Incidental Mutation 'R5869:Nlrp3'
| ID |
454341 |
| 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 |
044077-MU
|
| Accession Numbers |
Ncbi RefSeq: NM_145827.3; MGI:2653833
|
| Essential gene? |
Probably non essential
(E-score: 0.096)
|
| Stock # |
R5869 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
11 |
| Chromosomal Location |
59541568-59566956 bp(+) (GRCm38) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
G to A
at 59548134 bp (GRCm38)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Arginine to Glutamine
at position 179
(R179Q)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000098707
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000079476]
[ENSMUST00000101148]
[ENSMUST00000149126]
|
| AlphaFold |
Q8R4B8 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000079476
AA Change: R179Q
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000078440
Gene: ENSMUSG00000032691
AA Change: R179Q
| 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: R179Q
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000098707
Gene: ENSMUSG00000032691
AA Change: R179Q
| 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 |
0.6467 |
| Coding Region Coverage |
- 1x: 99.9%
- 3x: 99.5%
- 10x: 97.5%
- 20x: 92.1%
|
| Validation Efficiency |
93% (68/73) |
| 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: 60 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Adarb1 |
T |
C |
10: 77,325,616 (GRCm38) |
|
probably benign |
Het |
| Arsk |
T |
C |
13: 76,091,784 (GRCm38) |
E100G |
probably benign |
Het |
| Ascc3 |
C |
T |
10: 50,842,183 (GRCm38) |
R1991* |
probably null |
Het |
| Aspscr1 |
T |
C |
11: 120,688,920 (GRCm38) |
I31T |
possibly damaging |
Het |
| Asz1 |
T |
C |
6: 18,074,940 (GRCm38) |
|
probably benign |
Het |
| Calm5 |
T |
A |
13: 3,854,321 (GRCm38) |
|
probably benign |
Het |
| Car5a |
G |
A |
8: 121,916,380 (GRCm38) |
T295I |
probably benign |
Het |
| Ccdc174 |
T |
A |
6: 91,885,418 (GRCm38) |
|
probably benign |
Het |
| Celsr2 |
G |
A |
3: 108,413,909 (GRCm38) |
A529V |
probably damaging |
Het |
| Cep192 |
A |
G |
18: 67,815,864 (GRCm38) |
D252G |
probably benign |
Het |
| Clcnka |
A |
G |
4: 141,394,965 (GRCm38) |
F217L |
probably benign |
Het |
| Cnot3 |
A |
T |
7: 3,644,930 (GRCm38) |
|
probably benign |
Het |
| Coro1c |
A |
G |
5: 113,850,846 (GRCm38) |
|
probably benign |
Het |
| Cstf3 |
A |
G |
2: 104,659,240 (GRCm38) |
|
probably null |
Het |
| Dcdc2a |
C |
T |
13: 25,107,730 (GRCm38) |
P233S |
probably benign |
Het |
| Ddx55 |
A |
G |
5: 124,568,682 (GRCm38) |
T581A |
probably benign |
Het |
| Exo1 |
T |
C |
1: 175,901,283 (GRCm38) |
S638P |
possibly damaging |
Het |
| Fam135a |
T |
C |
1: 24,029,430 (GRCm38) |
E616G |
possibly damaging |
Het |
| Fignl2 |
T |
C |
15: 101,053,280 (GRCm38) |
S374G |
unknown |
Het |
| Gm4799 |
A |
T |
10: 82,954,449 (GRCm38) |
|
noncoding transcript |
Het |
| Hectd4 |
T |
C |
5: 121,343,225 (GRCm38) |
|
probably null |
Het |
| Ighv1-76 |
T |
C |
12: 115,848,038 (GRCm38) |
E65G |
probably damaging |
Het |
| Igsf9b |
C |
A |
9: 27,323,235 (GRCm38) |
H465Q |
probably benign |
Het |
| Itga9 |
A |
G |
9: 118,663,889 (GRCm38) |
D284G |
probably damaging |
Het |
| Itpr1 |
T |
C |
6: 108,473,529 (GRCm38) |
