Incidental Mutation 'R6580:Klhl3'
ID 524106
Institutional Source Beutler Lab
Gene Symbol Klhl3
Ensembl Gene ENSMUSG00000014164
Gene Name kelch-like 3
Synonyms EG627648, 7530408C15Rik
MMRRC Submission 044704-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R6580 (G1)
Quality Score 225.009
Status Validated
Chromosome 13
Chromosomal Location 58148042-58261406 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 58166701 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Phenylalanine at position 430 (I430F)
Ref Sequence ENSEMBL: ENSMUSP00000089173 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000091583] [ENSMUST00000160860]
AlphaFold E0CZ16
Predicted Effect possibly damaging
Transcript: ENSMUST00000091583
AA Change: I430F

PolyPhen 2 Score 0.752 (Sensitivity: 0.85; Specificity: 0.92)
SMART Domains Protein: ENSMUSP00000089173
Gene: ENSMUSG00000014164
AA Change: I430F

DomainStartEndE-ValueType
BTB 103 200 9.36e-30 SMART
BACK 205 307 7.49e-42 SMART
Kelch 355 400 3.31e-9 SMART
Kelch 401 447 3.82e-14 SMART
Kelch 448 494 1.49e-16 SMART
Kelch 495 543 8.58e-17 SMART
Kelch 544 590 4.93e-17 SMART
Kelch 591 638 4.16e-15 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000104769
Predicted Effect possibly damaging
Transcript: ENSMUST00000160860
AA Change: I377F

PolyPhen 2 Score 0.516 (Sensitivity: 0.88; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000123701
Gene: ENSMUSG00000014164
AA Change: I377F

