Mutagenetix > Incidental Mutation

Incidental Mutation 'R5338:Dnmt1'

423633

Institutional Source

Beutler Lab

Gene Symbol

Dnmt1

Ensembl Gene

ENSMUSG00000004099

Gene Name

DNA methyltransferase 1

Synonyms

MTase, Dnmt1o, Cxxc9, MommeD2

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R5338 (G1)

Quality Score

209

Status

Not validated

Chromosome

Chromosomal Location

20818501-20871084 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 20864015 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Glutamine at position 23 (H23Q)

Ref Sequence

ENSEMBL: ENSMUSP00000004202 (fasta)

Gene Model

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

AlphaFold

P13864

PDB Structure

Crystal structure of mouse DNA methyltransferase 1 [X-RAY DIFFRACTION]
Crystal structure of mouse DNA methyltransferase 1 with AdoHcy [X-RAY DIFFRACTION]
Crystal structure of mouse DNA methyltransferase 1 with AdoMet [X-RAY DIFFRACTION]
Crystal structure of mouse DNMT1(650-1602) in complex with DNA [X-RAY DIFFRACTION]
Crystal structure of mouse DNMT1(731-1602) in the free state [X-RAY DIFFRACTION]
Structure of mouse DNMT1 (731-1602) bound to hemimethylated CpG DNA [X-RAY DIFFRACTION]

Predicted Effect

probably benign
Transcript: ENSMUST00000004202
AA Change: H23Q

PolyPhen 2 Score 0.436 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000004202
Gene: ENSMUSG00000004099
AA Change: H23Q

