Mutagenetix > Incidental Mutation

Incidental Mutation 'R7097:Dot1l'

550572

Institutional Source

Beutler Lab

Gene Symbol

Dot1l

Ensembl Gene

ENSMUSG00000061589

Gene Name

DOT1 like histone lysine methyltransferase

Synonyms

KMT4, mDot1

MMRRC Submission

045189-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7097 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

80591040-80631295 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to G at 80626560 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Arginine at position 1260 (S1260R)

Ref Sequence

ENSEMBL: ENSMUSP00000100973 (fasta)

Gene Model

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

AlphaFold

Q6XZL8

Predicted Effect

probably damaging
Transcript: ENSMUST00000105336
AA Change: S1260R

PolyPhen 2 Score 0.979 (Sensitivity: 0.75; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000100973
Gene: ENSMUSG00000061589
AA Change: S1260R

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 damaging
Transcript: ENSMUST00000149394
AA Change: S139R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000127762
Gene: ENSMUSG00000061589
AA Change: S139R

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

probably benign
Transcript: ENSMUST00000150338

SMART Domains

Protein: ENSMUSP00000116581
Gene: ENSMUSG00000061589

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

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 99.1%

Validation Efficiency

99% (75/76)

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: 75 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700010I14Rik	A	G	17: 9,224,052 (GRCm39)	N435S	probably damaging	Het
Aip	A	T	19: 4,165,381 (GRCm39)	V195E	probably benign	Het
Amer3	A	T	1: 34,627,869 (GRCm39)	I703F	probably benign	Het
Amfr	T	C	8: 94,738,637 (GRCm39)	E7G	probably benign	Het
Angel1	A	G	12: 86,773,158 (GRCm39)	S4P	probably damaging	Het
Atp2c1	A	G	9: 105,341,850 (GRCm39)	I146T	probably damaging	Het
Atp6v0e	A	G	17: 26,914,390 (GRCm39)	T72A	probably benign	Het
Bahcc1	T	C	11: 120,163,472 (GRCm39)	V590A	possibly damaging	Het
Bcl6	A	G	16: 23,791,364 (GRCm39)	V330A	possibly damaging	Het
Bcl6	T	C	16: 23,791,652 (GRCm39)	D234G	probably damaging	Het
Btaf1	C	T	19: 36,926,502 (GRCm39)	T58I	probably damaging	Het
Ccdc175	A	T	12: 72,175,183 (GRCm39)		probably null	Het
Cdca4	C	A	12: 112,785,189 (GRCm39)	V180L	probably benign	Het
Ces1g	C	A	8: 94,043,665 (GRCm39)	G425C	possibly damaging	Het
Chl1	T	C	6: 103,683,409 (GRCm39)	L745P	probably damaging	Het
Clec4g	T	A	8: 3,769,518 (GRCm39)	T42S	possibly damaging	Het
Ctsg	A	C	14: 56,337,489 (GRCm39)	I238S	probably damaging	Het
Cyb5rl	A	T	4: 106,944,513 (GRCm39)	E41V	unknown	Het
Dcdc2a	A	G	13: 25,291,681 (GRCm39)	E222G	probably benign	Het
Dnaaf1	G	T	8: 120,323,538 (GRCm39)	G509V	possibly damaging	Het
Dnah5	A	G	15: 28,453,410 (GRCm39)	I4394V	probably benign	Het
Dst	T	G	1: 34,208,341 (GRCm39)	I1089S	probably damaging	Het
Efcab3	A	T	11: 104,899,787 (GRCm39)	I4350F	possibly damaging	Het
Eps8l3	A	G	3: 107,791,801 (GRCm39)		probably null	Het
Fam135b	A	G	15: 71,493,917 (GRCm39)	V4A	possibly damaging	Het
Fnip2	T	C	3: 79,388,313 (GRCm39)	E806G	probably benign	Het
Fryl	T	A	5: 73,231,251 (GRCm39)	I1609F	probably benign	Het
Gdi1	G	A	X: 73,350,461 (GRCm39)	R55H	probably benign	Het
