Mutagenetix > Incidental Mutation

Incidental Mutation 'R1862:Dot1l'

204048

Institutional Source

Beutler Lab

Gene Symbol

Dot1l

Ensembl Gene

ENSMUSG00000061589

Gene Name

DOT1-like, histone H3 methyltransferase (S. cerevisiae)

Synonyms

mDot1, KMT4

MMRRC Submission

039885-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1862 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

80755206-80795461 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 80783539 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Leucine at position 193 (R193L)

Ref Sequence

ENSEMBL: ENSMUSP00000116581 (fasta)

Gene Model

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

AlphaFold

Q6XZL8

Predicted Effect

probably damaging
Transcript: ENSMUST00000105336
AA Change: R410L

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000100973
Gene: ENSMUSG00000061589
AA Change: R410L

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 damaging
Transcript: ENSMUST00000150338
AA Change: R193L

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

SMART Domains

Protein: ENSMUSP00000116581
Gene: ENSMUSG00000061589
AA Change: R193L

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: 97.5%
3x: 96.8%
10x: 94.9%
20x: 90.5%

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: 82 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acox2	T	A	14: 8,241,416	E565D	probably benign	Het
Adam30	A	T	3: 98,162,113	K421*	probably null	Het
Atp6v1b1	A	G	6: 83,749,852		probably null	Het
Cacna1a	A	T	8: 84,415,930	I96F	possibly damaging	Het
Card10	G	A	15: 78,780,514	R747W	probably damaging	Het
Cdh8	T	A	8: 99,190,394	D363V	probably damaging	Het
Cecr2	T	C	6: 120,757,941	Y685H	probably damaging	Het
Cmklr1	T	C	5: 113,614,407	T178A	probably damaging	Het
Col16a1	G	A	4: 130,092,782		probably null	Het
Col4a1	C	T	8: 11,226,439		probably benign	Het
Coro2a	T	A	4: 46,548,797	I166F	possibly damaging	Het
Cry2	T	C	2: 92,424,566	H148R	probably damaging	Het
Crygd	T	C	1: 65,061,974	Y154C	probably benign	Het
Cubn	T	C	2: 13,308,561	Y3066C	probably damaging	Het
Defb15	C	T	8: 21,929,986	E42K	possibly damaging	Het
Dnah12	A	G	14: 26,697,398	D147G	probably benign	Het
Dnah12	A	T	14: 26,709,257	Y340F	probably benign	Het
Dupd1	A	G	14: 21,686,689	V115A	probably benign	Het
Esd	A	C	14: 74,742,074	Y119S	probably damaging	Het
Esp36	A	G	17: 38,419,439		probably benign	Het
Etfbkmt	T	A	6: 149,144,151	M1K	probably null	Het
Exph5	A	G	9: 53,376,248	H1543R	probably benign	Het
Fam92a	C	T	4: 12,155,717	V306I	possibly damaging	Het
Fbxo16	A	G	14: 65,270,803	T23A	probably damaging	Het
Gm11492	A	G	11: 87,567,235	H145R	possibly damaging	Het
Gm6614	T	C	6: 142,003,423	M76V	possibly damaging	Het
Gorasp2	C	A	2: 70,679,464	H136Q	probably damaging	Het
Hdc	T	A	2: 126,597,933	I367F	probably benign	Het
