Mutagenetix > Incidental Mutation

Incidental Mutation 'R0586:Ldlr'

55764

Institutional Source

Beutler Lab

Gene Symbol

Ldlr

Ensembl Gene

ENSMUSG00000032193

Gene Name

low density lipoprotein receptor

Synonyms

MMRRC Submission

038776-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R0586 (G1)

Quality Score

190

Status

Validated

Chromosome

Chromosomal Location

21634872-21661215 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 21651040 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Histidine at position 486 (R486H)

Ref Sequence

ENSEMBL: ENSMUSP00000034713 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000034713] [ENSMUST00000213114]

AlphaFold

P35951

Predicted Effect

probably benign
Transcript: ENSMUST00000034713
AA Change: R486H

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000034713
Gene: ENSMUSG00000032193
AA Change: R486H

Domain	Start	End	E-Value	Type
low complexity region	13	23	N/A	INTRINSIC
LDLa	26	65	1.89e-14	SMART
LDLa	67	106	9.81e-13	SMART
EGF_like	108	144	6.81e1	SMART
LDLa	108	145	3.77e-14	SMART
LDLa	147	186	6.67e-15	SMART
LDLa	197	234	1.16e-14	SMART
LDLa	236	273	3.24e-13	SMART
LDLa	276	316	1e-9	SMART
EGF	318	354	3.2e-4	SMART
EGF_CA	355	394	4.09e-11	SMART
LY	420	462	1.11e-3	SMART
LY	466	508	4.7e-11	SMART
LY	509	552	5.23e-9	SMART
LY	553	595	7.86e-13	SMART
LY	596	639	3.25e-5	SMART
EGF	666	713	7.64e-2	SMART
low complexity region	799	811	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000213114
AA Change: R486H

