
SMART Domains Protein: ENSMUSP00000127762
Gene: ENSMUSG00000061589

DomainStartEndE-ValueType
low complexity region 24 36 N/A INTRINSIC
low complexity region 65 77 N/A INTRINSIC
low complexity region 315 325 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000150338
AA Change: Y636C

PolyPhen 2 Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000116581
Gene: ENSMUSG00000061589
AA Change: Y636C

DomainStartEndE-ValueType
Pfam:DOT1 1 100 3.4e-37 PFAM
low complexity region 118 131 N/A INTRINSIC
AT_hook 190 202 4.64e-1 SMART
low complexity region 220 230 N/A INTRINSIC
low complexity region 371 390 N/A INTRINSIC
SCOP:d1fxkc_ 396 441 1e-3 SMART
low complexity region 700 719 N/A INTRINSIC
low complexity region 731 744 N/A INTRINSIC
low complexity region 867 878 N/A INTRINSIC
low complexity region 928 940 N/A INTRINSIC
low complexity region 969 981 N/A INTRINSIC
low complexity region 1020 1032 N/A INTRINSIC
low complexity region 1041 1055 N/A INTRINSIC
low complexity region 1060 1105 N/A INTRINSIC
low complexity region 1157 1174 N/A INTRINSIC
Meta Mutation Damage Score 0.2789 question?
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 100.0%
  • 10x: 99.7%
  • 20x: 99.0%
Validation Efficiency 94% (67/71)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a histone methyltransferase that methylates lysine-79 of histone H3. It is inactive against free core histones, but shows significant histone methyltransferase activity against nucleosomes. [provided by RefSeq, Aug 2011]
PHENOTYPE: Mice homozygous for a gene trap allele show late embryonic lethality. Mice homozygous for a null allele die by E10.5 displaying a growth arrest, abnormal yolk sac angiogenesis and heart dilation while mutant ES cells show elevated apoptosis, G2 cell cycle arrest, telomere elongation and aneuploidy. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 70 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4930553M12Rik T A 4: 88,786,486 (GRCm39) H44L unknown Het
Abcc3 T C 11: 94,256,051 (GRCm39) K478R probably benign Het
Ank2 A T 3: 126,736,952 (GRCm39) probably benign Het
Apod A G 16: 31,129,950 (GRCm39) V2A probably benign Het
Armh4 C A 14: 50,011,155 (GRCm39) S184I probably damaging Het
Aspg T A 12: 112,092,824 (GRCm39) D530E probably damaging Het
Atxn7 A T 14: 14,100,878 (GRCm38) T855S probably benign Het
Blmh G C 11: 76,859,451 (GRCm39) G351R probably damaging Het
Cc2d2a C T 5: 43,857,321 (GRCm39) R454* probably null Het
Cenpp T C 13: 49,619,233 (GRCm39) E188G probably damaging Het
Cimip3 A G 17: 47,748,114 (GRCm39) probably null Het
Creg2 T C 1: 39,662,376 (GRCm39) E252G probably benign Het
Dpy30 A G 17: 74,614,835 (GRCm39) I36T probably benign Het
Eed A G 7: 89,613,935 (GRCm39) probably null Het
Fmn1 A G 2: 113,195,353 (GRCm39) D351G unknown Het
Fra10ac1 C T 19: 38,212,567 (GRCm39) probably benign Het
Gdpd4 T A 7: 97,623,136 (GRCm39) I249N probably damaging Het
Glb1l2 A T 9: 26,676,423 (GRCm39) V600D probably null Het
Gm13889 A T 2: 93,787,459 (GRCm39) probably benign Het
Gm17654 T A 14: 43,813,327 (GRCm39) N188Y Het
Gm3327 T C 14: 44,363,732 (GRCm39) F112S Het
H2-Ab1 T C 17: 34,482,316 (GRCm39) S11P probably benign Het
Hcn4 T C 9: 58,763,000 (GRCm39) S522P unknown Het
Hfm1 T C 5: 107,043,909 (GRCm39) T576A probably benign Het
