Mutagenetix > Incidental Mutation

Incidental Mutation 'R6256:Dnase1'

506142

Institutional Source

Beutler Lab

Gene Symbol

Dnase1

Ensembl Gene

ENSMUSG00000005980

Gene Name

deoxyribonuclease I

Synonyms

DNaseI, Dnl1

MMRRC Submission

044373-MU

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.329) question?

Stock #

R6256 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

4036942-4040024 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 4037621 bp (GRCm38)

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] [ENSMUST00000175755] [ENSMUST00000177337]

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

noncoding transcript
Transcript: ENSMUST00000139334

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000144792

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000149670

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000150906

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: 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: ENSMUST00000176642

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

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: 72,451,428	Q361L	probably damaging	Het
Abca7	A	G	10: 80,002,622	T577A	probably damaging	Het
Acad12	A	T	5: 121,614,086	V54E	probably benign	Het
Ago4	A	G	4: 126,520,226	Y91H	probably damaging	Het
Akr1b10	T	C	6: 34,387,688	V28A	probably damaging	Het
Ccdc33	T	A	9: 58,101,918		probably null	Het
Ccdc7a	T	C	8: 128,935,593		probably null	Het
Ces1f	A	T	8: 93,265,794	V343E	probably damaging	Het
Cftr	T	C	6: 18,274,661	L896P	probably damaging	Het
Csmd3	G	A	15: 47,669,729	P2375S	probably damaging	Het
Dnajb14	G	C	3: 137,908,362	A345P	probably damaging	Het
Dnajb14	C	T	3: 137,908,363	A345V	probably damaging	Het
Dnmbp	C	T	19: 43,852,281	V560M	probably damaging	Het
Dopey2	T	A	16: 93,807,214	I1981N	possibly damaging	Het
Eif3a	A	C	19: 60,771,026	S770A	possibly damaging	Het
Fbxl7	A	T	15: 26,553,002	C60S	probably benign	Het
Fras1	A	T	5: 96,733,843	D2478V	possibly damaging	Het
Hrnr	A	G	3: 93,322,611	D52G	probably damaging	Het
Jmjd1c	T	A	10: 67,220,408	L823M	probably damaging	Het
Kdm1a	G	T	4: 136,568,600	C172*	probably null	Het
Kdm6b	C	T	11: 69,406,729	E295K	probably damaging	Het
Mepe	A	T	5: 104,337,074	M27L	probably benign	Het
Mogat2	A	T	7: 99,219,895	H305Q	probably damaging	Het
Mst1r	T	A	9: 107,917,266	Y1215N	probably damaging	Het
Muc5ac	A	T	7: 141,789,795	H48L	possibly damaging	Het
Myo7b	T	C	18: 31,983,695	D953G	probably damaging	Het
Ocel1	T	C	8: 71,371,828		probably benign	Het
Pcdhb6	A	G	18: 37,335,925	D633G	probably damaging	Het
Ppm1l	A	G	3: 69,497,897	I176V	probably benign	Het
Sall3	C	T	18: 80,969,861	R1120H	possibly damaging	Het
Sbf1	G	A	15: 89,300,867	P1018S	probably benign	Het
Setbp1	T	C	18: 78,857,257	Y1065C	probably damaging	Het
Slc25a2	T	C	18: 37,637,723		probably null	Het
Slc4a2	C	A	5: 24,435,890	T729K	probably damaging	Het
Sptlc2	T	C	12: 87,355,531	E207G	probably damaging	Het
Sult6b1	A	T	17: 78,906,914	F27I	probably benign	Het
Syf2	A	T	4: 134,934,578	K84N	probably damaging	Het
Tmem209	A	T	6: 30,497,167	N183K	probably benign	Het
Tmem232	G	T	17: 65,478,402	Q188K	possibly damaging	Het
Tomm70a	A	T	16: 57,152,692	T598S	probably benign	Het
Ttll13	A	G	7: 80,258,304	T556A	probably benign	Het
Vmn2r120	A	T	17: 57,524,700	L363*	probably null	Het
Xpo6	G	T	7: 126,108,619	Q872K	probably damaging	Het
Xrra1	A	C	7: 99,914,464	S553R	probably damaging	Het
Zfy1	A	T	Y: 738,765	V147E	unknown	Homo
Zfy2	T	C	Y: 2,116,267	I258V	probably benign	Homo

Other mutations in Dnase1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00649:Dnase1	APN	16	4039024	missense	probably damaging	1.00
IGL00896:Dnase1	APN	16	4039212	missense	probably benign	0.00
IGL00983:Dnase1	APN	16	4039553	missense	possibly damaging	0.70
IGL02186:Dnase1	APN	16	4039032	missense	probably benign	0.18
IGL03373:Dnase1	APN	16	4039843	missense	probably damaging	1.00
R0009:Dnase1	UTSW	16	4038946	missense	probably damaging	1.00
R0009:Dnase1	UTSW	16	4038946	missense	probably damaging	1.00
R0355:Dnase1	UTSW	16	4039549	missense	probably damaging	1.00
R0467:Dnase1	UTSW	16	4039149	missense	probably damaging	1.00
R4964:Dnase1	UTSW	16	4037907	intron	probably benign
R4966:Dnase1	UTSW	16	4037907	intron	probably benign
R5014:Dnase1	UTSW	16	4039016	nonsense	probably null
R5621:Dnase1	UTSW	16	4039118	missense	probably benign	0.01
R5858:Dnase1	UTSW	16	4039649	splice site	probably benign
R6519:Dnase1	UTSW	16	4038589	missense	probably damaging	1.00
R7002:Dnase1	UTSW	16	4039546	missense	possibly damaging	0.76
R7977:Dnase1	UTSW	16	4037970	missense	probably damaging	1.00
R7987:Dnase1	UTSW	16	4037970	missense	probably damaging	1.00
R8050:Dnase1	UTSW	16	4037997	missense	probably damaging	1.00
R9781:Dnase1	UTSW	16	4039190	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