Hmcn1	C	T	1: 150,638,900	V3574M	probably benign	Het
Ilvbl	A	G	10: 78,584,124	D592G	probably benign	Het
Inmt	G	A	6: 55,174,883	A34V	probably damaging	Het
Ints9	A	C	14: 65,026,413	H378P	probably benign	Het
Kcnh7	T	A	2: 62,787,754	I464L	possibly damaging	Het
Kcnt2	T	A	1: 140,425,330	V259D	probably damaging	Het
Lipo1	A	G	19: 33,784,692	F135S	probably damaging	Het
Lrba	T	C	3: 86,773,203		probably null	Het
Mapk1	T	A	16: 17,026,429	S22T	probably benign	Het
Mbd3l2	T	C	9: 18,444,921	S181P	possibly damaging	Het
Mgat5	C	T	1: 127,459,969	P554L	probably damaging	Het
Mki67	T	C	7: 135,699,361	T1315A	probably benign	Het
Mprip	C	T	11: 59,758,221	T917M	possibly damaging	Het
Mroh3	T	A	1: 136,185,988	I688F	probably benign	Het
Myo1d	A	T	11: 80,663,048	Y536N	probably damaging	Het
Neb	C	T	2: 52,162,187		probably null	Het
Noc2l	A	G	4: 156,237,708	R161G	probably benign	Het
Nup54	T	A	5: 92,419,567	I375L	possibly damaging	Het
Nup93	T	C	8: 94,306,102	F539L	probably damaging	Het
Olfr138	A	G	17: 38,275,344	E191G	probably damaging	Het
Olfr417	T	A	1: 174,369,452	H178Q	probably damaging	Het
Olfr480	A	C	7: 108,066,725	Y24*	probably null	Het
Olfr874	T	A	9: 37,746,968	M278K	probably benign	Het
Panx1	A	T	9: 15,007,428	D378E	probably damaging	Het
Papss1	T	A	3: 131,583,184	V170D	possibly damaging	Het
Pcnx	T	C	12: 81,918,732	S558P	probably damaging	Het
Pde3a	T	A	6: 141,250,353	I255N	probably damaging	Het
Pde3a	G	T	6: 141,487,513	A757S	probably damaging	Het
Pdzph1	A	G	17: 58,922,583	Y1027H	probably damaging	Het
Pkhd1	G	T	1: 20,551,020	R805S	probably benign	Het
Polr1a	G	A	6: 71,909,203	G14D	probably damaging	Het
Prg4	T	A	1: 150,460,669	D60V	probably damaging	Het
Ptprc	T	C	1: 138,112,227	S311G	probably benign	Het
Rapgefl1	G	A	11: 98,842,209	R205K	probably benign	Het
Rcan2	A	T	17: 44,037,089		probably null	Het
Rock1	A	G	18: 10,079,207	I1087T	probably damaging	Het
Sectm1b	A	G	11: 121,054,942	I191T	possibly damaging	Het
Setd1b	T	C	5: 123,147,613	S241P	unknown	Het
Srpk2	T	C	5: 23,524,150	K497R	probably benign	Het
Sspo	T	C	6: 48,491,006	S4296P	probably damaging	Het
Syne4	T	C	7: 30,316,883	V168A	probably benign	Het
Tank	T	C	2: 61,649,912	F264S	probably damaging	Het
Ticrr	T	C	7: 79,695,207	S1607P	probably damaging	Het
Trim30a	A	G	7: 104,411,198	V457A	probably damaging	Het
Trim43b	T	A	9: 89,085,571	K336N	probably damaging	Het
Trim47	T	C	11: 116,106,137	Q598R	probably damaging	Het
Tspan12	T	C	6: 21,851,023	N18S	probably damaging	Het
Ubap2	A	G	4: 41,221,607	S231P	probably benign	Het
Vit	A	G	17: 78,622,746	D380G	probably damaging	Het
Vmn2r2	T	C	3: 64,134,521	N258D	possibly damaging	Het
Vmn2r52	C	T	7: 10,173,406	C131Y	possibly damaging	Het
Zadh2	T	C	18: 84,095,318	V373A	possibly damaging	Het
Zfp58	A	T	13: 67,491,188	F395I	probably damaging	Het
Zfp940	C	A	7: 29,845,010	G491C	probably damaging	Het

