Incidental Mutation 'R9521:Keap1'
ID 718890
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
Accession Numbers
Essential gene? Probably essential (E-score: 0.965) question?
Stock # R9521 (G1)
Quality Score 225.009
Status Not validated
Chromosome 9
Chromosomal Location 21141026-21150628 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 21143136 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Glutamic Acid at position 463 (V463E)
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 damaging
Transcript: ENSMUST00000049567
AA Change: V463E

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000062467
Gene: ENSMUSG00000003308
AA Change: V463E

DomainStartEndE-ValueType
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 damaging
Transcript: ENSMUST00000164812
AA Change: V463E

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000131029
Gene: ENSMUSG00000003308
AA Change: V463E

DomainStartEndE-ValueType
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 damaging
Transcript: ENSMUST00000193982
AA Change: V463E

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000141840
Gene: ENSMUSG00000003308
AA Change: V463E

DomainStartEndE-ValueType
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 damaging
Transcript: ENSMUST00000194542
AA Change: V463E

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000141807
Gene: ENSMUSG00000003308
AA Change: V463E

DomainStartEndE-ValueType
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 damaging
Transcript: ENSMUST00000216436
AA Change: V459E

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.7%
  • 20x: 99.1%
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: 56 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4833420G17Rik T C 13: 119,608,778 (GRCm39) probably null Het
A030005K14Rik C A 1: 83,036,980 (GRCm39) G17V unknown Het
Afap1l1 C T 18: 61,879,863 (GRCm39) A336T probably benign Het
Akap8 C T 17: 32,530,036 (GRCm39) R395H possibly damaging Het
Ankrd26 G A 6: 118,517,420 (GRCm39) A467V possibly damaging Het
Ano9 A T 7: 140,682,227 (GRCm39) S683T probably benign Het
Aox3 C A 1: 58,164,222 (GRCm39) A164E probably benign Het
Apc T C 18: 34,445,738 (GRCm39) I878T probably benign Het
Apcdd1 C T 18: 63,055,731 (GRCm39) probably benign Het
Atg9b T C 5: 24,593,107 (GRCm39) N432S probably benign Het
Atp1b3 A G 9: 96,227,911 (GRCm39) F49L probably damaging Het
Cacnb2 A T 2: 14,609,138 (GRCm39) probably benign Het
Ccdc180 T A 4: 45,916,283 (GRCm39) L828Q probably null Het
Chd3 C T 11: 69,249,133 (GRCm39) R748Q probably benign Het
Chst13 G A 6: 90,286,506 (GRCm39) P152L probably damaging Het
Cldn18 T A 9: 99,581,028 (GRCm39) probably null Het
Cmklr1 C T 5: 113,752,480 (GRCm39) V174I probably benign Het
Cyp2d22 A T 15: 82,256,688 (GRCm39) V362D probably damaging Het
Dock10 T C 1: 80,501,763 (GRCm39) K1810R probably damaging Het
Duox1 T A 2: 122,159,216 (GRCm39) V661E possibly damaging Het
Ercc2 G A 7: 19,125,899 (GRCm39) R518Q probably damaging Het
Fam186a A G 15: 99,841,471 (GRCm39) L1591P probably damaging Het
Fam186b G T 15: 99,178,419 (GRCm39) D302E probably benign Het
Fap T C 2: 62,372,500 (GRCm39) D326G probably benign Het
Gm42669 T A 5: 107,655,892 (GRCm39) D135E Het
Mga T C 2: 119,794,979 (GRCm39) S2888P probably damaging Het
Mgam A G 6: 40,722,118 (GRCm39) D403G probably damaging Het
Mios C T 6: 8,233,171 (GRCm39) T773I probably benign Het
Nav3 T C 10: 109,835,845 (GRCm39) D79G possibly damaging Het
Nxt2 C T X: 141,020,747 (GRCm39) A118V possibly damaging Het
Or52d3 A G 7: 104,228,855 (GRCm39) M1V probably null Het
Or8k35 C A 2: 86,424,771 (GRCm39) V134F Het
Orc6 T C 8: 86,026,615 (GRCm39) V20A possibly damaging Het
Peli2 A G 14: 48,490,052 (GRCm39) K175E probably benign Het
Plec C G 15: 76,062,924 (GRCm39) R2382P possibly damaging Het
Ppp1r12b T A 1: 134,705,063 (GRCm39) D875V probably damaging Het
Pramel6 T A 2: 87,340,629 (GRCm39) C320* probably null Het
Qrich2 A T 11: 116,339,208 (GRCm39) M26K probably damaging Het
Rapgef1 A G 2: 29,624,291 (GRCm39) I1006V probably benign Het
Rasgrp3 T A 17: 75,821,158 (GRCm39) L455Q probably null Het
Scaf8 C T 17: 3,248,285 (GRCm39) R1203W probably damaging Het
Senp6 C T 9: 79,974,687 (GRCm39) probably benign Het
Senp7 A G 16: 55,992,144 (GRCm39) Y700C probably damaging Het
Siglec1 A G 2: 130,915,246 (GRCm39) probably null Het
Slc12a7 G A 13: 73,947,087 (GRCm39) V592I probably benign Het
Slfn3 T C 11: 83,103,825 (GRCm39) V232A probably benign Het
Tdp1 T C 12: 99,877,906 (GRCm39) V396A probably damaging Het
Ticam1 T C 17: 56,578,388 (GRCm39) T236A probably benign Het
Tob1 AGCAGCAGCAGCAGCAGCAGCCGTCATCATCCCAGCCGCCGCCTCCACTACCGCAGCAGCAGCAGCAGCAGCC AGCAGCAGCAGCAGCAGCAGCC 11: 94,105,205 (GRCm39) probably benign Het
Ttc21a C A 9: 119,787,181 (GRCm39) D729E probably damaging Het
Ubtd2 T C 11: 32,449,432 (GRCm39) I93T possibly damaging Het
Unc45b A G 11: 82,808,586 (GRCm39) D224G probably benign Het
Usp48 G A 4: 137,340,996 (GRCm39) G332E probably benign Het
Vmn2r61 A G 7: 41,916,626 (GRCm39) E413G probably damaging Het
Zfp423 A T 8: 88,509,033 (GRCm39) L437Q probably damaging Het
Zfp810 A G 9: 22,190,227 (GRCm39) V227A possibly damaging Het
Other mutations in Keap1
AlleleSourceChrCoordTypePredicted EffectPPH 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
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
Predicted Primers PCR Primer
(F):5'- AGCAAACGCTTCCTCGCTTC -3'
(R):5'- TGATGACCCCTCACTTCTGG -3'

Sequencing Primer
(F):5'- CTCGCTTCCTCGCTGGG -3'
(R):5'- GCTTGAACTACATAGCAGGGTTC -3'
Posted On 2022-07-18