Mutagenetix > Incidental Mutation

Incidental Mutation 'R1837:Nlrp3'

205419

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

039864-MU

Accession Numbers

Ncbi RefSeq: NM_145827.3; MGI:2653833

Essential gene?

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

Stock #

R1837 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

59541568-59566956 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 59548916 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Valine to Isoleucine at position 440 (V440I)

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: V440I

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000078440
Gene: ENSMUSG00000032691
AA Change: V440I

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: V440I

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000098707
Gene: ENSMUSG00000032691
AA Change: V440I

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

0.1137

Coding Region Coverage

1x: 97.4%
3x: 96.8%
10x: 94.9%
20x: 91.6%

Validation Efficiency

99% (86/87)

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: 85 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Actl10	G	T	2: 154,553,042	G305W	probably damaging	Het
Actr3b	A	T	5: 25,825,159	T74S	probably benign	Het
Add2	A	G	6: 86,118,558	E652G	probably damaging	Het
Alg9	T	A	9: 50,806,315	V83D	probably damaging	Het
Atp13a2	T	A	4: 140,994,332	Y244*	probably null	Het
BB014433	C	G	8: 15,042,629	V75L	unknown	Het
Bcr	A	G	10: 75,168,100		probably benign	Het
Begain	G	A	12: 109,035,323		probably benign	Het
Bzw1	A	G	1: 58,400,118	K67E	probably damaging	Het
Ccdc141	T	C	2: 77,011,665	E1474G	probably benign	Het
Cdc73	T	A	1: 143,667,657	T314S	possibly damaging	Het
Cfap206	T	C	4: 34,728,813	T31A	probably damaging	Het
Cfap58	G	A	19: 48,029,139	E813K	probably damaging	Het
Clstn2	C	A	9: 97,583,540	A133S	probably benign	Het
Col14a1	A	T	15: 55,382,495	D465V	unknown	Het
Col2a1	C	T	15: 97,996,641		probably benign	Het
Dab2	A	G	15: 6,336,476		probably benign	Het
Eme1	T	C	11: 94,645,961	D464G	probably benign	Het
Eml6	T	C	11: 29,749,802		probably null	Het
Ern1	C	A	11: 106,458,957	L44F	probably damaging	Het
Fam111a	T	A	19: 12,587,452	S188R	probably benign	Het
Fam151b	A	T	13: 92,474,131		probably benign	Het
Fmo6	T	C	1: 162,922,810	N226D	probably benign	Het
Ggt1	A	G	10: 75,579,294	D214G	probably benign	Het
Gm14226	A	G	2: 155,025,010	I296V	probably benign	Het
Gm9915	A	T	1: 42,230,687		noncoding transcript	Het
Heatr5b	T	C	17: 78,820,751	D485G	possibly damaging	Het
Helz2	A	T	2: 181,229,289	I2785N	probably damaging	Het
Htt	C	T	5: 34,819,023	T723M	probably benign	Het
Hydin	C	A	8: 110,569,625	H3595Q	probably benign	Het
Il6ra	T	C	3: 89,890,272	D96G	probably benign	Het
Kif5a	G	A	10: 127,236,815	Q702*	probably null	Het
Klhdc7a	G	T	4: 139,967,070	P189T	probably benign	Het
Krt7	A	G	15: 101,419,582	D252G	probably benign	Het
Lad1	C	A	1: 135,829,706	D394E	probably benign	Het
Lhx8	A	T	3: 154,328,055	C38S	possibly damaging	Het
Lta4h	C	T	10: 93,469,175	T280M	probably damaging	Het
Magi2	A	T	5: 20,465,827	T163S	probably damaging	Het
Med1	G	T	11: 98,169,412	D230E	probably damaging	Het
Mmp1b	A	T	9: 7,386,409	F171I	probably damaging	Het
Mprip	T	C	11: 59,766,745	V801A	probably damaging	Het
Mtrf1	A	G	14: 79,401,833	E135G	possibly damaging	Het
Muc5ac	T	A	7: 141,807,086	M1378K	probably benign	Het
Myo3a	A	T	2: 22,577,592	Q286L	possibly damaging	Het
Ndor1	C	T	2: 25,248,396	G391R	probably damaging	Het
Nefl	C	T	14: 68,086,626	R438C	probably damaging	Het
Notch3	A	T	17: 32,124,322	L1959Q	probably damaging	Het
Noto	A	G	6: 85,424,177	T63A	probably benign	Het
Oc90	G	A	15: 65,889,680	T163M	probably damaging	Het
Olfr1219	A	T	2: 89,074,832	Y86*	probably null	Het
Olfr1436	A	G	19: 12,298,376	V252A	probably damaging	Het
Olfr365	T	A	2: 37,202,102	M287K	probably benign	Het
Pdpr	C	A	8: 111,134,734	P787T	probably damaging	Het
Phlda1	A	G	10: 111,507,231	Q276R	probably benign	Het
Ptpn21	T	G	12: 98,733,626	K10Q	probably damaging	Het
Ptprb	A	G	10: 116,341,626	E1364G	probably benign	Het
Rabep1	T	A	11: 70,904,658	W237R	probably damaging	Het
Rai1	A	T	11: 60,189,398	K1429N	probably damaging	Het
Rapgef1	A	G	2: 29,737,426	I1027M	probably damaging	Het
Rit1	C	G	3: 88,729,170	T127S	probably damaging	Het
Rpap1	A	C	2: 119,769,885		probably null	Het
Senp7	T	A	16: 56,158,516	C471S	probably benign	Het
Slc16a14	A	G	1: 84,912,399	V395A	probably benign	Het
Slc45a1	C	T	4: 150,638,459	G323S	probably benign	Het
Syne2	A	T	12: 75,967,660	E3208D	probably damaging	Het
Tap1	C	T	17: 34,188,109	A77V	possibly damaging	Het
Ticam1	T	C	17: 56,270,799	E432G	possibly damaging	Het
Tmem192	C	A	8: 64,964,340		probably benign	Het
Trub1	T	C	19: 57,453,029	V28A	probably benign	Het
Ttc21b	A	T	2: 66,197,762	L1121H	probably benign	Het
Ttc38	A	G	15: 85,851,563	D290G	probably damaging	Het
Ulk1	C	T	5: 110,789,381	G683D	probably damaging	Het
Vmn1r122	A	T	7: 21,133,366	F255I	probably benign	Het
Vmn2r68	T	A	7: 85,233,678	I289F	probably damaging	Het
Vps39	A	T	2: 120,325,397	L514H	probably damaging	Het
Wdr48	T	G	9: 119,905,416	S134A	probably damaging	Het
Yap1	A	T	9: 7,962,349	Y139N	probably damaging	Het
Ylpm1	T	C	12: 85,029,333	V486A	possibly damaging	Het
Zbtb38	T	C	9: 96,686,995	T679A	probably benign	Het
Zfp292	A	G	4: 34,810,264	S927P	probably damaging	Het
Zfp324	C	T	7: 12,970,229	T115I	probably benign	Het
Zfp523	T	A	17: 28,194,993	I34N	probably damaging	Het
Zfp945	A	T	17: 22,851,273	C551S	probably damaging	Het
Zfp958	A	G	8: 4,628,590	H205R	probably damaging	Het
Zfp974	G	A	7: 27,910,356	P648L	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
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
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'- TTTCTCCAACGAGCTGCAGG -3'
(R):5'- GTAGAATCTCTCGCAGTCCAC -3'

Sequencing Primer
(F):5'- TCCAAGAGAATGAGGTCC -3'
(R):5'- TGGAACACGTTCATCCTCAGG -3'

Posted On

2014-06-23