Mutagenetix > Incidental Mutation

Incidental Mutation 'R1414:Nlrp3'

159748

Institutional Source

Beutler Lab

Gene Symbol

Nlrp3

Ensembl Gene

ENSMUSG00000032691

Gene Name

NLR family, pyrin domain containing 3

Synonyms

Mmig1, Cias1, NALP3, cryopyrin, Pypaf1

MMRRC Submission

039470-MU

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.076) question?

Stock #

R1414 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

59432395-59457781 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 59440357 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Methionine to Valine at position 645 (M645V)

Ref Sequence

ENSEMBL: ENSMUSP00000098707 (fasta)

Gene Model

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

AlphaFold

Q8R4B8

Predicted Effect

probably benign
Transcript: ENSMUST00000079476
AA Change: M645V

PolyPhen 2 Score 0.190 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000078440
Gene: ENSMUSG00000032691
AA Change: M645V

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: M645V

PolyPhen 2 Score 0.190 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000098707
Gene: ENSMUSG00000032691
AA Change: M645V

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

0.9135

Coding Region Coverage

1x: 99.0%
3x: 98.2%
10x: 95.8%
20x: 91.2%

Validation Efficiency

97% (36/37)

MGI Phenotype

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: 30 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Asap1	T	A	15: 64,030,733 (GRCm39)	S315C	possibly damaging	Het
Cdc27	A	G	11: 104,412,251 (GRCm39)	V452A	probably benign	Het
Cndp1	G	A	18: 84,652,777 (GRCm39)		probably benign	Het
Dnajc10	C	A	2: 80,178,021 (GRCm39)	T676K	probably damaging	Het
Efhc1	C	T	1: 21,031,513 (GRCm39)	T237I	probably damaging	Het
Fn1	A	G	1: 71,640,462 (GRCm39)		probably benign	Het
Gtf3c3	C	T	1: 54,456,937 (GRCm39)	A488T	probably damaging	Het
Hfm1	T	C	5: 107,020,219 (GRCm39)	D1069G	probably benign	Het
Hspa9	T	C	18: 35,071,644 (GRCm39)	Y652C	probably damaging	Het
Lrfn2	A	G	17: 49,377,857 (GRCm39)	I313V	probably benign	Het
Mroh2a	A	G	1: 88,186,386 (GRCm39)	S64G	probably benign	Het
Mxra8	A	G	4: 155,925,464 (GRCm39)	M58V	probably damaging	Het
Myh3	A	G	11: 66,989,491 (GRCm39)	E1537G	probably damaging	Het
Nlrp4d	T	A	7: 10,116,528 (GRCm39)	I118F	probably benign	Het
Oas1f	A	G	5: 120,989,522 (GRCm39)		probably benign	Het
Pkp1	A	G	1: 135,811,823 (GRCm39)		probably benign	Het
Plcb3	T	C	19: 6,940,385 (GRCm39)	Y428C	probably damaging	Het
Pomt1	C	A	2: 32,133,622 (GRCm39)		probably benign	Het
Prex1	G	A	2: 166,435,781 (GRCm39)	R589C	probably damaging	Het
Prr5	C	T	15: 84,583,912 (GRCm39)	Q171*	probably null	Het
Ptar1	T	A	19: 23,697,655 (GRCm39)	L389Q	possibly damaging	Het
Rufy2	T	A	10: 62,837,978 (GRCm39)	L375*	probably null	Het
Slc22a1	G	A	17: 12,881,487 (GRCm39)	S334L	probably damaging	Het
Slc34a1	T	C	13: 55,548,524 (GRCm39)	S45P	probably benign	Het
Sned1	G	A	1: 93,209,376 (GRCm39)	V830M	possibly damaging	Het
Tafa4	A	G	6: 96,991,440 (GRCm39)	V3A	probably benign	Het
Tnc	A	G	4: 63,883,932 (GRCm39)		probably benign	Het
Tpm3-rs7	T	C	14: 113,552,274 (GRCm39)	I56T	possibly damaging	Het
Zbtb11	T	A	16: 55,810,923 (GRCm39)	C360*	probably null	Het
Zfp263	T	C	16: 3,567,160 (GRCm39)	C204R	probably damaging	Het

