Mutagenetix > Incidental Mutation

Incidental Mutation 'R5579:Dnmt1'

501173

Institutional Source

Beutler Lab

Gene Symbol

Dnmt1

Ensembl Gene

ENSMUSG00000004099

Gene Name

DNA methyltransferase (cytosine-5) 1

Synonyms

MTase, Dnmt1o, Cxxc9, MommeD2

MMRRC Submission

043267-MU

Accession Numbers

Genbank: NM_010066

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R5579 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

20907209-20959888 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 20920205 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Valine to Aspartic acid at position 543 (V543D)

Ref Sequence

ENSEMBL: ENSMUSP00000150433 (fasta)

Gene Model

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

AlphaFold

P13864

Predicted Effect

probably damaging
Transcript: ENSMUST00000004202
AA Change: V661D

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

SMART Domains

Protein: ENSMUSP00000004202
Gene: ENSMUSG00000004099
AA Change: V661D

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: V542D

PolyPhen 2 Score 0.792 (Sensitivity: 0.85; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000136982
Gene: ENSMUSG00000004099
AA Change: V542D

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: V542D

PolyPhen 2 Score 0.792 (Sensitivity: 0.85; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000136669
Gene: ENSMUSG00000004099
AA Change: V542D

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

probably damaging
Transcript: ENSMUST00000216540
AA Change: V543D

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

Coding Region Coverage

1x: 99.9%
3x: 99.8%
10x: 98.9%
20x: 97.0%

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: 114 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2810403A07Rik	T	C	3: 88,700,275	S345P	probably benign	Het
6430573F11Rik	T	C	8: 36,512,041	V266A	probably benign	Het
Abca3	G	T	17: 24,376,729	C352F	probably damaging	Het
Abce1	A	T	8: 79,700,586	I237N	possibly damaging	Het
Acrbp	A	G	6: 125,061,099	D421G	probably benign	Het
Adam8	T	A	7: 139,988,984	Y201F	probably benign	Het
Adgrf1	T	A	17: 43,311,064	C731S	probably damaging	Het
AF067063	T	A	13: 119,828,415	M82L	probably benign	Het
Akap8l	A	T	17: 32,321,942	I529N	probably damaging	Het
Akap9	G	A	5: 4,064,714	G114D	possibly damaging	Het
Alox12b	T	A	11: 69,162,932	D158E	probably benign	Het
Ankrd11	A	G	8: 122,884,231	S2639P	probably damaging	Het
Ankrd42	T	C	7: 92,590,182	Y466C	possibly damaging	Het
Apobr	T	C	7: 126,587,675	I786T	probably benign	Het
Arhgef12	C	T	9: 43,010,193	G329R	probably benign	Het
Btnl1	T	C	17: 34,381,552		probably null	Het
Ccdc174	A	G	6: 91,881,350		probably null	Het
Ccdc183	T	C	2: 25,615,422	D177G	possibly damaging	Het
Cd14	A	G	18: 36,726,235	Y56H	probably benign	Het
Cep162	G	A	9: 87,203,671	A1200V	probably benign	Het
Clic3	T	C	2: 25,458,307	L128P	probably damaging	Het
Cntnap5b	A	T	1: 100,383,395	R538*	probably null	Het
