Incidental Mutation 'G5030:Il1r1'
| ID |
512 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Il1r1
|
| Ensembl Gene |
ENSMUSG00000026072 |
| Gene Name |
interleukin 1 receptor, type I |
| Synonyms |
IL-iR, IL-1R1, Il1r-1, CD121a, IL-1 receptor alpha chain |
| Accession Numbers |
|
| Essential gene? |
Probably non essential
(E-score: 0.060)
|
| Stock # |
G5030 (G3)
of strain
560
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
1 |
| Chromosomal Location |
40264240-40356417 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to G
at 40352323 bp (GRCm39)
|
| Zygosity |
Homozygous |
| Amino Acid Change |
Lysine to Glutamic Acid
at position 498
(K498E)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000110443
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000027241]
[ENSMUST00000114795]
|
| AlphaFold |
P13504 |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000027241
AA Change: K501E
PolyPhen 2
Score 0.477 (Sensitivity: 0.89; Specificity: 0.90)
|
| SMART Domains |
Protein: ENSMUSP00000027241
Gene: ENSMUSG00000026072
AA Change: K501E
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
19 |
N/A |
INTRINSIC |
|
IG
|
38 |
117 |
2.94e-1 |
SMART |
|
IG_like
|
132 |
218 |
5.56e0 |
SMART |
|
IG
|
236 |
333 |
1.35e0 |
SMART |
|
Blast:TIR
|
347 |
381 |
1e-7 |
BLAST |
|
TIR
|
387 |
544 |
1.93e-29 |
SMART |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000114795
AA Change: K498E
PolyPhen 2
Score 0.798 (Sensitivity: 0.84; Specificity: 0.93)
|
| SMART Domains |
Protein: ENSMUSP00000110443
Gene: ENSMUSG00000026072
AA Change: K498E
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
16 |
N/A |
INTRINSIC |
|
IG
|
35 |
114 |
2.94e-1 |
SMART |
|
IG_like
|
129 |
215 |
5.56e0 |
SMART |
|
IG
|
233 |
330 |
1.35e0 |
SMART |
|
Blast:TIR
|
344 |
378 |
1e-7 |
BLAST |
|
TIR
|
384 |
541 |
1.93e-29 |
SMART |
|
| Meta Mutation Damage Score |
0.0621 |
| Coding Region Coverage |
|
| Het Detection Efficiency |
35.6% |
| Validation Efficiency |
87% (206/237) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a cytokine receptor that belongs to the interleukin-1 receptor family. The encoded protein is a receptor for interleukin-1 alpha, interleukin-1 beta, and interleukin-1 receptor antagonist. It is an important mediator involved in many cytokine-induced immune and inflammatory responses. This gene is located in a cluster of related cytokine receptor genes on chromosome 2q12. [provided by RefSeq, Dec 2013]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit increased susceptibility to bacterial infection, reduced IL1b responsiveness, delayed tooth eruption, decreased susceptibility to experimental autoimmune uveoritinitis, decreased susceptibility to kidney reperfusion injury, and late onset obesity. [provided by MGI curators]
|
| Allele List at MGI |
All alleles(3) : Targeted, knock-out(2) Gene trapped(1) |
| Other mutations in this stock |
Total: 30 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Abca8a |
T |
A |
11: 109,961,165 (GRCm39) |
I585F |
probably damaging |
Het |
| Adam18 |
C |
G |
8: 25,141,872 (GRCm39) |
L232F |
probably benign |
Homo |
| Atp13a4 |
A |
G |
16: 29,274,306 (GRCm39) |
I385T |