S1940P |
probably benign |
Het |
| Kcnb1 |
A |
G |
2: 167,188,071 (GRCm38) |
S185P |
probably benign |
Het |
| Kif20a |
G |
A |
18: 34,632,415 (GRCm38) |
A822T |
probably benign |
Het |
| Krt1 |
A |
T |
15: 101,850,131 (GRCm38) |
F199L |
probably damaging |
Het |
| Lpin2 |
A |
G |
17: 71,232,276 (GRCm38) |
|
probably benign |
Het |
| Lrp1b |
A |
C |
2: 41,004,603 (GRCm38) |
D2204E |
probably damaging |
Het |
| Mier3 |
T |
A |
13: 111,714,850 (GRCm38) |
N427K |
probably damaging |
Het |
| Mmp12 |
GTAATAATAATAATAATAAT |
GTAATAATAATAATAAT |
9: 7,348,446 (GRCm38) |
|
probably benign |
Het |
| Mroh3 |
T |
A |
1: 136,186,123 (GRCm38) |
M643L |
probably benign |
Het |
| Myh11 |
A |
G |
16: 14,230,800 (GRCm38) |
S548P |
probably damaging |
Het |
| Nat8f6 |
A |
C |
6: 85,808,523 (GRCm38) |
L215V |
possibly damaging |
Het |
| Nup88 |
T |
C |
11: 70,969,671 (GRCm38) |
E94G |
probably benign |
Het |
| Pias1 |
A |
T |
9: 62,912,766 (GRCm38) |
D306E |
probably benign |
Het |
| Pick1 |
A |
G |
15: 79,248,895 (GRCm38) |
D385G |
probably benign |
Het |
| Pitx3 |
A |
T |
19: 46,137,296 (GRCm38) |
|
probably benign |
Het |
| Plpp3 |
T |
A |
4: 105,194,962 (GRCm38) |
|
probably null |
Het |
| Prlhr |
C |
A |
19: 60,467,621 (GRCm38) |
R169L |
probably damaging |
Het |
| Ptprf |
A |
C |
4: 118,210,382 (GRCm38) |
M1872R |
probably damaging |
Het |
| Ptprh |
T |
C |
7: 4,601,940 (GRCm38) |
D35G |
probably benign |
Het |
| Rnf130 |
A |
G |
11: 50,085,815 (GRCm38) |
|
probably null |
Het |
| Rnf17 |
A |
C |
14: 56,505,988 (GRCm38) |
E1337A |
possibly damaging |
Het |
| Sdk2 |
A |
G |
11: 113,851,882 (GRCm38) |
Y734H |
probably damaging |
Het |
| Slc25a10 |
C |
T |
11: 120,498,117 (GRCm38) |
T269I |
probably damaging |
Het |
| Slc4a11 |
A |
C |
2: 130,684,459 (GRCm38) |
V855G |
probably benign |
Het |
| Slc5a5 |
C |
A |
8: 70,892,330 (GRCm38) |
R111L |
probably damaging |
Het |
| Spg20 |
A |
T |
3: 55,135,510 (GRCm38) |
M616L |
probably benign |
Het |
| Tmem229a |
T |
C |
6: 24,954,687 (GRCm38) |
D356G |
probably damaging |
Het |
| Tmem30c |
A |
G |
16: 57,266,562 (GRCm38) |
S293P |
probably damaging |
Het |
| Tnfrsf14 |
C |
A |
4: 154,926,598 (GRCm38) |
|
probably null |
Het |
| Tnfrsf19 |
C |
T |
14: 60,971,178 (GRCm38) |
R298H |
possibly damaging |
Het |
| Ttc21a |
A |
G |
9: 119,958,792 (GRCm38) |
K809E |
probably benign |
Het |
| Ttn |
G |
A |
2: 76,750,209 (GRCm38) |
P23447S |
probably damaging |
Het |
| Uap1 |
T |
A |
1: 170,151,138 (GRCm38) |
|
probably null |
Het |
| Wdr82 |
A |
G |
9: 106,185,304 (GRCm38) |
Q252R |
probably benign |
Het |
| Zfp523 |
T |
C |
17: 28,194,993 (GRCm38) |
I34T |
probably benign |
Het |
| Zfp808 |
T |
A |
13: 62,171,255 (GRCm38) |
H99Q |
probably damaging |
Het |
|
| Other mutations in Nlrp3 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00421:Nlrp3
|
APN |
11 |
59,565,943 (GRCm38) |
missense |
probably damaging |
0.99 |
|
IGL00573:Nlrp3
|
APN |
11 |
59,565,116 (GRCm38) |
missense |
possibly damaging |
0.93 |
|
IGL01025:Nlrp3
|
APN |
11 |
59,551,887 (GRCm38) |
missense |
probably benign |
0.21 |
|
IGL01637:Nlrp3
|
APN |
11 |
59,549,378 (GRCm38) |
missense |
probably damaging |
0.99 |
|
IGL02010:Nlrp3
|
APN |
11 |
59,549,535 (GRCm38) |
missense |
probably benign |