Cntnap5b	A	T	1: 100,383,399	Q539L	probably benign	Het
Coq7	A	T	7: 118,517,335	N214K	unknown	Het
Cramp1l	G	A	17: 24,973,113	H1018Y	possibly damaging	Het
Crtac1	T	A	19: 42,304,806	D288V	probably damaging	Het
Dab2ip	C	T	2: 35,715,327	R132*	probably null	Het
Dis3l	C	A	9: 64,330,835	C125F	probably benign	Het
Dock9	A	T	14: 121,599,695	L67Q	probably damaging	Het
Ehbp1	A	T	11: 22,137,846	S413T	probably damaging	Het
Endov	A	G	11: 119,505,097	I158V	probably benign	Het
Epb41l4b	A	G	4: 57,064,802	V469A	possibly damaging	Het
Etf1	G	A	18: 34,913,601	P119S	probably damaging	Het
Fam135a	A	G	1: 24,029,727	L491P	possibly damaging	Het
Fancd2	A	T	6: 113,560,051		probably null	Het
Fank1	T	A	7: 133,869,329		probably null	Het
Fbxo18	A	G	2: 11,748,993	I846T	probably damaging	Het
Gas2l3	T	C	10: 89,414,066	T397A	probably benign	Het
Gga1	T	C	15: 78,893,188	V513A	probably damaging	Het
Ggt1	T	C	10: 75,585,948	V543A	probably damaging	Het
Gm11596	A	T	11: 99,792,891	C134*	probably null	Het
Gnal	C	T	18: 67,088,771	R82C	unknown	Het
Hat1	T	C	2: 71,410,238	V92A	possibly damaging	Het
Icosl	C	T	10: 78,073,763	R181C	probably damaging	Het
Ift46	A	G	9: 44,786,863	M208V	possibly damaging	Het
Ighv1-26	T	C	12: 114,788,599	K42E	possibly damaging	Het
Ipo5	A	G	14: 120,938,613	K617E	probably benign	Het
Irx5	A	G	8: 92,359,913	D208G	probably benign	Het
Itgal	T	G	7: 127,306,929	V397G	probably benign	Het
Itpr2	G	A	6: 146,173,366	R2297*	probably null	Het
Itpr3	A	G	17: 27,113,519	D1779G	probably damaging	Het
Krt4	T	A	15: 101,921,234	E286D	probably benign	Het
Loxl4	C	T	19: 42,604,290	G317E	probably damaging	Het
Mapk6	T	G	9: 75,388,062	H718P	possibly damaging	Het
Mark2	A	C	19: 7,282,816	V14G	probably damaging	Het
Mbd5	A	G	2: 49,272,814	T1103A	possibly damaging	Het
Mcph1	A	G	8: 18,632,293	E482G	probably benign	Het
Mme	G	A	3: 63,348,645	E509K	probably damaging	Het
Mrgbp	A	G	2: 180,585,483	T204A	probably damaging	Het
Mycbp2	A	T	14: 103,291,333	F430I	probably damaging	Het
Myo6	A	G	9: 80,217,720	D27G	probably damaging	Het
Ncoa6	A	G	2: 155,406,677	L1569S	probably damaging	Het
Ndc1	T	A	4: 107,380,704	F235Y	possibly damaging	Het
Nmur2	A	T	11: 56,033,009	S240T	probably benign	Het
Olfr1176	A	T	2: 88,340,413	I283F	possibly damaging	Het
Olfr301	T	A	7: 86,412,726	Y121*	probably null	Het
Olfr608	G	A	7: 103,470,914	V292M	probably damaging	Het
Osbpl1a	G	T	18: 12,841,192	A62E	probably damaging	Het
Osbpl1a	A	C	18: 12,892,262	S333A	probably benign	Het
Otud4	C	T	8: 79,664,108	T417I	probably benign	Het
Pagr1a	T	C	7: 127,015,442	E197G	probably damaging	Het
Pcdh18	T	C	3: 49,744,977	Q1012R	probably damaging	Het
Pcdhgb5	A	C	18: 37,731,637	I162L	probably benign	Het
Pdpr	T	A	8: 111,123,816	Y462N	probably damaging	Het
Pkhd1	A	T	1: 20,523,142	H1582Q	probably damaging	Het
Polr1b	A	G	2: 129,110,108	K352R	probably damaging	Het
Poteg	G	A	8: 27,448,037	V12M	probably damaging	Het
Pou2f1	A	C	1: 165,915,162	V54G	probably damaging	Het