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

probably benign
Transcript: ENSMUST00000177754

SMART Domains

Protein: ENSMUSP00000136982
Gene: ENSMUSG00000004099

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

probably benign
Transcript: ENSMUST00000178110

SMART Domains

Protein: ENSMUSP00000136669
Gene: ENSMUSG00000004099

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

probably benign
Transcript: ENSMUST00000216540

Coding Region Coverage

1x: 99.3%
3x: 98.7%
10x: 97.5%
20x: 95.8%

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: 67 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A4gnt	T	A	9: 99,502,597 (GRCm39)	N252K	probably damaging	Het
Abhd16a	A	G	17: 35,313,278 (GRCm39)	E132G	probably damaging	Het
Adgrv1	G	A	13: 81,677,165 (GRCm39)	R1889W	possibly damaging	Het
Aftph	A	T	11: 20,677,203 (GRCm39)	D135E	probably benign	Het
Arf1	A	C	11: 59,104,041 (GRCm39)	F63V	probably damaging	Het
Atg14	G	A	14: 47,805,656 (GRCm39)	R70C	probably damaging	Het
B3gnt7	T	A	1: 86,233,366 (GRCm39)	F87Y	probably damaging	Het
Bcat1	A	G	6: 144,953,353 (GRCm39)	Y345H	possibly damaging	Het
Birc2	G	T	9: 7,857,360 (GRCm39)	T371K	probably benign	Het
Ccdc175	A	T	12: 72,231,745 (GRCm39)	S5T	probably damaging	Het
Ccdc186	A	T	19: 56,801,689 (GRCm39)	S143T	possibly damaging	Het
Cct6b	A	T	11: 82,653,015 (GRCm39)	M28K	possibly damaging	Het
Cers4	C	A	8: 4,565,680 (GRCm39)	A42D	probably damaging	Het
Crmp1	G	T	5: 37,437,018 (GRCm39)	V236L	probably benign	Het
Ctdspl2	T	A	2: 121,811,793 (GRCm39)	N212K	probably benign	Het
Dclk3	T	C	9: 111,298,127 (GRCm39)	V557A	possibly damaging	Het
Dpp8	G	T	9: 64,971,206 (GRCm39)	E609*	probably null	Het
Dtx3	C	A	10: 127,028,919 (GRCm39)	M106I	probably benign	Het
Ero1b	A	C	13: 12,589,732 (GRCm39)	D45A	probably damaging	Het
Fcho2	T	A	13: 98,867,399 (GRCm39)	D688V	probably damaging	Het
Fhod3	A	T	18: 25,161,138 (GRCm39)	S557C	probably damaging	Het
Flnc	T	C	6: 29,444,063 (GRCm39)	S626P	possibly damaging	Het
Foxi3	G	T	6: 70,937,602 (GRCm39)	G278V	probably damaging	Het
Gbp10	A	G	5: 105,372,166 (GRCm39)	L198P	probably damaging	Het
Gcn1	A	G	5: 115,721,462 (GRCm39)	T458A	probably benign	Het
Gigyf1	C	T	5: 137,521,422 (GRCm39)		probably benign	Het
Gtpbp2	A	C	17: 46,478,760 (GRCm39)	T526P	probably damaging	Het
Gys2	A	G	6: 142,400,239 (GRCm39)	L324S	probably damaging	Het
Hpn	C	A	7: 30,802,781 (GRCm39)	V119L	probably benign	Het
Ino80d	C	A	1: 63,098,098 (GRCm39)	V599L	probably benign	Het
Kcnh3	G	T	15: 99,140,275 (GRCm39)	G1054*	probably null	Het
Maml1	A	T	11: 50,157,778 (GRCm39)	D132E	probably benign	Het
Mastl	A	T	2: 23,023,503 (GRCm39)	S407T	probably benign	Het
Mettl1	T	C	10: 126,878,954 (GRCm39)	W3R	probably damaging	Het
Mprip	A	G	11: 59,651,399 (GRCm39)	Y1701C	probably damaging	Het
Mylk3	T	C	8: 86,069,350 (GRCm39)	N484D	probably damaging	Het
Nod2	G	A	8: 89,399,413 (GRCm39)		probably null	Het
Nrde2	A	T	12: 100,097,037 (GRCm39)	F921Y	probably damaging	Het
Nup88	G	T	11: 70,835,734 (GRCm39)	T575N	probably damaging	Het
Nxpe3	T	C	16: 55,686,706 (GRCm39)	T101A	possibly damaging	Het
Or1o3	T	A	17: 37,574,532 (GRCm39)	T8S	probably benign	Het
Or2r11	A	G	6: 42,437,908 (GRCm39)	M15T	probably benign	Het
Or4c109	C	T	2: 88,817,809 (GRCm39)	V246I	possibly damaging	Het
Or52e15	A	G	7: 104,645,514 (GRCm39)	L199S	possibly damaging	Het
Or8g32	A	T	9: 39,305,371 (GRCm39)	I92F	probably damaging	Het
Pcnx3	A	T	19: 5,722,624 (GRCm39)	L1356Q	probably damaging	Het
Pkd1	A	T	17: 24,813,510 (GRCm39)	M4017L	probably benign	Het
Polg2	A	G	11: 106,670,064 (GRCm39)	C69R	possibly damaging	Het
Prr5l	T	G	2: 101,547,452 (GRCm39)	S358R	probably benign	Het
Ptprg	A	G	14: 12,154,111 (GRCm38)	T611A	probably benign	Het
Ryk	G	T	9: 102,774,516 (GRCm39)	E417*	probably null	Het
Sbp	T	C	17: 24,161,396 (GRCm39)		probably benign	Het
Sema4a	T	C	3: 88,358,804 (GRCm39)	T155A	probably benign	Het
Shank3	A	G	15: 89,415,914 (GRCm39)		probably null	Het
Slc35d2	A	T	13: 64,245,496 (GRCm39)	M294K	possibly damaging	Het
Slc41a3	A	T	6: 90,589,153 (GRCm39)	N88I	possibly damaging	Het
Slit3	A	G	11: 35,512,975 (GRCm39)	T534A	probably benign	Het
Ssx2ip	A	G	3: 146,142,296 (GRCm39)		probably null	Het
Stard13	T	C	5: 150,983,063 (GRCm39)	K648R	probably damaging	Het
Tanc1	A	T	2: 59,626,178 (GRCm39)	T512S	probably damaging	Het
Tbcc	T	C	17: 47,202,082 (GRCm39)	V156A	probably benign	Het
Terf1	T	G	1: 15,901,787 (GRCm39)	I273R	possibly damaging	Het
Tesc	A	G	5: 118,197,523 (GRCm39)	Y179C	probably damaging	Het
Ttc3	T	G	16: 94,184,900 (GRCm39)	V40G	probably damaging	Het
Tysnd1	T	A	10: 61,532,028 (GRCm39)	F227I	probably damaging	Het
Vps53	T	C	11: 75,972,034 (GRCm39)	E271G	probably damaging	Het
Wdfy4	C	T	14: 32,812,823 (GRCm39)	R1650H	probably damaging	Het

