Mutagenetix > Incidental Mutation

Incidental Mutation 'R0362:Nlrp3'

36264

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

038568-MU

Accession Numbers

Ncbi RefSeq: NM_145827.3; MGI:2653833

Essential gene?

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

Stock #

R0362 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

59541568-59566956 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 59548797 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 400 (V400A)

Ref Sequence

ENSEMBL: ENSMUSP00000098707 (fasta)

Gene Model

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

AlphaFold

Q8R4B8

Predicted Effect

possibly damaging
Transcript: ENSMUST00000079476
AA Change: V400A

PolyPhen 2 Score 0.488 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000078440
Gene: ENSMUSG00000032691
AA Change: V400A

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

possibly damaging
Transcript: ENSMUST00000101148
AA Change: V400A

PolyPhen 2 Score 0.488 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000098707
Gene: ENSMUSG00000032691
AA Change: V400A

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

Meta Mutation Damage Score

0.4259

Coding Region Coverage

1x: 99.4%
3x: 98.6%
10x: 96.8%
20x: 94.0%

Validation Efficiency

99% (104/105)

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: 103 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4932414N04Rik	A	G	2: 68,732,917	Q401R	probably benign	Het
Acpp	A	G	9: 104,314,427	F220S	probably damaging	Het
Adam7	A	G	14: 68,509,656		probably benign	Het
Adamts6	A	G	13: 104,390,076		probably null	Het
Ascc3	T	C	10: 50,748,955		probably benign	Het
Atg10	T	C	13: 91,040,990		probably null	Het
Atm	T	C	9: 53,458,838	I2325V	possibly damaging	Het
Btnl9	C	T	11: 49,169,616	R435H	possibly damaging	Het
Ccdc180	A	G	4: 45,923,551	K1111E	probably damaging	Het
Col11a2	T	A	17: 34,062,446		probably null	Het
Ctcfl	A	G	2: 173,118,443	W116R	probably damaging	Het
Ctsk	A	T	3: 95,500,944	Y37F	probably damaging	Het
Daam2	G	C	17: 49,480,785		probably null	Het
Dcdc2b	T	C	4: 129,610,238		probably null	Het
Ddx28	C	T	8: 106,011,294	R44Q	probably damaging	Het
Dhx29	T	A	13: 112,962,859	N1139K	probably benign	Het
Dnah17	A	T	11: 118,098,539	M1281K	probably benign	Het
Dnah6	T	C	6: 73,208,609	S110G	probably benign	Het
Drc7	T	C	8: 95,072,855	Y553H	probably benign	Het
Dync2h1	T	C	9: 7,005,487		probably null	Het
Ecm1	A	G	3: 95,737,057	I152T	possibly damaging	Het
Edc4	C	G	8: 105,886,775	P307R	probably damaging	Het
Egr1	A	G	18: 34,863,313	T383A	possibly damaging	Het
Eml2	A	G	7: 19,190,806		probably null	Het
Eno4	A	G	19: 58,943,624		probably benign	Het
Erbb4	A	T	1: 68,330,270	I404K	probably damaging	Het
Exoc7	G	T	11: 116,295,662	T310K	probably benign	Het
Fam102b	C	T	3: 108,980,181	E256K	probably benign	Het
Fam83e	G	T	7: 45,726,969	V369L	probably benign	Het
Fam96b	T	C	8: 104,641,590	D34G	probably null	Het
Fancc	A	T	13: 63,398,156	I91K	possibly damaging	Het
Fbn1	T	C	2: 125,309,777	Q2519R	probably damaging	Het
Fhod3	T	A	18: 25,090,076	C826*	probably null	Het
Foxi3	A	G	6: 70,956,628	D33G	probably benign	Het
Gcn1l1	T	C	5: 115,576,108		probably benign	Het
Gm14221	T	C	2: 160,568,390		noncoding transcript	Het
Golga4	T	A	9: 118,555,785	H630Q	probably benign	Het
Gpat4	T	C	8: 23,180,933	S88G	probably benign	Het
Gucy2d	A	T	7: 98,443,685	S90C	probably damaging	Het
Has2	A	C	15: 56,681,661	C182G	probably damaging	Het
Heatr5a	A	T	12: 51,888,861	S1647R	probably damaging	Het
