Mutagenetix > Incidental Mutations

Incidental Mutation 'R1654:Dnmt1'

188941

Institutional Source

Beutler Lab

Gene Symbol

Dnmt1

Ensembl Gene

ENSMUSG00000004099

Gene Name

DNA methyltransferase (cytosine-5) 1

Synonyms

MTase, Dnmt1o, Cxxc9, MommeD2

MMRRC Submission

039690-MU

Accession Numbers

Genbank: NM_010066

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R1654 (G1)

Quality Score

197

Status

Not validated

Chromosome

Chromosomal Location

20907209-20959888 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 20936574 bp

Zygosity

Heterozygous

Amino Acid Change

Threonine to Asparagine at position 105 (T105N)

Ref Sequence

ENSEMBL: ENSMUSP00000136669 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000004202] [ENSMUST00000177754] [ENSMUST00000178110] [ENSMUST00000216540]

Predicted Effect

probably benign
Transcript: ENSMUST00000004202
AA Change: T224N

PolyPhen 2 Score 0.081 (Sensitivity: 0.93; Specificity: 0.85)

SMART Domains

Protein: ENSMUSP00000004202
Gene: ENSMUSG00000004099
AA Change: T224N

Domain	Start	End	E-Value	Type
DMAP_binding	16	106	1.7e-13	SMART
low complexity region	121	143	N/A	INTRINSIC
low complexity region	156	166	N/A	INTRINSIC
low complexity region	180	194	N/A	INTRINSIC
low complexity region	273	290	N/A	INTRINSIC
low complexity region	306	328	N/A	INTRINSIC
Pfam:DNMT1-RFD	405	540	4.8e-46	PFAM
low complexity region	610	625	N/A	INTRINSIC
Pfam:zf-CXXC	648	694	2.7e-17	PFAM
low complexity region	701	711	N/A	INTRINSIC
low complexity region	719	731	N/A	INTRINSIC
BAH	758	884	4.62e-31	SMART
BAH	935	1103	1.79e-37	SMART
low complexity region	1110	1124	N/A	INTRINSIC
Pfam:DNA_methylase	1142	1596	1.3e-49	PFAM
low complexity region	1600	1619	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000177754
AA Change: T105N

PolyPhen 2 Score 0.754 (Sensitivity: 0.85; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000136982
Gene: ENSMUSG00000004099
AA Change: T105N

Domain	Start	End	E-Value	Type
low complexity region	3	25	N/A	INTRINSIC
low complexity region	37	47	N/A	INTRINSIC
low complexity region	61	75	N/A	INTRINSIC
low complexity region	154	171	N/A	INTRINSIC
low complexity region	187	209	N/A	INTRINSIC
Pfam:DNMT1-RFD	286	421	3.4e-40	PFAM
low complexity region	491	506	N/A	INTRINSIC
Pfam:zf-CXXC	529	575	2.3e-17	PFAM
low complexity region	582	592	N/A	INTRINSIC
low complexity region	600	612	N/A	INTRINSIC
BAH	639	765	4.62e-31	SMART
BAH	816	984	1.79e-37	SMART
low complexity region	991	1005	N/A	INTRINSIC
Pfam:DNA_methylase	1023	1477	1.3e-49	PFAM
low complexity region	1481	1500	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000178110
AA Change: T105N

PolyPhen 2 Score 0.754 (Sensitivity: 0.85; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000136669
Gene: ENSMUSG00000004099
AA Change: T105N

Domain	Start	End	E-Value	Type
low complexity region	3	25	N/A	INTRINSIC
low complexity region	38	48	N/A	INTRINSIC
low complexity region	62	76	N/A	INTRINSIC
low complexity region	155	172	N/A	INTRINSIC
low complexity region	188	210	N/A	INTRINSIC
Pfam:DNMT1-RFD	287	422	2.6e-40	PFAM
low complexity region	492	507	N/A	INTRINSIC
Pfam:zf-CXXC	530	576	4.7e-17	PFAM
low complexity region	583	593	N/A	INTRINSIC
low complexity region	601	613	N/A	INTRINSIC
BAH	640	766	4.62e-31	SMART
BAH	817	985	1.79e-37	SMART
low complexity region	992	1006	N/A	INTRINSIC
Pfam:DNA_methylase	1024	1478	8e-50	PFAM
low complexity region	1482	1501	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000215545