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000214359

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000215917

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000217111

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000217613

Meta Mutation Damage Score

0.0898

Coding Region Coverage

1x: 99.7%
3x: 99.1%
10x: 97.5%
20x: 94.4%

Validation Efficiency

100% (74/74)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The low density lipoprotein receptor (LDLR) gene family consists of cell surface proteins involved in receptor-mediated endocytosis of specific ligands. Low density lipoprotein (LDL) is normally bound at the cell membrane and taken into the cell ending up in lysosomes where the protein is degraded and the cholesterol is made available for repression of microsomal enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting step in cholesterol synthesis. At the same time, a reciprocal stimulation of cholesterol ester synthesis takes place. Mutations in this gene cause the autosomal dominant disorder, familial hypercholesterolemia. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Sep 2010]
PHENOTYPE: Homozygous targeted mutants exhibit 2X higher total plasma cholesterol and 7-9X higher IDL and LDL levels on a normal diet compared to controls. On a high cholesterol diet, mutant effects dramatically increase and mice develop xanthomatosis and atherosclerosis. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 69 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca1	A	T	4: 53,092,860 (GRCm39)	V308E	probably benign	Het
Amy1	A	G	3: 113,356,418 (GRCm39)		probably benign	Het
Astn2	C	T	4: 66,103,379 (GRCm39)	V345M	unknown	Het
Brwd1	T	C	16: 95,844,286 (GRCm39)	E756G	probably damaging	Het
Ccpg1	C	T	9: 72,909,103 (GRCm39)	L135F	probably benign	Het
Cecr2	C	T	6: 120,734,845 (GRCm39)	H694Y	probably damaging	Het
Cfh	G	A	1: 140,110,920 (GRCm39)	T14I	probably damaging	Het
Cfhr2	G	A	1: 139,741,172 (GRCm39)	R268*	probably null	Het
Clca3a1	T	A	3: 144,738,350 (GRCm39)	I53L	probably benign	Het
Clcn6	A	G	4: 148,123,206 (GRCm39)		probably benign	Het
Cnfn	C	T	7: 25,067,256 (GRCm39)	V98I	probably benign	Het
Cntnap1	C	T	11: 101,077,840 (GRCm39)	R1122W	probably damaging	Het
Cpne9	A	T	6: 113,272,024 (GRCm39)	E384V	probably damaging	Het
Ctr9	T	C	7: 110,648,705 (GRCm39)		probably benign	Het
Ctsj	T	A	13: 61,151,515 (GRCm39)		probably benign	Het
Cyp2c39	A	C	19: 39,501,934 (GRCm39)		probably benign	Het
Dock5	A	C	14: 68,046,481 (GRCm39)	I767S	probably damaging	Het
Eftud2	T	C	11: 102,737,446 (GRCm39)	T552A	probably damaging	Het
Epdr1	A	G	13: 19,778,715 (GRCm39)	I25T	probably damaging	Het
Fcgbp	A	T	7: 27,789,138 (GRCm39)	D568V	probably damaging	Het
Fcgbpl1	T	A	7: 27,836,516 (GRCm39)	V145D	probably damaging	Het
Fhip1b	T	C	7: 105,038,654 (GRCm39)	E195G	probably damaging	Het
Frem2	T	A	3: 53,555,342 (GRCm39)	T1732S	probably damaging	Het
Fuz	T	C	7: 44,547,982 (GRCm39)	V183A	possibly damaging	Het
Grb7	T	C	11: 98,344,046 (GRCm39)	S284P	probably damaging	Het
Hoxb4	G	T	11: 96,209,713 (GRCm39)	G40C	probably damaging	Het
Kcnn1	T	C	8: 71,316,513 (GRCm39)		probably benign	Het
Kmt2d	C	A	15: 98,733,088 (GRCm39)		probably benign	Het
L3mbtl3	A	G	10: 26,203,732 (GRCm39)	V366A	unknown	Het
Lnpep	A	T	17: 17,795,658 (GRCm39)		probably benign	Het
Mical3	A	T	6: 121,006,602 (GRCm39)		probably benign	Het
Myh15	T	C	16: 48,992,250 (GRCm39)		probably benign	Het
Nup155	T	A	15: 8,159,716 (GRCm39)	H542Q	probably benign	Het
Opn4	A	G	14: 34,320,930 (GRCm39)		probably benign	Het
Or13a20	T	C	7: 140,231,976 (GRCm39)	F28S	probably benign	Het
Or4a68	T	A	2: 89,269,698 (GRCm39)	R308S	possibly damaging	Het
Or6c68	A	G	10: 129,157,916 (GRCm39)	I141M	probably benign	Het
Or8g4	A	T	9: 39,662,414 (GRCm39)	H244L	probably damaging	Het
Or8h10	T	C	2: 86,809,126 (GRCm39)	N5D	probably damaging	Het
Pak3	TTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTC	TTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTC	X: 142,526,889 (GRCm39)		probably benign	Het
Parp14	T	C	16: 35,661,382 (GRCm39)	K1522R	probably benign	Het
Pkhd1	A	T	1: 20,594,335 (GRCm39)	D1259E	probably benign	Het
Pogz	C	T	3: 94,786,664 (GRCm39)	A1084V	probably damaging	Het
Popdc3	G	A	10: 45,191,359 (GRCm39)	V157M	probably benign	Het
Prrt4	T	C	6: 29,171,183 (GRCm39)	Y423C	probably damaging	Het
Qrich1	C	T	9: 108,411,719 (GRCm39)	H415Y	probably damaging	Het
Rabgap1	A	G	2: 37,433,235 (GRCm39)	N801D	probably benign	Het
Rb1	A	G	14: 73,525,124 (GRCm39)		probably benign	Het
Rp1	A	T	1: 4,418,060 (GRCm39)	N1017K	possibly damaging	Het
Ryr2	T	C	13: 11,650,445 (GRCm39)	D356G	probably null	Het
Skint8	C	G	4: 111,794,126 (GRCm39)	P172R	probably damaging	Het
Slc12a8	T	G	16: 33,478,600 (GRCm39)	M643R	possibly damaging	Het
Sult1c2	A	T	17: 54,271,113 (GRCm39)		probably benign	Het
Tasor2	A	G	13: 3,640,321 (GRCm39)	L272P	probably damaging	Het
Tcaf1	T	A	6: 42,650,473 (GRCm39)	M869L	probably damaging	Het
Tecpr1	T	C	5: 144,154,219 (GRCm39)	N78S	probably damaging	Het
Tectb	A	T	19: 55,170,356 (GRCm39)	Y69F	probably damaging	Het
Them4	A	T	3: 94,237,101 (GRCm39)	N187I	possibly damaging	Het
Tm9sf3	A	G	19: 41,244,582 (GRCm39)		probably null	Het
Tnik	G	T	3: 28,631,510 (GRCm39)		probably benign	Het
Tns2	G	T	15: 102,018,020 (GRCm39)		probably benign	Het
Tnxb	A	G	17: 34,891,118 (GRCm39)	D487G	probably damaging	Het
Trim33	T	A	3: 103,217,660 (GRCm39)	C202S	probably damaging	Het
Trpm2	T	A	10: 77,759,350 (GRCm39)	I1145F	probably damaging	Het
Trpv2	A	G	11: 62,483,596 (GRCm39)	T478A	probably benign	Het
Ube2e3	T	C	2: 78,750,334 (GRCm39)	Y187H	probably benign	Het
Ubxn11	A	G	4: 133,836,963 (GRCm39)	R64G	possibly damaging	Het
Wwtr1	T	C	3: 57,366,487 (GRCm39)	T407A	probably damaging	Het
Zfyve26	A	T	12: 79,315,502 (GRCm39)	S1325T	possibly damaging	Het