Ifi35	T	C	11: 101,457,212	V48A	probably benign	Het
Lig1	T	A	7: 13,296,804		probably benign	Het
Magi2	A	G	5: 19,227,575	K96R	probably damaging	Het
Map7d1	G	T	4: 126,234,994	P462Q	probably damaging	Het
Mdn1	A	T	4: 32,746,439		probably null	Het
Mfsd4a	A	T	1: 132,059,275	V105E	probably damaging	Het
Mrpl53	C	T	6: 83,109,545	R77C	probably damaging	Het
Mtnr1b	C	T	9: 15,874,304	V53M	probably damaging	Het
Myo9b	T	C	8: 71,347,770	W990R	probably damaging	Het
Myt1	A	T	2: 181,763,393		probably benign	Het
Nf1	C	T	11: 79,536,878	A1766V	probably damaging	Het
Nup205	T	A	6: 35,196,714		probably null	Het
Nxf1	T	C	19: 8,764,151		probably null	Het
Olfr1352	A	T	10: 78,984,386	M199L	probably benign	Het
P4hb	T	C	11: 120,563,336	K311E	probably benign	Het
Pafah1b1	T	C	11: 74,683,631	N243S	probably benign	Het
Parp8	G	A	13: 116,924,968	Q141*	probably null	Het
Pkd2l2	A	C	18: 34,435,327	D543A	probably benign	Het
Pld5	A	T	1: 175,975,580	L311*	probably null	Het
Plekha5	G	A	6: 140,591,747	R646K	possibly damaging	Het
Plpp5	A	T	8: 25,724,192	T144S	probably benign	Het
Ppp6r3	A	G	19: 3,478,285	L542S	probably damaging	Het
Prkar2b	A	T	12: 31,987,974		probably null	Het
Psmg1	A	T	16: 95,987,971	S129T	possibly damaging	Het
Radil	T	C	5: 142,543,827	D38G	probably benign	Het
Ric1	T	C	19: 29,601,011		probably null	Het
Rp1l1	T	A	14: 64,031,066	L1367*	probably null	Het
Rxfp1	A	T	3: 79,737,793	M1K	probably null	Het
Serpina6	G	T	12: 103,651,949	L202I	probably damaging	Het
Simc1	T	C	13: 54,528,467	I98T	probably damaging	Het
Slc17a6	A	G	7: 51,658,771	Y281C	probably damaging	Het
Slc26a11	T	A	11: 119,379,941		probably benign	Het
Slc34a1	T	A	13: 55,402,898		probably null	Het
Slfn10-ps	T	A	11: 83,035,774		noncoding transcript	Het
Sohlh2	A	G	3: 55,207,742	N383D	probably damaging	Het
Spag6	T	A	2: 18,710,491	L27H	probably damaging	Het
Sptlc3	A	G	2: 139,546,555		probably benign	Het
St3gal4	T	A	9: 35,053,173	K199*	probably null	Het
Stat5a	T	A	11: 100,882,083	D712E	probably benign	Het
Stmn2	A	T	3: 8,545,690	D78V	probably damaging	Het
Stpg1	C	T	4: 135,506,466	P20S	possibly damaging	Het
Taf2	A	T	15: 55,045,929	V640E	probably damaging	Het
Tbce	T	C	13: 13,998,162	E501G	probably benign	Het
Tecpr2	A	G	12: 110,968,940	S1398G	probably damaging	Het
Tenm4	T	A	7: 96,772,035	Y598*	probably null	Het
Ticrr	A	G	7: 79,677,340	S599G	probably damaging	Het
Tnc	A	C	4: 64,017,442	V419G	probably damaging	Het
Trappc1	C	A	11: 69,325,576	P110T	probably benign	Het
Trbv12-2	C	T	6: 41,119,059		probably benign	Het
Ttbk2	A	T	2: 120,745,783	N835K	possibly damaging	Het
Tubgcp5	A	G	7: 55,800,684	D181G	probably damaging	Het
Tut1	T	C	19: 8,955,527	Y75H	possibly damaging	Het
Ulk2	C	A	11: 61,787,586	C769F	probably benign	Het
Vdac1	T	C	11: 52,374,973		probably benign	Het
Vmn2r124	T	C	17: 18,064,224		probably null	Het
Vps8	T	C	16: 21,608,227		probably benign	Het
Wdr35	T	C	12: 8,995,625		probably benign	Het
Zdhhc7	T	A	8: 120,086,647	E141V	probably null	Het
Zfp12	C	A	5: 143,245,223	S435Y	probably damaging	Het
Zfp974	A	T	7: 27,927,394		probably benign	Het
Zfyve9	T	A	4: 108,680,969	K1033N	probably damaging	Het
Zswim8	T	A	14: 20,721,945	S1572T	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
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
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'- ACATTCTGCTAAGCAGCCTCATCC -3'
(R):5'- AGAAGAGATGCTCCTCAATGCCCC -3'

Sequencing Primer
(F):5'- AGAAACTGCTGCCCAAGG -3'
(R):5'- ATTGCAGCAGGCTGGAAA -3'

Posted On

2013-05-09