Hoxa1 A G 6: 52,135,180 (GRCm39) S8P probably damaging Het
Hoxd13 A G 2: 74,499,369 (GRCm39) Y239C probably damaging Het
Ifih1 T A 2: 62,440,859 (GRCm39) I485L probably benign Het
Ift52 G A 2: 162,871,716 (GRCm39) V183M probably damaging Het
Ikbkb A G 8: 23,161,658 (GRCm39) V410A possibly damaging Het
Il22ra1 G A 4: 135,478,473 (GRCm39) V515I probably benign Het
Klk1b3 A T 7: 43,850,863 (GRCm39) I132F probably damaging Het
Limk2 T C 11: 3,305,448 (GRCm39) T206A possibly damaging Het
Llph A T 10: 120,067,240 (GRCm39) probably benign Het
Lrrc26 T A 2: 25,180,087 (GRCm39) D29E probably benign Het
Ltbp4 A G 7: 27,007,191 (GRCm39) probably null Het
Mageb3 A T 2: 121,784,973 (GRCm39) V243E probably damaging Het
Mfhas1 T C 8: 36,055,792 (GRCm39) V89A probably benign Het
Mycbp2 G A 14: 103,393,534 (GRCm39) T2899I possibly damaging Het
Nckap5 A T 1: 126,186,449 (GRCm39) probably null Het
Ncor1 T C 11: 62,275,619 (GRCm39) D530G probably null Het
Or10ag55-ps1 T A 2: 87,114,775 (GRCm39) M47K probably benign Het
Or56a3b C T 7: 104,771,170 (GRCm39) R169* probably null Het
Pax4 A G 6: 28,446,322 (GRCm39) I57T probably damaging Het
Peg12 T C 7: 62,113,711 (GRCm39) I129V possibly damaging Het
Pex6 G A 17: 47,031,447 (GRCm39) A416T probably benign Het
Pgghg G A 7: 140,524,631 (GRCm39) R326H probably benign Het
Pgk2 T A 17: 40,519,366 (GRCm39) M21L probably benign Het
Polh A T 17: 46,509,642 (GRCm39) W64R probably benign Het
Rassf7 T A 7: 140,797,556 (GRCm39) H256Q probably benign Het
Rc3h2 A G 2: 37,265,258 (GRCm39) M1184T probably benign Het
Ror1 A T 4: 100,299,436 (GRCm39) E936D probably benign Het
Skic3 G A 13: 76,283,079 (GRCm39) A769T probably damaging Het
Slco1b2 A T 6: 141,617,974 (GRCm39) T440S probably damaging Het
Specc1 T A 11: 62,008,604 (GRCm39) V40E probably damaging Het
Tarbp1 T A 8: 127,201,234 (GRCm39) S191C possibly damaging Het
Timm22 A G 11: 76,298,071 (GRCm39) E14G possibly damaging Het
Tpp2 T A 1: 44,022,318 (GRCm39) D905E probably damaging Het
Trav7-5 T C 14: 53,768,756 (GRCm39) L108P probably damaging Het
Ttc9b A G 7: 27,353,667 (GRCm39) T106A probably benign Het
Ttn T C 2: 76,545,012 (GRCm39) S32697G probably damaging Het
Usp17la T G 7: 104,510,514 (GRCm39) L373R probably benign Het
Vmn1r113 A G 7: 20,521,427 (GRCm39) N73S probably benign Het
Vmn1r42 T C 6: 89,822,051 (GRCm39) T173A possibly damaging Het
Vmn2r106 A G 17: 20,499,182 (GRCm39) V243A probably damaging Het
Vmn2r111 T C 17: 22,778,032 (GRCm39) N549S possibly damaging Het
Vmn2r25 T A 6: 123,800,569 (GRCm39) D591V probably damaging Het
Zc3h13 T C 14: 75,559,227 (GRCm39) S379P probably benign Het
Zfp870 T C 17: 33,102,456 (GRCm39) Y292C probably damaging Het
Zfp977 A T 7: 42,229,786 (GRCm39) N246K possibly damaging Het
Zp1 G A 19: 10,896,104 (GRCm39) T207M probably damaging Het
Other mutations in Dot1l
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01836:Dot1l APN 10 80,621,700 (GRCm39) missense probably benign 0.00
IGL01915:Dot1l APN 10 80,616,728 (GRCm39) missense probably damaging 0.99
IGL02287:Dot1l APN 10 80,600,443 (GRCm39) missense possibly damaging 0.66
IGL02695:Dot1l APN 10 80,613,442 (GRCm39) missense probably damaging 1.00
IGL03058:Dot1l APN 10 80,626,831 (GRCm39) missense probably benign 0.00