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000216135

Predicted Effect

probably benign
Transcript: ENSMUST00000216540
AA Change: T106N

PolyPhen 2 Score 0.081 (Sensitivity: 0.93; Specificity: 0.85)

Coding Region Coverage

1x: 99.1%
3x: 98.4%
10x: 96.5%
20x: 93.0%

Validation Efficiency

MGI Phenotype

FUNCTION: This gene encodes a methyltransferase that preferentially methylates cytosines of CpG residues in hemimethylated DNA to generate fully methylated CpG base pairs during DNA replication. This enzyme plays roles in diverse cellular processes including cell cycle regulation, DNA repair, and telomere maintenance. The encoded protein is composed of an N-terminal domain with a nuclear localization sequence and replication fork-targeting domain, a DNA-binding CXXC domain, two bromo-adjacent homology domains, and a C-terminal catalytic domain. Mouse embryonic stem cells mutant for this gene are viable, but when introduced into the germ line, cause a recessive lethal phenotype with mutant embryos displaying stunted growth and developmental defects. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]
PHENOTYPE: Mutations causing partial or severe loss of function were homozygous lethal by embryonic day 9.5, with lack of appropriate genomic imprinting observed at several loci. [provided by MGI curators]

Allele List at MGI

All alleles(109) : Targeted, knock-out(5) Targeted, other(11) Gene trapped(92) Chemically induced(1)

