Mutagenetix > Incidental Mutation

Incidental Mutation 'R7687:Dot1l'

593158

Institutional Source

Beutler Lab

Gene Symbol

Dot1l

Ensembl Gene

ENSMUSG00000061589

Gene Name

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

Synonyms

mDot1, KMT4

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7687 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

80755206-80795461 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to G at 80789368 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Serine to Alanine at position 1150 (S1150A)

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: S1150A

PolyPhen 2 Score 0.705 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000100973
Gene: ENSMUSG00000061589
AA Change: S1150A

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: S29A

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000127762
Gene: ENSMUSG00000061589
AA Change: S29A

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 damaging
Transcript: ENSMUST00000150338
AA Change: S933A

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000116581
Gene: ENSMUSG00000061589
AA Change: S933A

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

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: 51 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca12	T	C	1: 71,258,182	K2383R	probably benign	Het
Acly	C	T	11: 100,504,854		probably null	Het
Baiap3	T	A	17: 25,249,337	I276F	possibly damaging	Het
Cdc14b	A	T	13: 64,209,193	D419E	probably benign	Het
Celsr2	G	T	3: 108,397,769	P2165T	probably benign	Het
Clk4	A	G	11: 51,281,398	D476G	probably benign	Het
Dera	A	G	6: 137,836,880	T10A		Het
Dip2c	A	T	13: 9,604,581	T742S	probably benign	Het
Dohh	C	A	10: 81,387,806	A231E	probably benign	Het
Eea1	T	A	10: 96,026,598	I794N	probably benign	Het
En2	T	C	5: 28,170,289	S277P	probably damaging	Het
Erich1	A	G	8: 14,030,691	L276P	probably damaging	Het
Flnb	A	G	14: 7,924,224	N1779S	probably damaging	Het
Frzb	T	A	2: 80,424,635	T186S	probably benign	Het
Gdf7	T	A	12: 8,298,257	R347*	probably null	Het
Ighv9-4	T	C	12: 114,300,263	I17V	not run	Het
Ipo13	G	A	4: 117,911,891	P235S	probably benign	Het
Itga2	C	A	13: 114,866,260	G565C	probably damaging	Het
Kcnc4	CCCGCCGCCGCCGCCGCCGCCGC	CCCGCCGCCGCCGCCGCCGCCGCCGC	3: 107,458,609		probably benign	Het
Kcnk10	A	G	12: 98,435,096	I440T	probably damaging	Het
Kdm3a	T	A	6: 71,599,492	K779N	possibly damaging	Het
Kmt2d	C	T	15: 98,862,120	D1086N	unknown	Het
Kntc1	A	G	5: 123,759,089	I172V	probably benign	Het
Maip1	A	G	1: 57,411,844	E215G	probably damaging	Het
Mms19	A	T	19: 41,955,168	M417K	possibly damaging	Het
Mslnl	T	C	17: 25,743,183	V185A	probably damaging	Het
Naa11	A	T	5: 97,391,789	V170E	probably benign	Het
Ncapg	C	T	5: 45,699,885	P980S	probably benign	Het
Olfr170	T	C	16: 19,605,735	N310S	probably benign	Het
Pbxip1	A	G	3: 89,448,199	D675G	probably damaging	Het
Pdlim5	A	G	3: 142,277,847	S382P	probably benign	Het
Pkd1l1	T	A	11: 8,854,390	I2184F		Het
Plau	A	G	14: 20,839,798	Y237C	probably damaging	Het
Ppl	T	C	16: 5,097,942	T586A	probably benign	Het
Rapgef6	T	G	11: 54,661,075	I923S	possibly damaging	Het
Rbfox2	C	T	15: 77,306,494	G17D	unknown	Het
Sema3b	T	C	9: 107,603,814	D108G	probably damaging	Het
Slc6a20a	A	G	9: 123,656,266	I297T	probably damaging	Het
Slit1	A	G	19: 41,650,689	F261L	probably benign	Het
Tcp10a	T	A	17: 7,345,108	V433D	probably damaging	Het
Tktl2	A	G	8: 66,513,101	E437G	probably damaging	Het
Tll1	G	T	8: 64,121,492	Y109*	probably null	Het
Tmem79	A	G	3: 88,332,581	V274A	probably damaging	Het
Tnfrsf23	G	A	7: 143,681,462	S55L	probably benign	Het
Ubd	T	C	17: 37,193,974		probably null	Het
Ubl3	C	A	5: 148,506,175	R105L	possibly damaging	Het
Ubl7	A	T	9: 57,914,584	D72V	probably damaging	Het
Wdr55	T	C	18: 36,762,023	S81P	probably damaging	Het
Wtip	T	C	7: 34,116,619	Y344C	probably damaging	Het
Zfp488	A	G	14: 33,970,400	S269P	possibly damaging	Het
Zkscan2	A	C	7: 123,499,862	S36A	probably benign	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
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
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'- ATCCAGAGACATAGCAGCTAGG -3'
(R):5'- CACCTGGTCCAAGACTTTCAC -3'

Sequencing Primer
(F):5'- CATAGCAGCTAGGCGTGG -3'
(R):5'- TTTCACCCCACAGAGCAGTTC -3'

Posted On

2019-11-12