IGL03071:Dot1l APN 10 80,624,513 (GRCm39) missense probably benign 0.00
IGL03120:Dot1l APN 10 80,622,107 (GRCm39) splice site probably benign
R0220:Dot1l UTSW 10 80,621,692 (GRCm39) missense probably damaging 0.99
R1342:Dot1l UTSW 10 80,621,859 (GRCm39) missense probably benign 0.14
R1701:Dot1l UTSW 10 80,626,576 (GRCm39) missense possibly damaging 0.93
R1862:Dot1l UTSW 10 80,619,373 (GRCm39) missense probably damaging 1.00
R2094:Dot1l UTSW 10 80,621,712 (GRCm39) missense probably damaging 1.00
R2308:Dot1l UTSW 10 80,624,903 (GRCm39) missense probably damaging 1.00
R4274:Dot1l UTSW 10 80,619,822 (GRCm39) critical splice donor site probably null
R4617:Dot1l UTSW 10 80,620,918 (GRCm39) missense probably damaging 0.97
R4623:Dot1l UTSW 10 80,617,984 (GRCm39) missense probably benign 0.18
R4690:Dot1l UTSW 10 80,622,016 (GRCm39) nonsense probably null
R5009:Dot1l UTSW 10 80,607,030 (GRCm39) missense probably benign 0.25
R5072:Dot1l UTSW 10 80,620,480 (GRCm39) missense possibly damaging 0.83
R5073:Dot1l UTSW 10 80,620,480 (GRCm39) missense possibly damaging 0.83
R5074:Dot1l UTSW 10 80,620,480 (GRCm39) missense possibly damaging 0.83
R5305:Dot1l UTSW 10 80,626,627 (GRCm39) missense probably benign 0.03
R5312:Dot1l UTSW 10 80,620,471 (GRCm39) missense possibly damaging 0.94
R5512:Dot1l UTSW 10 80,624,825 (GRCm39) missense possibly damaging 0.92
R5551:Dot1l UTSW 10 80,619,462 (GRCm39) small deletion probably benign
R5552:Dot1l UTSW 10 80,619,462 (GRCm39) small deletion probably benign
R5553:Dot1l UTSW 10 80,619,462 (GRCm39) small deletion probably benign
R6056:Dot1l UTSW 10 80,621,929 (GRCm39) missense probably damaging 0.96
R6207:Dot1l UTSW 10 80,622,277 (GRCm39) missense probably benign 0.06
R6419:Dot1l UTSW 10 80,627,315 (GRCm39) missense possibly damaging 0.85
R6782:Dot1l UTSW 10 80,625,224 (GRCm39) missense probably damaging 1.00
R7071:Dot1l UTSW 10 80,628,079 (GRCm39) missense probably benign 0.01
R7097:Dot1l UTSW 10 80,626,560 (GRCm39) missense probably damaging 0.98
R7131:Dot1l UTSW 10 80,628,175 (GRCm39) missense unknown
R7459:Dot1l UTSW 10 80,609,007 (GRCm39) missense probably damaging 0.96
R7687:Dot1l UTSW 10 80,625,202 (GRCm39) missense possibly damaging 0.70
R7741:Dot1l UTSW 10 80,619,378 (GRCm39) missense probably damaging 1.00
R8513:Dot1l UTSW 10 80,627,260 (GRCm39) missense possibly damaging 0.93
R8830:Dot1l UTSW 10 80,607,033 (GRCm39) missense possibly damaging 0.68
R8881:Dot1l UTSW 10 80,621,429 (GRCm39) missense probably damaging 1.00
R9069:Dot1l UTSW 10 80,626,560 (GRCm39) missense probably damaging 0.98
R9438:Dot1l UTSW 10 80,627,120 (GRCm39) missense probably benign
R9439:Dot1l UTSW 10 80,621,438 (GRCm39) missense possibly damaging 0.71
R9664:Dot1l UTSW 10 80,624,361 (GRCm39) missense probably damaging 1.00
R9671:Dot1l UTSW 10 80,620,613 (GRCm39) missense probably damaging 1.00
R9727:Dot1l UTSW 10 80,628,382 (GRCm39) missense unknown
R9787:Dot1l UTSW 10 80,600,472 (GRCm39) missense probably benign 0.06
X0066:Dot1l UTSW 10 80,624,518 (GRCm39) missense probably damaging 1.00
X0066:Dot1l UTSW 10 80,624,517 (GRCm39) missense possibly damaging 0.94
Predicted Primers PCR Primer
(F):5'- GTGACAGGTCTCAAACAGGC -3'
(R):5'- GGATTGCTCCTGAAACCAACC -3'

Sequencing Primer
(F):5'- GTCTCAAACAGGCGGGAAG -3'
(R):5'- ACAGCCAGTGCCTCTGC -3'
Posted On 2019-05-13