Gsn	A	T	2: 35,185,061 (GRCm39)	K339*	probably null	Het
Hecw2	T	A	1: 53,904,283 (GRCm39)	Y1155F	possibly damaging	Het
Kif20b	T	A	19: 34,951,892 (GRCm39)	N1723K	probably damaging	Het
Kif2b	T	C	11: 91,467,650 (GRCm39)	D211G	probably benign	Het
Lhfpl4	C	T	6: 113,153,632 (GRCm39)	V140I	probably benign	Het
Med16	C	T	10: 79,739,177 (GRCm39)	G203D	probably damaging	Het
Mrgpra3	T	A	7: 47,239,389 (GRCm39)	Y179F	probably benign	Het
Muc6	AGGCGCAGAAACCCTGGC	AGGC	7: 141,214,363 (GRCm39)		probably null	Het
Myo18b	A	G	5: 113,022,271 (GRCm39)	S374P	unknown	Het
Myoz1	A	G	14: 20,699,477 (GRCm39)	I287T	possibly damaging	Het
Ncoa6	T	C	2: 155,279,983 (GRCm39)	D11G	probably benign	Het
Nlrp9c	A	G	7: 26,085,046 (GRCm39)	Y178H	probably damaging	Het
Nmur1	T	C	1: 86,315,230 (GRCm39)	T212A	probably damaging	Het
Oacyl	A	G	18: 65,853,323 (GRCm39)	D143G	probably benign	Het
Obox5	A	G	7: 15,492,732 (GRCm39)	Y229C	probably damaging	Het
Or10d1c	A	T	9: 38,893,914 (GRCm39)	M142K	probably benign	Het
Or1j12	A	G	2: 36,342,702 (GRCm39)	Y35C	probably damaging	Het
Or1j18	G	T	2: 36,624,436 (GRCm39)	M34I	probably benign	Het
Or1x2	C	A	11: 50,918,428 (GRCm39)	L200I	probably benign	Het
Or8c13	A	T	9: 38,091,632 (GRCm39)	C162*	probably null	Het
Pcdhb17	A	C	18: 37,619,566 (GRCm39)	N452T	probably benign	Het
Pear1	T	G	3: 87,658,752 (GRCm39)	H901P	probably benign	Het
Peds1	C	G	2: 167,503,398 (GRCm39)	A7P	probably benign	Het
Pi16	A	G	17: 29,545,313 (GRCm39)	Y192C	probably damaging	Het
Pip5k1b	T	G	19: 24,335,424 (GRCm39)	E362D	probably damaging	Het
Pla2g5	T	C	4: 138,531,830 (GRCm39)	D58G	probably damaging	Het
Pole	T	A	5: 110,472,968 (GRCm39)		probably null	Het
Prdm16	G	T	4: 154,429,925 (GRCm39)	T348K	probably damaging	Het
Prkdc	T	A	16: 15,507,207 (GRCm39)	F896I	probably damaging	Het
Prmt7	T	C	8: 106,961,732 (GRCm39)	F215S	unknown	Het
Prss23	T	A	7: 89,159,392 (GRCm39)	T226S	probably damaging	Het
Ptpn14	G	A	1: 189,595,595 (GRCm39)	W739*	probably null	Het
Rfx5	G	T	3: 94,863,850 (GRCm39)	G135C	probably damaging	Het
Scmh1	A	G	4: 120,382,252 (GRCm39)	H573R	probably benign	Het
Serpina5	G	T	12: 104,068,554 (GRCm39)		probably null	Het
Sh3rf2	G	A	18: 42,237,227 (GRCm39)		probably null	Het
Slc38a2	T	C	15: 96,591,182 (GRCm39)	M229V	probably damaging	Het
Slc6a17	C	G	3: 107,400,464 (GRCm39)	G222R	probably damaging	Het
Sp110	C	T	1: 85,507,406 (GRCm39)	G367D	possibly damaging	Het
Srcap	C	A	7: 127,138,213 (GRCm39)	L1128M	probably damaging	Het
Tpra1	T	A	6: 88,885,276 (GRCm39)	I76N	probably damaging	Het
Trav6-4	A	T	14: 53,692,049 (GRCm39)	Y52F	probably benign	Het
Trp63	C	A	16: 25,639,227 (GRCm39)	H138Q	probably damaging	Het
Trub2	A	G	2: 29,669,838 (GRCm39)	V177A	possibly damaging	Het
Ugt2a2	T	C	5: 87,608,255 (GRCm39)	D528G	possibly damaging	Het
Wnk2	C	A	13: 49,256,314 (GRCm39)	R269L	possibly damaging	Het
Zc3h12c	T	A	9: 52,027,226 (GRCm39)	Q731L	possibly damaging	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
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
R7071:Dot1l	UTSW	10	80,628,079 (GRCm39)	missense	probably benign	0.01
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'- ACGTTGCATGCACCTCTTAG -3'
(R):5'- AAACCGAGGTCTGCAGCAAG -3'

Sequencing Primer
(F):5'- AGCTGTCTTCACCCCAGGAAG -3'
(R):5'- AAGGCCCCCACTGAAGG -3'

Posted On

2019-05-15