Other mutations in this stock

Total: 77 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700012B07Rik	C	T	11: 109,797,399	S90N	probably benign	Het
Apc2	C	T	10: 80,301,842	T39I	possibly damaging	Het
Arfgef3	C	T	10: 18,625,148	R1118K	probably null	Het
Arhgef12	T	C	9: 42,997,660	D658G	possibly damaging	Het
Asph	G	T	4: 9,453,315	R736S	probably benign	Het
Bcas1	C	T	2: 170,349,246	G542E	probably damaging	Het
Brd8	A	T	18: 34,611,226	V183E	probably damaging	Het
C1rl	G	A	6: 124,493,910	G59E	probably damaging	Het
Cacna1i	C	A	15: 80,389,210	A1699D	probably damaging	Het
Card6	G	T	15: 5,098,732	Q1061K	probably benign	Het
Cd163	G	T	6: 124,317,581	C566F	probably damaging	Het
Cd84	C	T	1: 171,884,606	T263I	possibly damaging	Het
Cep63	T	C	9: 102,586,913	I740V	possibly damaging	Het
Chaf1b	C	A	16: 93,894,903	A279D	probably damaging	Het
Chsy3	A	T	18: 59,176,416	Y247F	probably damaging	Het
Cpxm1	G	A	2: 130,393,546	L509F	possibly damaging	Het
Disc1	A	T	8: 125,148,465	Q558L	possibly damaging	Het
Dnah3	A	T	7: 119,926,449	L3894Q	probably damaging	Het
Dock6	A	T	9: 21,804,843	L1732Q	probably damaging	Het
Dsc2	T	C	18: 20,046,246	N255S	probably benign	Het
Dsel	A	T	1: 111,862,512	Y98N	probably damaging	Het
Enox1	T	A	14: 77,611,374	I375N	possibly damaging	Het
Epha4	T	A	1: 77,374,768		probably null	Het
Fam71a	T	C	1: 191,163,481	R322G	probably benign	Het
Fktn	A	G	4: 53,761,220	I446V	probably benign	Het
Gm7361	G	T	5: 26,261,099	R153L	probably damaging	Het
Grin2c	C	T	11: 115,260,853	V94I	probably benign	Het
Kalrn	T	G	16: 33,975,738	L1222F	probably damaging	Het
Krt80	T	C	15: 101,351,709	K255E	probably damaging	Het
Lcn6	T	A	2: 25,680,775		probably null	Het
Lonp2	T	G	8: 86,631,450	L100V	probably damaging	Het
Lyn	G	A	4: 3,789,912	A482T	probably damaging	Het
Mapk4	A	G	18: 73,930,939	F404S	probably damaging	Het
Mast2	T	C	4: 116,316,550		probably null	Het
Medag	T	C	5: 149,422,135	Y94H	probably damaging	Het
Megf8	T	C	7: 25,338,486	L809P	possibly damaging	Het
Mgam	T	C	6: 40,757,487	S743P	probably damaging	Het
Mia2	C	A	12: 59,108,833	T445K	possibly damaging	Het
Nars	C	G	18: 64,512,049	A43P	probably damaging	Het
Nav3	T	C	10: 109,853,123	N431S	possibly damaging	Het
Ndufaf5	A	G	2: 140,177,300		probably null	Het
Nlrp1b	T	G	11: 71,181,298	E573A	probably damaging	Het
Nlrp3	T	C	11: 59,543,123	V4A	probably benign	Het
Olfr1389	G	A	11: 49,430,502	G9R	probably benign	Het
Olfr194	T	C	16: 59,119,689	N127S	possibly damaging	Het
Olfr661	A	T	7: 104,688,213	Y66F	probably benign	Het
Pcdhb12	A	T	18: 37,436,701	D300V	probably damaging	Het
Pik3c2a	A	T	7: 116,368,848	C804S	probably benign	Het
Pkp4	A	T	2: 59,337,619	Q725L	probably damaging	Het
Ptpre	T	A	7: 135,653,928	S119T	probably benign	Het
Ptprk	G	A	10: 28,383,647	R361H	probably damaging	Het
Ptprr	T	C	10: 116,188,363	V193A	probably benign	Het
Rfx2	C	T	17: 56,808,263	A19T	probably benign	Het
Rgs4	T	A	1: 169,745,311	M19L	probably benign	Het
Rnf157	T	C	11: 116,358,715	H225R	probably damaging	Het
Rnf44	A	T	13: 54,681,779	D341E	possibly damaging	Het
Sct	T	A	7: 141,278,854	Q55L	probably damaging	Het
Sh3rf1	A	T	8: 61,361,745	H446L	possibly damaging	Het
Shisa3	A	T	5: 67,611,059	I101F	probably damaging	Het
Slc6a13	A	G	6: 121,336,926	I543V	probably benign	Het
Soga3	A	T	10: 29,146,935		probably null	Het
Spef2	G	A	15: 9,634,652	A1024V	probably damaging	Het
St6galnac6	T	C	2: 32,619,509	S330P	probably damaging	Het
Stard9	G	T	2: 120,703,722	A3487S	probably benign	Het
Suclg2	T	C	6: 95,655,551	S46G	probably damaging	Het
Syne2	T	C	12: 76,101,094	V6469A	possibly damaging	Het
Tada2b	C	T	5: 36,483,795	G88D	probably damaging	Het
Tll1	A	T	8: 64,117,903		probably null	Het
Tph2	T	A	10: 115,184,807	H28L	probably benign	Het
Trmt6	C	A	2: 132,815,835	V34L	possibly damaging	Het
Ttc22	A	G	4: 106,634,211	T204A	probably damaging	Het
Umodl1	A	T	17: 30,987,968	M778L	probably benign	Het
Vcan	T	C	13: 89,661,946	H2282R	probably damaging	Het
Vmn2r77	T	A	7: 86,811,915	S816R	probably damaging	Het
Vps13c	T	A	9: 67,951,687	F2806L	probably damaging	Het
Zbtb4	C	A	11: 69,779,169	A906D	probably damaging	Het
Zscan29	A	G	2: 121,164,779	V421A	probably benign	Het

