Mutagenetix > Incidental Mutation

Incidental Mutation 'R4723:Keap1'

354610

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

041959-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.965) question?

Stock #

R4723 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

21141026-21150628 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 21142706 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Glutamine at position 516 (H516Q)

Ref Sequence

ENSEMBL: ENSMUSP00000141807 (fasta)

Gene Model

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

AlphaFold

Q9Z2X8

Predicted Effect

probably benign
Transcript: ENSMUST00000049567
AA Change: H516Q

PolyPhen 2 Score 0.153 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000062467
Gene: ENSMUSG00000003308
AA Change: H516Q

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: H516Q

PolyPhen 2 Score 0.153 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000131029
Gene: ENSMUSG00000003308
AA Change: H516Q

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

noncoding transcript
Transcript: ENSMUST00000193875

Predicted Effect

probably benign
Transcript: ENSMUST00000193982
AA Change: H516Q

PolyPhen 2 Score 0.153 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000141840
Gene: ENSMUSG00000003308
AA Change: H516Q

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: H516Q

PolyPhen 2 Score 0.153 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000141807
Gene: ENSMUSG00000003308
AA Change: H516Q

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: H512Q

PolyPhen 2 Score 0.126 (Sensitivity: 0.93; Specificity: 0.86)

Meta Mutation Damage Score

0.1022

Coding Region Coverage

1x: 99.1%
3x: 98.4%
10x: 96.6%
20x: 93.3%

Validation Efficiency

94% (77/82)

