Mutagenetix > Incidental Mutation

Incidental Mutation 'R5312:Dot1l'

405657

Institutional Source

Beutler Lab

Gene Symbol

Dot1l

Ensembl Gene

ENSMUSG00000061589

Gene Name

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

Synonyms

mDot1, KMT4

MMRRC Submission

042895-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R5312 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

80755206-80795461 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 80784637 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Glutamine to Arginine at position 511 (Q511R)

Ref Sequence

ENSEMBL: ENSMUSP00000100973 (fasta)

Gene Model

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

AlphaFold

Q6XZL8

Predicted Effect

possibly damaging
Transcript: ENSMUST00000105336
AA Change: Q511R

PolyPhen 2 Score 0.935 (Sensitivity: 0.80; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000100973
Gene: ENSMUSG00000061589
AA Change: Q511R

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: 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: Q294R

PolyPhen 2 Score 0.795 (Sensitivity: 0.85; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000116581
Gene: ENSMUSG00000061589
AA Change: Q294R

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

Meta Mutation Damage Score

0.1795

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 97.0%
20x: 94.2%

Validation Efficiency

100% (60/60)

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: 50 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
9030624J02Rik	T	C	7: 118,813,576	I629T	probably damaging	Het
Abca15	T	C	7: 120,345,369	V409A	probably damaging	Het
Abtb1	A	G	6: 88,838,258	F297L	probably damaging	Het
Adam22	C	A	5: 8,090,182	G202W	probably damaging	Het
Adgrg3	G	A	8: 95,039,864	V388I	probably benign	Het
Adnp	T	C	2: 168,184,188	T396A	probably benign	Het
Ank2	T	C	3: 126,959,768	Q288R	probably damaging	Het
Bdp1	T	C	13: 100,097,601		probably null	Het
Ccdc173	T	C	2: 69,787,258	T60A	possibly damaging	Het
Cdc45	C	T	16: 18,795,897	R205H	probably damaging	Het
Cntnap5c	A	T	17: 58,359,254	E1093V	probably benign	Het
Dmrta1	A	C	4: 89,692,047	N415H	probably damaging	Het
Dnaaf5	T	A	5: 139,152,862	V266E	probably damaging	Het
Ehmt1	A	G	2: 24,884,195	V201A	probably damaging	Het
Fancg	A	G	4: 43,003,019	F613L	probably benign	Het
Fbxo10	A	T	4: 45,042,036	I731N	possibly damaging	Het
Fchsd1	C	T	18: 37,959,873		probably benign	Het
Gm5155	T	G	7: 17,909,142	H492Q	probably damaging	Het
Gm6614	A	T	6: 141,972,332	F606Y	probably benign	Het
Ighv1-74	A	G	12: 115,802,881	S39P	probably damaging	Het
Kbtbd11	A	G	8: 15,028,589	D396G	possibly damaging	Het
Klc1	A	G	12: 111,795,621	K575R	possibly damaging	Het
Lman1l	A	T	9: 57,611,077	L343Q	probably damaging	Het
Mki67	A	T	7: 135,700,830	V825E	probably damaging	Het
Mus81	T	C	19: 5,483,494	K489R	possibly damaging	Het
Myog	A	G	1: 134,290,326	K91E	probably damaging	Het
Nfil3	A	T	13: 52,967,620	V416E	probably damaging	Het
Nup160	G	T	2: 90,732,832	E1314*	probably null	Het
Nwd2	C	T	5: 63,806,072	Q1000*	probably null	Het
Olfr1277	T	G	2: 111,270,310	D19A	probably benign	Het
Olfr1284	T	C	2: 111,379,834	V278A	possibly damaging	Het
Olfr790	T	A	10: 129,501,514	V210E	probably damaging	Het
Olfr792	A	C	10: 129,541,265	M243L	probably benign	Het
Ppp4r4	T	A	12: 103,606,888		probably null	Het
Pramef25	A	T	4: 143,949,095	I387N	possibly damaging	Het
Psg27	C	A	7: 18,557,033	R415L	probably benign	Het
Ptprr	T	A	10: 116,188,419	S212T	probably benign	Het
Ramp3	T	C	11: 6,674,888	F61L	probably damaging	Het
Rap1gds1	A	G	3: 138,958,628	L322P	probably damaging	Het
Rnf5	A	G	17: 34,601,588	F175S	probably benign	Het
Sema4a	G	A	3: 88,437,036	S636F	probably damaging	Het
Sfrp2	A	G	3: 83,769,401	D193G	probably damaging	Het
Slc26a5	T	C	5: 21,847,260	S24G	probably damaging	Het
Spg21	A	G	9: 65,468,802	I31V	probably benign	Het
Tmem45a2	T	C	16: 57,039,007	D287G	possibly damaging	Het
Utrn	A	T	10: 12,727,769	D627E	probably damaging	Het
Vmn2r103	A	T	17: 19,793,034	N139I	probably benign	Het
Washc5	A	T	15: 59,345,528		probably null	Het
Zfp667	T	C	7: 6,305,467	I378T	probably benign	Het
Zfp949	A	C	9: 88,567,183	T14P	possibly 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
R1862:Dot1l	UTSW	10	80783539	missense	probably damaging	1.00
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
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'- ACCTCCCACATTGTGAGAAAAG -3'
(R):5'- AACAGCCTGCGGATTTCTTC -3'

Sequencing Primer
(F):5'- TCCCACATTGTGAGAAAAGCTGAAAG -3'
(R):5'- CCTTTTGGGCCTGGCAATG -3'

Posted On

2016-07-22