Incidental Mutation 'R6508:Keap1'
| ID |
524003 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Keap1
|
| Ensembl Gene |
ENSMUSG00000003308 |
| Gene Name |
kelch-like ECH-associated protein 1 |
| Synonyms |
INrf2, ring canal protein |
| MMRRC Submission |
044638-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably essential
(E-score: 0.961)
|
| Stock # |
R6508 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Not validated
|
| Chromosome |
9 |
| Chromosomal Location |
21141026-21150628 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
G to A
at 21143010 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Threonine to Isoleucine
at position 501
(T501I)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000149705
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000049567]
[ENSMUST00000164812]
[ENSMUST00000193982]
[ENSMUST00000194542]
[ENSMUST00000216436]
|
| AlphaFold |
Q9Z2X8 |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000049567
AA Change: T505I
PolyPhen 2
Score 0.537 (Sensitivity: 0.88; Specificity: 0.90)
|
| SMART Domains |
Protein: ENSMUSP00000062467
Gene: ENSMUSG00000003308
AA Change: T505I
| Domain | Start | End | E-Value | Type |
|---|
|
BTB
|
77 |
179 |
1.33e-25 |
SMART |
|
BACK
|
184 |
286 |
2.19e-34 |
SMART |
|
Kelch
|
327 |
372 |
4.2e-11 |
SMART |
|
Kelch
|
373 |
423 |
4.1e-14 |
SMART |
|
Kelch
|
424 |
470 |
5.12e-15 |
SMART |
|
Kelch
|
471 |
517 |
1.02e-18 |
SMART |
|
Kelch
|
518 |
564 |
1.23e-17 |
SMART |
|
Kelch
|
565 |
611 |
7.58e-18 |
SMART |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000164812
AA Change: T505I
PolyPhen 2
Score 0.537 (Sensitivity: 0.88; Specificity: 0.90)
|
| SMART Domains |
Protein: ENSMUSP00000131029
Gene: ENSMUSG00000003308
AA Change: T505I
| Domain | Start | End | E-Value | Type |
|---|
|
BTB
|
77 |
179 |
1.33e-25 |
SMART |
|
BACK
|
184 |
286 |
2.19e-34 |
SMART |
|
Kelch
|
327 |
372 |
4.2e-11 |
SMART |
|
Kelch
|
373 |
423 |
4.1e-14 |
SMART |
|
Kelch
|
424 |
470 |
5.12e-15 |
SMART |
|
Kelch
|
471 |
517 |
1.02e-18 |
SMART |
|
Kelch
|
518 |
564 |
1.23e-17 |
SMART |
|
Kelch
|
565 |
611 |
7.58e-18 |
SMART |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000181222
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000193247
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000193429
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000193982
AA Change: T505I
PolyPhen 2
Score 0.537 (Sensitivity: 0.88; Specificity: 0.90)
|
| SMART Domains |
Protein: ENSMUSP00000141840
Gene: ENSMUSG00000003308
AA Change: T505I
| Domain | Start | End | E-Value | Type |
|---|
|
BTB
|
77 |
179 |
1.33e-25 |
SMART |
|
BACK
|
184 |
286 |
2.19e-34 |
SMART |
|
Kelch
|
327 |
372 |
4.2e-11 |
SMART |
|
Kelch
|
373 |
423 |
4.1e-14 |
SMART |
|
Kelch
|
424 |
470 |
5.12e-15 |
SMART |
|
Kelch
|
471 |
517 |
1.02e-18 |
SMART |
|
Kelch
|
518 |
564 |
1.23e-17 |
SMART |
|
Kelch
|
565 |
611 |
7.58e-18 |
SMART |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000194542
AA Change: T505I
PolyPhen 2
Score 0.537 (Sensitivity: 0.88; Specificity: 0.90)
|
| SMART Domains |
Protein: ENSMUSP00000141807
Gene: ENSMUSG00000003308
AA Change: T505I
| Domain | Start | End | E-Value | Type |
|---|
|
BTB
|
77 |
179 |
1.33e-25 |
SMART |
|
BACK
|
184 |
286 |
2.19e-34 |
SMART |
|
Kelch
|
327 |
372 |
4.2e-11 |
SMART |
|
Kelch
|
373 |
423 |
