Incidental Mutation 'R8222:Nlrp3'
| ID |
636777 |
| 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 |
067640-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably non essential
(E-score: 0.076)
|
| Stock # |
R8222 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Validated
|
| Chromosome |
11 |
| Chromosomal Location |
59432395-59457781 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to G
at 59439614 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Glutamic Acid to Glycine
at position 397
(E397G)
|
| 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: E397G
PolyPhen 2
Score 0.977 (Sensitivity: 0.76; Specificity: 0.96)
|
| SMART Domains |
Protein: ENSMUSP00000078440
Gene: ENSMUSG00000032691
AA Change: E397G
| 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: E397G
PolyPhen 2
Score 0.977 (Sensitivity: 0.76; Specificity: 0.96)
|
| SMART Domains |
Protein: ENSMUSP00000098707
Gene: ENSMUSG00000032691
AA Change: E397G
| 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 |
|
| Coding Region Coverage |
- 1x: 99.9%
- 3x: 99.9%
- 10x: 99.5%
- 20x: 98.6%
|
| Validation Efficiency |
100% (56/56) |
| 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: 57 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Aldh18a1 |
C |
T |
19: 40,562,296 (GRCm39) |
V243I |
probably benign |
Het |
| Ankrd11 |
A |
T |
8: 123,622,347 (GRCm39) |
S481T |
probably damaging |
Het |
| Atg2b |
A |
G |
12: 105,618,475 (GRCm39) |
I859T |
possibly damaging |
Het |
| B4galt3 |
G |
A |
1: 171,100,253 (GRCm39) |
R141Q |
possibly damaging |
Het |
| Bace1 |
T |
C |
9: 45,768,491 (GRCm39) |
V262A |
probably damaging |
Het |
| BC106179 |
A |
T |
16: 23,043,055 (GRCm39) |
I47N |
noncoding transcript |
Het |
| Brpf1 |
C |
T |
6: 113,286,999 (GRCm39) |
P76S |
probably benign |
Het |
| Cdk1 |
A |
G |
10: 69,176,426 (GRCm39) |
V227A |
probably benign |
Het |
| Ceacam20 |
T |
C |
7: 19,705,618 (GRCm39) |
V203A |
probably benign |
Het |
| Cfap251 |
T |
A |
5: 123,440,486 (GRCm39) |
Y1091N |
probably damaging |
Het |
| Cma2 |
T |
C |
14: 56,210,727 (GRCm39) |
V194A |
probably benign |
Het |
| Cnnm4 |
A |
G |
1: 36,545,617 (GRCm39) |
D749G |
probably benign |
Het |
| Cyp11b2 |
T |
C |
15: 74,728,059 (GRCm39) |
T8A |
probably benign |
Het |
| Dlk2 |
A |
G |
17: 46,613,384 (GRCm39) |
H170R |
probably benign |
Het |
| Esyt1 |
C |
T |
10: 128,347,647 (GRCm39) |
R987Q |
possibly damaging |
Het |
| Ganc |
T |
C |
2: 120,276,933 (GRCm39) |
I665T |
probably damaging |
Het |
| Gas6 |
T |
C |
8: 13,520,276 (GRCm39) |
T471A |
probably benign |
Het |
| Grik2 |
A |
G |
10: 49,449,744 (GRCm39) |
F153L |
probably benign |
Het |
| Heatr5b |
A |
G |
17: 79,109,130 (GRCm39) |
V1043A |
possibly damaging |
Het |
| Ipo5 |
A |
G |
14: 121,157,414 (GRCm39) |
D84G |
probably benign |
Het |
| Irak4 |
T |
A |
15: 94,459,110 (GRCm39) |
|
probably null |
Het |
| Lrp4 |
T |
A |
2: 91,305,086 (GRCm39) |
C238S |
probably damaging |
Het |
| Mau2 |
A |
T |
8: 70,485,827 (GRCm39) |
|
probably null |
Het |
| Mdn1 |
T |