Ppme1	A	G	7: 100,344,975	L177P	probably damaging	Het
Prkce	A	G	17: 86,619,948	D550G	probably damaging	Het
Prrc2c	A	G	1: 162,680,758		probably null	Het
Ptpn22	A	G	3: 103,882,139		probably null	Het
Rabif	G	A	1: 134,506,205	V86M	probably damaging	Het
Rbm25	T	A	12: 83,668,507	M484K	probably benign	Het
Rcn2	G	A	9: 56,057,429	A224T	probably benign	Het
Rexo5	T	A	7: 119,834,403		probably null	Het
Rnase1	A	T	14: 51,145,762	I45N	probably benign	Het
Rnmt	T	A	18: 68,306,115	D98E	possibly damaging	Het
Rprd2	A	G	3: 95,785,059	F188L	probably damaging	Het
Scube2	G	A	7: 109,810,737	T643M	probably damaging	Het
Slc7a15	T	C	12: 8,539,344	I68V	probably benign	Het
Slco1a5	A	T	6: 142,242,125	V496D	possibly damaging	Het
Slitrk6	T	G	14: 110,751,217	S353R	possibly damaging	Het
Smpd5	T	A	15: 76,295,125	I53K	possibly damaging	Het
Tas2r108	T	C	6: 40,494,087	S166P	probably benign	Het
Tecpr1	C	A	5: 144,214,344	V245L	possibly damaging	Het
Tenm3	G	T	8: 48,236,764	N1929K	probably damaging	Het
Tigd5	T	G	15: 75,911,025	F412C	probably damaging	Het
Timm17a	A	T	1: 135,306,188	S74T	possibly damaging	Het
Tle1	A	T	4: 72,139,808	L60Q	probably damaging	Het
Tmem132d	T	C	5: 127,796,000	E515G	possibly damaging	Het
Tmem65	T	C	15: 58,794,397	N115S	probably benign	Het
Trmt5	C	A	12: 73,281,652	R259L	possibly damaging	Het
Ttc37	T	C	13: 76,185,200	W25R	probably damaging	Het
Vmn2r50	A	T	7: 10,050,089	W153R	probably benign	Het
Vwa3a	T	G	7: 120,768,173	S184A	probably benign	Het
Zbtb25	A	G	12: 76,349,164	L428P	possibly damaging	Het
Zbtb49	C	T	5: 38,200,816	D698N	probably damaging	Het
Zbtb8os	T	G	4: 129,340,735	D35E	probably damaging	Het
Zfp316	T	C	5: 143,264,491	T56A	unknown	Het
Zfp334	A	T	2: 165,380,487	C545*	probably null	Het
Zmiz1	C	A	14: 25,644,856	S247R	probably damaging	Het
Zscan18	A	G	7: 12,775,381		probably benign	Het
Zzef1	T	C	11: 72,900,637	V2189A	probably damaging	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
Midrash	UTSW	9	20909793	nonsense	probably null
Rashi	UTSW	9	20922112	missense	possibly damaging	0.94
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
R1654:Dnmt1	UTSW	9	20936574	missense	possibly damaging	0.75
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
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
R8692:Dnmt1	UTSW	9	20941781	missense	probably damaging	1.00
R9016:Dnmt1	UTSW	9	20936559	missense	possibly damaging	0.67
R9101:Dnmt1	UTSW	9	20941543	missense	probably damaging	1.00
R9200:Dnmt1	UTSW	9	20908600	missense	probably benign	0.00
R9248:Dnmt1	UTSW	9	20922112	missense	possibly damaging	0.94
R9317:Dnmt1	UTSW	9	20918279	missense	probably damaging	0.99
R9352:Dnmt1	UTSW	9	20929088	missense	probably benign	0.00
R9438:Dnmt1	UTSW	9	20915894	missense	probably benign
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'- AGCAAAGCGCATGTCAGCTC -3'
(R):5'- CACAAGGCCAGTATGTTTTCAGAG -3'

Sequencing Primer
(F):5'- GCGCATGTCAGCTCCACAC -3'
(R):5'- GGCCCAACATGCAGATTTTTG -3'

Posted On

2017-12-01