Other mutations in Dnmt1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00334:Dnmt1	APN	9	20910270	missense	possibly damaging	0.94
IGL01093:Dnmt1	APN	9	20909785	missense	possibly damaging	0.88
IGL01160:Dnmt1	APN	9	20917319	missense	possibly damaging	0.90
IGL01704:Dnmt1	APN	9	20910180	missense	probably damaging	1.00
IGL02105:Dnmt1	APN	9	20907882	missense	unknown
IGL02124:Dnmt1	APN	9	20908549	missense	probably damaging	1.00
IGL02188:Dnmt1	APN	9	20941738	nonsense	probably null
IGL02409:Dnmt1	APN	9	20926497	missense	probably benign	0.00
IGL02579:Dnmt1	APN	9	20918120	missense	possibly damaging	0.79
IGL02625:Dnmt1	APN	9	20927146	missense	probably benign	0.01
IGL02794:Dnmt1	APN	9	20936551	missense	probably benign
IGL02795:Dnmt1	APN	9	20927111	missense	probably benign	0.12
IGL02938:Dnmt1	APN	9	20941373	missense	probably benign	0.23
IGL03245:Dnmt1	APN	9	20915760	missense	probably damaging	0.99
IGL03303:Dnmt1	APN	9	20926710	missense	probably benign
Blankslate	UTSW	9	20912225	missense	possibly damaging	0.86
B5639:Dnmt1	UTSW	9	20907968	splice site	probably benign
BB003:Dnmt1	UTSW	9	20907559	missense	unknown
BB013:Dnmt1	UTSW	9	20907559	missense	unknown
PIT4576001:Dnmt1	UTSW	9	20911775	missense	probably benign	0.28
R0071:Dnmt1	UTSW	9	20908620	missense	probably damaging	0.99
R0180:Dnmt1	UTSW	9	20908620	missense	probably damaging	0.99
R0368:Dnmt1	UTSW	9	20941757	missense	probably damaging	0.99
R0387:Dnmt1	UTSW	9	20918213	missense	probably damaging	1.00
R0529:Dnmt1	UTSW	9	20911550	missense	probably damaging	1.00
R0532:Dnmt1	UTSW	9	20918556	splice site	probably benign
R0612:Dnmt1	UTSW	9	20918193	missense	probably damaging	0.98
R1109:Dnmt1	UTSW	9	20922388	missense	probably damaging	1.00
R1298:Dnmt1	UTSW	9	20941456	missense	probably benign
R1345:Dnmt1	UTSW	9	20908518	missense	probably damaging	1.00
R1472:Dnmt1	UTSW	9	20932176	missense	probably benign	0.28
R1817:Dnmt1	UTSW	9	20927126	missense	probably benign
R1836:Dnmt1	UTSW	9	20918246	missense	probably damaging	1.00
R1957:Dnmt1	UTSW	9	20927146	missense	probably benign	0.01
R1958:Dnmt1	UTSW	9	20927146	missense	probably benign	0.01
R2097:Dnmt1	UTSW	9	20909788	missense	probably benign	0.00
R2145:Dnmt1	UTSW	9	20937155	splice site	probably benign
R2326:Dnmt1	UTSW	9	20924146	splice site	probably benign
R4199:Dnmt1	UTSW	9	20938118	missense	probably benign	0.00
R4456:Dnmt1	UTSW	9	20909842	missense	probably damaging	1.00
R4518:Dnmt1	UTSW	9	20911978	missense	probably benign	0.00
R4586:Dnmt1	UTSW	9	20926693	missense	probably benign	0.05
R4836:Dnmt1	UTSW	9	20908558	missense	probably damaging	1.00
R5014:Dnmt1	UTSW	9	20912254	missense	probably benign	0.07
R5338:Dnmt1	UTSW	9	20952719	missense	probably benign	0.44
R5385:Dnmt1	UTSW	9	20918480	missense	probably damaging	1.00
R5579:Dnmt1	UTSW	9	20920205	missense	probably damaging	1.00
R5645:Dnmt1	UTSW	9	20922147	missense	probably damaging	1.00
R5719:Dnmt1	UTSW	9	20912595	missense	possibly damaging	0.86
