Mutagenetix > Incidental Mutation

Incidental Mutation 'R1953:Klhl3'

217501

Institutional Source

Beutler Lab

Gene Symbol

Klhl3

Ensembl Gene

ENSMUSG00000014164

Gene Name

kelch-like 3

Synonyms

EG627648, 7530408C15Rik

MMRRC Submission

039967-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R1953 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

58148042-58261406 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 58159022 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Histidine at position 546 (Y546H)

Ref Sequence

ENSEMBL: ENSMUSP00000089173 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000091583] [ENSMUST00000160860]

AlphaFold

E0CZ16

Predicted Effect

probably damaging
Transcript: ENSMUST00000091583
AA Change: Y546H

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000089173
Gene: ENSMUSG00000014164
AA Change: Y546H

Domain	Start	End	E-Value	Type
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

possibly damaging
Transcript: ENSMUST00000160860
AA Change: Y493H

PolyPhen 2 Score 0.903 (Sensitivity: 0.82; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000123701
Gene: ENSMUSG00000014164
AA Change: Y493H

Domain	Start	End	E-Value	Type
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

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 96.9%
20x: 94.4%

Validation Efficiency

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: 71 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
5730455P16Rik	A	T	11: 80,268,772 (GRCm39)	D12E	probably damaging	Het
Abca15	C	T	7: 119,960,655 (GRCm39)	R706C	probably damaging	Het
Actr1a	G	A	19: 46,369,387 (GRCm39)	S209F	probably benign	Het
Adcy1	A	G	11: 7,028,991 (GRCm39)	N247S	probably benign	Het
Anapc4	T	C	5: 52,997,030 (GRCm39)	L101S	probably damaging	Het
Asap3	C	T	4: 135,954,767 (GRCm39)	R60*	probably null	Het
Ascc3	T	C	10: 50,721,726 (GRCm39)	S2060P	probably benign	Het
Atp9b	G	A	18: 80,797,522 (GRCm39)	T851I	possibly damaging	Het
Borcs5	A	G	6: 134,687,230 (GRCm39)	H196R	unknown	Het
Bpifb9b	A	C	2: 154,153,234 (GRCm39)	D100A	probably damaging	Het
Cant1	G	C	11: 118,299,609 (GRCm39)	P247A	probably damaging	Het
Capza3	A	T	6: 139,988,294 (GRCm39)	I298L	possibly damaging	Het
Cdh10	T	C	15: 18,966,997 (GRCm39)		probably null	Het
Celsr3	T	C	9: 108,720,381 (GRCm39)	V2551A	probably benign	Het
Ces4a	G	A	8: 105,864,729 (GRCm39)	G69S	probably damaging	Het
Cmtr2	T	C	8: 110,948,551 (GRCm39)	L287P	probably damaging	Het
Crebbp	G	A	16: 3,997,313 (GRCm39)	T257I	probably benign	Het
Crispld2	G	A	8: 120,742,035 (GRCm39)	V128M	probably damaging	Het
Crnkl1	G	A	2: 145,770,120 (GRCm39)	A241V	probably damaging	Het
Dmd	T	A	X: 82,874,123 (GRCm39)	I1342N	probably damaging	Het
Dnah10	A	G	5: 124,859,332 (GRCm39)	T2043A	probably benign	Het
Dscaml1	C	T	9: 45,581,522 (GRCm39)	T447I	probably benign	Het
Eif2ak3	A	G	6: 70,869,538 (GRCm39)	T742A	probably benign	Het
Farp1	A	G	14: 121,492,894 (GRCm39)	T499A	probably benign	Het
Fcgr1	G	A	3: 96,194,386 (GRCm39)	T167I	probably damaging	Het
Fgd5	C	A	6: 92,001,611 (GRCm39)	H935Q	probably benign	Het
Fhl4	A	T	10: 84,934,171 (GRCm39)	D203E	probably benign	Het
