Mutagenetix > Incidental Mutation

Incidental Mutation 'R4857:Klhl3'

374090

Institutional Source

Beutler Lab

Gene Symbol

Klhl3

Ensembl Gene

ENSMUSG00000014164

Gene Name

kelch-like 3

Synonyms

EG627648, 7530408C15Rik

MMRRC Submission

042468-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R4857 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

58148042-58261406 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 58166620 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glycine to Serine at position 404 (G404S)

Ref Sequence

ENSEMBL: ENSMUSP00000123701 (fasta)

Gene Model

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

AlphaFold

E0CZ16

Predicted Effect

probably damaging
Transcript: ENSMUST00000091583
AA Change: G457S

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000089173
Gene: ENSMUSG00000014164
AA Change: G457S

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

noncoding transcript
Transcript: ENSMUST00000104769

Predicted Effect

probably damaging
Transcript: ENSMUST00000160860
AA Change: G404S

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000123701
Gene: ENSMUSG00000014164
AA Change: G404S

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

Meta Mutation Damage Score

0.8372

Coding Region Coverage

1x: 99.1%
3x: 98.3%
10x: 96.3%
20x: 92.3%

Validation Efficiency

97% (115/119)

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: 101 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930548G14Rik	C	T	15: 46,488,927 (GRCm39)		noncoding transcript	Het
Aasdh	A	T	5: 77,035,131 (GRCm39)	F428L	probably benign	Het
Abca13	A	G	11: 9,244,143 (GRCm39)	N2002S	probably benign	Het
Acot7	T	G	4: 152,322,211 (GRCm39)	F248V	possibly damaging	Het
Acsf2	A	G	11: 94,460,164 (GRCm39)	I396T	probably benign	Het
Agbl1	A	G	7: 76,069,583 (GRCm39)	N372D	probably benign	Het
Ahctf1	A	T	1: 179,626,922 (GRCm39)		probably benign	Het
Akap11	T	C	14: 78,736,300 (GRCm39)	D1830G		Het
Bcl7b	A	G	5: 135,202,033 (GRCm39)	*59W	probably null	Het
Bdh1	A	G	16: 31,266,366 (GRCm39)		probably null	Het
Bin3	A	G	14: 70,366,344 (GRCm39)	N69S	probably benign	Het
Bltp3b	A	T	10: 89,615,825 (GRCm39)	N156I	probably damaging	Het
Bsdc1	T	C	4: 129,365,685 (GRCm39)		probably benign	Het
Cacna1i	T	C	15: 80,253,863 (GRCm39)	V700A	probably damaging	Het
Calcr	T	C	6: 3,708,511 (GRCm39)	N225S	probably benign	Het
Cby2	C	T	14: 75,830,478 (GRCm39)	E8K	probably damaging	Het
Cdh23	A	G	10: 60,227,563 (GRCm39)	S1173P	probably damaging	Het
Cftr	C	T	6: 18,320,974 (GRCm39)	T1428M	possibly damaging	Het
Chd1l	T	C	3: 97,479,975 (GRCm39)	K591E	probably benign	Het
Chrd	C	T	16: 20,557,508 (GRCm39)	P709L	possibly damaging	Het
Ckap4	T	C	10: 84,369,352 (GRCm39)	R127G	possibly damaging	Het
Cnbd2	T	C	2: 156,209,485 (GRCm39)	F476S	probably benign	Het
Dclk3	T	C	9: 111,297,716 (GRCm39)	V420A	probably benign	Het
Dnah5	A	G	15: 28,345,953 (GRCm39)	D2431G	probably benign	Het
Duox1	T	A	2: 122,146,212 (GRCm39)	I10N	probably benign	Het
Ece2	T	A	16: 20,436,556 (GRCm39)	V126D	probably damaging	Het
Elfn1	T	C	5: 139,958,840 (GRCm39)	Y615H	probably damaging	Het
Epha1	T	C	6: 42,338,416 (GRCm39)	D720G	probably benign	Het
Fras1	A	G	5: 96,926,018 (GRCm39)	I3741V	probably benign	Het
Gm53	A	T	11: 96,142,562 (GRCm39)		noncoding transcript	Het
Grb10	G	T	11: 11,901,469 (GRCm39)		probably benign	Het
Grid2ip	A	G	5: 143,368,384 (GRCm39)	H568R	probably damaging	Het
Gsap	A	T	5: 21,492,797 (GRCm39)		probably null	Het
Gse1	T	C	8: 121,299,496 (GRCm39)		probably benign	Het
Gstm1	T	C	3: 107,923,724 (GRCm39)	R94G	possibly damaging	Het
Gtf2ird1	A	G	5: 134,391,398 (GRCm39)	F866L	probably damaging	Het
Haao	T	A	17: 84,146,009 (GRCm39)		probably null	Het
Hcn4	A	T	9: 58,766,853 (GRCm39)	I805F	unknown	Het
Hemk1	A	T	9: 107,206,647 (GRCm39)		probably benign	Het
Il12rb1	A	T	8: 71,263,232 (GRCm39)	Y33F	possibly damaging	Het
Il19	T	A	1: 130,863,683 (GRCm39)	I103F	probably damaging	Het