Other mutations in Dnmt1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00334:Dnmt1	APN	9	20,821,566 (GRCm39)	missense	possibly damaging	0.94
IGL01093:Dnmt1	APN	9	20,821,081 (GRCm39)	missense	possibly damaging	0.88
IGL01160:Dnmt1	APN	9	20,828,615 (GRCm39)	missense	possibly damaging	0.90
IGL01704:Dnmt1	APN	9	20,821,476 (GRCm39)	missense	probably damaging	1.00
IGL02105:Dnmt1	APN	9	20,819,178 (GRCm39)	missense	unknown
IGL02124:Dnmt1	APN	9	20,819,845 (GRCm39)	missense	probably damaging	1.00
IGL02188:Dnmt1	APN	9	20,853,034 (GRCm39)	nonsense	probably null
IGL02409:Dnmt1	APN	9	20,837,793 (GRCm39)	missense	probably benign	0.00
IGL02579:Dnmt1	APN	9	20,829,416 (GRCm39)	missense	possibly damaging	0.79
IGL02625:Dnmt1	APN	9	20,838,442 (GRCm39)	missense	probably benign	0.01
IGL02794:Dnmt1	APN	9	20,847,847 (GRCm39)	missense	probably benign
IGL02795:Dnmt1	APN	9	20,838,407 (GRCm39)	missense	probably benign	0.12
IGL02938:Dnmt1	APN	9	20,852,669 (GRCm39)	missense	probably benign	0.23
IGL03245:Dnmt1	APN	9	20,827,056 (GRCm39)	missense	probably damaging	0.99
IGL03303:Dnmt1	APN	9	20,838,006 (GRCm39)	missense	probably benign
Blankslate	UTSW	9	20,823,521 (GRCm39)	missense	possibly damaging	0.86
Midrash	UTSW	9	20,821,089 (GRCm39)	nonsense	probably null
Rashi	UTSW	9	20,833,408 (GRCm39)	missense	possibly damaging	0.94
B5639:Dnmt1	UTSW	9	20,819,264 (GRCm39)	splice site	probably benign
BB003:Dnmt1	UTSW	9	20,818,855 (GRCm39)	missense	unknown
BB013:Dnmt1	UTSW	9	20,818,855 (GRCm39)	missense	unknown
PIT4576001:Dnmt1	UTSW	9	20,823,071 (GRCm39)	missense	probably benign	0.28
R0071:Dnmt1	UTSW	9	20,819,916 (GRCm39)	missense	probably damaging	0.99
R0180:Dnmt1	UTSW	9	20,819,916 (GRCm39)	missense	probably damaging	0.99
R0368:Dnmt1	UTSW	9	20,853,053 (GRCm39)	missense	probably damaging	0.99
R0387:Dnmt1	UTSW	9	20,829,509 (GRCm39)	missense	probably damaging	1.00
R0529:Dnmt1	UTSW	9	20,822,846 (GRCm39)	missense	probably damaging	1.00
R0532:Dnmt1	UTSW	9	20,829,852 (GRCm39)	splice site	probably benign
R0612:Dnmt1	UTSW	9	20,829,489 (GRCm39)	missense	probably damaging	0.98
R1109:Dnmt1	UTSW	9	20,833,684 (GRCm39)	missense	probably damaging	1.00
R1298:Dnmt1	UTSW	9	20,852,752 (GRCm39)	missense	probably benign
R1345:Dnmt1	UTSW	9	20,819,814 (GRCm39)	missense	probably damaging	1.00
R1472:Dnmt1	UTSW	9	20,843,472 (GRCm39)	missense	probably benign	0.28
R1654:Dnmt1	UTSW	9	20,847,870 (GRCm39)	missense	possibly damaging	0.75
R1817:Dnmt1	UTSW	9	20,838,422 (GRCm39)	missense	probably benign
R1836:Dnmt1	UTSW	9	20,829,542 (GRCm39)	missense	probably damaging	1.00
