Mutagenetix > Incidental Mutations

Incidental Mutation 'R0863:Nlrp3'

82208

Institutional Source

Beutler Lab

Gene Symbol

Nlrp3

Ensembl Gene

ENSMUSG00000032691

Gene Name

NLR family, pyrin domain containing 3

Synonyms

Cias1, cryopyrin, Pypaf1, NALP3, Mmig1

MMRRC Submission

039037-MU

Accession Numbers

Ncbi RefSeq: NM_145827.3; MGI:2653833

Is this an essential gene?

Probably non essential (E-score: 0.100) question?

Stock #

R0863 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

59541568-59566956 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 59565850 bp

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glycine at position 946 (D946G)

Ref Sequence

ENSEMBL: ENSMUSP00000098707 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000071943] [ENSMUST00000079476] [ENSMUST00000101148] [ENSMUST00000214351] [ENSMUST00000215339]

Predicted Effect

probably benign
Transcript: ENSMUST00000071943

SMART Domains

Protein: ENSMUSP00000071835
Gene: ENSMUSG00000059610

Domain	Start	End	E-Value	Type
Pfam:7TM_GPCR_Srv	29	311	4.3e-9	PFAM
Pfam:7tm_4	35	312	3.4e-54	PFAM
Pfam:7tm_1	45	294	1.3e-28	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000079476
AA Change: D946G

PolyPhen 2 Score 0.017 (Sensitivity: 0.95; Specificity: 0.80)

SMART Domains

Protein: ENSMUSP00000078440
Gene: ENSMUSG00000032691
AA Change: D946G

Domain	Start	End	E-Value	Type
PYRIN	4	87	6.39e-33	SMART
FISNA	135	206	1.45e-22	SMART
Pfam:NACHT	216	385	6.7e-52	PFAM
low complexity region	533	539	N/A	INTRINSIC
low complexity region	688	697	N/A	INTRINSIC
LRR_RI	737	764	1.07e-9	SMART
LRR	766	793	5.13e1	SMART
LRR	794	821	3.86e-7	SMART
LRR	823	850	1.62e0	SMART
LRR	851	878	3.39e-3	SMART
LRR	880	907	1.2e2	SMART
LRR	908	935	2.24e-3	SMART
LRR	937	964	2.16e2	SMART
LRR	965	992	8.73e-6	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000101148
AA Change: D946G

PolyPhen 2 Score 0.017 (Sensitivity: 0.95; Specificity: 0.80)

SMART Domains

Protein: ENSMUSP00000098707
Gene: ENSMUSG00000032691
AA Change: D946G

Domain	Start	End	E-Value	Type
PYRIN	4	87	6.39e-33	SMART
FISNA	135	206	1.45e-22	SMART
Pfam:NACHT	216	385	6.7e-52	PFAM
low complexity region	533	539	N/A	INTRINSIC
low complexity region	688	697	N/A	INTRINSIC
LRR_RI	737	764	1.07e-9	SMART
LRR	766	793	5.13e1	SMART
LRR	794	821	3.86e-7	SMART
LRR	823	850	1.62e0	SMART
LRR	851	878	3.39e-3	SMART
LRR	880	907	1.2e2	SMART
LRR	908	935	2.24e-3	SMART
LRR	937	964	2.16e2	SMART
LRR	965	992	8.73e-6	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000214351

Predicted Effect

probably benign
Transcript: ENSMUST00000215339

Meta Mutation Damage Score

0.3192

Coding Region Coverage

1x: 99.5%
3x: 98.9%
10x: 97.4%
20x: 94.8%

Validation Efficiency

94% (59/63)

