Mutagenetix > Incidental Mutation

Incidental Mutation 'R4947:Keap1'

383507

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

042544-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.965) question?

Stock #

R4947 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

21141026-21150628 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to G at 21148849 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Arginine at position 53 (S53R)

Ref Sequence

ENSEMBL: ENSMUSP00000149705 (fasta)

Gene Model

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

AlphaFold

Q9Z2X8

Predicted Effect

probably benign
Transcript: ENSMUST00000049567
AA Change: S53R

PolyPhen 2 Score 0.039 (Sensitivity: 0.94; Specificity: 0.83)

SMART Domains

Protein: ENSMUSP00000062467
Gene: ENSMUSG00000003308
AA Change: S53R

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: S53R

PolyPhen 2 Score 0.039 (Sensitivity: 0.94; Specificity: 0.83)

SMART Domains

Protein: ENSMUSP00000131029
Gene: ENSMUSG00000003308
AA Change: S53R

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

probably benign
Transcript: ENSMUST00000193982
AA Change: S53R

PolyPhen 2 Score 0.039 (Sensitivity: 0.94; Specificity: 0.83)

SMART Domains

Protein: ENSMUSP00000141840
Gene: ENSMUSG00000003308
AA Change: S53R

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: S53R

PolyPhen 2 Score 0.039 (Sensitivity: 0.94; Specificity: 0.83)

SMART Domains

Protein: ENSMUSP00000141807
Gene: ENSMUSG00000003308
AA Change: S53R

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: S53R

PolyPhen 2 Score 0.066 (Sensitivity: 0.94; Specificity: 0.84)

Meta Mutation Damage Score

0.0885

Coding Region Coverage

1x: 98.9%
3x: 98.0%
10x: 95.0%
20x: 87.4%

Validation Efficiency

100% (88/88)