Itpr1	A	G	6: 108,387,828 (GRCm39)	N1522S	probably benign	Het
Klhdc8a	A	G	1: 132,230,843 (GRCm39)	Y236C	probably damaging	Het
Large2	T	C	2: 92,196,979 (GRCm39)		probably benign	Het
Lgi1	C	A	19: 38,294,698 (GRCm39)	A490E	probably damaging	Het
Lmbr1	A	G	5: 29,528,807 (GRCm39)	L112P	probably damaging	Het
Lmo7	T	A	14: 102,124,784 (GRCm39)		probably null	Het
Lpin1	A	C	12: 16,613,631 (GRCm39)	I479S	possibly damaging	Het
Lrrc40	T	A	3: 157,771,866 (GRCm39)		probably benign	Het
Lrrc9	A	G	12: 72,546,466 (GRCm39)	N1218S	possibly damaging	Het
Map3k9	A	G	12: 81,771,401 (GRCm39)	V729A	probably benign	Het
Marf1	A	T	16: 13,946,475 (GRCm39)	Y1215*	probably null	Het
Moap1	T	A	12: 102,708,824 (GRCm39)	I242L	probably benign	Het
Mpo	A	G	11: 87,687,107 (GRCm39)	K218E	probably benign	Het
Mpz	C	T	1: 170,986,379 (GRCm39)	R98C	probably damaging	Het
Neb	T	G	2: 52,091,992 (GRCm39)	K5024T	probably damaging	Het
Nlrp4b	C	T	7: 10,449,225 (GRCm39)	T109I	probably benign	Het
Noc3l	T	A	19: 38,781,244 (GRCm39)		probably null	Het
Nosip	G	A	7: 44,726,102 (GRCm39)	V220I	probably benign	Het
Nyap1	A	C	5: 137,733,840 (GRCm39)	S398A	probably damaging	Het
Or12d17	A	G	17: 37,777,714 (GRCm39)	M206V	possibly damaging	Het
Or4a68	T	G	2: 89,269,967 (GRCm39)	I219L	probably damaging	Het
Or4f54	A	G	2: 111,123,488 (GRCm39)	N292D	possibly damaging	Het
Osbpl7	T	C	11: 96,947,495 (GRCm39)		probably benign	Het
Pard3	A	T	8: 128,050,535 (GRCm39)	Y199F	probably damaging	Het
Pcdha11	G	A	18: 37,144,505 (GRCm39)	V199I	probably benign	Het
Pcdhga8	A	T	18: 37,859,967 (GRCm39)	N341I	probably damaging	Het
Pcsk4	A	G	10: 80,160,873 (GRCm39)	S318P	probably damaging	Het
Phldb1	C	A	9: 44,607,389 (GRCm39)	R1272L	probably damaging	Het
Phlpp2	A	G	8: 110,603,642 (GRCm39)	T103A	probably damaging	Het
Pibf1	T	A	14: 99,423,937 (GRCm39)	Y503*	probably null	Het
Pkn1	A	T	8: 84,410,856 (GRCm39)		probably null	Het
Pramel22	A	T	4: 143,383,158 (GRCm39)	N20K	possibly damaging	Het
Ptprf	A	G	4: 118,074,394 (GRCm39)		probably benign	Het
Rbm19	C	A	5: 120,270,898 (GRCm39)		probably benign	Het
Rcan1	T	C	16: 92,262,794 (GRCm39)	D5G	possibly damaging	Het
Recql5	A	T	11: 115,819,038 (GRCm39)	L176Q	probably damaging	Het
Rev3l	T	A	10: 39,714,455 (GRCm39)	L2393Q	probably damaging	Het
Rp1	C	A	1: 4,422,539 (GRCm39)	K180N	probably damaging	Het
Rp1	T	A	1: 4,422,540 (GRCm39)	K180M	probably damaging	Het
Sdk1	T	C	5: 142,147,531 (GRCm39)	V1461A	probably benign	Het
Sdk2	A	T	11: 113,712,208 (GRCm39)	L1653*	probably null	Het
Shroom3	G	T	5: 93,090,945 (GRCm39)	V1151F	probably damaging	Het
Skint10	A	T	4: 112,603,830 (GRCm39)	V119D	possibly damaging	Het
Sncaip	T	C	18: 53,002,297 (GRCm39)	S273P	probably benign	Het
Sp1	T	G	15: 102,339,409 (GRCm39)	I449S	probably damaging	Het
Spata31h1	T	C	10: 82,119,682 (GRCm39)	T4443A	possibly damaging	Het
Spats2	T	C	15: 99,072,301 (GRCm39)	L78P	probably damaging	Het
Stambp	T	A	6: 83,533,348 (GRCm39)	N305I	probably benign	Het
Stim2	A	T	5: 54,275,888 (GRCm39)	S688C	probably damaging	Het
Sytl3	A	G	17: 7,003,980 (GRCm39)	N355S	probably damaging	Het
Taf4b	C	T	18: 14,937,635 (GRCm39)	A236V	probably null	Het
Tnfaip6	A	G	2: 51,941,086 (GRCm39)		probably null	Het
Trpc2	T	A	7: 101,733,176 (GRCm39)	S416T	probably benign	Het
Ttn	T	C	2: 76,569,210 (GRCm39)	T27228A	probably damaging	Het
Ush2a	T	A	1: 188,269,917 (GRCm39)	D1721E	probably benign	Het
Usp47	T	A	7: 111,681,759 (GRCm39)	H523Q	probably damaging	Het
Vmn1r8	A	T	6: 57,013,338 (GRCm39)	I130F	probably benign	Het
Vps13b	A	G	15: 35,456,800 (GRCm39)	S749G	probably benign	Het
Xrcc5	C	A	1: 72,365,424 (GRCm39)	T283K	possibly damaging	Het
Ydjc	A	G	16: 16,966,002 (GRCm39)		probably benign	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
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
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'- ACTGGAGGTGACCTTTAAGATCTC -3'
(R):5'- ATCAGGTTGGGCAGTCATCC -3'

Sequencing Primer
(F):5'- CCTGCTTCCTGGCTAATGAAGAGAG -3'
(R):5'- GTTGGGCAGTCATCCCCATC -3'

Posted On

2016-03-01