Mutagenetix > Incidental Mutation

Incidental Mutation 'R7075:Keap1'

549165

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

045170-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.961) question?

Stock #

R7075 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

21141026-21150628 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 21142552 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Isoleucine at position 568 (V568I)

Ref Sequence

ENSEMBL: ENSMUSP00000062467 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000049567] [ENSMUST00000164812] [ENSMUST00000193982] [ENSMUST00000194542] [ENSMUST00000216436]

AlphaFold

Q9Z2X8

PDB Structure

Structural basis for the defects of human lung cancer somatic mutations in the repression activity of Keap1 on Nrf2 [X-RAY DIFFRACTION]
Structural basis for the defects of human lung cancer somatic mutations in the repression activity of Keap1 on Nrf2 [X-RAY DIFFRACTION]
Crystal structure of the Keap1 protein in complexed with the N-terminal region of the Nrf2 transcription factor [X-RAY DIFFRACTION]
Crystal structure of Keap1 complexed with Prothymosin alpha [X-RAY DIFFRACTION]
Crystal Structure of Keap1 in Complex with Sequestosome-1/p62 [X-RAY DIFFRACTION]
Crystal Structure of Keap1 in Complex with phosphorylated p62 [X-RAY DIFFRACTION]
Crystal Structure of Keap1 in Complex with the N-terminal region of the Nrf2 transcription factor [X-RAY DIFFRACTION]

Predicted Effect

probably benign
Transcript: ENSMUST00000049567
AA Change: V568I

PolyPhen 2 Score 0.303 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000062467
Gene: ENSMUSG00000003308
AA Change: V568I

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

probably benign
Transcript: ENSMUST00000164812
AA Change: V568I

PolyPhen 2 Score 0.303 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000131029
Gene: ENSMUSG00000003308
AA Change: V568I

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

probably benign
Transcript: ENSMUST00000193982
AA Change: V568I

PolyPhen 2 Score 0.303 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000141840
Gene: ENSMUSG00000003308
AA Change: V568I

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

probably benign
Transcript: ENSMUST00000194542
AA Change: V568I

PolyPhen 2 Score 0.303 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000141807
Gene: ENSMUSG00000003308
AA Change: V568I

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

probably benign
Transcript: ENSMUST00000216436
AA Change: V564I

PolyPhen 2 Score 0.258 (Sensitivity: 0.91; Specificity: 0.88)

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 98.9%

Validation Efficiency

95% (60/63)