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: 78 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2310057M21Rik	T	A	7: 130,959,343 (GRCm39)	H119L	probably damaging	Het
Acvr1c	T	A	2: 58,205,987 (GRCm39)	Q41L	probably benign	Het
Adamtsl1	A	T	4: 85,683,037 (GRCm39)	Q36L	possibly damaging	Het
Bcl2a1a	G	A	9: 88,839,335 (GRCm39)	E78K	probably damaging	Het
Cdk5rap2	A	G	4: 70,146,829 (GRCm39)		probably null	Het
Copg1	C	A	6: 87,880,455 (GRCm39)		probably benign	Het
Crb2	C	T	2: 37,685,343 (GRCm39)		probably benign	Het
Cstdc6	T	C	16: 36,142,127 (GRCm39)	Y83C	probably damaging	Het
Ctbp2	C	A	7: 132,601,012 (GRCm39)	G584C	probably damaging	Het
Cyp11b2	T	C	15: 74,723,419 (GRCm39)	N415S	possibly damaging	Het
D630003M21Rik	T	A	2: 158,028,116 (GRCm39)	T1095S	unknown	Het
D630045J12Rik	C	T	6: 38,125,478 (GRCm39)	R1512H	probably damaging	Het
Dnah5	T	A	15: 28,272,518 (GRCm39)	V1078E	probably benign	Het
Donson	A	T	16: 91,479,439 (GRCm39)	D366E	probably damaging	Het
Evpl	T	C	11: 116,114,201 (GRCm39)	E1163G	possibly damaging	Het
Fcgbp	A	G	7: 27,789,237 (GRCm39)	K601R	probably benign	Het
Fez1	A	C	9: 36,780,171 (GRCm39)	I323L	probably damaging	Het
Flacc1	T	A	1: 58,715,698 (GRCm39)	T173S	probably benign	Het
Fmnl2	T	G	2: 52,963,722 (GRCm39)	S285A	probably benign	Het
Frem1	A	G	4: 82,884,371 (GRCm39)	S1194P	probably damaging	Het
Gm10754	A	T	10: 97,518,010 (GRCm39)		probably benign	Het
Gm14226	A	T	2: 154,866,879 (GRCm39)	T279S	probably benign	Het
Gm16332	G	A	1: 139,793,730 (GRCm39)		noncoding transcript	Het
Gm21718	T	A	14: 51,553,416 (GRCm39)		noncoding transcript	Het
Gm9871	A	G	6: 101,773,734 (GRCm39)		noncoding transcript	Het
Grm1	A	G	10: 10,658,377 (GRCm39)	F371S	probably damaging	Het
Gtdc1	T	C	2: 44,481,968 (GRCm39)	I128V	probably null	Het
H2-Q3	T	A	17: 35,578,708 (GRCm39)		noncoding transcript	Het
Ibtk	T	C	9: 85,592,465 (GRCm39)	T998A	probably benign	Het
Ifi204	A	G	1: 173,583,316 (GRCm39)	S301P	probably damaging	Het
Kcnn1	C	A	8: 71,297,073 (GRCm39)	A545S	probably benign	Het
Lat	A	G	7: 125,967,110 (GRCm39)	V138A	probably benign	Het
Lrpprc	A	T	17: 85,078,966 (GRCm39)	N249K	probably benign	Het
Lrrc40	A	G	3: 157,769,472 (GRCm39)	I557V	probably benign	Het
Maml3	A	G	3: 51,763,960 (GRCm39)	F335L	probably benign	Het
Mcmbp	A	T	7: 128,314,420 (GRCm39)	D265E	probably damaging	Het
Me3	A	G	7: 89,282,222 (GRCm39)	H35R	probably benign	Het
Mif4gd	C	A	11: 115,500,463 (GRCm39)	V32L	probably benign	Het
Mlana	T	C	19: 29,677,551 (GRCm39)	S18P	probably damaging	Het
Mpnd	T	A	17: 56,317,268 (GRCm39)		probably benign	Het
Ms4a4b	T	C	19: 11,432,101 (GRCm39)	V74A	probably benign	Het
Mta2	T	C	19: 8,923,655 (GRCm39)	F133L	possibly damaging	Het
Myo5a	A	G	9: 75,030,330 (GRCm39)	M150V	probably damaging	Het
Nbr1	T	C	11: 101,465,903 (GRCm39)	V487A	probably benign	Het
Nos3	G	A	5: 24,582,853 (GRCm39)	C660Y	probably damaging	Het
Ocln	T	C	13: 100,676,223 (GRCm39)	D90G	probably damaging	Het
Or12d17	T	C	17: 37,777,634 (GRCm39)	V179A	probably damaging	Het
Or1e1c	C	T	11: 73,266,243 (GRCm39)	R223*	probably null	Het
Or52n5	A	G	7: 104,587,949 (GRCm39)	D72G	possibly damaging	Het
Or5h18	A	G	16: 58,847,808 (GRCm39)	L154P	probably damaging	Het
Pcdh7	A	G	5: 57,879,258 (GRCm39)	K938E	probably damaging	Het
Pcgf3	T	C	5: 108,635,827 (GRCm39)	F166L	probably benign	Het
Pid1	A	T	1: 84,015,981 (GRCm39)	V128E	possibly damaging	Het
Polr3a	A	C	14: 24,532,532 (GRCm39)	D187E	probably benign	Het
Prokr2	T	C	2: 132,215,573 (GRCm39)	D135G	probably damaging	Het
Rnf141	T	C	7: 110,424,527 (GRCm39)	T14A	possibly damaging	Het
Serinc1	T	C	10: 57,399,141 (GRCm39)	E254G	probably damaging	Het
Silc1	A	T	12: 27,210,227 (GRCm39)		noncoding transcript	Het
Skint11	T	C	4: 114,048,707 (GRCm39)	F11L	possibly damaging	Het
Slc22a28	T	C	19: 8,108,816 (GRCm39)	T109A	probably benign	Het
Sntg1	C	A	1: 8,853,022 (GRCm39)	V43L	probably damaging	Het
Sp140l2	G	A	1: 85,090,203 (GRCm39)	A124V	probably damaging	Het
Strn	T	C	17: 78,969,208 (GRCm39)	D398G	probably damaging	Het
Tacc2	A	T	7: 130,227,629 (GRCm39)	E1438V	probably damaging	Het
Tas2r139	A	G	6: 42,118,500 (GRCm39)	T211A	possibly damaging	Het
Tbkbp1	T	C	11: 97,029,770 (GRCm39)		probably benign	Het
Thbs3	T	C	3: 89,133,738 (GRCm39)	Y897H	probably damaging	Het
Timm50	G	T	7: 28,009,469 (GRCm39)		probably benign	Het
Tmem132a	T	C	19: 10,844,298 (GRCm39)	Q100R	possibly damaging	Het
Ugt1a1	CAGAGAGAGAGAGA	CAGAGAGAGAGA	1: 88,139,706 (GRCm39)		probably benign	Het
Unc93b1	C	A	19: 3,985,871 (GRCm39)	T90K	probably benign	Het
Upk3bl	T	C	5: 136,086,099 (GRCm39)		probably benign	Het
Vmn2r112	T	A	17: 22,821,860 (GRCm39)	H179Q	probably benign	Het
Vmn2r57	A	T	7: 41,049,919 (GRCm39)	F610Y	probably damaging	Het
Vmn2r80	T	G	10: 79,030,532 (GRCm39)	L786R	probably damaging	Het
Zc3h14	A	G	12: 98,726,083 (GRCm39)	T323A	probably benign	Het
Zfp532	T	C	18: 65,758,137 (GRCm39)	I690T	possibly damaging	Het
Zfp729b	T	C	13: 67,744,791 (GRCm39)	N47S	probably damaging	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
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
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'- TGGATGCCTTCGATGGACAC -3'
(R):5'- TCATCAGGAACCCCATGCAG -3'

Sequencing Primer
(F):5'- AGCCCGTTGGTGAACATG -3'
(R):5'- GCCCGAACCCAAGCTTAG -3'

Posted On

2016-04-27