Incidental Mutation 'R7071:Dot1l'
ID 548913
Institutional Source Beutler Lab
Gene Symbol Dot1l
Ensembl Gene ENSMUSG00000061589
Gene Name DOT1 like histone lysine methyltransferase
Synonyms KMT4, mDot1
MMRRC Submission 045167-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R7071 (G1)
Quality Score 225.009
Status Validated
Chromosome 10
Chromosomal Location 80591040-80631295 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 80628079 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Leucine to Glutamine at position 1039 (L1039Q)
Ref Sequence ENSEMBL: ENSMUSP00000116581 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000036805] [ENSMUST00000105336] [ENSMUST00000127740] [ENSMUST00000149394] [ENSMUST00000150338] [ENSMUST00000219378] [ENSMUST00000219959]
AlphaFold Q6XZL8
Predicted Effect probably benign
Transcript: ENSMUST00000036805
SMART Domains Protein: ENSMUSP00000042334
Gene: ENSMUSG00000035278

DomainStartEndE-ValueType
PH 16 110 1.48e-7 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000105336
SMART Domains Protein: ENSMUSP00000100973
Gene: ENSMUSG00000061589

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
SMART Domains Protein: ENSMUSP00000119492
Gene: ENSMUSG00000061589
AA Change: L70Q

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 benign
Transcript: ENSMUST00000150338
AA Change: L1039Q

PolyPhen 2 Score 0.007 (Sensitivity: 0.96; Specificity: 0.75)
SMART Domains Protein: ENSMUSP00000116581
Gene: ENSMUSG00000061589
AA Change: L1039Q

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
Predicted Effect probably benign
Transcript: ENSMUST00000219378
Predicted Effect probably benign
Transcript: ENSMUST00000219959
Meta Mutation Damage Score 0.0708 question?
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.7%
  • 20x: 99.1%
Validation Efficiency 95% (41/43)
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: 41 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abi3bp C T 16: 56,449,503 (GRCm39) Q854* probably null Het
Arl2bp G T 8: 95,393,794 (GRCm39) probably benign Het
Astl T C 2: 127,187,885 (GRCm39) M121T probably benign Het
Atrip T C 9: 108,896,082 (GRCm39) probably null Het
Camk1g A T 1: 193,042,117 (GRCm39) V44E probably benign Het
Cc2d2a A G 5: 43,866,455 (GRCm39) H804R probably benign Het
Cd300a T C 11: 114,792,099 (GRCm39) S314P probably damaging Het
Ceacam5 A T 7: 17,484,577 (GRCm39) I440L possibly damaging Het
Cfap61 T G 2: 145,843,832 (GRCm39) I306R probably benign Het
Cnot10 T C 9: 114,446,787 (GRCm39) probably null Het
Cntln T A 4: 85,018,622 (GRCm39) L76Q probably damaging Het
Cobl A G 11: 12,204,795 (GRCm39) C636R probably benign Het
Dnm3 A T 1: 161,847,412 (GRCm39) H148Q probably damaging Het
Faiml T A 9: 99,118,400 (GRCm39) M1L unknown Het
Fat1 T G 8: 45,442,145 (GRCm39) I1149S possibly damaging Het
Gatad1 T C 5: 3,693,540 (GRCm39) R210G probably benign Het
Gm11938 A T 11: 99,493,910 (GRCm39) C62S probably damaging Het
Gtf2i A G 5: 134,292,475 (GRCm39) L423S probably damaging Het
Hmcn1 A T 1: 150,479,853 (GRCm39) C4582S probably damaging Het
Ifitm3 A G 7: 140,590,437 (GRCm39) V41A probably benign Het
Ipo11 T A 13: 107,061,604 (GRCm39) S19C probably damaging Het
Khsrp C A 17: 57,332,386 (GRCm39) M268I possibly damaging Het
Lrp1b T G 2: 41,298,276 (GRCm39) D1036A Het
Mecom T G 3: 30,034,857 (GRCm39) H273P probably damaging Het
Mfn1 G A 3: 32,622,544 (GRCm39) V601I probably benign Het
Mrps5 T A 2: 127,442,772 (GRCm39) Y280* probably null Het
Myo18a A G 11: 77,714,653 (GRCm39) T811A probably damaging Het
Ndfip2 A C 14: 105,539,760 (GRCm39) N292H possibly damaging Het
Or2ak5 C A 11: 58,610,984 (GRCm39) V297F possibly damaging Het
Otog T A 7: 45,916,747 (GRCm39) C895S probably damaging Het
Pacs1 A T 19: 5,206,402 (GRCm39) I261N possibly damaging Het
Pira13 A G 7: 3,824,667 (GRCm39) S573P unknown Het
Ptprn A T 1: 75,237,263 (GRCm39) M113K possibly damaging Het
Rag1 T C 2: 101,473,807 (GRCm39) H445R probably damaging Het
Ranbp2 T G 10: 58,328,659 (GRCm39) F2853V probably damaging Het
Skint5 A T 4: 113,636,277 (GRCm39) F647Y unknown Het
Stt3b T C 9: 115,083,085 (GRCm39) Y449C probably damaging Het
Ythdc2 A G 18: 44,978,855 (GRCm39) D455G probably benign Het
Zfp451 A C 1: 33,815,825 (GRCm39) D708E possibly damaging Het
Zfp456 T C 13: 67,520,896 (GRCm39) E33G probably damaging Het
Zfp599 T C 9: 22,169,392 (GRCm39) T27A probably benign 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
R7054:Dot1l UTSW 10 80,622,857 (GRCm39) missense probably damaging 0.99
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'- GCCTGGTGAGAAATGAGTCCAG -3'
(R):5'- ACTGGCTCAGGGTTAGAAGC -3'

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