Mutagenetix > Incidental Mutation

Incidental Mutation 'R4591:Nlrp3'

342839

Institutional Source

Beutler Lab

Gene Symbol

Nlrp3

Ensembl Gene

ENSMUSG00000032691

Gene Name

NLR family, pyrin domain containing 3

Synonyms

Cias1, cryopyrin, Pypaf1, NALP3, Mmig1

Accession Numbers

Ncbi RefSeq: NM_145827.3; MGI:2653833

Essential gene?

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

Stock #

R4591 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

59541568-59566956 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 59549222 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Glycine at position 542 (R542G)

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: R542G

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000078440
Gene: ENSMUSG00000032691
AA Change: R542G

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: R542G

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000098707
Gene: ENSMUSG00000032691
AA Change: R542G

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: 99.3%
3x: 98.6%
10x: 97.3%
20x: 95.3%

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: 76 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1110032F04Rik	T	C	3: 68,870,266	S187P	possibly damaging	Het
4932438H23Rik	T	C	16: 91,056,071	N59S	probably damaging	Het
Abca15	A	T	7: 120,382,413	D1030V	probably damaging	Het
Acmsd	A	T	1: 127,749,197	N153I	probably damaging	Het
Adprh	C	A	16: 38,445,983	V266L	probably benign	Het
Aldh5a1	G	A	13: 24,924,008	P217S	probably damaging	Het
Alpk2	A	T	18: 65,305,823	L1300Q	probably benign	Het
Alyref	C	T	11: 120,595,973	R154Q	probably benign	Het
Ano6	T	A	15: 95,943,427	C468*	probably null	Het
Aox3	A	T	1: 58,152,656	I456F	probably damaging	Het
Art4	A	G	6: 136,854,757	Y129H	probably damaging	Het
Asb16	C	A	11: 102,276,725	H306N	probably damaging	Het
Atp8a2	C	A	14: 59,654,629	R1090L	probably benign	Het
Brap	G	T	5: 121,662,050	V1F	probably null	Het
C1qb	C	A	4: 136,882,217	G31W	probably damaging	Het
Cacna2d4	T	C	6: 119,298,464	Y666H	probably benign	Het
Casr	T	C	16: 36,500,370	N472S	probably benign	Het
Ccdc91	T	G	6: 147,590,465	S282A	unknown	Het
Cd300lg	A	G	11: 102,046,180	T164A	probably benign	Het
Cd79b	A	T	11: 106,312,046	D243E	probably damaging	Het
Cdh6	C	A	15: 13,051,486	V354F	possibly damaging	Het
Cdhr2	A	G	13: 54,715,684	N126S	probably benign	Het
Cep192	A	T	18: 67,834,968	N841I	probably damaging	Het
Cngb1	T	C	8: 95,253,384	T963A	probably damaging	Het
Col16a1	A	G	4: 130,061,799		probably null	Het
Coro1a	A	G	7: 126,702,992	V61A	probably damaging	Het
Crocc	T	A	4: 141,018,672	D1712V	probably damaging	Het
Ddn	T	C	15: 98,807,806	D3G	possibly damaging	Het
Dnal1	T	C	12: 84,133,853	F89S	probably benign	Het
Dusp3	T	A	11: 101,973,620		probably benign	Het
Dyrk3	C	A	1: 131,130,158	G58C	probably damaging	Het
Fat1	T	C	8: 45,026,242	F2775S	probably benign	Het
Frk	A	G	10: 34,605,833	N373S	probably benign	Het
Glmn	A	G	5: 107,561,051		probably null	Het
Gm11565	A	T	11: 99,914,943	T54S	possibly damaging	Het
Gm14410	A	G	2: 177,194,027	I148T	possibly damaging	Het
Gm21834	T	A	17: 57,741,885	H112L	possibly damaging	Het
Gm5862	A	G	5: 26,019,488	I161T	possibly damaging	Het
Grid2	G	T	6: 64,320,102	G483V	probably damaging	Het
Hfm1	A	T	5: 106,847,667	S1293T	probably benign	Het
Il1a	G	A	2: 129,306,527	R88W	probably damaging	Het
Il20rb	A	T	9: 100,474,990	V29D	possibly damaging	Het
Ilvbl	C	T	10: 78,583,305	L463F	probably benign	Het
Kif17	A	G	4: 138,277,799	E225G	probably benign	Het
Lrp2	A	G	2: 69,536,075	F227L	probably damaging	Het
Lrrc43	A	G	5: 123,501,164	M419V	probably benign	Het
Magel2	A	G	7: 62,381,089	Q1247R	unknown	Het
Mamdc4	T	A	2: 25,564,597	M1068L	possibly damaging	Het
Marc1	T	C	1: 184,807,168	E102G	probably benign	Het
Mdn1	T	G	4: 32,707,636	S1642A	probably damaging	Het
Mtcl1	T	C	17: 66,348,511	E819G	probably benign	Het
Naa15	T	C	3: 51,441,924	L38P	probably damaging	Het
Olfr1456-ps1	ACAC	ACACGCAC	19: 13,078,902		noncoding transcript	Het
Olfr201	A	C	16: 59,269,413	F85V	possibly damaging	Het
Olfr462	A	G	11: 87,889,549	S116P	probably benign	Het
Olfr95	C	T	17: 37,211,119	V245I	probably benign	Het
Pbxip1	T	A	3: 89,446,160	L249Q	probably benign	Het
Pla2g7	T	C	17: 43,600,559	S201P	probably damaging	Het
Psmd1	G	T	1: 86,128,204	V763F	probably benign	Het
Ptp4a2	A	G	4: 129,846,515	E124G	probably benign	Het
Rab6b	T	C	9: 103,167,174		probably null	Het
Rbks	T	A	5: 31,660,008	K139M	possibly damaging	Het
Rgs22	T	A	15: 36,100,136	E268D	probably benign	Het
Slc16a9	T	G	10: 70,282,880	L343R	probably damaging	Het
Smagp	T	C	15: 100,621,979	I55V	probably damaging	Het
Sox13	T	C	1: 133,383,683	S604G	probably damaging	Het
St6gal1	G	T	16: 23,321,294	V72F	probably benign	Het
Stxbp4	A	G	11: 90,594,780	V247A	probably benign	Het
Susd3	A	T	13: 49,231,260	M217K	possibly damaging	Het
Tas2r129	T	A	6: 132,951,611	N170K	probably benign	Het
Tmem245	C	A	4: 56,910,204	A515S	probably damaging	Het
Tpte	T	C	8: 22,327,775	V259A	probably benign	Het
Trpa1	T	C	1: 14,882,108		probably null	Het
Ttc28	G	A	5: 111,223,281	R532H	probably damaging	Het
Vwa5a	A	T	9: 38,735,620	N529I	possibly damaging	Het
Zfp574	T	C	7: 25,079,544		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
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
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'- TGCGGATGGAATTTGGAACC -3'
(R):5'- TCTGACTTGCTGAGAGATCTTG -3'

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

Posted On

2015-09-24