Other mutations in Nlrp3

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00421:Nlrp3	APN	11	59,456,769 (GRCm39)	missense	probably damaging	0.99
IGL00573:Nlrp3	APN	11	59,455,942 (GRCm39)	missense	possibly damaging	0.93
IGL01025:Nlrp3	APN	11	59,442,713 (GRCm39)	missense	probably benign	0.21
IGL01637:Nlrp3	APN	11	59,440,204 (GRCm39)	missense	probably damaging	0.99
IGL02010:Nlrp3	APN	11	59,440,361 (GRCm39)	missense	probably benign
IGL02334:Nlrp3	APN	11	59,455,909 (GRCm39)	missense	probably benign
IGL02417:Nlrp3	APN	11	59,456,849 (GRCm39)	unclassified	probably benign
IGL02578:Nlrp3	APN	11	59,439,227 (GRCm39)	missense	probably damaging	1.00
IGL02710:Nlrp3	APN	11	59,456,802 (GRCm39)	missense	probably damaging	0.99
IGL02816:Nlrp3	APN	11	59,446,608 (GRCm39)	missense	probably benign	0.03
IGL03157:Nlrp3	APN	11	59,440,372 (GRCm39)	missense	possibly damaging	0.80
IGL03334:Nlrp3	APN	11	59,439,842 (GRCm39)	missense	probably damaging	1.00
Flogiston	UTSW	11	59,449,274 (GRCm39)	missense	probably benign	0.00
nd1	UTSW	11	59,456,800 (GRCm39)	missense	probably benign	0.45
Nd14	UTSW	11	59,446,701 (GRCm39)	missense	possibly damaging	0.89
Nd3	UTSW	11	59,456,800 (GRCm39)	missense	probably benign	0.45
nd5	UTSW	11	59,456,705 (GRCm39)	missense	probably benign	0.01
nd6	UTSW	11	59,440,180 (GRCm39)	missense	probably damaging	1.00
nd7	UTSW	11	59,446,701 (GRCm39)	missense	possibly damaging	0.89
Nd9	UTSW	11	59,440,180 (GRCm39)	missense	probably damaging	1.00
Park2	UTSW	11	59,455,954 (GRCm39)	nonsense	probably null
Park3	UTSW	11	59,456,676 (GRCm39)	missense	probably benign	0.02
Park4	UTSW	11	59,440,357 (GRCm39)	missense	probably benign	0.19
Park5	UTSW	11	59,439,302 (GRCm39)	missense	probably damaging	0.99
Park6	UTSW	11	59,439,862 (GRCm39)	missense	probably damaging	1.00
Park7	UTSW	11	59,438,836 (GRCm39)	nonsense	probably null
Park8	UTSW	11	59,457,025 (GRCm39)	missense	probably benign	0.19
R0008:Nlrp3	UTSW	11	59,449,274 (GRCm39)	missense	probably benign	0.00
R0008:Nlrp3	UTSW	11	59,449,274 (GRCm39)	missense	probably benign	0.00
R0052:Nlrp3	UTSW	11	59,455,954 (GRCm39)	nonsense	probably null
R0362:Nlrp3	UTSW	11	59,439,623 (GRCm39)	missense	possibly damaging	0.49
R0416:Nlrp3	UTSW	11	59,446,750 (GRCm39)	splice site	probably benign
R0649:Nlrp3	UTSW	11	59,439,368 (GRCm39)	missense	possibly damaging	0.83
R0740:Nlrp3	UTSW	11	59,439,082 (GRCm39)	missense	probably benign	0.01
R0863:Nlrp3	UTSW	11	59,456,676 (GRCm39)	missense	probably benign	0.02
R1300:Nlrp3	UTSW	11	59,446,594 (GRCm39)	missense	possibly damaging	0.86
R1622:Nlrp3	UTSW	11	59,439,302 (GRCm39)	missense	probably damaging	0.99
R1654:Nlrp3	UTSW	11	59,433,949 (GRCm39)	missense	probably benign	0.03
R1715:Nlrp3	UTSW	11	59,434,177 (GRCm39)	missense	probably damaging	1.00
R1754:Nlrp3	UTSW	11	59,449,228 (GRCm39)	missense	possibly damaging	0.80
R1837:Nlrp3	UTSW	11	59,439,742 (GRCm39)	missense	probably benign	0.00