Gapt	T	G	13: 110,490,340 (GRCm39)	T108P	probably damaging	Het
Gpt2	A	G	8: 86,248,013 (GRCm39)	T419A	probably benign	Het
Gucy2c	A	G	6: 136,681,291 (GRCm39)	V907A	probably damaging	Het
Hmbs	T	C	9: 44,248,741 (GRCm39)	D211G	probably damaging	Het
Irx5	A	G	8: 93,086,438 (GRCm39)	N174D	probably damaging	Het
Itfg1	A	G	8: 86,557,860 (GRCm39)	V170A	probably benign	Het
Itga2b	T	A	11: 102,349,009 (GRCm39)	T732S	probably benign	Het
Lama5	G	A	2: 179,832,540 (GRCm39)	H1670Y	possibly damaging	Het
Mlst8	AT	ATT	17: 24,696,987 (GRCm39)		probably null	Het
Nbeal1	T	C	1: 60,273,999 (GRCm39)	V409A	probably damaging	Het
Nlgn1	T	A	3: 25,490,464 (GRCm39)	D421V	probably damaging	Het
Nlrp10	T	C	7: 108,524,325 (GRCm39)	D385G	probably benign	Het
Nr2e3	T	A	9: 59,857,079 (GRCm39)	D30V	probably benign	Het
Nyap1	A	G	5: 137,733,294 (GRCm39)	S580P	probably benign	Het
Or4c108	G	A	2: 88,804,224 (GRCm39)	Q4*	probably null	Het
Or4c12	A	G	2: 89,774,267 (GRCm39)	L64P	probably damaging	Het
Or4e2	T	A	14: 52,688,344 (GRCm39)	V158E	probably benign	Het
Pex1	A	G	5: 3,680,038 (GRCm39)	H952R	probably damaging	Het
Plin4	T	A	17: 56,410,849 (GRCm39)	I1061F	possibly damaging	Het
Pnkp	C	A	7: 44,512,026 (GRCm39)	R517S	probably benign	Het
Polr2e	T	A	10: 79,874,388 (GRCm39)	E39D	probably benign	Het
Pramel18	T	C	4: 101,767,312 (GRCm39)	I187T	probably benign	Het
Prokr1	T	C	6: 87,565,575 (GRCm39)	Y90C	probably benign	Het
Ptprm	A	T	17: 67,247,575 (GRCm39)	S587T	probably benign	Het
Rere	G	A	4: 150,701,294 (GRCm39)	E1225K	probably damaging	Het
Rsl24d1	G	T	9: 73,021,896 (GRCm39)		probably benign	Het
Selp	A	G	1: 163,954,081 (GRCm39)	N127S	probably benign	Het
Slc22a18	C	T	7: 143,029,984 (GRCm39)	T17I	probably damaging	Het
Smad2	A	G	18: 76,395,776 (GRCm39)	T72A	possibly damaging	Het
Snx29	G	A	16: 11,217,647 (GRCm39)	W149*	probably null	Het
Stk31	G	T	6: 49,423,412 (GRCm39)		probably null	Het
Sult1e1	T	G	5: 87,735,530 (GRCm39)		probably null	Het
Syngap1	G	A	17: 27,163,661 (GRCm39)	R41H	possibly damaging	Het
Tbc1d17	T	A	7: 44,490,822 (GRCm39)		probably null	Het
Tex55	G	T	16: 38,648,275 (GRCm39)	T278K	possibly damaging	Het
Tie1	A	T	4: 118,329,987 (GRCm39)		probably null	Het
Ttn	A	T	2: 76,641,587 (GRCm39)	L5176Q	possibly damaging	Het
Usp47	T	A	7: 111,692,083 (GRCm39)	D848E	probably benign	Het
Vmn1r72	A	G	7: 11,403,731 (GRCm39)	L239P	probably damaging	Het
Vmn2r124	T	C	17: 18,283,122 (GRCm39)	I272T	probably benign	Het
Vwa1	C	T	4: 155,857,571 (GRCm39)	V76M	probably damaging	Het
Xrn1	G	T	9: 95,906,274 (GRCm39)		probably null	Het
Zfp667	G	T	7: 6,308,087 (GRCm39)	V252F	probably benign	Het
Zranb3	A	T	1: 127,927,136 (GRCm39)	V343D	probably damaging	Het

Other mutations in Klhl3

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH 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
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
R6580:Klhl3	UTSW	13	58,166,701 (GRCm39)	missense	possibly damaging	0.75
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'- TATCACTCAGAGCTGGAGGG -3'
(R):5'- TTGAACCTCCTTATTTGCAGGC -3'

Sequencing Primer
(F):5'- AGGGAAGAACTGTGACCCCC -3'
(R):5'- CCAGGCAGGGGATTATCAC -3'

Posted On

2014-08-01