Mutagenetix > Incidental Mutation

Incidental Mutation 'R9673:Nlrp3'

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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

Accession Numbers

Ncbi RefSeq: NM_145827.3; MGI:2653833

Essential gene?

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

Stock #

R9673 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

59541568-59566956 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 59549322 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Valine to Aspartic acid at position 575 (V575D)

Ref Sequence

ENSEMBL: ENSMUSP00000078440 (fasta)

Gene Model

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

AlphaFold

Q8R4B8

Predicted Effect

probably damaging
Transcript: ENSMUST00000079476
AA Change: V575D

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000078440
Gene: ENSMUSG00000032691
AA Change: V575D

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 damaging
Transcript: ENSMUST00000101148
AA Change: V575D

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000098707
Gene: ENSMUSG00000032691
AA Change: V575D

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: 100.0%
3x: 100.0%
10x: 99.7%
20x: 99.2%

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: 79 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930568D16Rik	T	C	2: 35,354,387	K318E	probably benign	Het
9530053A07Rik	A	G	7: 28,156,619	T1944A	probably benign	Het
AI314180	T	C	4: 58,822,060	N1169S	probably benign	Het
Ap5z1	T	C	5: 142,477,358	F766L	probably benign	Het
Atrnl1	A	G	19: 57,611,354	M1V	probably null	Het
Atxn1	T	C	13: 45,557,146	E770G	probably benign	Het
Brwd1	T	G	16: 96,011,896	I1471L	probably benign	Het
Bud23	T	C	5: 135,053,717	E66G	probably benign	Het
Cdh8	T	A	8: 99,030,735	I744L	possibly damaging	Het
Celsr1	G	T	15: 86,033,085	S229*	probably null	Het
Cep95	C	A	11: 106,812,496	H467Q	probably benign	Het
Chd1	A	G	17: 15,768,761	Y1592C	probably benign	Het
Chkb	C	G	15: 89,429,425	G59A	probably damaging	Het
Copa	A	G	1: 172,118,081	S915G	probably benign	Het
Creb3	G	T	4: 43,563,191	V97F	probably damaging	Het
Csmd2	T	A	4: 128,414,269	H1273Q		Het
Cxcr1	T	C	1: 74,191,915	N316S	probably benign	Het
Cyct	A	T	2: 76,354,179	I76N	probably damaging	Het
Dmxl2	G	T	9: 54,387,556	R2412S	probably damaging	Het
Dnah11	A	G	12: 118,018,778	M2552T	possibly damaging	Het
Dnph1	G	A	17: 46,498,975	E148K	possibly damaging	Het
Esp16	T	A	17: 39,537,840	Y8*	probably null	Het
Fam186a	T	C	15: 99,943,143	D1740G	possibly damaging	Het
Fam76a	C	A	4: 132,901,246	K300N	probably damaging	Het
Frrs1l	A	C	4: 56,990,191	D27E		Het
G6pc	T	C	11: 101,376,554	S277P	probably damaging	Het
Gabrg3	T	A	7: 57,323,674	I82F	probably damaging	Het
Gm3604	G	T	13: 62,370,155	Q130K	probably benign	Het
Gm8879	T	A	5: 11,129,023	N55K	probably benign	Het
Hhip	T	A	8: 79,992,479	D473V	probably damaging	Het
Ifi209	T	C	1: 173,642,766	S307P	probably damaging	Het
Ino80c	C	T	18: 24,121,799	M1I	probably null	Het
Jag2	G	T	12: 112,911,796	C872*	probably null	Het
Kcnma1	A	C	14: 23,508,055	H474Q	probably benign	Het
Krr1	G	A	10: 111,983,058		probably null	Het
Lats1	T	G	10: 7,712,623	D1001E	probably benign	Het
Lilr4b	T	C	10: 51,481,657	L149P	probably benign	Het
Lrrk2	T	A	15: 91,765,681	S1674T	probably damaging	Het
Magi2	A	G	5: 20,465,584	I309V	possibly damaging	Het
Mtmr4	A	G	11: 87,612,312	D1064G	probably damaging	Het
Mtmr4	T	C	11: 87,614,090	V1137A	probably damaging	Het
Neb	C	T	2: 52,243,841		probably null	Het
Nhsl1	T	A	10: 18,526,917	V1297E	possibly damaging	Het
Nptx2	T	C	5: 144,555,349	I312T	possibly damaging	Het
Osm	A	G	11: 4,239,926	T237A	probably benign	Het
Pcdha12	T	C	18: 37,022,181	V651A	possibly damaging	Het
Pclo	A	G	5: 14,858,744		probably null	Het
Pdlim3	C	T	8: 45,915,158	S183L	possibly damaging	Het
Peg10	GC	GCTCC	6: 4,756,452		probably benign	Het
Pgm1	T	A	5: 64,116,328	M552K	probably damaging	Het
Pkhd1l1	T	C	15: 44,523,505	L1258S	probably benign	Het
Proser3	T	G	7: 30,549,105	T55P	probably damaging	Het
Ranbp2	C	A	10: 58,465,141	P611Q	probably damaging	Het
Rangap1	T	C	15: 81,706,436	D485G	probably benign	Het
Rp1	G	A	1: 4,267,569	T421I	unknown	Het
Ryr3	G	A	2: 112,656,538	L3862F	possibly damaging	Het
Sbf1	C	T	15: 89,295,472	G1337R	possibly damaging	Het
Setd2	A	G	9: 110,549,070	E651G	probably damaging	Het
Shmt1	A	G	11: 60,801,943	W105R	probably damaging	Het
Skor2	C	T	18: 76,858,681	H33Y	unknown	Het
Slc22a29	T	C	19: 8,162,740	I434V	probably benign	Het
Sord	C	T	2: 122,260,231	T221I	probably benign	Het
Tbcd	T	C	11: 121,573,821	Y561H	probably damaging	Het
Tcaf1	G	A	6: 42,686,874	S24F	probably benign	Het
Tenm4	A	T	7: 96,867,989	D1429V	probably damaging	Het
Tesk1	A	G	4: 43,444,574	Y126C	probably damaging	Het
Tmem176a	G	A	6: 48,844,018	V141I	probably benign	Het
Tmem204	A	T	17: 25,080,269	V92D	probably damaging	Het
Ttn	T	A	2: 76,742,261	D26096V	probably damaging	Het
Vmn1r70	T	A	7: 10,634,437	L284Q	probably damaging	Het
Vmn2r77	T	C	7: 86,800,963	V139A	possibly damaging	Het
Wdpcp	A	G	11: 21,721,285	R509G	possibly damaging	Het
Wee1	C	T	7: 110,126,003	T284I	probably damaging	Het
Wfs1	A	G	5: 36,967,769	S593P	probably damaging	Het
Zbtb11	A	G	16: 56,006,973	H934R	probably damaging	Het
Zfp277	A	T	12: 40,320,612	V446E	probably benign	Het
Zfp874a	C	A	13: 67,443,037	R176L	probably benign	Het
Znrf2	A	T	6: 54,863,993	N184I	probably damaging	Het
Zp2	T	A	7: 120,134,015	T568S	probably 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
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
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'- CTTCAGCCACATGACTTTCCAG -3'
(R):5'- AAAGTGGTCCATGGCACTCTG -3'

Sequencing Primer
(F):5'- AGCCACATGACTTTCCAGGAGTTC -3'
(R):5'- TGCATCTCGTACAGGCAGTAG -3'

Posted On

2022-10-06