C |
4: 32,707,477 (GRCm39) |
F1589L |
probably benign |
Het |
| Mlxip |
T |
G |
5: 123,585,596 (GRCm39) |
S662A |
probably benign |
Het |
| Mn1 |
A |
T |
5: 111,566,546 (GRCm39) |
N172I |
probably damaging |
Het |
| Mup2 |
A |
C |
4: 60,138,454 (GRCm39) |
D79E |
probably benign |
Het |
| Nab2 |
C |
A |
10: 127,498,645 (GRCm39) |
V475L |
probably benign |
Het |
| Odf2l |
A |
G |
3: 144,833,799 (GRCm39) |
E153G |
probably damaging |
Het |
| Or13p10 |
T |
C |
4: 118,523,113 (GRCm39) |
L133P |
probably damaging |
Het |
| Or51f5 |
G |
T |
7: 102,424,099 (GRCm39) |
D123Y |
probably damaging |
Het |
| Or5d36 |
T |
A |
2: 87,901,381 (GRCm39) |
Y115F |
probably benign |
Het |
| Or5l13 |
T |
C |
2: 87,779,788 (GRCm39) |
N263S |
probably benign |
Het |
| Pkdrej |
T |
A |
15: 85,701,640 (GRCm39) |
H1432L |
probably benign |
Het |
| Plec |
C |
T |
15: 76,063,374 (GRCm39) |
R2232H |
possibly damaging |
Het |
| Polk |
T |
C |
13: 96,632,023 (GRCm39) |
M317V |
possibly damaging |
Het |
| Ppp4r3a |
A |
G |
12: 101,008,164 (GRCm39) |
S758P |
probably benign |
Het |
| Pramel26 |
A |
T |
4: 143,536,893 (GRCm39) |
D479E |
possibly damaging |
Het |
| Prdm9 |
A |
G |
17: 15,765,035 (GRCm39) |
S582P |
possibly damaging |
Het |
| R3hcc1l |
T |
A |
19: 42,564,616 (GRCm39) |
L643H |
probably damaging |
Het |
| Rassf8 |
G |
A |
6: 145,765,783 (GRCm39) |
V38M |
unknown |
Het |
| Reln |
G |
A |
5: 22,136,475 (GRCm39) |
Q2518* |
probably null |
Het |
| Sel1l3 |
A |
G |
5: 53,345,296 (GRCm39) |
|
probably null |
Het |
| Serpina3m |
A |
T |
12: 104,358,960 (GRCm39) |
D324V |
possibly damaging |
Het |
| Slc12a6 |
T |
A |
2: 112,169,870 (GRCm39) |
|
probably null |
Het |
| Slc25a3 |
A |
G |
10: 90,954,053 (GRCm39) |
W219R |
probably damaging |
Het |
| Sort1 |
T |
A |
3: 108,241,951 (GRCm39) |
V299E |
probably benign |
Het |
| Stx6 |
A |
G |
1: 155,073,889 (GRCm39) |
D233G |
possibly damaging |
Het |
| Tefm |
A |
G |
11: 80,031,230 (GRCm39) |
V2A |
|
Het |
| Tfdp2 |
T |
C |
9: 96,192,666 (GRCm39) |
S190P |
possibly damaging |
Het |
| Tmprss7 |
A |
T |
16: 45,478,461 (GRCm39) |
I755N |
probably damaging |
Het |
| Trpm8 |
A |
G |
1: 88,253,390 (GRCm39) |
|
probably null |
Het |
| Ube2q2l |
A |
G |
6: 136,377,882 (GRCm39) |
I316T |
probably damaging |
Het |
| Ugt2a2 |
A |
G |
5: 87,608,369 (GRCm39) |
L490P |
probably damaging |
Het |
| Utp20 |
A |
G |
10: 88,614,234 (GRCm39) |
L1240P |
probably damaging |
Het |
| Vmn1r159 |
G |
T |
7: 22,542,608 (GRCm39) |
Y141* |
probably null |
Het |
| Vmn2r56 |
T |
A |
7: 12,444,960 (GRCm39) |
Y431F |
probably benign |
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 |
|
R1414:Nlrp3
|
UTSW |
11 |
59,440,357 (GRCm39) |
missense |
probably benign |
0.19 |
|
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 |
|
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'- GCCTCTCTGCTCATAACGAC -3'
(R):5'- AAATTCCATCCGCAGCCAGTG -3'
Sequencing Primer
(F):5'- TCTCTGCTCATAACGACGAGGC -3'
(R):5'- TCAGAGAAGAGATGCTCCTCAATGC -3'
|
| Posted On |
2020-07-13 |
Incidental Mutation