4.1e-14 |
SMART |
|
Kelch
|
424 |
470 |
5.12e-15 |
SMART |
|
Kelch
|
471 |
517 |
1.02e-18 |
SMART |
|
Kelch
|
518 |
564 |
1.23e-17 |
SMART |
|
Kelch
|
565 |
611 |
7.58e-18 |
SMART |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000216436
AA Change: T501I
PolyPhen 2
Score 0.667 (Sensitivity: 0.86; Specificity: 0.91)
|
| Coding Region Coverage |
- 1x: 99.9%
- 3x: 99.6%
- 10x: 98.0%
- 20x: 94.2%
|
| Validation Efficiency |
|
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a protein containing KELCH-1 like domains, as well as a BTB/POZ domain. Kelch-like ECH-associated protein 1 interacts with NF-E2-related factor 2 in a redox-sensitive manner and the dissociation of the proteins in the cytoplasm is followed by transportation of NF-E2-related factor 2 to the nucleus. This interaction results in the expression of the catalytic subunit of gamma-glutamylcysteine synthetase. Two alternatively spliced transcript variants encoding the same isoform have been found for this gene. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous null mice exhibit scaly skin, hyperkeratosis of the esophagus and stomach mucosa, and die around 3 weeks of age, putatively due to malnutrition resulting from the abnormal alimentary epithelium. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 45 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Aadacl4fm2 |
G |
A |
4: 144,291,590 (GRCm39) |
R39* |
probably null |
Het |
| Brca2 |
A |
T |
5: 150,460,058 (GRCm39) |
E444D |
possibly damaging |
Het |
| Camkk2 |
G |
T |
5: 122,884,382 (GRCm39) |
N346K |
probably damaging |
Het |
| Car4 |
C |
A |
11: 84,856,469 (GRCm39) |
D252E |
possibly damaging |
Het |
| Chd1 |
A |
G |
17: 15,958,895 (GRCm39) |
K649R |
probably benign |
Het |
| Col12a1 |
A |
G |
9: 79,557,231 (GRCm39) |
Y1966H |
probably damaging |
Het |
| Crppa |
C |
T |
12: 36,476,298 (GRCm39) |
A180V |
possibly damaging |
Het |
| Cts6 |
T |
A |
13: 61,344,221 (GRCm39) |
H277L |
probably damaging |
Het |
| Dcc |
G |
T |
18: 71,439,144 (GRCm39) |
P1246Q |
probably damaging |
Het |
| Dlg5 |
G |
A |
14: 24,188,774 (GRCm39) |
T1739I |
probably benign |
Het |
| Eci1 |
T |
A |
17: 24,656,283 (GRCm39) |
N164K |
probably damaging |
Het |
| Entpd7 |
G |
A |
19: 43,679,525 (GRCm39) |
R26H |
probably damaging |
Het |
| Fanci |
A |
G |
7: 79,093,516 (GRCm39) |
K1008E |
probably damaging |
Het |
| Htr2b |
T |
C |
1: 86,030,186 (GRCm39) |
T170A |
possibly damaging |
Het |
| Irgm2 |
A |
G |
11: 58,110,327 (GRCm39) |
E18G |
probably benign |
Het |
| Kdm1a |
A |
T |
4: 136,281,621 (GRCm39) |
V630E |
probably damaging |
Het |
| L3mbtl3 |
T |
A |
10: 26,194,325 (GRCm39) |
H424L |
unknown |
Het |
| Lrrc14b |
C |
T |
13: 74,511,337 (GRCm39) |
D248N |
possibly damaging |
Het |
| Macf1 |
T |
A |
4: 123,363,535 (GRCm39) |
D3364V |
probably damaging |
Het |
| Map3k20 |
G |
A |
2: 72,272,253 (GRCm39) |
G794S |
probably benign |
Het |
| Mcat |
T |
C |
15: 83,433,452 (GRCm39) |
Q34R |
probably benign |
Het |
| Mettl4 |
T |
C |
17: 95,051,373 (GRCm39) |
E148G |
probably damaging |
Het |
| Mgat3 |
T |
C |
15: 80,096,225 (GRCm39) |
S351P |
possibly damaging |
Het |
| Mllt1 |
A |
T |
17: 57,234,054 (GRCm39) |
I44N |
probably damaging |
Het |
| Mlxipl |
G |
T |
5: 135,157,474 (GRCm39) |
A337S |
probably benign |
Het |
| Naip1 |
A |
G |
13: 100,572,973 (GRCm39) |
