Mutagenetix > Incidental Mutation

Incidental Mutation 'R0467:Dnase1'

41713

Institutional Source

Beutler Lab

Gene Symbol

Dnase1

Ensembl Gene

ENSMUSG00000005980

Gene Name

deoxyribonuclease I

Synonyms

Dnl1, DNaseI

MMRRC Submission

038667-MU

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.465) question?

Stock #

R0467 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

3855007-3857888 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 3857013 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glycine at position 7 (D7G)

Ref Sequence

ENSEMBL: ENSMUSP00000135060 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000006136] [ENSMUST00000006137] [ENSMUST00000120009] [ENSMUST00000137748] [ENSMUST00000175755] [ENSMUST00000177337] [ENSMUST00000157044]

AlphaFold

P49183

Predicted Effect

probably damaging
Transcript: ENSMUST00000006136
AA Change: D190G

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

SMART Domains

Protein: ENSMUSP00000006136
Gene: ENSMUSG00000005980
AA Change: D190G

Domain	Start	End	E-Value	Type
DNaseIc	6	282	5.04e-220	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000006137

SMART Domains

Protein: ENSMUSP00000006137
Gene: ENSMUSG00000005981

Domain	Start	End	E-Value	Type
HATPase_c	110	263	3.68e-3	SMART
Pfam:HSP90	290	706	2.6e-98	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000120009
AA Change: D190G

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

SMART Domains

Protein: ENSMUSP00000113119
Gene: ENSMUSG00000005980
AA Change: D190G

Domain	Start	End	E-Value	Type
DNaseIc	6	282	5.04e-220	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000125961

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000132466

Predicted Effect

probably damaging
Transcript: ENSMUST00000137748
AA Change: D190G

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

SMART Domains

Protein: ENSMUSP00000119934
Gene: ENSMUSG00000005980
AA Change: D190G

Domain	Start	End	E-Value	Type
DNaseIc	6	225	7.51e-146	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000137945

Predicted Effect

probably damaging
Transcript: ENSMUST00000175755
AA Change: D7G

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

SMART Domains

Protein: ENSMUSP00000135060
Gene: ENSMUSG00000005980
AA Change: D7G

Domain	Start	End	E-Value	Type
SCOP:d2dnja_	1	52	3e-9	SMART
Blast:DNaseIc	1	61	2e-31	BLAST
PDB:3W3D\|B	1	61	5e-27	PDB

Predicted Effect

silent
Transcript: ENSMUST00000177337

SMART Domains

Protein: ENSMUSP00000135442
Gene: ENSMUSG00000005980

Domain	Start	End	E-Value	Type
DNaseIc	6	200	6.86e-67	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000149670

