Mutagenetix > Incidental Mutation

Incidental Mutation 'R6256:Dnase1'

506142

Institutional Source

Beutler Lab

Gene Symbol

Dnase1

Ensembl Gene

ENSMUSG00000005980

Gene Name

deoxyribonuclease I

Synonyms

Dnl1, DNaseI

MMRRC Submission

044373-MU

Accession Numbers

Essential gene?

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

Stock #

R6256 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

3855007-3857888 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 3855485 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Lysine at position 24 (R24K)

Ref Sequence

ENSEMBL: ENSMUSP00000135442 (fasta)

Gene Model

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

AlphaFold

P49183

Predicted Effect

probably benign
Transcript: ENSMUST00000006136
AA Change: R24K

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000006136
Gene: ENSMUSG00000005980
AA Change: R24K

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 benign
Transcript: ENSMUST00000120009
AA Change: R24K

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000113119
Gene: ENSMUSG00000005980
AA Change: R24K

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 benign
Transcript: ENSMUST00000137748
AA Change: R24K

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000119934
Gene: ENSMUSG00000005980
AA Change: R24K

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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000137945

Predicted Effect

unknown
Transcript: ENSMUST00000157044
AA Change: R24K

SMART Domains

Protein: ENSMUSP00000120642
Gene: ENSMUSG00000005980
AA Change: R24K

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

Predicted Effect

probably benign
Transcript: ENSMUST00000177337
AA Change: R24K

PolyPhen 2 Score 0.060 (Sensitivity: 0.94; Specificity: 0.84)

SMART Domains

Protein: ENSMUSP00000135442
Gene: ENSMUSG00000005980
AA Change: R24K

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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000150906

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000144792

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000176642

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000139334

Predicted Effect

probably benign
Transcript: ENSMUST00000175755

SMART Domains

Protein: ENSMUSP00000135060
Gene: ENSMUSG00000005980

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

noncoding transcript
Transcript: ENSMUST00000149670

Meta Mutation Damage Score

0.0898

Coding Region Coverage

1x: 99.9%
3x: 99.6%
10x: 97.9%
20x: 93.5%

Validation Efficiency

99% (74/75)

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: 46 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700030K09Rik	A	T	8: 73,205,272 (GRCm39)	Q361L	probably damaging	Het
Abca7	A	G	10: 79,838,456 (GRCm39)	T577A	probably damaging	Het
Acad12	A	T	5: 121,752,149 (GRCm39)	V54E	probably benign	Het
Ago4	A	G	4: 126,414,019 (GRCm39)	Y91H	probably damaging	Het
Akr1b10	T	C	6: 34,364,623 (GRCm39)	V28A	probably damaging	Het
Ccdc33	T	A	9: 58,009,201 (GRCm39)		probably null	Het
Ccdc7a	T	C	8: 129,662,074 (GRCm39)		probably null	Het
Ces1f	A	T	8: 93,992,422 (GRCm39)	V343E	probably damaging	Het
Cftr	T	C	6: 18,274,660 (GRCm39)	L896P	probably damaging	Het
Csmd3	G	A	15: 47,533,125 (GRCm39)	P2375S	probably damaging	Het
Dnajb14	C	T	3: 137,614,124 (GRCm39)	A345V	probably damaging	Het
Dnajb14	G	C	3: 137,614,123 (GRCm39)	A345P	probably damaging	Het
Dnmbp	C	T	19: 43,840,720 (GRCm39)	V560M	probably damaging	Het
Dop1b	T	A	16: 93,604,102 (GRCm39)	I1981N	possibly damaging	Het
Eif3a	A	C	19: 60,759,464 (GRCm39)	S770A	possibly damaging	Het
Fbxl7	A	T	15: 26,553,088 (GRCm39)	C60S	probably benign	Het
Fras1	A	T	5: 96,881,702 (GRCm39)	D2478V	possibly damaging	Het
Hrnr	A	G	3: 93,229,918 (GRCm39)	D52G	probably damaging	Het
Jmjd1c	T	A	10: 67,056,187 (GRCm39)	L823M	probably damaging	Het
Kdm1a	G	T	4: 136,295,911 (GRCm39)	C172*	probably null	Het
Kdm6b	C	T	11: 69,297,555 (GRCm39)	E295K	probably damaging	Het
Mepe	A	T	5: 104,484,940 (GRCm39)	M27L	probably benign	Het
Mogat2	A	T	7: 98,869,102 (GRCm39)	H305Q	probably damaging	Het
Mst1r	T	A	9: 107,794,465 (GRCm39)	Y1215N	probably damaging	Het
Muc5ac	A	T	7: 141,343,532 (GRCm39)	H48L	possibly damaging	Het
Myo7b	T	C	18: 32,116,748 (GRCm39)	D953G	probably damaging	Het
Ocel1	T	C	8: 71,824,472 (GRCm39)		probably benign	Het
Pcdhb6	A	G	18: 37,468,978 (GRCm39)	D633G	probably damaging	Het
Ppm1l	A	G	3: 69,405,230 (GRCm39)	I176V	probably benign	Het
Sall3	C	T	18: 81,013,076 (GRCm39)	R1120H	possibly damaging	Het
Sbf1	G	A	15: 89,185,070 (GRCm39)	P1018S	probably benign	Het
Setbp1	T	C	18: 78,900,472 (GRCm39)	Y1065C	probably damaging	Het
Slc25a2	T	C	18: 37,770,776 (GRCm39)		probably null	Het
Slc4a2	C	A	5: 24,640,888 (GRCm39)	T729K	probably damaging	Het
Sptlc2	T	C	12: 87,402,305 (GRCm39)	E207G	probably damaging	Het
Sult6b1	A	T	17: 79,214,343 (GRCm39)	F27I	probably benign	Het
Syf2	A	T	4: 134,661,889 (GRCm39)	K84N	probably damaging	Het
Tmem209	A	T	6: 30,497,166 (GRCm39)	N183K	probably benign	Het
Tmem232	G	T	17: 65,785,397 (GRCm39)	Q188K	possibly damaging	Het
Tomm70a	A	T	16: 56,973,055 (GRCm39)	T598S	probably benign	Het
Ttll13	A	G	7: 79,908,052 (GRCm39)	T556A	probably benign	Het
Vmn2r120	A	T	17: 57,831,700 (GRCm39)	L363*	probably null	Het
Xpo6	G	T	7: 125,707,791 (GRCm39)	Q872K	probably damaging	Het
Xrra1	A	C	7: 99,563,671 (GRCm39)	S553R	probably damaging	Het
Zfy1	A	T	Y: 738,765 (GRCm39)	V147E	unknown	Homo
Zfy2	T	C	Y: 2,116,267 (GRCm39)	I258V	probably benign	Homo

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
R0467:Dnase1	UTSW	16	3,857,013 (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
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'- AGCAGGTCTGTTCTGACTGC -3'
(R):5'- ATCCACCCAGCTATGGTAAGG -3'

Sequencing Primer
(F):5'- TGCAGCCGTCTCAGATTG -3'
(R):5'- CTATGGTAAGGCCTCAGGTTCAC -3'

Posted On

2018-02-28