MGI Phenotype

Strain: 3686871
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a pyrin-like protein containing a pyrin domain, a nucleotide-binding site (NBS) domain, and a leucine-rich repeat (LRR) motif. This protein interacts with the apoptosis-associated speck-like protein PYCARD/ASC, which contains a caspase recruitment domain, and is a member of the NALP3 inflammasome complex. This complex functions as an upstream activator of NF-kappaB signaling, and it plays a role in the regulation of inflammation, the immune response, and apoptosis. Mutations in this gene are associated with familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), chronic infantile neurological cutaneous and articular (CINCA) syndrome, and neonatal-onset multisystem inflammatory disease (NOMID). Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. Alternative 5' UTR structures are suggested by available data; however, insufficient evidence is available to determine if all of the represented 5' UTR splice patterns are biologically valid. [provided by RefSeq, Oct 2008]
PHENOTYPE: Mice homozygous for null mutations exhibit attenuated inflammatory responses related to decrease secretion of IL-1beta and IL-18. Mice heterozygous for activating mutations suffer from autoinflammatory attacks that lead to organ failure and death before weaning. [provided by MGI curators]

Allele List at MGI

All alleles(13) : Targeted(9) Chemically induced(4)

Other mutations in this stock

Total: 59 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700057G04Rik	A	T	9: 92,351,087	I88L	possibly damaging	Het
2310016G11Rik	A	G	7: 44,677,808		noncoding transcript	Het
4930433I11Rik	A	T	7: 40,993,056	T141S	probably benign	Het
Abca14	A	T	7: 120,216,230	T234S	probably benign	Het
Acap1	C	A	11: 69,887,056	V119L	probably damaging	Het
Actr2	C	T	11: 20,080,760	V163I	probably benign	Het
Adcy4	T	C	14: 55,783,599	Y27C	probably damaging	Het
Arnt2	T	A	7: 84,265,584	K524M	probably damaging	Het
Brca1	T	C	11: 101,524,770	Y846C	probably benign	Het
Capn7	T	A	14: 31,369,757	C704S	possibly damaging	Het
Cep350	T	A	1: 155,862,235	I2621L	probably benign	Het
Col11a1	G	A	3: 114,138,765	R113H	unknown	Het
Ctnnbl1	C	T	2: 157,799,417		probably benign	Het
Cul9	T	C	17: 46,537,822		probably null	Het
Erc2	A	C	14: 28,025,148	N345T	probably benign	Het
Fank1	A	G	7: 133,880,623	R73G	possibly damaging	Het
Fes	A	T	7: 80,380,886	W552R	probably damaging	Het
Fsd2	A	G	7: 81,542,165	V488A	possibly damaging	Het
Gfm1	T	C	3: 67,474,595	S705P	probably damaging	Het
Gm9493	A	T	19: 23,619,809	Q23L	probably benign	Het
Gucy1b2	T	C	14: 62,419,062	D282G	probably benign	Het
H2-Ab1	T	C	17: 34,267,354	I129T	probably damaging	Het
H2-M10.3	T	A	17: 36,366,690	Y232F	probably damaging	Het
Iqca	C	A	1: 90,142,731	G133V	probably null	Het
Lonp1	T	C	17: 56,618,331	K487R	probably damaging	Het
Ltbp1	A	G	17: 75,252,386	Y290C	probably damaging	Het
Mgea5	C	T	19: 45,782,986	A49T	probably benign	Het
Ms4a10	C	T	19: 10,968,593	G58D	probably damaging	Het
Muc5b	A	G	7: 141,867,717	S4315G	probably benign	Het
Nlrp1b	T	A	11: 71,181,347	T557S	probably benign	Het
Obscn	T	C	11: 58,995,415		probably benign	Het
Olfr469	T	C	7: 107,823,374	S32G	probably benign	Het
Olfr509	A	G	7: 108,645,658	I306T	probably benign	Het
Olfr866	A	T	9: 20,027,213	S242T	probably damaging	Het
Pask	A	T	1: 93,314,339	F1219I	probably damaging	Het
Pcdhb2	G	A	18: 37,295,657	V228I	possibly damaging	Het
Phf1	T	C	17: 26,937,140		probably benign	Het
Plec	G	A	15: 76,174,080	Q3751*	probably null	Het
Ppp1r12c	G	T	7: 4,486,366	Q240K	probably damaging	Het
Ralgapa1	A	T	12: 55,762,681	Y436*	probably null	Het
Ralgapa1	C	A	12: 55,782,777		probably benign	Het
Scel	T	A	14: 103,586,480	S381R	possibly damaging	Het
Sema4a	C	T	3: 88,448,149		probably benign	Het
Sltm	A	G	9: 70,561,908	T150A	probably benign	Het
Spag1	G	T	15: 36,192,047	K217N	probably damaging	Het
Ssh1	C	T	5: 113,966,731	R9H	probably damaging	Het
St3gal4	C	A	9: 35,053,448	V155F	probably damaging	Het
Stxbp5	C	T	10: 9,809,040	E539K	possibly damaging	Het
Tbc1d7	G	T	13: 43,154,685		probably benign	Het
Thnsl2	A	T	6: 71,134,224	L220*	probably null	Het
Tinf2	G	A	14: 55,680,109	P308S	probably benign	Het
Tnf	T	C	17: 35,201,144		probably benign	Het
Ttc21b	T	C	2: 66,242,773	I190V	probably benign	Het
Ttn	T	C	2: 76,707,047	T34846A	probably benign	Het
Ube4a	A	G	9: 44,949,816	V232A	possibly damaging	Het
Uri1	A	T	7: 37,969,675	D122E	probably damaging	Het
Vmn2r94	T	G	17: 18,257,711	Q146P	probably damaging	Het
Zan	T	A	5: 137,458,639	E1278D	unknown	Het
Zfhx4	T	A	3: 5,245,315	S919R	possibly damaging	Het