Other mutations in Dot1l

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01836:Dot1l	APN	10	80785866	missense	probably benign	0.00
IGL01915:Dot1l	APN	10	80780894	missense	probably damaging	0.99
IGL02287:Dot1l	APN	10	80764609	missense	possibly damaging	0.66
IGL02695:Dot1l	APN	10	80777608	missense	probably damaging	1.00
IGL03058:Dot1l	APN	10	80790997	missense	probably benign	0.00
IGL03071:Dot1l	APN	10	80788679	missense	probably benign	0.00
IGL03120:Dot1l	APN	10	80786273	splice site	probably benign
R0220:Dot1l	UTSW	10	80785858	missense	probably damaging	0.99
R1342:Dot1l	UTSW	10	80786025	missense	probably benign	0.14
R1701:Dot1l	UTSW	10	80790742	missense	possibly damaging	0.93
R2094:Dot1l	UTSW	10	80785878	missense	probably damaging	1.00
R2308:Dot1l	UTSW	10	80789069	missense	probably damaging	1.00
R4274:Dot1l	UTSW	10	80783988	critical splice donor site	probably null
R4617:Dot1l	UTSW	10	80785084	missense	probably damaging	0.97
R4623:Dot1l	UTSW	10	80782150	missense	probably benign	0.18
R4690:Dot1l	UTSW	10	80786182	nonsense	probably null
R5009:Dot1l	UTSW	10	80771196	missense	probably benign	0.25
R5072:Dot1l	UTSW	10	80784646	missense	possibly damaging	0.83
R5073:Dot1l	UTSW	10	80784646	missense	possibly damaging	0.83
R5074:Dot1l	UTSW	10	80784646	missense	possibly damaging	0.83
R5305:Dot1l	UTSW	10	80790793	missense	probably benign	0.03
R5312:Dot1l	UTSW	10	80784637	missense	possibly damaging	0.94
R5512:Dot1l	UTSW	10	80788991	missense	possibly damaging	0.92
R5551:Dot1l	UTSW	10	80783628	small deletion	probably benign
R5552:Dot1l	UTSW	10	80783628	small deletion	probably benign
R5553:Dot1l	UTSW	10	80783628	small deletion	probably benign
R6056:Dot1l	UTSW	10	80786095	missense	probably damaging	0.96
R6207:Dot1l	UTSW	10	80786443	missense	probably benign	0.06
R6419:Dot1l	UTSW	10	80791481	missense	possibly damaging	0.85
R6782:Dot1l	UTSW	10	80789390	missense	probably damaging	1.00
R7054:Dot1l	UTSW	10	80787023	missense	probably damaging	0.99
R7071:Dot1l	UTSW	10	80792245	missense	probably benign	0.01
R7097:Dot1l	UTSW	10	80790726	missense	probably damaging	0.98
R7131:Dot1l	UTSW	10	80792341	missense	unknown
R7459:Dot1l	UTSW	10	80773173	missense	probably damaging	0.96
R7687:Dot1l	UTSW	10	80789368	missense	possibly damaging	0.70
R7741:Dot1l	UTSW	10	80783544	missense	probably damaging	1.00
R8513:Dot1l	UTSW	10	80791426	missense	possibly damaging	0.93
R8830:Dot1l	UTSW	10	80771199	missense	possibly damaging	0.68
R8881:Dot1l	UTSW	10	80785595	missense	probably damaging	1.00
R9069:Dot1l	UTSW	10	80790726	missense	probably damaging	0.98
R9438:Dot1l	UTSW	10	80791286	missense	probably benign
R9439:Dot1l	UTSW	10	80785604	missense	possibly damaging	0.71
R9664:Dot1l	UTSW	10	80788527	missense	probably damaging	1.00
R9671:Dot1l	UTSW	10	80784779	missense	probably damaging	1.00
R9727:Dot1l	UTSW	10	80792548	missense	unknown
R9787:Dot1l	UTSW	10	80764638	missense	probably benign	0.06
X0066:Dot1l	UTSW	10	80788683	missense	possibly damaging	0.94
X0066:Dot1l	UTSW	10	80788684	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- CTCAGCCTATGGTCTTGTGAG -3'
(R):5'- ACTGAGCTCCTCCTGGTTTG -3'

Sequencing Primer
(F):5'- GGTCTTGTGAGCACTCCTGC -3'
(R):5'- TGGCAGAGTCCCATAGTCACATG -3'

Posted On

2014-06-23