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: 74 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adgrv1	T	C	13: 81,581,644 (GRCm39)	D4800G	probably benign	Het
Akna	T	C	4: 63,305,269 (GRCm39)	D499G	probably benign	Het
Arid1b	A	C	17: 5,387,565 (GRCm39)	I1673L	probably benign	Het
Bcr	T	A	10: 75,011,161 (GRCm39)	M24K	probably benign	Het
Bsn	A	G	9: 107,989,854 (GRCm39)	V1966A	probably benign	Het
Ccdc39	T	C	3: 33,867,227 (GRCm39)	N928S	possibly damaging	Het
Cd109	CATTTATTTATTTATTTATTTATTTATTTATTTAT	CATTTATTTATTTATTTATTTATTTATTTATTTATTTAT	9: 78,619,782 (GRCm39)		probably benign	Het
Cdc6	G	A	11: 98,799,657 (GRCm39)		probably null	Het
Cfap97d2	A	T	8: 13,785,937 (GRCm39)	N69I	probably damaging	Het
Cmtm1	C	T	8: 105,020,307 (GRCm39)	A371T	probably damaging	Het
Cmtm7	A	C	9: 114,592,459 (GRCm39)	V46G	possibly damaging	Het
Cmtr1	A	G	17: 29,906,131 (GRCm39)		probably null	Het
Col5a3	T	C	9: 20,720,887 (GRCm39)	H149R	unknown	Het
Coro7	T	G	16: 4,449,858 (GRCm39)	Q634P	probably benign	Het
Crym	A	G	7: 119,800,298 (GRCm39)		probably null	Het
Csmd3	A	T	15: 47,532,556 (GRCm39)	F2546L	probably benign	Het
Dmap1	T	C	4: 117,533,236 (GRCm39)	T273A	probably benign	Het
Dnah1	T	C	14: 30,994,899 (GRCm39)	Y2786C	probably damaging	Het
Echs1	A	C	7: 139,690,561 (GRCm39)		probably benign	Het
Edem3	T	A	1: 151,680,449 (GRCm39)	F525I	possibly damaging	Het
Exosc3	T	C	4: 45,319,642 (GRCm39)	I127V	probably benign	Het
Fam193a	A	G	5: 34,578,130 (GRCm39)	D208G	probably benign	Het
Farp2	T	C	1: 93,508,621 (GRCm39)	V773A	probably benign	Het
Gas6	A	G	8: 13,516,848 (GRCm39)	V550A	probably damaging	Het
Gkn3	C	T	6: 87,360,507 (GRCm39)	A163T	probably damaging	Het
Gm2423	A	G	13: 13,406,961 (GRCm39)		noncoding transcript	Het
Grin1	T	C	2: 25,184,482 (GRCm39)	S911G	probably benign	Het
Hkdc1	T	C	10: 62,236,133 (GRCm39)	I470V	probably benign	Het
Hsdl2	T	A	4: 59,593,270 (GRCm39)		probably benign	Het
Iars2	A	G	1: 185,048,176 (GRCm39)	Y519H	probably damaging	Het
Ikbkb	A	T	8: 23,159,623 (GRCm39)	M455K	probably benign	Het
Klk1b27	A	T	7: 43,705,956 (GRCm39)	I220F	probably damaging	Het
Knop1	G	A	7: 118,455,087 (GRCm39)		probably benign	Het
Lhcgr	T	C	17: 89,050,030 (GRCm39)	T499A	probably benign	Het
Lrch3	A	T	16: 32,808,854 (GRCm39)		probably null	Het
Lrrc2	G	A	9: 110,799,228 (GRCm39)		probably null	Het
Lrrk2	T	C	15: 91,648,962 (GRCm39)	L1652P	probably damaging	Het
Mbl1	T	C	14: 40,876,515 (GRCm39)	V71A	possibly damaging	Het
Med8	T	A	4: 118,268,998 (GRCm39)	M1K	probably null	Het
Mfsd2b	A	G	12: 4,918,992 (GRCm39)	L88P	probably benign	Het
Mkrn2	T	A	6: 115,588,811 (GRCm39)	C185S	probably damaging	Het
Myo1d	A	G	11: 80,670,667 (GRCm39)		probably benign	Het
Napg	T	G	18: 63,125,563 (GRCm39)		probably null	Het
Ncor1	A	G	11: 62,269,438 (GRCm39)	M253T	probably benign	Het
Oas3	T	C	5: 120,904,321 (GRCm39)	T518A	unknown	Het
Obox3-ps8	A	G	17: 36,764,036 (GRCm39)		noncoding transcript	Het
Opn5	A	T	17: 42,918,091 (GRCm39)	M57K	probably damaging	Het
Or10a3n	A	T	7: 108,493,028 (GRCm39)	F195L	probably benign	Het
Or13j1	T	C	4: 43,705,785 (GRCm39)	K261R	probably damaging	Het
Or52p1	T	C	7: 104,267,696 (GRCm39)	V270A	possibly damaging	Het
Pde2a	C	G	7: 101,143,825 (GRCm39)	P148R	possibly damaging	Het
Prss56	C	T	1: 87,113,059 (GRCm39)	L158F	possibly damaging	Het
Psmg3	G	A	5: 139,812,125 (GRCm39)		probably benign	Het
Rnase9	C	T	14: 51,276,901 (GRCm39)	G26R	probably damaging	Het
Skint4	T	C	4: 111,975,433 (GRCm39)	V131A	possibly damaging	Het
Slc10a4	T	A	5: 73,169,398 (GRCm39)	V341E	probably damaging	Het
Slc16a14	T	C	1: 84,890,741 (GRCm39)	Y188C	probably damaging	Het
Slc7a1	G	T	5: 148,272,250 (GRCm39)	P476T	probably damaging	Het
Smchd1	A	T	17: 71,743,742 (GRCm39)	C474*	probably null	Het
Smurf1	A	T	5: 144,829,994 (GRCm39)	D336E	probably damaging	Het
Sox30	G	A	11: 45,875,592 (GRCm39)	S448N	probably benign	Het
Spag11a	G	A	8: 19,209,398 (GRCm39)	V63I	possibly damaging	Het
Sprr1b	T	G	3: 92,344,600 (GRCm39)	K92T	probably damaging	Het
Stam2	T	C	2: 52,610,962 (GRCm39)	Y20C	probably benign	Het
Sult2b1	T	A	7: 45,391,489 (GRCm39)	Y97F	probably damaging	Het
Tecpr2	C	T	12: 110,899,410 (GRCm39)	P593S	probably benign	Het
Tek	T	C	4: 94,687,397 (GRCm39)	V170A	possibly damaging	Het
Tiam2	A	G	17: 3,500,592 (GRCm39)	Y891C	probably benign	Het
Tmem220	A	G	11: 66,920,819 (GRCm39)	T75A	possibly damaging	Het
Traf3	T	G	12: 111,228,470 (GRCm39)	D560E	probably damaging	Het
Txlnb	A	G	10: 17,675,015 (GRCm39)	H56R	probably benign	Het
Vmn2r98	A	T	17: 19,286,602 (GRCm39)	N367Y	probably benign	Het
Vnn3	A	G	10: 23,727,589 (GRCm39)	I36M	possibly damaging	Het
Zbtb7a	G	A	10: 80,980,274 (GRCm39)	R156H	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
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
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'- GGTTTTCACCCTGATCCAGC -3'
(R):5'- ACCGATGAATACCATCCGGAG -3'

Sequencing Primer
(F):5'- TGATCCAGCCTCCAAGGG -3'
(R):5'- TTACATGACTGAGGCTGCC -3'

Posted On

2015-10-21