Mutagenetix > Incidental Mutation

Incidental Mutation 'R4913:Nlrp3'

379725

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

042515-MU

Accession Numbers

Ncbi RefSeq: NM_145827.3; MGI:2653833

Essential gene?

Probably non essential (E-score: 0.081) question?

Stock #

R4913 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

59541568-59566956 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 59549238 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Glycine to Aspartic acid at position 547 (G547D)

Ref Sequence

ENSEMBL: ENSMUSP00000098707 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000079476] [ENSMUST00000101148] [ENSMUST00000149126]

AlphaFold

Q8R4B8

Predicted Effect

probably benign
Transcript: ENSMUST00000079476
AA Change: G547D

PolyPhen 2 Score 0.095 (Sensitivity: 0.93; Specificity: 0.85)

SMART Domains

Protein: ENSMUSP00000078440
Gene: ENSMUSG00000032691
AA Change: G547D

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: G547D

PolyPhen 2 Score 0.095 (Sensitivity: 0.93; Specificity: 0.85)

SMART Domains

Protein: ENSMUSP00000098707
Gene: ENSMUSG00000032691
AA Change: G547D

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: ENSMUST00000149126

SMART Domains

Protein: ENSMUSP00000114231
Gene: ENSMUSG00000032691

Domain	Start	End	E-Value	Type
PYRIN	4	87	6.39e-33	SMART
Pfam:FISNA	135	173	1.6e-12	PFAM