Other mutations in Nlrp3

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00421:Nlrp3	APN	11	59565943	missense	probably damaging	0.99
IGL00573:Nlrp3	APN	11	59565116	missense	possibly damaging	0.93
IGL01025:Nlrp3	APN	11	59551887	missense	probably benign	0.21
IGL01637:Nlrp3	APN	11	59549378	missense	probably damaging	0.99
IGL02010:Nlrp3	APN	11	59549535	missense	probably benign
IGL02334:Nlrp3	APN	11	59565083	missense	probably benign
IGL02417:Nlrp3	APN	11	59566023	unclassified	probably benign
IGL02578:Nlrp3	APN	11	59548401	missense	probably damaging	1.00
IGL02710:Nlrp3	APN	11	59565976	missense	probably damaging	0.99
IGL02816:Nlrp3	APN	11	59555782	missense	probably benign	0.03
IGL03157:Nlrp3	APN	11	59549546	missense	possibly damaging	0.80
IGL03334:Nlrp3	APN	11	59549016	missense	probably damaging	1.00
Flogiston	UTSW	11	59558448	missense	probably benign	0.00
nd1	UTSW	11	59565974	missense	probably benign	0.45
Nd14	UTSW	11	59555875	missense	possibly damaging	0.89
Nd3	UTSW	11	59565974	missense	probably benign	0.45
nd5	UTSW	11	59565879	missense	probably benign	0.01
nd6	UTSW	11	59549354	missense	probably damaging	1.00
nd7	UTSW	11	59555875	missense	possibly damaging	0.89
Nd9	UTSW	11	59549354	missense	probably damaging	1.00
Park2	UTSW	11	59565128	nonsense	probably null
Park3	UTSW	11	59565850	missense	probably benign	0.02
Park4	UTSW	11	59549531	missense	probably benign	0.19
Park5	UTSW	11	59548476	missense	probably damaging	0.99
Park6	UTSW	11	59549036	missense	probably damaging	1.00
Park7	UTSW	11	59548010	nonsense	probably null
Park8	UTSW	11	59566199	missense	probably benign	0.19
R0008:Nlrp3	UTSW	11	59558448	missense	probably benign	0.00
R0008:Nlrp3	UTSW	11	59558448	missense	probably benign	0.00
R0052:Nlrp3	UTSW	11	59565128	nonsense	probably null
R0362:Nlrp3	UTSW	11	59548797	missense	possibly damaging	0.49
R0416:Nlrp3	UTSW	11	59555924	splice site	probably benign
R0649:Nlrp3	UTSW	11	59548542	missense	possibly damaging	0.83
R0740:Nlrp3	UTSW	11	59548256	missense	probably benign	0.01
R1300:Nlrp3	UTSW	11	59555768	missense	possibly damaging	0.86
R1414:Nlrp3	UTSW	11	59549531	missense	probably benign	0.19
R1622:Nlrp3	UTSW	11	59548476	missense	probably damaging	0.99
R1654:Nlrp3	UTSW	11	59543123	missense	probably benign	0.03