DomainStartEndE-ValueType
BTB 64 161 9.36e-30 SMART
BACK 166 268 7.49e-42 SMART
Kelch 316 361 3.31e-9 SMART
Kelch 362 408 3.82e-14 SMART
Kelch 409 455 1.49e-16 SMART
Kelch 456 504 8.58e-17 SMART
Kelch 505 551 4.93e-17 SMART
Kelch 552 599 4.16e-15 SMART
Meta Mutation Damage Score 0.3911 question?
Coding Region Coverage
  • 1x: 99.9%
  • 3x: 99.5%
  • 10x: 97.7%
  • 20x: 93.2%
Validation Efficiency 97% (32/33)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is ubiquitously expressed and encodes a full-length protein which has an N-terminal BTB domain followed by a BACK domain and six kelch-like repeats in the C-terminus. These kelch-like repeats promote substrate ubiquitination of bound proteins via interaction of the BTB domain with the CUL3 (cullin 3) component of a cullin-RING E3 ubiquitin ligase (CRL) complex. Muatations in this gene cause pseudohypoaldosteronism type IID (PHA2D); a rare Mendelian syndrome featuring hypertension, hyperkalaemia and metabolic acidosis. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Mar 2012]
PHENOTYPE: Mice carrying a point mutation display salt-sensitive hypertension, hyperkalemia and metabolic acidosis. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 34 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1110002E22Rik G A 3: 137,772,386 (GRCm39) R525H probably benign Het
Acox3 T A 5: 35,765,747 (GRCm39) L600Q probably damaging Het
Ankrd49 A G 9: 14,692,694 (GRCm39) S157P probably damaging Het
Ccdc141 A G 2: 76,842,099 (GRCm39) F1444S possibly damaging Het
Cimap2 G T 4: 106,468,711 (GRCm39) H271N possibly damaging Het
Defb28 C T 2: 152,360,215 (GRCm39) S10L possibly damaging Het
Epha6 T G 16: 59,502,979 (GRCm39) N976T probably damaging Het
Gm45861 A G 8: 28,034,979 (GRCm39) K976E unknown Het
Gtf2ird1 T G 5: 134,389,893 (GRCm39) N920H probably damaging Het
Gtf3c1 A T 7: 125,243,519 (GRCm39) M1695K probably benign Het
Hfm1 C T 5: 106,995,575 (GRCm39) E1279K probably benign Het
Il31ra C T 13: 112,688,476 (GRCm39) D34N possibly damaging Het
Mfhas1 A G 8: 36,056,419 (GRCm39) Y298C probably damaging Het
Muc20 A T 16: 32,613,859 (GRCm39) M506K possibly damaging Het
Myo1c C T 11: 75,562,461 (GRCm39) P918S probably benign Het
Naip1 T A 13: 100,581,157 (GRCm39) D30V probably damaging Het
Nol9 A G 4: 152,136,218 (GRCm39) N430S probably benign Het
Or8b44 T C 9: 38,410,319 (GRCm39) M118T probably damaging Het
Palm3 A G 8: 84,756,177 (GRCm39) E563G probably damaging Het
Pcdhga4 A G 18: 37,820,370 (GRCm39) S640G possibly damaging Het
Pi4ka A G 16: 17,168,694 (GRCm39) F679L probably damaging Het
Pierce1 A G 2: 28,356,062 (GRCm39) W74R probably damaging Het
Polr3c A G 3: 96,634,659 (GRCm39) probably null Het
Ptdss2 T A 7: 140,732,925 (GRCm39) I236N probably damaging Het
Rapgef1 A G 2: 29,620,621 (GRCm39) Y879C possibly damaging Het
Shc3 T C 13: 51,596,809 (GRCm39) T405A probably benign Het
Smtnl2 G T 11: 72,293,859 (GRCm39) S232R probably benign Het
Taar8a G A 10: 23,952,791 (GRCm39) A132T probably damaging Het
Tex47 T C 5: 7,355,212 (GRCm39) I131T probably damaging Het
Tiam2 CGGG CGGGG 17: 3,464,897 (GRCm39) probably null Het
Vmn1r63 A G 7: 5,805,913 (GRCm39) S240P probably benign Het
Vmn2r130 T C 17: 23,282,740 (GRCm39) V140A probably benign Het
Vmn2r84 A G 10: 130,225,110 (GRCm39) W467R possibly damaging Het
Zscan12 T C 13: 21,553,328 (GRCm39) L384P probably damaging Het
Other mutations in Klhl3
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01790:Klhl3 APN 13 58,157,236 (GRCm39) critical splice acceptor site probably null
IGL01984:Klhl3 APN 13 58,159,057 (GRCm39) splice site probably benign
IGL02022:Klhl3 APN 13 58,198,878 (GRCm39) missense possibly damaging 0.95
IGL02543:Klhl3 APN 13 58,166,685 (GRCm39) missense probably damaging 1.00
bearded_dragon UTSW 13 58,158,966 (GRCm39) missense probably benign 0.00
R0975:Klhl3 UTSW 13 58,161,677 (GRCm39) missense possibly damaging 0.81
R1386:Klhl3 UTSW 13 58,178,247 (GRCm39) missense probably damaging 0.99
R1588:Klhl3 UTSW 13 58,161,712 (GRCm39) missense probably damaging 1.00
R1791:Klhl3 UTSW 13 58,181,044 (GRCm39) missense possibly damaging 0.87
R1894:Klhl3 UTSW 13 58,157,189 (GRCm39) missense probably damaging 1.00
R1953:Klhl3 UTSW 13 58,159,022 (GRCm39) missense probably damaging 1.00
R2116:Klhl3 UTSW 13 58,166,805 (GRCm39) missense probably damaging 0.99
R3114:Klhl3 UTSW 13 58,198,841 (GRCm39) critical splice donor site probably null
R4082:Klhl3 UTSW 13 58,166,611 (GRCm39) missense probably null 1.00
R4717:Klhl3 UTSW 13 58,178,330 (GRCm39) missense probably damaging 1.00
R4857:Klhl3 UTSW 13 58,166,620 (GRCm39) missense probably damaging 1.00
R4934:Klhl3 UTSW 13 58,250,231 (GRCm39) nonsense probably null
R5112:Klhl3 UTSW 13 58,166,703 (GRCm39) missense probably damaging 1.00
R5114:Klhl3 UTSW 13 58,166,781 (GRCm39) missense probably benign 0.24
R5547:Klhl3 UTSW 13 58,250,243 (GRCm39) splice site probably null
R5776:Klhl3 UTSW 13 58,152,998 (GRCm39) missense probably benign 0.00
R6236:Klhl3 UTSW 13 58,232,876 (GRCm39) missense probably damaging 1.00
R6268:Klhl3 UTSW 13 58,161,656 (GRCm39) missense probably damaging 1.00
R6457:Klhl3 UTSW 13 58,248,192 (GRCm39) missense probably benign 0.01
R6559:Klhl3 UTSW 13 58,164,290 (GRCm39) missense probably damaging 1.00
R6601:Klhl3 UTSW 13 58,242,930 (GRCm39) missense probably damaging 0.96
R6669:Klhl3 UTSW 13 58,158,966 (GRCm39) missense probably benign 0.00
R6904:Klhl3 UTSW 13 58,178,259 (GRCm39) missense probably damaging 1.00
R7652:Klhl3 UTSW 13 58,261,146 (GRCm39) start gained probably benign
R7979:Klhl3 UTSW 13 58,211,611 (GRCm39) missense probably benign 0.39
R8112:Klhl3 UTSW 13 58,161,677 (GRCm39) missense possibly damaging 0.81
R8114:Klhl3 UTSW 13 58,161,677 (GRCm39) missense possibly damaging 0.81
R8270:Klhl3 UTSW 13 58,260,968 (GRCm39) missense
R8409:Klhl3 UTSW 13 58,167,242 (GRCm39) missense probably damaging 1.00
R8742:Klhl3 UTSW 13 58,159,021 (GRCm39) missense probably damaging 1.00
R9112:Klhl3 UTSW 13 58,248,212 (GRCm39) missense unknown
R9396:Klhl3 UTSW 13 58,161,662 (GRCm39) missense probably damaging 1.00
R9474:Klhl3 UTSW 13 58,167,273 (GRCm39) missense probably damaging 1.00
R9568:Klhl3 UTSW 13 58,157,126 (GRCm39) missense probably damaging 0.99
R9636:Klhl3 UTSW 13 58,198,863 (GRCm39) missense probably damaging 1.00
Z1177:Klhl3 UTSW 13 58,157,223 (GRCm39) missense probably benign 0.02
Predicted Primers PCR Primer
(F):5'- AGCATCTTGTGTCGGGGAAG -3'
(R):5'- ATCAGGTTGGGCAGTCATCC -3'

Sequencing Primer
(F):5'- GAGCTCACTAGATCTGACAGGTTC -3'
(R):5'- GTTGGGCAGTCATCCCCATC -3'
Posted On 2018-06-22