Coding Region Coverage

1x: 99.1%
3x: 98.3%
10x: 96.0%
20x: 91.3%

Validation Efficiency

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: 85 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2810474O19Rik	C	G	6: 149,329,389	S1311C	probably damaging	Het
9430007A20Rik	T	A	4: 144,528,811	M267K	possibly damaging	Het
Acsm5	T	C	7: 119,534,343	S244P	probably damaging	Het
Actr6	A	G	10: 89,714,946	F329L	probably benign	Het
Actrt3	A	G	3: 30,598,439	S169P	probably benign	Het
Agtpbp1	C	A	13: 59,500,072	G645C	probably damaging	Het
AI661453	C	T	17: 47,468,555	R1069*	probably null	Het
Akr1c6	T	C	13: 4,454,525	I303T	probably benign	Het
Arnt	A	G	3: 95,490,654	R588G	probably damaging	Het
Atf1	A	G	15: 100,252,098		probably null	Het
BC052040	A	G	2: 115,670,087		probably null	Het
Casp12	T	C	9: 5,358,726	V318A	probably damaging	Het
Cblb	C	T	16: 52,166,029	P545L	possibly damaging	Het
Cc2d2a	A	T	5: 43,739,323	I1521F	probably benign	Het
Ccnb1ip1	T	A	14: 50,792,144	K154*	probably null	Het
Cd300a	A	T	11: 114,893,372	K69*	probably null	Het
Clec10a	A	G	11: 70,170,025	Y78C	probably damaging	Het
Cnot1	T	C	8: 95,763,067	I503V	possibly damaging	Het
Cpa2	A	G	6: 30,554,293	H304R	probably damaging	Het
Crb2	A	T	2: 37,790,245	H395L	probably benign	Het
Ctgf	T	C	10: 24,597,327	C255R	probably damaging	Het
Dnah8	T	A	17: 30,819,139	N4257K	probably damaging	Het
Dnase2a	G	A	8: 84,908,848	D25N	probably damaging	Het
Drd1	T	C	13: 54,053,167	T343A	probably benign	Het
Emid1	G	A	11: 5,132,012	T161I	probably benign	Het
Epn2	A	G	11: 61,534,576		probably null	Het
Esp36	A	T	17: 38,417,164	N75K	possibly damaging	Het
Faf1	A	G	4: 109,935,549	S573G	possibly damaging	Het
Fam149a	T	G	8: 45,353,883	S231R	probably damaging	Het
Fam78a	T	C	2: 32,069,762	E112G	probably damaging	Het
Fgf18	T	C	11: 33,134,316	D46G	probably benign	Het
Fggy	G	A	4: 95,697,076		probably null	Het
Foxb1	T	C	9: 69,759,577	M224V	probably benign	Het
Gpr75	T	C	11: 30,891,808	C238R	possibly damaging	Het
Gsdmc3	A	G	15: 63,858,273	*481R	probably null	Het
H2afv	C	A	11: 6,433,750	A57S	probably damaging	Het
Hsd17b11	T	C	5: 103,992,882	I250V	probably benign	Het
Hus1	C	A	11: 8,996,856	L280F	probably benign	Het
Ide	A	T	19: 37,329,070	H101Q	unknown	Het
Ido1	T	C	8: 24,584,517	D279G	probably benign	Het
Inpp5b	T	C	4: 124,780,421	V307A	probably benign	Het
Ipo5	G	A	14: 120,935,086	V519I	probably damaging	Het
Krba1	T	C	6: 48,406,957	V239A	probably benign	Het
Lmod3	A	G	6: 97,247,164		probably null	Het
Macf1	T	C	4: 123,499,889	D836G	probably damaging	Het
Malt1	G	T	18: 65,476,280	C774F	probably damaging	Het
Map2k4	C	A	11: 65,709,932	D58Y	probably damaging	Het
Mc2r	T	C	18: 68,407,340	N294S	probably benign	Het
Mybpc1	A	G	10: 88,553,254		probably null	Het
Mybpc3	A	G	2: 91,126,264	E637G	possibly damaging	Het
Narf	A	G	11: 121,244,643	Q107R	probably damaging	Het
Nucb2	G	T	7: 116,524,305	G51*	probably null	Het
Olfr121	T	A	17: 37,752,424	V190D	possibly damaging	Het
Otog	C	A	7: 46,264,102	D786E	probably benign	Het
Otogl	T	C	10: 107,876,855	T543A	probably damaging	Het
Phf20l1	A	G	15: 66,604,855	N266S	probably benign	Het
Pink1	G	T	4: 138,315,555	S446*	probably null	Het
Pkp4	T	G	2: 59,305,450	H186Q	probably damaging	Het
Prl3b1	T	C	13: 27,249,477	V205A	probably damaging	Het
Prss32	T	C	17: 23,859,183	V281A	probably damaging	Het
Psd3	C	T	8: 68,121,169	C120Y	probably damaging	Het
Ptcra	A	G	17: 46,758,648	L99P	probably damaging	Het
Rab3gap2	C	T	1: 185,262,829	T855I	probably benign	Het
Rabgap1l	T	C	1: 160,238,541	E199G	probably damaging	Het
Rbm44	T	A	1: 91,155,494	C580S	probably damaging	Het
Rhoq	T	C	17: 86,995,065	V143A	probably benign	Het
Sacs	T	A	14: 61,213,797	Y4431N	probably benign	Het
Sec24b	A	T	3: 130,002,379	S367T	probably benign	Het
Sema4c	G	A	1: 36,550,185	S620F	probably benign	Het
Slc12a1	G	A	2: 125,228,750	G1054E	probably damaging	Het
Slc16a3	A	G	11: 120,957,968	R417G	probably benign	Het
Slc22a29	A	T	19: 8,218,358	S106T	probably benign	Het
Slc41a2	T	C	10: 83,313,420	T220A	probably damaging	Het
Tap1	T	C	17: 34,193,494	F474L	possibly damaging	Het
Tas2r106	G	T	6: 131,678,459	A143D	probably benign	Het
Tbx6	A	T	7: 126,784,535		probably null	Het
Tfap2a	T	A	13: 40,717,230	N402I	probably damaging	Het
Tle3	T	A	9: 61,373,993	V22E	probably damaging	Het
Tmem8	T	C	17: 26,120,539	F584L	probably damaging	Het
Trip4	T	C	9: 65,858,357	I353M	probably damaging	Het
Ubr2	C	A	17: 46,959,459		probably null	Het
Ugdh	A	G	5: 65,423,448		probably null	Het
Uhrf1	T	C	17: 56,315,478	V431A	probably damaging	Het
Usp5	C	G	6: 124,822,630	K318N	possibly damaging	Het
Zfp820	T	C	17: 21,819,219	K376R	probably benign	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
R0863:Nlrp3	UTSW	11	59565850	missense	probably benign	0.02
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
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
R8738:Nlrp3	UTSW	11	59549390	missense	probably benign	0.00
R8940:Nlrp3	UTSW	11	59565044	missense	probably benign	0.26
R8990:Nlrp3	UTSW	11	59548758	missense	probably damaging	0.99
R9324:Nlrp3	UTSW	11	59543315	missense	probably damaging	1.00
R9673:Nlrp3	UTSW	11	59549322	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'- CTGCGGATGGAATTTGGAAC -3'
(R):5'- TCTGACTTGCTGAGAGATCTTGC -3'

Sequencing Primer
(F):5'- TGGAATTTGGAACCAGAAAATCC -3'
(R):5'- CTTGCTGAGAGATCTTGCAACTTAG -3'

Posted On

2016-04-15