probably damaging |
Homo |
| Ccdc17 |
T |
A |
4: 116,455,699 (GRCm39) |
S277T |
probably benign |
Het |
| Ccng1 |
A |
G |
11: 40,644,629 (GRCm39) |
|
probably benign |
Het |
| Ces1f |
T |
C |
8: 94,000,847 (GRCm39) |
D99G |
probably benign |
Het |
| Clec16a |
G |
A |
16: 10,389,425 (GRCm39) |
R187Q |
probably damaging |
Homo |
| Cryl1 |
C |
T |
14: 57,579,595 (GRCm39) |
|
probably benign |
Het |
| Cryzl2 |
C |
T |
1: 157,292,580 (GRCm39) |
Q48* |
probably null |
Het |
| Dtx4 |
A |
G |
19: 12,446,943 (GRCm39) |
L583P |
probably benign |
Het |
| Ephx4 |
A |
T |
5: 107,577,693 (GRCm39) |
D339V |
probably damaging |
Het |
| Eri2 |
A |
T |
7: 119,385,601 (GRCm39) |
V300E |
possibly damaging |
Het |
| F3 |
T |
A |
3: 121,518,648 (GRCm39) |
N37K |
probably damaging |
Homo |
| Fpr1 |
A |
T |
17: 18,097,068 (GRCm39) |
L307H |
probably damaging |
Het |
| Fv1 |
T |
A |
4: 147,953,618 (GRCm39) |
N61K |
possibly damaging |
Het |
| Gm5548 |
T |
C |
3: 112,961,512 (GRCm39) |
|
noncoding transcript |
Homo |
| Myh11 |
T |
C |
16: 14,068,443 (GRCm39) |
I192M |
probably damaging |
Homo |
| Nckap5 |
T |
C |
1: 125,953,591 (GRCm39) |
K923R |
probably damaging |
Het |
| Nmbr |
A |
T |
10: 14,642,747 (GRCm39) |
Y102F |
possibly damaging |
Het |
| Or6c75 |
A |
G |
10: 129,337,406 (GRCm39) |
T218A |
probably benign |
Homo |
| Pde1a |
C |
T |
2: 79,718,180 (GRCm39) |
|
probably benign |
Het |
| Pex6 |
T |
C |
17: 47,026,382 (GRCm39) |
|
probably benign |
Het |
| Rtn2 |
T |
C |
7: 19,027,099 (GRCm39) |
S305P |
probably damaging |
Homo |
| Saal1 |
G |
A |
7: 46,342,207 (GRCm39) |
T412I |
probably damaging |
Homo |
| Slc46a2 |
A |
T |
4: 59,913,867 (GRCm39) |
I352N |
probably damaging |
Het |
| Trim37 |
A |
T |
11: 87,033,967 (GRCm39) |
H99L |
probably damaging |
Het |
| Tubgcp4 |
C |
T |
2: 121,014,815 (GRCm39) |
R242C |
probably damaging |
Het |
| Twf2 |
C |
A |
9: 106,084,141 (GRCm39) |
L27I |
possibly damaging |
Het |
| Usp40 |
A |
T |
1: 87,921,941 (GRCm39) |
H307Q |
probably damaging |
Het |
| Zfhx3 |
T |
G |
8: 109,678,091 (GRCm39) |
V3047G |
possibly damaging |
Het |
|
| Other mutations in Il1r1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL01457:Il1r1
|
APN |
1 |
40,352,330 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01532:Il1r1
|
APN |
1 |
40,334,088 (GRCm39) |
critical splice donor site |
probably null |
|
|
IGL01610:Il1r1
|
APN |
1 |
40,341,560 (GRCm39) |
missense |
probably benign |
0.09 |
|
IGL01668:Il1r1
|
APN |
1 |
40,352,489 (GRCm39) |
missense |
probably benign |
0.31 |
|
IGL01729:Il1r1
|
APN |
1 |
40,333,986 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02201:Il1r1
|
APN |
1 |
40,352,428 (GRCm39) |
missense |
probably damaging |
0.97 |
|
IGL02229:Il1r1
|
APN |
1 |
40,352,518 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL02428:Il1r1
|
APN |
1 |
40,352,392 (GRCm39) |
missense |
possibly damaging |
0.74 |
|
IGL02902:Il1r1
|
APN |
1 |
40,341,569 (GRCm39) |
missense |
probably benign |
0.09 |
|
R0604:Il1r1
|
UTSW |
1 |
40,321,406 (GRCm39) |
missense |
probably benign |
0.36 |
|
R1515:Il1r1
|
UTSW |
1 |
40,332,509 (GRCm39) |
nonsense |
probably null |
|
|
R1530:Il1r1
|
UTSW |
1 |
40,351,521 (GRCm39) |
