Mutagenetix > Incidental Mutation

Incidental Mutation 'R5051:Nlrp3'

394661

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

042641-MU

Accession Numbers

Ncbi RefSeq: NM_145827.3; MGI:2653833

Essential gene?

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

Stock #

R5051 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

59541568-59566956 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to C at 59566199 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Proline at position 1013 (R1013P)

Ref Sequence

ENSEMBL: ENSMUSP00000098707 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000071943] [ENSMUST00000079476] [ENSMUST00000101148] [ENSMUST00000214351] [ENSMUST00000215339]

AlphaFold

Q8R4B8

Predicted Effect

probably benign
Transcript: ENSMUST00000071943

SMART Domains

Protein: ENSMUSP00000071835
Gene: ENSMUSG00000059610

Domain	Start	End	E-Value	Type
Pfam:7TM_GPCR_Srv	29	311	4.3e-9	PFAM
Pfam:7tm_4	35	312	3.4e-54	PFAM
Pfam:7tm_1	45	294	1.3e-28	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000079476
AA Change: R1013P

PolyPhen 2 Score 0.195 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000078440
Gene: ENSMUSG00000032691
AA Change: R1013P

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: R1013P

PolyPhen 2 Score 0.195 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000098707
Gene: ENSMUSG00000032691
AA Change: R1013P

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: ENSMUST00000214351

Predicted Effect

probably benign
Transcript: ENSMUST00000215339

Meta Mutation Damage Score

0.0898

Coding Region Coverage

1x: 99.3%
3x: 98.3%
10x: 95.9%
20x: 90.6%

Validation Efficiency

98% (62/63)

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: 49 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2310035C23Rik	T	A	1: 105,691,986	N313K	possibly damaging	Het
5730522E02Rik	G	A	11: 25,768,990	T51I	unknown	Het
Alms1	C	T	6: 85,627,934	Q2189*	probably null	Het
Ank1	A	T	8: 23,119,381	D1363V	probably damaging	Het
Ap3d1	T	G	10: 80,719,199	T431P	probably damaging	Het
Arnt	A	G	3: 95,470,337	T125A	probably benign	Het
Atp10a	TGTCCGTC	TGTC	7: 58,740,246		probably null	Het
Bscl2	A	T	19: 8,845,279	R195*	probably null	Het
Ccdc146	C	T	5: 21,303,083	V656I	possibly damaging	Het
Ccr4	T	C	9: 114,492,646	Y117C	probably damaging	Het
Cd55	T	A	1: 130,448,348	D355V	probably damaging	Het
Cntn6	T	A	6: 104,772,597	I259N	probably damaging	Het
Cspg4	A	G	9: 56,885,736	I252V	possibly damaging	Het
Dmbt1	T	C	7: 131,094,742	V895A	probably benign	Het
Ect2	A	G	3: 27,102,486	V775A	probably benign	Het
Gm14486	T	C	2: 30,658,877		noncoding transcript	Het
Grin2b	T	C	6: 135,779,395	N444S	possibly damaging	Het
Heatr5b	T	C	17: 78,795,274	D1225G	probably damaging	Het
Il1rl2	G	A	1: 40,343,094	V189I	probably benign	Het
Kif1a	G	A	1: 93,076,154		probably null	Het
Ltbr	T	A	6: 125,312,770	T154S	probably damaging	Het
Mrgpra6	C	T	7: 47,185,942	V244I	probably benign	Het
Myo15	G	A	11: 60,487,425		probably null	Het
Ndufs1	A	G	1: 63,164,947		probably null	Het
Nectin3	A	T	16: 46,448,550	N496K	possibly damaging	Het
Nkd2	A	G	13: 73,825,076	V147A	probably benign	Het
Olfr1280	T	A	2: 111,316,254	Y258*	probably null	Het
Olfr1423	C	A	19: 12,035,924	V273F	possibly damaging	Het
Pdk2	T	C	11: 95,028,772	S263G	probably benign	Het
Pla2g4e	T	A	2: 120,174,304	I520F	probably damaging	Het
Plat	A	G	8: 22,773,672	T196A	probably benign	Het
Podn	T	A	4: 108,014,846	D400V	probably benign	Het
Poteg	T	C	8: 27,453,329	V147A	possibly damaging	Het
Prkar2a	A	G	9: 108,745,491	N315D	probably benign	Het
Rac2	A	G	15: 78,564,934	I13T	possibly damaging	Het
Rangap1	A	C	15: 81,710,463	D388E	probably benign	Het
Sp140	T	A	1: 85,610,828	D95E	possibly damaging	Het
Supv3l1	A	C	10: 62,443,417	I240S	probably damaging	Het
Sympk	C	T	7: 19,036,042	R215C	probably benign	Het
Tead4	A	C	6: 128,294,299		probably benign	Het
Tex10	G	A	4: 48,460,019	A444V	possibly damaging	Het
Tgds	A	T	14: 118,128,227	I73K	probably damaging	Het
Tmem117	C	A	15: 94,714,913	T110K	probably damaging	Het
Trim30a	T	A	7: 104,411,706		probably benign	Het
Unc80	C	T	1: 66,509,477	T636I	probably damaging	Het
Wisp3	A	G	10: 39,155,156	F124L	probably benign	Het
Ybey	G	A	10: 76,468,339	R10W	probably damaging	Het
Zap70	A	G	1: 36,781,451	I576V	probably benign	Het
Zfp64	T	C	2: 168,926,384	D436G	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
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'- TGCCTAGAGCTTCTCATGGG -3'
(R):5'- ATTTGGTCCCACACAAGCC -3'

Sequencing Primer
(F):5'- CCTAGAGCTTCTCATGGGGTAGG -3'
(R):5'- CCTCGGCTGTGATCCTGATG -3'

Posted On

2016-06-15