Mutagenetix > Incidental Mutation

Incidental Mutation 'R9324:Nlrp3'

706398

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 #

R9324 (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 59543315 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Methionine to Lysine at position 68 (M68K)

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: M68K

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

SMART Domains

Protein: ENSMUSP00000078440
Gene: ENSMUSG00000032691
AA Change: M68K

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: M68K

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

SMART Domains

Protein: ENSMUSP00000098707
Gene: ENSMUSG00000032691
AA Change: M68K

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: ENSMUST00000149126
AA Change: M68K

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

SMART Domains

Protein: ENSMUSP00000114231
Gene: ENSMUSG00000032691
AA Change: M68K

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: 99.9%
10x: 99.7%
20x: 98.9%

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: 68 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acsm2	A	G	7: 119,580,633	H358R	probably benign	Het
Arid3c	A	G	4: 41,730,138	L19S	possibly damaging	Het
Arpp21	T	A	9: 112,157,697	D262V	probably damaging	Het
Atp4a	A	C	7: 30,715,782	I276L	probably benign	Het
Axl	C	G	7: 25,761,557	E676Q	probably damaging	Het
Ccdc151	T	C	9: 21,991,911	E402G	probably damaging	Het
Ces1g	T	C	8: 93,328,490	D193G	probably damaging	Het
Crym	A	G	7: 120,189,782	V274A	probably damaging	Het
Efcab5	T	A	11: 77,113,720	H924L	possibly damaging	Het
Eif3l	T	A	15: 79,094,223	M560K	probably benign	Het
Fam160a1	T	C	3: 85,730,746	D82G	probably benign	Het
Fam234b	C	A	6: 135,225,795	Y382*	probably null	Het
Fam71b	A	T	11: 46,404,983	I61F		Het
Fbxw19	T	C	9: 109,484,372	K253E	possibly damaging	Het
Flt3	A	G	5: 147,376,980	S87P	probably benign	Het
Ggnbp2	A	G	11: 84,834,348	L627S	probably damaging	Het
Gm16486	C	T	8: 70,709,145	T329I	possibly damaging	Het
Gm26661	T	G	14: 7,791,765	V60G	unknown	Het
Gm5065	G	A	7: 5,359,528	V53I	possibly damaging	Het
Gm5662	T	A	12: 88,271,939	N17I	unknown	Het
Golt1a	T	C	1: 133,319,356	L34P	probably damaging	Het
Gp5	T	C	16: 30,308,990	M289V	possibly damaging	Het
Gpr63	C	G	4: 25,008,432	H385Q	possibly damaging	Het
Hcn1	G	A	13: 117,975,365	V622I	unknown	Het
Hipk4	A	G	7: 27,529,409	D428G	probably damaging	Het
Hs3st1	T	C	5: 39,614,802	Y166C	probably damaging	Het
Hsd17b3	A	G	13: 64,058,645	F281S	possibly damaging	Het
Ifih1	T	C	2: 62,645,606	T109A	probably benign	Het
Ighv1-64	T	A	12: 115,508,025		probably benign	Het
Ina	T	C	19: 47,015,377	L208P		Het
Irak2	T	C	6: 113,638,643		probably null	Het
Klhl10	G	A	11: 100,447,655	E407K	probably benign	Het
Krt81	A	G	15: 101,463,454	S82P	probably damaging	Het
Ktn1	C	A	14: 47,710,896	Q963K	probably benign	Het
Lrrc42	A	T	4: 107,247,716	Y17*	probably null	Het
Lrrc9	A	C	12: 72,449,397	E15D	probably damaging	Het
Mak	G	A	13: 41,049,363	T203I	probably benign	Het
Masp2	T	C	4: 148,608,028	V326A	possibly damaging	Het
Mdc1	T	C	17: 35,853,366	S1269P	probably benign	Het
Mink1	G	A	11: 70,611,651	V1027M	probably damaging	Het
Mrps10	C	A	17: 47,375,978	S123*	probably null	Het
Myl10	C	T	5: 136,700,933	H142Y	probably damaging	Het
Ncan	T	C	8: 70,107,998	Q773R	possibly damaging	Het
Ntrk1	C	T	3: 87,791,438	V99M	possibly damaging	Het
Olfr1184	C	T	2: 88,487,443	T237I	probably damaging	Het
Olfr143	A	G	9: 38,253,666	K80R	probably benign	Het
Olfr1434	A	G	19: 12,283,575	R176G	probably benign	Het
Phldb2	A	G	16: 45,775,074	V830A	probably damaging	Het
Phospho2	T	C	2: 69,795,569	V23A	probably damaging	Het
Plxnc1	G	A	10: 94,944,823		probably benign	Het
Ppcdc	T	C	9: 57,434,997	E14G	probably benign	Het
Ralgapa2	T	C	2: 146,460,725	Y106C	probably damaging	Het
Rgs22	T	C	15: 36,087,398	Q582R	probably benign	Het
Rngtt	T	A	4: 33,320,613	Y53*	probably null	Het
Slc12a3	T	G	8: 94,356,400		probably null	Het
Slc26a11	A	G	11: 119,376,904	T456A	probably benign	Het
Slc26a5	G	T	5: 21,813,336	A677E	possibly damaging	Het
Smurf1	T	C	5: 144,880,653	T690A	probably benign	Het
Spata24	A	T	18: 35,657,011	N142K	probably damaging	Het
Ubqlnl	A	T	7: 104,149,755	N178K	possibly damaging	Het
Uggt2	A	G	14: 119,075,329		probably null	Het
Vmn1r2	C	A	4: 3,172,678	A199D	probably damaging	Het
Vmn2r39	T	C	7: 9,027,685	N128S	probably damaging	Het
Vmn2r61	G	T	7: 42,267,195	V411F	probably benign	Het
Vmn2r-ps117	T	A	17: 18,822,649	F106L	probably benign	Het
Zfp503	A	T	14: 21,985,285	I521N	possibly damaging	Het
Zfp831	T	C	2: 174,705,320	V1432A	probably benign	Het
Zfp981	T	A	4: 146,535,427	L13I	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
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
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'- CTAGAGGACCTTGAAGATGTGG -3'
(R):5'- AGCCTGGGATACTTGAGACTC -3'

Sequencing Primer
(F):5'- GACCTTGAAGATGTGGACCTC -3'
(R):5'- TTATGCTAAGTGAAGTAAGCCAGCC -3'

Posted On

2022-04-18