Mutagenetix > Incidental Mutation

Incidental Mutation 'R7695:Dnmt1'

593612

Institutional Source

Beutler Lab

Gene Symbol

Dnmt1

Ensembl Gene

ENSMUSG00000004099

Gene Name

DNA methyltransferase 1

Synonyms

MTase, Dnmt1o, Cxxc9, MommeD2

MMRRC Submission

045758-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7695 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

20818501-20871084 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to A at 20825281 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glycine to Valine at position 1061 (G1061V)

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 null
Transcript: ENSMUST00000004202
AA Change: G1061V

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000004202
Gene: ENSMUSG00000004099
AA Change: G1061V

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 null
Transcript: ENSMUST00000177754
AA Change: G942V

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000136982
Gene: ENSMUSG00000004099
AA Change: G942V

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 null
Transcript: ENSMUST00000178110
AA Change: G942V

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000136669
Gene: ENSMUSG00000004099
AA Change: G942V

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 null
Transcript: ENSMUST00000216540
AA Change: G943V

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 99.2%

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: 55 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adgrb1	T	C	15: 74,415,487 (GRCm39)	V689A	possibly damaging	Het
Casp12	A	G	9: 5,353,641 (GRCm39)	E225G	probably damaging	Het
Ccdc39	A	G	3: 33,868,668 (GRCm39)	L806P	probably damaging	Het
Ccnd3	T	A	17: 47,908,421 (GRCm39)	I164N	probably damaging	Het
Cd209b	A	G	8: 3,976,005 (GRCm39)	V52A	probably benign	Het
Celsr2	G	A	3: 108,310,069 (GRCm39)	R1554W	probably damaging	Het
Cnot1	A	T	8: 96,497,260 (GRCm39)	I239N	probably benign	Het
Csmd3	A	T	15: 47,683,777 (GRCm39)	V948D		Het
Dpysl4	A	G	7: 138,666,039 (GRCm39)	M1V	probably null	Het
Elp5	T	C	11: 69,860,327 (GRCm39)	T227A	probably benign	Het
Exosc1	G	A	19: 41,916,519 (GRCm39)	H86Y	possibly damaging	Het
Foxn4	G	T	5: 114,394,648 (GRCm39)	D426E	probably damaging	Het
Gabbr2	A	G	4: 46,875,687 (GRCm39)	L145P	probably damaging	Het
Gkn3	A	G	6: 87,361,422 (GRCm39)	Y126H	probably damaging	Het
Gm16506	A	G	14: 43,962,463 (GRCm39)	F148S		Het
Gm3558	A	G	14: 19,121,623 (GRCm39)	I76T	probably benign	Het
Gm49359	A	G	13: 62,604,558 (GRCm39)	F45S	possibly damaging	Het
Gpc5	A	T	14: 115,330,026 (GRCm39)	H63L	unknown	Het
H2bl1	T	C	13: 99,120,766 (GRCm39)	T87A	probably damaging	Het
Hbs1l	A	T	10: 21,175,116 (GRCm39)	D28V	possibly damaging	Het
Ide	G	A	19: 37,306,435 (GRCm39)	H113Y		Het
Igkv3-3	A	T	6: 70,664,295 (GRCm39)	S46C	probably damaging	Het
Igsf10	A	T	3: 59,233,612 (GRCm39)	V1707D	probably damaging	Het
Kcna5	A	T	6: 126,511,174 (GRCm39)	V318E	probably damaging	Het
Kdm3b	T	C	18: 34,927,612 (GRCm39)	F158S	possibly damaging	Het
Lrrc14b	T	A	13: 74,511,297 (GRCm39)	D261V	possibly damaging	Het
Lrrc71	T	A	3: 87,646,769 (GRCm39)	I485F	probably damaging	Het
Map6	C	T	7: 98,985,499 (GRCm39)	L671F	possibly damaging	Het
Mast1	A	G	8: 85,647,557 (GRCm39)	V560A	probably damaging	Het
Mfap4	A	T	11: 61,376,545 (GRCm39)		probably null	Het
Myh9	A	G	15: 77,650,936 (GRCm39)	I1637T	probably benign	Het
Neo1	A	T	9: 58,810,212 (GRCm39)	F1080I	possibly damaging	Het
Or1e17	T	A	11: 73,831,720 (GRCm39)	V216E	possibly damaging	Het
Or4k48	A	G	2: 111,475,970 (GRCm39)	V124A	probably damaging	Het
Or4x6	A	G	2: 89,949,207 (GRCm39)	V245A	probably benign	Het
Or51a25	T	C	7: 102,372,866 (GRCm39)	H277R	probably benign	Het
Pax2	A	G	19: 44,821,638 (GRCm39)	Y318C	probably damaging	Het
Pcnx4	A	T	12: 72,588,350 (GRCm39)	M53L	probably benign	Het
Pkd2l2	T	A	18: 34,561,298 (GRCm39)	D435E	possibly damaging	Het
Plec	G	A	15: 76,068,055 (GRCm39)	Q1117*	probably null	Het
Ppp2r2c	T	C	5: 37,104,526 (GRCm39)	L302P	probably damaging	Het
Prex2	T	C	1: 11,232,497 (GRCm39)	F855L	probably benign	Het
Reg3d	A	T	6: 78,354,119 (GRCm39)	W103R	probably benign	Het
Rnf216	A	C	5: 143,071,659 (GRCm39)	H440Q	possibly damaging	Het
Scn2a	A	G	2: 65,542,251 (GRCm39)	T785A	probably damaging	Het
Sh3pxd2a	T	A	19: 47,256,270 (GRCm39)	Y844F	probably damaging	Het
Sp110	G	A	1: 85,506,813 (GRCm39)	R417C	probably benign	Het
Spp1	T	C	5: 104,583,009 (GRCm39)		probably benign	Het
Tacc2	T	A	7: 130,330,633 (GRCm39)	S196T	probably benign	Het
Thrap3	G	A	4: 126,073,891 (GRCm39)	S285L	probably damaging	Het
Ttn	T	A	2: 76,666,305 (GRCm39)	R11584*	probably null	Het
Ubap2	A	G	4: 41,211,740 (GRCm39)	S341P	probably damaging	Het
Upf3a	T	G	8: 13,848,279 (GRCm39)	S358R	probably benign	Het
Zdbf2	T	A	1: 63,346,529 (GRCm39)	I1636N	possibly damaging	Het
Zfp946	C	A	17: 22,674,002 (GRCm39)	T252N	probably benign	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
R5338:Dnmt1	UTSW	9	20,864,015 (GRCm39)	missense	probably benign	0.44
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
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'- TCTGCTGAACAAAGGCCCTG -3'
(R):5'- TCTCAGACTCGGCTCTCAGTTG -3'

Sequencing Primer
(F):5'- AAAGGCCCTGTCTCACTGAG -3'
(R):5'- CTGGTCCAGGCATTTCAGAG -3'

Posted On

2019-11-12