Mutagenetix > Incidental Mutation

Incidental Mutation 'R5512:Dot1l'

440113

Institutional Source

Beutler Lab

Gene Symbol

Dot1l

Ensembl Gene

ENSMUSG00000061589

Gene Name

DOT1 like histone lysine methyltransferase

Synonyms

KMT4, mDot1

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R5512 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

80591040-80631295 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 80624825 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Proline to Serine at position 881 (P881S)

Ref Sequence

ENSEMBL: ENSMUSP00000116581 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000105336] [ENSMUST00000127740] [ENSMUST00000149394] [ENSMUST00000150338]

AlphaFold

Q6XZL8

Predicted Effect

probably benign
Transcript: ENSMUST00000105336
AA Change: P1098S

PolyPhen 2 Score 0.141 (Sensitivity: 0.92; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000100973
Gene: ENSMUSG00000061589
AA Change: P1098S

Domain	Start	End	E-Value	Type
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

Domain	Start	End	E-Value	Type
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

Domain	Start	End	E-Value	Type
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

possibly damaging
Transcript: ENSMUST00000150338
AA Change: P881S

PolyPhen 2 Score 0.922 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000116581
Gene: ENSMUSG00000061589
AA Change: P881S

Domain	Start	End	E-Value	Type
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

noncoding transcript
Transcript: ENSMUST00000163526

Coding Region Coverage

1x: 99.3%
3x: 98.7%
10x: 97.3%
20x: 95.4%

Validation Efficiency

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: 77 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2310057M21Rik	A	G	7: 130,952,389 (GRCm39)	V364A	possibly damaging	Het
Abca8b	C	A	11: 109,868,639 (GRCm39)	G175V	probably damaging	Het
Adgre5	T	C	8: 84,455,715 (GRCm39)	N198D	probably benign	Het
Adgrf4	G	T	17: 42,978,176 (GRCm39)	T389K	probably benign	Het
Apc	T	A	18: 34,443,962 (GRCm39)		probably benign	Het
Appl2	T	A	10: 83,441,682 (GRCm39)	I524F	probably damaging	Het
Arhgef37	G	A	18: 61,632,845 (GRCm39)	Q531*	probably null	Het
Atp7b	T	C	8: 22,502,755 (GRCm39)	T694A	probably benign	Het
Cacna1g	T	A	11: 94,334,968 (GRCm39)	I780F	probably damaging	Het
Calcoco2	T	C	11: 95,994,162 (GRCm39)	K95E	probably damaging	Het
Cars1	T	C	7: 143,123,870 (GRCm39)	D388G	possibly damaging	Het
Ccdc150	A	C	1: 54,393,806 (GRCm39)	E690A	probably damaging	Het
Cdc73	G	T	1: 143,578,354 (GRCm39)	D3E	probably damaging	Het
Cdh23	C	A	10: 60,370,165 (GRCm39)		probably null	Het
Cep170b	T	C	12: 112,699,919 (GRCm39)	S143P	possibly damaging	Het
Cherp	T	C	8: 73,217,110 (GRCm39)	I607V	possibly damaging	Het
CN725425	T	A	15: 91,124,959 (GRCm39)	H166Q	probably benign	Het
Dcaf6	A	G	1: 165,227,404 (GRCm39)	V241A	possibly damaging	Het
Drgx	A	G	14: 32,322,001 (GRCm39)	H5R	probably damaging	Het
Dsg1c	A	T	18: 20,405,568 (GRCm39)	N327I	probably damaging	Het
Fbxw7	G	A	3: 84,862,216 (GRCm39)	R182H	probably damaging	Het
Fkbp1b	A	T	12: 4,888,183 (GRCm39)	V24E	probably benign	Het
Fut11	T	C	14: 20,746,069 (GRCm39)	S304P	probably damaging	Het
Ggt1	C	T	10: 75,420,718 (GRCm39)	T361I	probably damaging	Het
Gimap7	G	T	6: 48,700,530 (GRCm39)	A39S	probably benign	Het
Gm12689	T	C	4: 99,184,402 (GRCm39)	I85T	unknown	Het
Gm17541	G	T	12: 4,739,452 (GRCm39)		probably benign	Het
Gmip	T	A	8: 70,270,540 (GRCm39)	V750E	probably benign	Het