|
|
IGL02334:Nlrp3
|
APN |
11 |
59,565,083 (GRCm38) |
missense |
probably benign |
|
|
IGL02417:Nlrp3
|
APN |
11 |
59,566,023 (GRCm38) |
unclassified |
probably benign |
|
|
IGL02578:Nlrp3
|
APN |
11 |
59,548,401 (GRCm38) |
missense |
probably damaging |
1.00 |
|
IGL02710:Nlrp3
|
APN |
11 |
59,565,976 (GRCm38) |
missense |
probably damaging |
0.99 |
|
IGL02816:Nlrp3
|
APN |
11 |
59,555,782 (GRCm38) |
missense |
probably benign |
0.03 |
|
IGL03157:Nlrp3
|
APN |
11 |
59,549,546 (GRCm38) |
missense |
possibly damaging |
0.80 |
|
IGL03334:Nlrp3
|
APN |
11 |
59,549,016 (GRCm38) |
missense |
probably damaging |
1.00 |
|
Flogiston
|
UTSW |
11 |
59,558,448 (GRCm38) |
missense |
probably benign |
0.00 |
|
nd1
|
UTSW |
11 |
59,565,974 (GRCm38) |
missense |
probably benign |
0.45 |
|
Nd14
|
UTSW |
11 |
59,555,875 (GRCm38) |
missense |
possibly damaging |
0.89 |
|
Nd3
|
UTSW |
11 |
59,565,974 (GRCm38) |
missense |
probably benign |
0.45 |
|
nd5
|
UTSW |
11 |
59,565,879 (GRCm38) |
missense |
probably benign |
0.01 |
|
nd6
|
UTSW |
11 |
59,549,354 (GRCm38) |
missense |
probably damaging |
1.00 |
|
nd7
|
UTSW |
11 |
59,555,875 (GRCm38) |
missense |
possibly damaging |
0.89 |
|
Nd9
|
UTSW |
11 |
59,549,354 (GRCm38) |
missense |
probably damaging |
1.00 |
|
Park2
|
UTSW |
11 |
59,565,128 (GRCm38) |
nonsense |
probably null |
|
|
Park3
|
UTSW |
11 |
59,565,850 (GRCm38) |
missense |
probably benign |
0.02 |
|
Park4
|
UTSW |
11 |
59,549,531 (GRCm38) |
missense |
probably benign |
0.19 |
|
Park5
|
UTSW |
11 |
59,548,476 (GRCm38) |
missense |
probably damaging |
0.99 |
|
Park6
|
UTSW |
11 |
59,549,036 (GRCm38) |
missense |
probably damaging |
1.00 |
|
Park7
|
UTSW |
11 |
59,548,010 (GRCm38) |
nonsense |
probably null |
|
|
Park8
|
UTSW |
11 |
59,566,199 (GRCm38) |
missense |
probably benign |
0.19 |
|
R0008:Nlrp3
|
UTSW |
11 |
59,558,448 (GRCm38) |
missense |
probably benign |
0.00 |
|
R0008:Nlrp3
|
UTSW |
11 |
59,558,448 (GRCm38) |
missense |
probably benign |
0.00 |
|
R0052:Nlrp3
|
UTSW |
11 |
59,565,128 (GRCm38) |
nonsense |
probably null |
|
|
R0362:Nlrp3
|
UTSW |
11 |
59,548,797 (GRCm38) |
missense |
possibly damaging |
0.49 |
|
R0416:Nlrp3
|
UTSW |
11 |
59,555,924 (GRCm38) |
splice site |
probably benign |
|
|
R0649:Nlrp3
|
UTSW |
11 |
59,548,542 (GRCm38) |
missense |
possibly damaging |
0.83 |
|
R0740:Nlrp3
|
UTSW |
11 |
59,548,256 (GRCm38) |
missense |
probably benign |
0.01 |
|
R0863:Nlrp3
|
UTSW |
11 |
59,565,850 (GRCm38) |
missense |
probably benign |
0.02 |
|
R1300:Nlrp3
|
UTSW |
11 |
59,555,768 (GRCm38) |
missense |
possibly damaging |
0.86 |
|
R1414:Nlrp3
|
UTSW |
11 |
59,549,531 (GRCm38) |
missense |
probably benign |
0.19 |
|
R1622:Nlrp3
|
UTSW |
11 |
59,548,476 (GRCm38) |
missense |
probably damaging |
0.99 |
|
R1654:Nlrp3
|
UTSW |
11 |
59,543,123 (GRCm38) |
missense |
probably benign |
0.03 |
|
R1715:Nlrp3
|
UTSW |
11 |
59,543,351 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R1754:Nlrp3
|
UTSW |
11 |
59,558,402 (GRCm38) |
missense |
possibly damaging |
0.80 |
|
R1837:Nlrp3
|
UTSW |
11 |
59,548,916 (GRCm38) |
missense |
probably benign |
0.00 |
|
R1905:Nlrp3
|
UTSW |
11 |
59,549,036 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R2281:Nlrp3
|
UTSW |
11 |