R1957:Dnmt1	UTSW	9	20,838,442 (GRCm39)	missense	probably benign	0.01
R1958:Dnmt1	UTSW	9	20,838,442 (GRCm39)	missense	probably benign	0.01
R2097:Dnmt1	UTSW	9	20,821,084 (GRCm39)	missense	probably benign	0.00
R2145:Dnmt1	UTSW	9	20,848,451 (GRCm39)	splice site	probably benign
R2326:Dnmt1	UTSW	9	20,835,442 (GRCm39)	splice site	probably benign
R4199:Dnmt1	UTSW	9	20,849,414 (GRCm39)	missense	probably benign	0.00
R4456:Dnmt1	UTSW	9	20,821,138 (GRCm39)	missense	probably damaging	1.00
R4518:Dnmt1	UTSW	9	20,823,274 (GRCm39)	missense	probably benign	0.00
R4586:Dnmt1	UTSW	9	20,837,989 (GRCm39)	missense	probably benign	0.05
R4836:Dnmt1	UTSW	9	20,819,854 (GRCm39)	missense	probably damaging	1.00
R5014:Dnmt1	UTSW	9	20,823,550 (GRCm39)	missense	probably benign	0.07
R5385:Dnmt1	UTSW	9	20,829,776 (GRCm39)	missense	probably damaging	1.00
R5579:Dnmt1	UTSW	9	20,831,501 (GRCm39)	missense	probably damaging	1.00
R5645:Dnmt1	UTSW	9	20,833,443 (GRCm39)	missense	probably damaging	1.00
R5719:Dnmt1	UTSW	9	20,823,891 (GRCm39)	missense	possibly damaging	0.86
R5881:Dnmt1	UTSW	9	20,864,013 (GRCm39)	missense	probably damaging	0.97
R6039:Dnmt1	UTSW	9	20,837,716 (GRCm39)	intron	probably benign
R6039:Dnmt1	UTSW	9	20,837,716 (GRCm39)	intron	probably benign
R6143:Dnmt1	UTSW	9	20,838,430 (GRCm39)	missense	probably benign	0.30
R6342:Dnmt1	UTSW	9	20,821,089 (GRCm39)	nonsense	probably null
R6374:Dnmt1	UTSW	9	20,835,341 (GRCm39)	missense	possibly damaging	0.73
R6953:Dnmt1	UTSW	9	20,829,822 (GRCm39)	missense	probably benign
R6990:Dnmt1	UTSW	9	20,827,110 (GRCm39)	nonsense	probably null
R7089:Dnmt1	UTSW	9	20,819,785 (GRCm39)	missense	probably damaging	0.99
R7463:Dnmt1	UTSW	9	20,823,521 (GRCm39)	missense	possibly damaging	0.86
R7522:Dnmt1	UTSW	9	20,831,498 (GRCm39)	missense	probably damaging	0.99
R7695:Dnmt1	UTSW	9	20,825,281 (GRCm39)	missense	probably null	1.00
R7785:Dnmt1	UTSW	9	20,833,345 (GRCm39)	missense	probably damaging	0.98
R7926:Dnmt1	UTSW	9	20,818,855 (GRCm39)	missense	unknown
R8037:Dnmt1	UTSW	9	20,852,860 (GRCm39)	missense	probably damaging	0.99
R8038:Dnmt1	UTSW	9	20,852,860 (GRCm39)	missense	probably damaging	0.99
R8424:Dnmt1	UTSW	9	20,829,836 (GRCm39)	missense	probably benign	0.07
R8692:Dnmt1	UTSW	9	20,853,077 (GRCm39)	missense	probably damaging	1.00
R9016:Dnmt1	UTSW	9	20,847,855 (GRCm39)	missense	possibly damaging	0.67
R9101:Dnmt1	UTSW	9	20,852,839 (GRCm39)	missense	probably damaging	1.00
R9200:Dnmt1	UTSW	9	20,819,896 (GRCm39)	missense	probably benign	0.00
R9248:Dnmt1	UTSW	9	20,833,408 (GRCm39)	missense	possibly damaging	0.94
