Incidental Mutation 'R4305:Nlrp3'
| ID |
324003 |
| 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 |
041091-MU
|
| Accession Numbers |
Ncbi RefSeq: NM_145827.3; MGI:2653833
|
| Essential gene? |
Probably non essential
(E-score: 0.093)
|
| Stock # |
R4305 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
11 |
| Chromosomal Location |
59541568-59566956 bp(+) (GRCm38) |
| Type of Mutation |
nonsense |
| DNA Base Change (assembly) |
C to T
at 59548010 bp (GRCm38)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Arginine to Stop codon
at position 138
(R138*)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000114231
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000079476]
[ENSMUST00000101148]
[ENSMUST00000149126]
|
| AlphaFold |
Q8R4B8 |
| Predicted Effect |
probably null
Transcript: ENSMUST00000079476
AA Change: R138*
|
| SMART Domains |
Protein: ENSMUSP00000078440
Gene: ENSMUSG00000032691
AA Change: R138*
| 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 null
Transcript: ENSMUST00000101148
AA Change: R138*
|
| SMART Domains |
Protein: ENSMUSP00000098707
Gene: ENSMUSG00000032691
AA Change: R138*
| 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 null
Transcript: ENSMUST00000149126
AA Change: R138*
|
| SMART Domains |
Protein: ENSMUSP00000114231
Gene: ENSMUSG00000032691
AA Change: R138*
| 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 |
0.9755 |
| Coding Region Coverage |
- 1x: 99.3%
- 3x: 98.7%
- 10x: 97.3%
- 20x: 95.2%
|
| Validation Efficiency |
92% (36/39) |
| 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: 26 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| A830018L16Rik |
C |
A |
1: 11,972,076 |
S440* |
probably null |
Het |
| Abl2 |
T |
A |
1: 156,641,563 |
M695K |
probably damaging |
Het |
| Asap2 |
T |
C |
12: 21,229,481 |
I426T |
probably damaging |
Het |
| Atxn7l1 |
T |
C |
12: 33,341,992 |
M93T |
probably damaging |
Het |
| Ccr5 |
T |
C |
9: 124,125,074 |
L238P |
possibly damaging |
Het |
| Cd27 |
A |
G |
6: 125,234,670 |
V98A |
probably benign |
Het |
| Chrdl2 |
A |
G |
7: 100,022,022 |
T116A |
probably damaging |
Het |
| Epha6 |
T |
C |
16: 60,526,520 |
|
probably null |
Het |
| Fam71f1 |
A |
G |
6: 29,326,612 |
S243G |
probably damaging |
Het |
| Gart |
T |
C |
16: 91,633,992 |
E394G |
possibly damaging |
Het |
| Gm5155 |
T |
A |
7: 17,905,193 |
Y372N |
probably benign |
Het |
| Gm7173 |
C |
G |
X: 79,498,029 |
K469N |
probably damaging |
Het |
| Krt1 |
AAGCTGCCACCCCCAAAGCCACCACCGCCGTAGCTGCCACCCCCAAAGCCACCACCGCCGTAGCTGCCACCCCCAAAGCCACCAC |
AAGCTGCCACCCCCAAAGCCACCACCGCCGTAGCTGCCACCCCCAAAGCCACCAC |
15: 101,850,378 |
|
probably benign |
Het |
| Lpar6 |
G |
A |
14: 73,238,941 |
R114Q |
probably damaging |
Het |
| Med23 |
G |
T |
10: 24,904,270 |
E573* |
probably null |
Het |
| Mtch2 |
A |
G |
2: 90,859,483 |
I183V |
probably benign |
Het |
| Notch1 |
T |
C |
2: 26,477,924 |
D657G |
probably damaging |
Het |
| Olfr1281 |
A |
G |
2: 111,329,298 |
D293G |
probably null |
Het |
| Rbm20 |
A |
G |
19: 53,843,260 |
S642G |
probably damaging |
Het |
| Tex11 |
C |
A |
X: 100,933,415 |
A487S |
possibly damaging |
Het |
| Ttn |
T |
C |
2: 76,918,337 |
S4123G |
probably benign |
Het |
| Ugt3a1 |
A |
C |
15: 9,306,274 |
S170R |
possibly damaging |
Het |
| Vmn2r71 |
G |
T |
7: 85,624,152 |
D725Y |
probably damaging |
Het |
| Vps9d1 |
G |
T |
8: 123,248,237 |
|
probably benign |
Het |
| Yeats2 |
A |
G |
16: 20,208,422 |
T808A |
probably damaging |
Het |
| Zdhhc4 |
C |
T |
5: 143,324,344 |
|
probably benign |
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 |
|
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'- CAATGACGACAGCTCGCTCTATAC -3'
(R):5'- GGCTGTCCCGCATTTTAGTC -3'
Sequencing Primer
(F):5'- GCTTCTAGTTGACAGTCAGCAC -3'
(R):5'- CGCATTTTAGTCCGGCCGATG -3'
|
| Posted On |
2015-06-24 |
Incidental Mutation