Mutagenetix > Incidental Mutation

Incidental Mutation 'R8940:Nlrp3'

680929

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 #

R8940 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

59541568-59566956 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 59565044 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Valine to Methionine at position 889 (V889M)

Ref Sequence

ENSEMBL: ENSMUSP00000098707 (fasta)

Gene Model

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

AlphaFold

Q8R4B8

Predicted Effect

probably benign
Transcript: ENSMUST00000079476
AA Change: V889M

PolyPhen 2 Score 0.263 (Sensitivity: 0.91; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000078440
Gene: ENSMUSG00000032691
AA Change: V889M

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: V889M

PolyPhen 2 Score 0.263 (Sensitivity: 0.91; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000098707
Gene: ENSMUSG00000032691
AA Change: V889M

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

Meta Mutation Damage Score

0.0944

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 99.1%

Validation Efficiency

99% (73/74)

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: 77 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2900026A02Rik	A	T	5: 113,093,202	S1709T	probably benign	Het
Abcc12	A	G	8: 86,560,811	V135A	probably benign	Het
Alkbh3	G	T	2: 94,008,046	P60H	probably damaging	Het
Armc3	A	C	2: 19,235,582	Y50S	probably damaging	Het
Arpc4	T	C	6: 113,385,638	V70A	probably benign	Het
Atp13a4	A	G	16: 29,454,690		probably null	Het
Bco1	A	T	8: 117,130,608	Y438F	probably benign	Het
Cacna1b	C	A	2: 24,763,072		probably benign	Het
Cdh17	C	T	4: 11,783,226	S189L	probably damaging	Het
Cltc	T	C	11: 86,730,246	T312A	probably benign	Het
Crym	T	A	7: 120,195,480	N172I	probably benign	Het
Depdc7	A	G	2: 104,724,568		probably null	Het
Dnhd1	T	A	7: 105,714,647		probably benign	Het
Dntt	T	A	19: 41,058,551		probably benign	Het
Elovl5	T	A	9: 77,982,725	S273T	possibly damaging	Het
Fat2	A	T	11: 55,256,810	L3869M	possibly damaging	Het
Garnl3	T	C	2: 33,005,229		probably null	Het
Gldc	C	T	19: 30,151,484	M196I	probably benign	Het
Gm17078	C	T	14: 51,608,885	V120M	probably damaging	Het
Gm5157	G	A	7: 21,184,760	S286F	probably damaging	Het
Gm6337	C	T	14: 6,055,308	C187Y	probably damaging	Het
Gm9833	A	T	3: 10,088,346	L58F	probably benign	Het
Golgb1	A	G	16: 36,916,397	D2002G	probably damaging	Het
Gpr179	T	C	11: 97,337,849	N1160S	probably damaging	Het
Gulo	A	G	14: 65,997,591	V227A	probably benign	Het
Hlcs	G	A	16: 94,231,226	A31V	probably benign	Het
Hs1bp3	T	C	12: 8,341,980	S361P	probably benign	Het
Ifi44	G	A	3: 151,749,309	P93L	probably benign	Het
Izumo2	T	A	7: 44,713,046	M78K	probably benign	Het
Lin54	T	C	5: 100,446,671	E545G	probably damaging	Het
Map3k13	A	T	16: 21,908,704	I439F	possibly damaging	Het
Matr3	T	G	18: 35,572,587	S188R	probably damaging	Het
Mug1	A	T	6: 121,881,683	H1120L		Het
Ndst4	A	G	3: 125,681,153		probably benign	Het
Olfr1030	A	T	2: 85,984,199	M120L	probably benign	Het
Olfr1375	A	G	11: 51,048,628	I174V	probably benign	Het
Olfr456	A	G	6: 42,486,278	M305T	probably benign	Het
Olfr985	T	A	9: 40,127,184	Y259F	probably damaging	Het
Olfr998	A	G	2: 85,591,184	I215V	probably benign	Het
P4hb	A	T	11: 120,568,002	D182E	probably benign	Het
Pcdh10	A	G	3: 45,384,185	T926A	possibly damaging	Het
Pikfyve	T	C	1: 65,246,970	S1078P	probably benign	Het
Plcl2	A	T	17: 50,608,762	D933V	probably damaging	Het
Pramel7	G	A	2: 87,491,268	T141I	probably benign	Het
Prepl	A	T	17: 85,068,926	C567S	probably damaging	Het
Prpsap1	A	T	11: 116,479,789	M114K	probably damaging	Het
Ptk2b	A	C	14: 66,170,236		probably null	Het
Rest	T	C	5: 77,282,868	F1045L	possibly damaging	Het
Rnf19a	A	G	15: 36,260,138	C254R	probably damaging	Het
Rrad	C	T	8: 104,628,590	R262Q	possibly damaging	Het
Rsf1	GGCG	GGCGACTGCCGCG	7: 97,579,906		probably benign	Het
Setdb1	T	A	3: 95,356,172	M8L	probably benign	Het
Setdb2	A	G	14: 59,409,507	S536P	probably damaging	Het
Sipa1l1	T	C	12: 82,357,266	L511P	probably damaging	Het
Slc12a9	T	A	5: 137,328,493	H234L	probably benign	Het
Slc35e2	G	T	4: 155,610,085	G30W	probably damaging	Het
Slc6a15	T	C	10: 103,393,496	V132A	probably damaging	Het
Slc7a10	A	G	7: 35,200,450	T486A	probably benign	Het
Smc5	T	C	19: 23,259,762	Y235C	probably benign	Het
Sorcs3	T	C	19: 48,796,469		probably null	Het
Spata21	T	C	4: 141,104,905	L459P	probably damaging	Het
Tbc1d9	A	G	8: 83,254,823	I706M	probably damaging	Het
Tcp11	T	A	17: 28,080,230	E17V	probably damaging	Het
Tiparp	A	G	3: 65,531,878	D23G	probably benign	Het
Tmem108	A	G	9: 103,499,957	S98P	possibly damaging	Het
Tmem35b	A	G	4: 127,127,880	D56G	probably damaging	Het
Tnr	G	C	1: 159,858,297	G366A	probably damaging	Het
Ttc3	A	G	16: 94,429,499	S852G	possibly damaging	Het
Ttn	G	A	2: 76,766,594	L19992F	probably damaging	Het
Ush2a	T	A	1: 188,400,308	M909K	probably benign	Het
Wdr90	G	A	17: 25,857,172	R104C		Het
Wif1	A	G	10: 121,099,779	H333R	probably benign	Het
Zfp119a	A	G	17: 55,865,551	C431R	probably damaging	Het
Zfp345	G	A	2: 150,472,357	P420L	probably benign	Het
Zfp608	C	T	18: 54,900,229	D411N	possibly damaging	Het
Zfp609	C	T	9: 65,703,279	A801T	possibly damaging	Het
Zfp74	A	G	7: 29,935,347	V312A	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
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'- ATGCTGAGACCATTGTCCATC -3'
(R):5'- CATGTTCCCATCACCTCAGG -3'

Sequencing Primer
(F):5'- ATCTCTCCTGTGGGATCCAGAGAC -3'
(R):5'- TCAGGCAGCCCATGAACTC -3'

Posted On

2021-08-31