F254L |
probably damaging |
Het |
| Obscn |
A |
T |
11: 58,944,973 (GRCm39) |
|
probably null |
Het |
| Or10q1 |
C |
T |
19: 13,726,718 (GRCm39) |
P83S |
probably damaging |
Het |
| Pcdh12 |
G |
A |
18: 38,414,390 (GRCm39) |
R912* |
probably null |
Het |
| Pcdh17 |
A |
G |
14: 84,685,419 (GRCm39) |
N629D |
probably damaging |
Het |
| Pcnx1 |
T |
C |
12: 81,959,479 (GRCm39) |
I170T |
probably damaging |
Het |
| Pgr |
A |
G |
9: 8,956,290 (GRCm39) |
Y746C |
probably damaging |
Het |
| Pramel29 |
A |
T |
4: 143,934,171 (GRCm39) |
L312* |
probably null |
Het |
| Pum2 |
T |
C |
12: 8,798,861 (GRCm39) |
Y991H |
probably benign |
Het |
| Rcc1l |
A |
T |
5: 134,198,077 (GRCm39) |
V185D |
probably damaging |
Het |
| Scarb1 |
A |
T |
5: 125,381,389 (GRCm39) |
S52T |
possibly damaging |
Het |
| Smc1b |
C |
T |
15: 84,976,232 (GRCm39) |
R825Q |
probably benign |
Het |
| Spata4 |
T |
C |
8: 55,053,887 (GRCm39) |
S18P |
probably benign |
Het |
| Stard13 |
G |
A |
5: 150,986,754 (GRCm39) |
T134I |
probably benign |
Het |
| Tbc1d32 |
C |
T |
10: 56,100,786 (GRCm39) |
C64Y |
probably damaging |
Het |
| Tll1 |
T |
G |
8: 64,551,494 (GRCm39) |
I296L |
probably damaging |
Het |
| Tmem229b |
T |
G |
12: 79,011,680 (GRCm39) |
T84P |
probably damaging |
Het |
| Ttn |
T |
C |
2: 76,544,757 (GRCm39) |
T32782A |
possibly damaging |
Het |
| Vmn1r73 |
G |
A |
7: 11,490,631 (GRCm39) |
V150I |
possibly damaging |
Het |
| Vmn2r80 |
T |
A |
10: 79,030,290 (GRCm39) |
F705L |
probably benign |
Het |
|
| Other mutations in Keap1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
cubs
|
UTSW |
9 |
21,148,849 (GRCm39) |
missense |
probably benign |
0.07 |
|
R1917:Keap1
|
UTSW |
9 |
21,145,102 (GRCm39) |
missense |
probably benign |
|
|
R4296:Keap1
|
UTSW |
9 |
21,145,282 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4590:Keap1
|
UTSW |
9 |
21,148,905 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R4723:Keap1
|
UTSW |
9 |
21,142,706 (GRCm39) |
missense |
probably benign |
0.15 |
|
R4947:Keap1
|
UTSW |
9 |
21,148,849 (GRCm39) |
missense |
probably benign |
0.07 |
|
R4952:Keap1
|
UTSW |
9 |
21,148,582 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5024:Keap1
|
UTSW |
9 |
21,148,522 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6001:Keap1
|
UTSW |
9 |
21,142,135 (GRCm39) |
missense |
possibly damaging |
0.45 |
|
R7075:Keap1
|
UTSW |
9 |
21,142,552 (GRCm39) |
missense |
probably benign |
0.30 |
|
R7184:Keap1
|
UTSW |
9 |
21,145,134 (GRCm39) |
missense |
probably benign |
|
|
R7520:Keap1
|
UTSW |
9 |
21,144,787 (GRCm39) |
missense |
probably benign |
|
|
R7531:Keap1
|
UTSW |
9 |
21,148,623 (GRCm39) |
missense |
probably benign |
0.20 |
|
R7811:Keap1
|
UTSW |
9 |
21,148,956 (GRCm39) |
missense |
possibly damaging |
0.92 |
|
R8424:Keap1
|
UTSW |
9 |
21,142,086 (GRCm39) |
missense |
probably benign |
0.00 |
|
R8976:Keap1
|
UTSW |
9 |
21,142,663 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9154:Keap1
|
UTSW |
9 |
21,142,121 (GRCm39) |
nonsense |
probably null |
|
|
R9521:Keap1
|
UTSW |
9 |
21,143,136 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Predicted Primers |
PCR Primer
(F):5'- GACTTTAGTAGCCACTGCCC -3'
(R):5'- TTTGCAGATATGAGCCAGAGC -3'
Sequencing Primer
(F):5'- TCCACCACTGGAGAAGCTG -3'
(R):5'- TATGAGCCAGAGCGGGAC -3'
|
| Posted On |
2018-06-22 |
Incidental Mutation