R1715:Nlrp3	UTSW	11	59543351	missense	probably damaging	1.00
R1754:Nlrp3	UTSW	11	59558402	missense	possibly damaging	0.80
R1837:Nlrp3	UTSW	11	59548916	missense	probably benign	0.00
R1905:Nlrp3	UTSW	11	59549036	missense	probably damaging	1.00
R2281:Nlrp3	UTSW	11	59549136	missense	possibly damaging	0.70
R4296:Nlrp3	UTSW	11	59549661	missense	possibly damaging	0.89
R4305:Nlrp3	UTSW	11	59548010	nonsense	probably null
R4540:Nlrp3	UTSW	11	59551899	missense	possibly damaging	0.83
R4591:Nlrp3	UTSW	11	59549222	missense	probably benign	0.00
R4816:Nlrp3	UTSW	11	59548301	missense	probably benign	0.32
R4913:Nlrp3	UTSW	11	59549238	missense	probably benign	0.09
R4970:Nlrp3	UTSW	11	59548728	missense	probably damaging	1.00
R5051:Nlrp3	UTSW	11	59566199	missense	probably benign	0.19
R5112:Nlrp3	UTSW	11	59548728	missense	probably damaging	1.00
R5185:Nlrp3	UTSW	11	59565084	missense	probably benign	0.05
R5417:Nlrp3	UTSW	11	59549063	missense	probably damaging	1.00
R5709:Nlrp3	UTSW	11	59555748	nonsense	probably null
R5869:Nlrp3	UTSW	11	59548134	missense	probably damaging	1.00
R5898:Nlrp3	UTSW	11	59546852	missense	probably benign	0.00
R5953:Nlrp3	UTSW	11	59546791	missense	probably benign
R5979:Nlrp3	UTSW	11	59548971	missense	probably benign	0.06
R6359:Nlrp3	UTSW	11	59548566	missense	probably damaging	0.97
R6723:Nlrp3	UTSW	11	59565192	missense	probably damaging	1.00
R7261:Nlrp3	UTSW	11	59548446	missense	possibly damaging	0.83
R7349:Nlrp3	UTSW	11	59548086	missense	probably damaging	1.00
R7388:Nlrp3	UTSW	11	59565066	missense	probably benign	0.00
R7715:Nlrp3	UTSW	11	59543003	splice site	probably null
R7916:Nlrp3	UTSW	11	59551863	missense	probably benign	0.00
R8222:Nlrp3	UTSW	11	59548788	missense	probably damaging	0.98
R8360:Nlrp3	UTSW	11	59549403	missense	probably benign	0.02
R8390:Nlrp3	UTSW	11	59551790	missense	possibly damaging	0.47
R8550:Nlrp3	UTSW	11	59549271	missense	probably damaging	1.00
RF031:Nlrp3	UTSW	11	59558552	frame shift	probably null
RF040:Nlrp3	UTSW	11	59558552	frame shift	probably null
Z1088:Nlrp3	UTSW	11	59551860	missense	possibly damaging	0.67

Predicted Primers

PCR Primer
(F):5'- CCCTGATGCAAATCTGTGTCTGAGG -3'
(R):5'- CAAACCACACTCACTGTAGGCTCTG -3'

Sequencing Primer
(F):5'- cctggcttgcctggaac -3'
(R):5'- TTGTTGCCCAGGTTCAGCTT -3'

Posted On

2013-11-08