Gna14	A	G	19: 16,585,492 (GRCm39)	E290G	probably benign	Het
Gpnmb	T	C	6: 49,022,398 (GRCm39)	V176A	possibly damaging	Het
Hhla1	T	C	15: 65,795,865 (GRCm39)	K447R	probably benign	Het
Hsd3b1	A	G	3: 98,760,521 (GRCm39)	Y157H	probably benign	Het
Iqgap2	G	A	13: 95,811,884 (GRCm39)	Q706*	probably null	Het
Krt222	A	C	11: 99,125,781 (GRCm39)	S283R	probably damaging	Het
Ldb2	G	A	5: 44,637,586 (GRCm39)	R241W	probably damaging	Het
Lrrc8d	G	A	5: 105,960,651 (GRCm39)	E354K	probably benign	Het
Lrrc8d	C	G	5: 105,960,650 (GRCm39)	F353L	probably damaging	Het
Masp2	A	T	4: 148,698,526 (GRCm39)	I536F	probably damaging	Het
Mptx1	A	G	1: 174,160,315 (GRCm39)	D207G	probably benign	Het
Mtpn	C	T	6: 35,489,225 (GRCm39)	D100N	probably benign	Het
Napsa	A	G	7: 44,222,040 (GRCm39)	M1V	probably null	Het
Ncam1	A	T	9: 49,420,999 (GRCm39)		probably null	Het
Nckap5	G	A	1: 125,955,481 (GRCm39)	P425L	possibly damaging	Het
Nol8	A	G	13: 49,830,263 (GRCm39)	S1116G	probably benign	Het
Nrde2	G	T	12: 100,108,509 (GRCm39)	Q361K	probably benign	Het
Nudt13	G	A	14: 20,357,800 (GRCm39)	G133D	probably damaging	Het
Ofcc1	G	T	13: 40,360,286 (GRCm39)	Q248K	probably benign	Het
Olfm4	A	G	14: 80,258,787 (GRCm39)	D345G	probably benign	Het
Or2t6	C	A	14: 14,175,633 (GRCm38)	G150C	probably damaging	Het
Or4k41	G	A	2: 111,280,099 (GRCm39)	V205I	probably benign	Het
Osbpl3	T	G	6: 50,286,340 (GRCm39)	K659N	probably damaging	Het
Pdk2	G	A	11: 94,930,292 (GRCm39)	T48M	probably damaging	Het
Phf11a	A	T	14: 59,524,999 (GRCm39)	D68E	probably benign	Het
Purb	A	G	11: 6,425,702 (GRCm39)	V62A	probably damaging	Het
Rabep2	A	G	7: 126,037,971 (GRCm39)	T248A	possibly damaging	Het
Rps19bp1	CCTTCTTCTTCTTCTTCTTCTT	CCTTCTTCTTCTTCTTCTT	15: 80,145,250 (GRCm39)		probably benign	Het
Rtl1	C	T	12: 109,557,805 (GRCm39)	E1345K	unknown	Het
Sema3e	G	A	5: 14,280,194 (GRCm39)	A358T	probably damaging	Het
Slc29a2	A	G	19: 5,076,426 (GRCm39)	I105V	probably benign	Het
Slc35e2	C	T	4: 155,694,483 (GRCm39)	P10L	probably benign	Het
Slc6a5	G	A	7: 49,591,573 (GRCm39)	V513I	probably damaging	Het
Slco4a1	T	A	2: 180,115,907 (GRCm39)	F681Y	possibly damaging	Het
Sp1	A	G	15: 102,339,445 (GRCm39)	N775S	possibly damaging	Het
Sspo	T	A	6: 48,432,605 (GRCm39)	V827D	probably damaging	Het
Taar7f	C	T	10: 23,926,321 (GRCm39)	T305M	possibly damaging	Het
Tars2	A	T	3: 95,657,728 (GRCm39)	C238S	probably damaging	Het
Tasor2	A	T	13: 3,645,517 (GRCm39)	Y111N	probably damaging	Het
Tnks1bp1	C	A	2: 84,893,178 (GRCm39)	P373Q	probably benign	Het
Tnpo3	A	G	6: 29,575,045 (GRCm39)	L373P	probably damaging	Het
Unc45b	A	C	11: 82,805,898 (GRCm39)	D135A	possibly damaging	Het
Vmn1r235	A	T	17: 21,481,677 (GRCm39)	M1L	probably benign	Het
Vmn2r66	T	C	7: 84,657,149 (GRCm39)	I85M	probably damaging	Het
Vmn2r80	T	G	10: 79,004,066 (GRCm39)	L93W	probably benign	Het
Vwf	G	T	6: 125,650,850 (GRCm39)		probably benign	Het
Ythdf3	A	G	3: 16,238,086 (GRCm39)	R9G	probably damaging	Het
Zfp229	A	G	17: 21,964,017 (GRCm39)		probably null	Het
Zfp958	A	C	8: 4,675,838 (GRCm39)		probably null	Het

Other mutations in Dot1l

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH 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
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
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'- GAACTGCCTTCTGATCCTGC -3'
(R):5'- CTAGCTGCTATGTCTCTGGATC -3'

Sequencing Primer
(F):5'- TGCCTTCTCAGACCCAGAGAG -3'
(R):5'- ATCTGCCCCACTGGACTGTAG -3'

Posted On

2016-11-08