R9317:Dnmt1	UTSW	9	20,829,575 (GRCm39)	missense	probably damaging	0.99
R9352:Dnmt1	UTSW	9	20,840,384 (GRCm39)	missense	probably benign	0.00
R9438:Dnmt1	UTSW	9	20,827,190 (GRCm39)	missense	probably benign
RF003:Dnmt1	UTSW	9	20,821,427 (GRCm39)	nonsense	probably null
RF004:Dnmt1	UTSW	9	20,821,423 (GRCm39)	nonsense	probably null
RF011:Dnmt1	UTSW	9	20,821,440 (GRCm39)	nonsense	probably null
RF011:Dnmt1	UTSW	9	20,821,424 (GRCm39)	nonsense	probably null
RF015:Dnmt1	UTSW	9	20,821,425 (GRCm39)	nonsense	probably null
RF015:Dnmt1	UTSW	9	20,821,420 (GRCm39)	nonsense	probably null
RF017:Dnmt1	UTSW	9	20,821,422 (GRCm39)	nonsense	probably null
RF023:Dnmt1	UTSW	9	20,821,427 (GRCm39)	nonsense	probably null
RF024:Dnmt1	UTSW	9	20,821,434 (GRCm39)	small insertion	probably benign
RF024:Dnmt1	UTSW	9	20,821,426 (GRCm39)	nonsense	probably null
RF025:Dnmt1	UTSW	9	20,821,431 (GRCm39)	nonsense	probably null
RF025:Dnmt1	UTSW	9	20,821,416 (GRCm39)	nonsense	probably null
RF029:Dnmt1	UTSW	9	20,821,419 (GRCm39)	nonsense	probably null
RF034:Dnmt1	UTSW	9	20,821,416 (GRCm39)	nonsense	probably null
RF037:Dnmt1	UTSW	9	20,821,437 (GRCm39)	nonsense	probably null
RF037:Dnmt1	UTSW	9	20,821,429 (GRCm39)	nonsense	probably null
RF037:Dnmt1	UTSW	9	20,821,415 (GRCm39)	critical splice donor site	probably benign
RF042:Dnmt1	UTSW	9	20,821,415 (GRCm39)	nonsense	probably null
RF045:Dnmt1	UTSW	9	20,821,433 (GRCm39)	small insertion	probably benign
RF045:Dnmt1	UTSW	9	20,821,425 (GRCm39)	nonsense	probably null
RF047:Dnmt1	UTSW	9	20,821,421 (GRCm39)	nonsense	probably null
RF048:Dnmt1	UTSW	9	20,821,422 (GRCm39)	nonsense	probably null
RF054:Dnmt1	UTSW	9	20,821,435 (GRCm39)	nonsense	probably null
RF055:Dnmt1	UTSW	9	20,821,432 (GRCm39)	small insertion	probably benign
RF055:Dnmt1	UTSW	9	20,821,431 (GRCm39)	nonsense	probably null
RF055:Dnmt1	UTSW	9	20,821,424 (GRCm39)	nonsense	probably null
RF059:Dnmt1	UTSW	9	20,821,434 (GRCm39)	small insertion	probably benign
RF059:Dnmt1	UTSW	9	20,821,435 (GRCm39)	nonsense	probably null
RF060:Dnmt1	UTSW	9	20,821,438 (GRCm39)	nonsense	probably null
RF061:Dnmt1	UTSW	9	20,821,426 (GRCm39)	nonsense	probably null
X0026:Dnmt1	UTSW	9	20,825,210 (GRCm39)	missense	probably damaging	1.00
Z1176:Dnmt1	UTSW	9	20,837,850 (GRCm39)	missense	probably benign	0.00
Z1176:Dnmt1	UTSW	9	20,827,159 (GRCm39)	missense	probably damaging	0.99

Predicted Primers

PCR Primer
(F):5'- AGCTTGTTCTATTTCAGAGGGC -3'
(R):5'- GTACATGCTGCTTCCGCTTG -3'

Sequencing Primer
(F):5'- TTTTGGCGCCAACAGCTAAG -3'
(R):5'- TTCAGAGCTGTTCTGTCG -3'

Posted On

2016-08-04