missense |
probably benign |
0.00 |
|
R1727:Il1r1
|
UTSW |
1 |
40,332,424 (GRCm39) |
missense |
probably benign |
0.16 |
|
R1957:Il1r1
|
UTSW |
1 |
40,352,300 (GRCm39) |
nonsense |
probably null |
|
|
R2163:Il1r1
|
UTSW |
1 |
40,334,023 (GRCm39) |
missense |
probably benign |
0.00 |
|
R2313:Il1r1
|
UTSW |
1 |
40,352,470 (GRCm39) |
missense |
probably benign |
0.19 |
|
R4345:Il1r1
|
UTSW |
1 |
40,337,084 (GRCm39) |
missense |
probably benign |
0.00 |
|
R4622:Il1r1
|
UTSW |
1 |
40,351,580 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R4735:Il1r1
|
UTSW |
1 |
40,332,455 (GRCm39) |
missense |
probably benign |
0.00 |
|
R5033:Il1r1
|
UTSW |
1 |
40,332,684 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5586:Il1r1
|
UTSW |
1 |
40,264,411 (GRCm39) |
start gained |
probably benign |
|
|
R6375:Il1r1
|
UTSW |
1 |
40,334,050 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6383:Il1r1
|
UTSW |
1 |
40,352,495 (GRCm39) |
missense |
possibly damaging |
0.58 |
|
R6618:Il1r1
|
UTSW |
1 |
40,339,971 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R7169:Il1r1
|
UTSW |
1 |
40,332,519 (GRCm39) |
critical splice donor site |
probably null |
|
|
R7384:Il1r1
|
UTSW |
1 |
40,321,421 (GRCm39) |
missense |
possibly damaging |
0.64 |
|
R7798:Il1r1
|
UTSW |
1 |
40,349,526 (GRCm39) |
missense |
probably benign |
|
|
R8040:Il1r1
|
UTSW |
1 |
40,352,509 (GRCm39) |
missense |
probably benign |
0.01 |
|
R8129:Il1r1
|
UTSW |
1 |
40,341,447 (GRCm39) |
missense |
probably benign |
0.04 |
|
R9158:Il1r1
|
UTSW |
1 |
40,332,391 (GRCm39) |
nonsense |
probably null |
|
|
R9643:Il1r1
|
UTSW |
1 |
40,341,532 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9723:Il1r1
|
UTSW |
1 |
40,332,721 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9748:Il1r1
|
UTSW |
1 |
40,349,496 (GRCm39) |
missense |
probably benign |
|
|
RF007:Il1r1
|
UTSW |
1 |
40,352,438 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Nature of Mutation |
 DNA sequencing using the SOLiD technique identified an A to G transition at position 1725 of the Il1r1 transcript using Genbank record NM_008362 in exon 11 of 11 total exons. Two transcripts of the Il1r1 gene are displayed on Ensembl and Vega. The mutated nucleotide causes a lysine to glutamic acid substitution at amino acid 104 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
|
| Protein Function and Prediction |
The Il1r1 gene encodes the 576 amino acid receptor for interleukin-1 alpha (IL-1A), beta (IL-1B), and interleukin-1 receptor antagonist protein (IL-1RA). Binding to the agonist leads to the activation of NF-kappaB. Signaling involves formation of a ternary complex containing IL1RAP, TOLLIP, MYD88, and IRAK1 or IRAK2. IL1R1 is a single-pass type I membrane protein that contains three immunoglobulin (Ig)-like domains at residues 25-115, 121-213 and 229-329, and a cytoplasmic TIR domain at residues 386-544 (Uniprot P13504). Homozygous null mice are grossly normal but fail to respond to IL-1. Mice have decreased skeletal growth.
The K501E change occurs in the TIR domain, but is predicted to be benign by the PolyPhen program (see report). |
| Posted On |
2010-10-26 |
Incidental Mutation