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000176642

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000139334

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000150906

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000144792

Predicted Effect

probably benign
Transcript: ENSMUST00000157044

SMART Domains

Protein: ENSMUSP00000120642
Gene: ENSMUSG00000005980

Domain	Start	End	E-Value	Type
DNaseIc	6	70	4.5e-5	SMART

Meta Mutation Damage Score

0.9620

Coding Region Coverage

1x: 99.6%
3x: 98.8%
10x: 96.7%
20x: 93.3%

Validation Efficiency

98% (52/53)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the DNase family. This protein is stored in the zymogen granules of the nuclear envelope and functions by cleaving DNA in an endonucleolytic manner. At least six autosomal codominant alleles have been characterized, DNASE1*1 through DNASE1*6, and the sequence of DNASE1*2 represented in this record. Mutations in this gene have been associated with systemic lupus erythematosus (SLE), an autoimmune disease. A recombinant form of this protein is used to treat the one of the symptoms of cystic fibrosis by hydrolyzing the extracellular DNA in sputum and reducing its viscosity. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]
PHENOTYPE: Some heterozygote and homozygote null mice have autoimmune symptoms similar to systemic lupus erythematosus. These include enlarged lymph nodes, circulating auto-antibodies, kidney inflammation and premature death. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 49 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca17	A	G	17: 24,532,151 (GRCm39)		probably benign	Het
Anapc1	A	G	2: 128,510,963 (GRCm39)	I511T	probably damaging	Het
Atf6	A	T	1: 170,621,589 (GRCm39)	H477Q	probably damaging	Het
C4b	A	G	17: 34,955,101 (GRCm39)	V795A	probably benign	Het
Cdh26	C	T	2: 178,123,425 (GRCm39)	R675C	possibly damaging	Het
Cdk12	T	C	11: 98,094,405 (GRCm39)	V71A	probably damaging	Het
Cul3	A	T	1: 80,258,580 (GRCm39)	D419E	probably benign	Het
Ddi2	A	G	4: 141,412,495 (GRCm39)	I139T	probably benign	Het
Dnaaf1	T	A	8: 120,317,471 (GRCm39)	D333E	probably benign	Het
G3bp1	T	C	11: 55,389,452 (GRCm39)	F383L	probably damaging	Het
Galc	A	C	12: 98,208,904 (GRCm39)	I250R	probably damaging	Het
Garin1b	G	A	6: 29,326,606 (GRCm39)	S241N	probably damaging	Het
Gcfc2	T	C	6: 81,900,863 (GRCm39)	V59A	possibly damaging	Het
Gm6133	A	C	18: 78,393,305 (GRCm39)	S100R	probably benign	Het
Iba57	T	C	11: 59,054,265 (GRCm39)	T85A	probably benign	Het
Ipo4	A	T	14: 55,872,983 (GRCm39)	M1K	probably null	Het
Ippk	A	G	13: 49,584,341 (GRCm39)		probably null	Het
Kcnk10	A	T	12: 98,456,204 (GRCm39)	I209N	probably benign	Het
Klk14	T	C	7: 43,343,534 (GRCm39)	L122P	probably benign	Het
Ltbp1	T	A	17: 75,589,424 (GRCm39)		probably null	Het
Mab21l4	A	T	1: 93,080,766 (GRCm39)	I380N	probably damaging	Het
Mcm3	T	C	1: 20,875,071 (GRCm39)	D737G	probably benign	Het
Naip2	A	C	13: 100,298,290 (GRCm39)	I582S	probably benign	Het
Nalcn	T	A	14: 123,528,459 (GRCm39)	T1456S	probably benign	Het
Nckap1l	C	T	15: 103,405,854 (GRCm39)	P1097S	probably benign	Het
Ncoa1	A	G	12: 4,317,687 (GRCm39)	M1215T	possibly damaging	Het
Nomo1	T	A	7: 45,721,911 (GRCm39)		probably null	Het
Obox5	T	A	7: 15,491,932 (GRCm39)	C116S	possibly damaging	Het
Or2ag2b	T	A	7: 106,417,568 (GRCm39)	S93T	possibly damaging	Het
Or51a43	C	T	7: 103,717,332 (GRCm39)	R302H	probably benign	Het
Or5a1	C	A	19: 12,097,900 (GRCm39)	A59S	probably benign	Het
Pcdhb14	G	T	18: 37,582,277 (GRCm39)	R461L	probably damaging	Het
Pdgfra	A	G	5: 75,355,697 (GRCm39)	D1069G	probably damaging	Het
Pgr	C	T	9: 8,900,779 (GRCm39)	A104V	possibly damaging	Het
Pkd1l3	C	G	8: 110,350,281 (GRCm39)	D375E	possibly damaging	Het
Potegl	A	G	2: 23,102,832 (GRCm39)	E190G	possibly damaging	Het
Rassf3	A	G	10: 121,253,109 (GRCm39)		probably benign	Het
Rgs22	G	T	15: 36,099,941 (GRCm39)	S258*	probably null	Het
Rsph6a	C	A	7: 18,791,594 (GRCm39)	D254E	possibly damaging	Het
Sgk1	A	G	10: 21,872,257 (GRCm39)		probably benign	Het
Shcbp1l	G	A	1: 153,308,928 (GRCm39)	C174Y	probably damaging	Het
Spata31g1	T	C	4: 42,972,715 (GRCm39)	S683P	probably benign	Het
Sulf1	T	A	1: 12,867,144 (GRCm39)	N109K	probably damaging	Het
Taf7l2	G	A	10: 115,949,058 (GRCm39)	A156V	probably benign	Het
Tas2r115	T	A	6: 132,714,682 (GRCm39)	I90L	probably benign	Het
Tmem200a	T	C	10: 25,870,002 (GRCm39)	H89R	probably benign	Het
Ubxn4	G	A	1: 128,190,641 (GRCm39)	E256K	probably benign	Het
Xrn1	T	C	9: 95,906,244 (GRCm39)	S1212P	probably damaging	Het
Zfp408	T	C	2: 91,475,882 (GRCm39)	Y424C	possibly damaging	Het

Other mutations in Dnase1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00649:Dnase1	APN	16	3,856,888 (GRCm39)	missense	probably damaging	1.00
IGL00896:Dnase1	APN	16	3,857,076 (GRCm39)	missense	probably benign	0.00
IGL00983:Dnase1	APN	16	3,857,417 (GRCm39)	missense	possibly damaging	0.70
IGL02186:Dnase1	APN	16	3,856,896 (GRCm39)	missense	probably benign	0.18
IGL03373:Dnase1	APN	16	3,857,707 (GRCm39)	missense	probably damaging	1.00
R0009:Dnase1	UTSW	16	3,856,810 (GRCm39)	missense	probably damaging	1.00
R0009:Dnase1	UTSW	16	3,856,810 (GRCm39)	missense	probably damaging	1.00
R0355:Dnase1	UTSW	16	3,857,413 (GRCm39)	missense	probably damaging	1.00
R4964:Dnase1	UTSW	16	3,855,771 (GRCm39)	intron	probably benign
R4966:Dnase1	UTSW	16	3,855,771 (GRCm39)	intron	probably benign
R5014:Dnase1	UTSW	16	3,856,880 (GRCm39)	nonsense	probably null
R5621:Dnase1	UTSW	16	3,856,982 (GRCm39)	missense	probably benign	0.01
R5858:Dnase1	UTSW	16	3,857,513 (GRCm39)	splice site	probably benign
R6256:Dnase1	UTSW	16	3,855,485 (GRCm39)	missense	probably benign	0.06
R6519:Dnase1	UTSW	16	3,856,453 (GRCm39)	missense	probably damaging	1.00
R7002:Dnase1	UTSW	16	3,857,410 (GRCm39)	missense	possibly damaging	0.76
R7977:Dnase1	UTSW	16	3,855,834 (GRCm39)	missense	probably damaging	1.00
R7987:Dnase1	UTSW	16	3,855,834 (GRCm39)	missense	probably damaging	1.00
R8050:Dnase1	UTSW	16	3,855,861 (GRCm39)	missense	probably damaging	1.00
R9781:Dnase1	UTSW	16	3,857,054 (GRCm39)	missense	probably benign	0.01

Predicted Primers

PCR Primer
(F):5'- TTCACCTCTGCTCGAAGCTAAAACC -3'
(R):5'- TTGGGGCTGCTCACCTGTCATAAG -3'

Sequencing Primer
(F):5'- TCCTCAGAGGTCCAAGAATTTGC -3'
(R):5'- TCACCTGTCATAAGCACAGTG -3'

Posted On

2013-05-23