R5881:Dnmt1	UTSW	9	20952717	missense	probably damaging	0.97
R6039:Dnmt1	UTSW	9	20926420	intron	probably benign
R6039:Dnmt1	UTSW	9	20926420	intron	probably benign
R6143:Dnmt1	UTSW	9	20927134	missense	probably benign	0.30
R6342:Dnmt1	UTSW	9	20909793	nonsense	probably null
R6374:Dnmt1	UTSW	9	20924045	missense	possibly damaging	0.73
R6953:Dnmt1	UTSW	9	20918526	missense	probably benign
R6990:Dnmt1	UTSW	9	20915814	nonsense	probably null
R7089:Dnmt1	UTSW	9	20908489	missense	probably damaging	0.99
R7463:Dnmt1	UTSW	9	20912225	missense	possibly damaging	0.86
R7522:Dnmt1	UTSW	9	20920202	missense	probably damaging	0.99
R7695:Dnmt1	UTSW	9	20913985	missense	probably null	1.00
R7785:Dnmt1	UTSW	9	20922049	missense	probably damaging	0.98
R7926:Dnmt1	UTSW	9	20907559	missense	unknown
R8037:Dnmt1	UTSW	9	20941564	missense	probably damaging	0.99
R8038:Dnmt1	UTSW	9	20941564	missense	probably damaging	0.99
R8424:Dnmt1	UTSW	9	20918540	missense	probably benign	0.07
RF003:Dnmt1	UTSW	9	20910131	nonsense	probably null
RF004:Dnmt1	UTSW	9	20910127	nonsense	probably null
RF011:Dnmt1	UTSW	9	20910128	nonsense	probably null
RF011:Dnmt1	UTSW	9	20910144	nonsense	probably null
RF015:Dnmt1	UTSW	9	20910124	nonsense	probably null
RF015:Dnmt1	UTSW	9	20910129	nonsense	probably null
RF017:Dnmt1	UTSW	9	20910126	nonsense	probably null
RF023:Dnmt1	UTSW	9	20910131	nonsense	probably null
RF024:Dnmt1	UTSW	9	20910130	nonsense	probably null
RF024:Dnmt1	UTSW	9	20910138	small insertion	probably benign
RF025:Dnmt1	UTSW	9	20910120	nonsense	probably null
RF025:Dnmt1	UTSW	9	20910135	nonsense	probably null
RF029:Dnmt1	UTSW	9	20910123	nonsense	probably null
RF034:Dnmt1	UTSW	9	20910120	nonsense	probably null
RF037:Dnmt1	UTSW	9	20910119	critical splice donor site	probably benign
RF037:Dnmt1	UTSW	9	20910133	nonsense	probably null
RF037:Dnmt1	UTSW	9	20910141	nonsense	probably null
RF042:Dnmt1	UTSW	9	20910119	nonsense	probably null
RF045:Dnmt1	UTSW	9	20910129	nonsense	probably null
RF045:Dnmt1	UTSW	9	20910137	small insertion	probably benign
RF047:Dnmt1	UTSW	9	20910125	nonsense	probably null
RF048:Dnmt1	UTSW	9	20910126	nonsense	probably null
RF054:Dnmt1	UTSW	9	20910139	nonsense	probably null
RF055:Dnmt1	UTSW	9	20910128	nonsense	probably null
RF055:Dnmt1	UTSW	9	20910135	nonsense	probably null
RF055:Dnmt1	UTSW	9	20910136	small insertion	probably benign
RF059:Dnmt1	UTSW	9	20910138	small insertion	probably benign
RF059:Dnmt1	UTSW	9	20910139	nonsense	probably null
RF060:Dnmt1	UTSW	9	20910142	nonsense	probably null
RF061:Dnmt1	UTSW	9	20910130	nonsense	probably null
X0026:Dnmt1	UTSW	9	20913914	missense	probably damaging	1.00
Z1176:Dnmt1	UTSW	9	20915863	missense	probably damaging	0.99
Z1176:Dnmt1	UTSW	9	20926554	missense	probably benign	0.00

Predicted Primers

PCR Primer
(F):5'- GGATGCTGCTACGGAACCTCTAAC -3'
(R):5'- TCCTCCTCACAGAAGGAGATGAGGTC -3'

Sequencing Primer
(F):5'- GCTACGGAACCTCTAACCTGTAAG -3'
(R):5'- CTCCTGGTGTCATGAGGC -3'

Posted On

2014-05-09