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: 62 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acyp1	A	T	12: 85,325,782 (GRCm39)	H72Q	unknown	Het
Afmid	T	A	11: 117,726,531 (GRCm39)	D218E	probably benign	Het
Ankhd1	T	C	18: 36,693,042 (GRCm39)	V1A		Het
Atf7ip	T	C	6: 136,573,513 (GRCm39)		probably null	Het
BC024139	C	T	15: 76,008,599 (GRCm39)	V326I	probably benign	Het
Bfsp1	T	A	2: 143,690,885 (GRCm39)	Q159L	probably damaging	Het
Cct2	A	T	10: 116,897,370 (GRCm39)	W125R	unknown	Het
Cnksr3	G	T	10: 7,102,931 (GRCm39)	T147K	probably benign	Het
Colq	C	G	14: 31,274,866 (GRCm39)	G101R	probably damaging	Het
Dlg5	G	T	14: 24,227,865 (GRCm39)	T352K	possibly damaging	Het
Dusp9	TAAAGCGGAGGCCAAAGCGGAGGCCAAAGCGGAGGCTAAAGCGGAGGCCAAAGCGGAGGCCAAAGCGGAGGCCAAAGCGGAGGCTAAAGCGGAGGCCAAAGCGGAGGCCAAAG	TAAAGCGGAGGCCAAAGCGGAGGCCAAAGCGGAGGCTAAAGCGGAGGCCAAAGCGGAGGCCAAAG	X: 72,684,217 (GRCm39)		probably benign	Het
Ebna1bp2	T	C	4: 118,479,299 (GRCm39)	V119A	probably benign	Het
Eif2ak4	C	T	2: 118,251,291 (GRCm39)	Q318*	probably null	Het
Eif2b1	G	A	5: 124,709,314 (GRCm39)	T286M	probably damaging	Het
Fam53b	G	T	7: 132,361,352 (GRCm39)	D225E	probably damaging	Het
Fh1	A	G	1: 175,435,421 (GRCm39)	I354T	probably benign	Het
Fnbp1	T	C	2: 30,948,926 (GRCm39)	H206R	probably benign	Het
Gabrg3	A	T	7: 56,973,444 (GRCm39)	D74E	probably damaging	Het
Galnt18	A	T	7: 111,155,595 (GRCm39)	V246E	possibly damaging	Het
Glt6d1	T	C	2: 25,685,292 (GRCm39)	R44G	probably benign	Het
Gm17087	T	C	17: 8,785,635 (GRCm39)	M23V	probably benign	Het
Gpr160	A	T	3: 30,950,926 (GRCm39)	I333L	possibly damaging	Het
Hars1	T	C	18: 36,905,408 (GRCm39)	N142S	possibly damaging	Het
Hmgcll1	T	C	9: 75,963,834 (GRCm39)	V97A	possibly damaging	Het
Itih4	T	G	14: 30,614,560 (GRCm39)	V474G	probably damaging	Het
Itprid2	T	A	2: 79,466,004 (GRCm39)	S41T	probably damaging	Het
Kifc5b	A	G	17: 27,144,872 (GRCm39)	M633V	probably benign	Het
Lsm4	A	G	8: 71,130,435 (GRCm39)	E18G	probably damaging	Het
Meox1	T	A	11: 101,784,569 (GRCm39)	Q88L	probably damaging	Het
Mettl25	T	C	10: 105,665,785 (GRCm39)	N147S	possibly damaging	Het
Mphosph9	A	C	5: 124,458,922 (GRCm39)	W83G	probably damaging	Het
Or1j15	T	C	2: 36,459,192 (GRCm39)	I194T	probably benign	Het
Or5ak22	T	C	2: 85,230,544 (GRCm39)	D111G	probably damaging	Het
Or7e170	T	A	9: 19,795,359 (GRCm39)	M81L	probably benign	Het
Or8b4	T	C	9: 37,830,370 (GRCm39)	V139A	probably benign	Het
Or8h8	T	G	2: 86,752,990 (GRCm39)	K295N	possibly damaging	Het
Or9g4	T	A	2: 85,505,168 (GRCm39)	Y109F		Het
Otogl	G	T	10: 107,614,790 (GRCm39)	T1954K	probably benign	Het
Padi2	T	C	4: 140,660,528 (GRCm39)	V336A	probably damaging	Het
Phf21a	C	T	2: 92,190,724 (GRCm39)	Q675*	probably null	Het
Ppip5k1	T	C	2: 121,152,231 (GRCm39)	E1092G	probably damaging	Het
Psg21	T	C	7: 18,388,786 (GRCm39)	N102S	probably damaging	Het
Ralgapa1	C	A	12: 55,867,508 (GRCm39)	Q15H	possibly damaging	Het
Rbm26	A	T	14: 105,398,043 (GRCm39)	D26E	unknown	Het
Rbp4	T	C	19: 38,112,509 (GRCm39)	Y152C	probably damaging	Het
Recql4	A	G	15: 76,590,624 (GRCm39)	V646A	possibly damaging	Het
Rnf220	A	T	4: 117,143,079 (GRCm39)	M63K	probably benign	Het
Selenok	T	C	14: 29,692,024 (GRCm39)	S21P	probably damaging	Het
Senp1	A	G	15: 97,956,207 (GRCm39)	V404A	probably benign	Het
Sh3yl1	A	G	12: 30,990,165 (GRCm39)		probably null	Het
Snx32	A	G	19: 5,547,018 (GRCm39)	L275P	probably damaging	Het
Stat5a	T	C	11: 100,770,519 (GRCm39)	V519A	possibly damaging	Het
Tbc1d10b	A	T	7: 126,802,410 (GRCm39)	V388E	possibly damaging	Het
Tdrd6	A	G	17: 43,936,065 (GRCm39)	V1661A	probably benign	Het
Tmem63a	T	A	1: 180,788,714 (GRCm39)	F350L	probably damaging	Het
Trio	A	T	15: 27,898,086 (GRCm39)	I401K	unknown	Het
Ttn	T	C	2: 76,547,173 (GRCm39)	E32291G	probably damaging	Het
Tubgcp5	G	T	7: 55,479,155 (GRCm39)	V1002L	probably benign	Het
Vav3	C	T	3: 109,433,240 (GRCm39)	T410I	possibly damaging	Het
Vmn1r1	A	T	1: 181,985,597 (GRCm39)	F23I	probably benign	Het
Vmn2r84	T	A	10: 130,226,941 (GRCm39)	Q299L	probably damaging	Het
Vmn2r85	T	A	10: 130,258,557 (GRCm39)	E499D	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
R6508:Keap1	UTSW	9	21,143,010 (GRCm39)	missense	possibly damaging	0.67
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'- AATGAAGAGAATGGTCACCCC -3'
(R):5'- ACTGTGCGCTTTCCTTTAGG -3'

Sequencing Primer
(F):5'- AATGTGGTTCAGTCTAGAGCCCC -3'
(R):5'- CGCTTTCCTTTAGGGGTCTGC -3'

Posted On

2019-05-15