R1905:Nlrp3	UTSW	11	59,439,862 (GRCm39)	missense	probably damaging	1.00
R2281:Nlrp3	UTSW	11	59,439,962 (GRCm39)	missense	possibly damaging	0.70
R4296:Nlrp3	UTSW	11	59,440,487 (GRCm39)	missense	possibly damaging	0.89
R4305:Nlrp3	UTSW	11	59,438,836 (GRCm39)	nonsense	probably null
R4540:Nlrp3	UTSW	11	59,442,725 (GRCm39)	missense	possibly damaging	0.83
R4591:Nlrp3	UTSW	11	59,440,048 (GRCm39)	missense	probably benign	0.00
R4816:Nlrp3	UTSW	11	59,439,127 (GRCm39)	missense	probably benign	0.32
R4913:Nlrp3	UTSW	11	59,440,064 (GRCm39)	missense	probably benign	0.09
R4970:Nlrp3	UTSW	11	59,439,554 (GRCm39)	missense	probably damaging	1.00
R5051:Nlrp3	UTSW	11	59,457,025 (GRCm39)	missense	probably benign	0.19
R5112:Nlrp3	UTSW	11	59,439,554 (GRCm39)	missense	probably damaging	1.00
R5185:Nlrp3	UTSW	11	59,455,910 (GRCm39)	missense	probably benign	0.05
R5417:Nlrp3	UTSW	11	59,439,889 (GRCm39)	missense	probably damaging	1.00
R5709:Nlrp3	UTSW	11	59,446,574 (GRCm39)	nonsense	probably null
R5869:Nlrp3	UTSW	11	59,438,960 (GRCm39)	missense	probably damaging	1.00
R5898:Nlrp3	UTSW	11	59,437,678 (GRCm39)	missense	probably benign	0.00
R5953:Nlrp3	UTSW	11	59,437,617 (GRCm39)	missense	probably benign
R5979:Nlrp3	UTSW	11	59,439,797 (GRCm39)	missense	probably benign	0.06
R6359:Nlrp3	UTSW	11	59,439,392 (GRCm39)	missense	probably damaging	0.97
R6723:Nlrp3	UTSW	11	59,456,018 (GRCm39)	missense	probably damaging	1.00
R7261:Nlrp3	UTSW	11	59,439,272 (GRCm39)	missense	possibly damaging	0.83
R7349:Nlrp3	UTSW	11	59,438,912 (GRCm39)	missense	probably damaging	1.00
R7388:Nlrp3	UTSW	11	59,455,892 (GRCm39)	missense	probably benign	0.00
R7715:Nlrp3	UTSW	11	59,433,829 (GRCm39)	splice site	probably null
R7916:Nlrp3	UTSW	11	59,442,689 (GRCm39)	missense	probably benign	0.00
R8222:Nlrp3	UTSW	11	59,439,614 (GRCm39)	missense	probably damaging	0.98
R8360:Nlrp3	UTSW	11	59,440,229 (GRCm39)	missense	probably benign	0.02
R8390:Nlrp3	UTSW	11	59,442,616 (GRCm39)	missense	possibly damaging	0.47
R8550:Nlrp3	UTSW	11	59,440,097 (GRCm39)	missense	probably damaging	1.00
R8738:Nlrp3	UTSW	11	59,440,216 (GRCm39)	missense	probably benign	0.00
R8940:Nlrp3	UTSW	11	59,455,870 (GRCm39)	missense	probably benign	0.26
R8990:Nlrp3	UTSW	11	59,439,584 (GRCm39)	missense	probably damaging	0.99
R9324:Nlrp3	UTSW	11	59,434,141 (GRCm39)	missense	probably damaging	1.00
R9673:Nlrp3	UTSW	11	59,440,148 (GRCm39)	missense	probably damaging	1.00
RF031:Nlrp3	UTSW	11	59,449,378 (GRCm39)	frame shift	probably null
RF040:Nlrp3	UTSW	11	59,449,378 (GRCm39)	frame shift	probably null
Z1088:Nlrp3	UTSW	11	59,442,686 (GRCm39)	missense	possibly damaging	0.67

Predicted Primers

PCR Primer
(F):5'- TGAACCGAGACGTGAAGGTCCTAC -3'
(R):5'- GCCCGAAGCCAAATTACCTGGAAG -3'

Sequencing Primer
(F):5'- CTTTGGCCTTGTAAACCAGGAG -3'
(R):5'- TGTCTGGGAAAACACACTGAAC -3'

Posted On

2014-03-14