59,549,136 (GRCm38) |
missense |
possibly damaging |
0.70 |
|
R4296:Nlrp3
|
UTSW |
11 |
59,549,661 (GRCm38) |
missense |
possibly damaging |
0.89 |
|
R4305:Nlrp3
|
UTSW |
11 |
59,548,010 (GRCm38) |
nonsense |
probably null |
|
|
R4540:Nlrp3
|
UTSW |
11 |
59,551,899 (GRCm38) |
missense |
possibly damaging |
0.83 |
|
R4591:Nlrp3
|
UTSW |
11 |
59,549,222 (GRCm38) |
missense |
probably benign |
0.00 |
|
R4816:Nlrp3
|
UTSW |
11 |
59,548,301 (GRCm38) |
missense |
probably benign |
0.32 |
|
R4913:Nlrp3
|
UTSW |
11 |
59,549,238 (GRCm38) |
missense |
probably benign |
0.09 |
|
R4970:Nlrp3
|
UTSW |
11 |
59,548,728 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R5051:Nlrp3
|
UTSW |
11 |
59,566,199 (GRCm38) |
missense |
probably benign |
0.19 |
|
R5112:Nlrp3
|
UTSW |
11 |
59,548,728 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R5185:Nlrp3
|
UTSW |
11 |
59,565,084 (GRCm38) |
missense |
probably benign |
0.05 |
|
R5417:Nlrp3
|
UTSW |
11 |
59,549,063 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R5709:Nlrp3
|
UTSW |
11 |
59,555,748 (GRCm38) |
nonsense |
probably null |
|
|
R5898:Nlrp3
|
UTSW |
11 |
59,546,852 (GRCm38) |
missense |
probably benign |
0.00 |
|
R5953:Nlrp3
|
UTSW |
11 |
59,546,791 (GRCm38) |
missense |
probably benign |
|
|
R5979:Nlrp3
|
UTSW |
11 |
59,548,971 (GRCm38) |
missense |
probably benign |
0.06 |
|
R6359:Nlrp3
|
UTSW |
11 |
59,548,566 (GRCm38) |
missense |
probably damaging |
0.97 |
|
R6723:Nlrp3
|
UTSW |
11 |
59,565,192 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R7261:Nlrp3
|
UTSW |
11 |
59,548,446 (GRCm38) |
missense |
possibly damaging |
0.83 |
|
R7349:Nlrp3
|
UTSW |
11 |
59,548,086 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R7388:Nlrp3
|
UTSW |
11 |
59,565,066 (GRCm38) |
missense |
probably benign |
0.00 |
|
R7715:Nlrp3
|
UTSW |
11 |
59,543,003 (GRCm38) |
splice site |
probably null |
|
|
R7916:Nlrp3
|
UTSW |
11 |
59,551,863 (GRCm38) |
missense |
probably benign |
0.00 |
|
R8222:Nlrp3
|
UTSW |
11 |
59,548,788 (GRCm38) |
missense |
probably damaging |
0.98 |
|
R8360:Nlrp3
|
UTSW |
11 |
59,549,403 (GRCm38) |
missense |
probably benign |
0.02 |
|
R8390:Nlrp3
|
UTSW |
11 |
59,551,790 (GRCm38) |
missense |
possibly damaging |
0.47 |
|
R8550:Nlrp3
|
UTSW |
11 |
59,549,271 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R8738:Nlrp3
|
UTSW |
11 |
59,549,390 (GRCm38) |
missense |
probably benign |
0.00 |
|
R8940:Nlrp3
|
UTSW |
11 |
59,565,044 (GRCm38) |
missense |
probably benign |
0.26 |
|
R8990:Nlrp3
|
UTSW |
11 |
59,548,758 (GRCm38) |
missense |
probably damaging |
0.99 |
|
R9324:Nlrp3
|
UTSW |
11 |
59,543,315 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R9673:Nlrp3
|
UTSW |
11 |
59,549,322 (GRCm38) |
missense |
probably damaging |
1.00 |
|
RF031:Nlrp3
|
UTSW |
11 |
59,558,552 (GRCm38) |
frame shift |
probably null |
|
|
RF040:Nlrp3
|
UTSW |
11 |
59,558,552 (GRCm38) |
frame shift |
probably null |
|
|
Z1088:Nlrp3
|
UTSW |
11 |
59,551,860 (GRCm38) |
missense |
possibly damaging |
0.67 |
|
| Predicted Primers |
PCR Primer
(F):5'- GGTCCGCTAGCAGCTTATTG -3'
(R):5'- AGTCCAACATAATCTTCCTGGC -3'
Sequencing Primer
(F):5'- GGGCTTTTCCTGGATCCCG -3'
(R):5'- CTAGGATGGTTTTCCCGATGCC -3'
|
| Posted On |
2017-02-10 |
Incidental Mutation