Other mutations in Ldlr

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00501:Ldlr	APN	9	21,646,657 (GRCm39)	critical splice donor site	probably null
IGL01975:Ldlr	APN	9	21,644,993 (GRCm39)	missense	probably benign	0.05
IGL02043:Ldlr	APN	9	21,644,795 (GRCm39)	missense	probably benign	0.03
IGL02524:Ldlr	APN	9	21,644,977 (GRCm39)	missense	probably damaging	1.00
IGL03049:Ldlr	APN	9	21,657,115 (GRCm39)	missense	probably benign	0.00
IGL03113:Ldlr	APN	9	21,651,124 (GRCm39)	missense	possibly damaging	0.85
R0240:Ldlr	UTSW	9	21,649,295 (GRCm39)	splice site	probably benign
R1398:Ldlr	UTSW	9	21,650,838 (GRCm39)	missense	probably benign	0.01
R1587:Ldlr	UTSW	9	21,649,209 (GRCm39)	missense	probably damaging	0.99
R2198:Ldlr	UTSW	9	21,643,698 (GRCm39)	missense	probably damaging	1.00
R3730:Ldlr	UTSW	9	21,643,097 (GRCm39)	missense	probably benign	0.09
R4422:Ldlr	UTSW	9	21,649,248 (GRCm39)	missense	probably damaging	1.00
R5044:Ldlr	UTSW	9	21,646,538 (GRCm39)	missense	probably benign	0.00
R5046:Ldlr	UTSW	9	21,657,203 (GRCm39)	critical splice donor site	probably null
R6186:Ldlr	UTSW	9	21,635,055 (GRCm39)	start gained	probably benign
R6195:Ldlr	UTSW	9	21,643,077 (GRCm39)	nonsense	probably null
R6523:Ldlr	UTSW	9	21,648,549 (GRCm39)	missense	probably damaging	1.00
R6682:Ldlr	UTSW	9	21,643,671 (GRCm39)	missense	probably benign
R7256:Ldlr	UTSW	9	21,657,040 (GRCm39)	missense	probably benign	0.01
R7384:Ldlr	UTSW	9	21,651,090 (GRCm39)	missense	probably benign	0.07
R7823:Ldlr	UTSW	9	21,653,602 (GRCm39)	critical splice donor site	probably null
R8065:Ldlr	UTSW	9	21,649,241 (GRCm39)	missense	probably damaging	1.00
R8223:Ldlr	UTSW	9	21,658,546 (GRCm39)	missense	probably damaging	1.00
R8732:Ldlr	UTSW	9	21,650,985 (GRCm39)	missense	probably benign	0.00
R8931:Ldlr	UTSW	9	21,643,108 (GRCm39)	missense	probably damaging	0.99
R8954:Ldlr	UTSW	9	21,650,828 (GRCm39)	missense	possibly damaging	0.87
R9315:Ldlr	UTSW	9	21,644,782 (GRCm39)	splice site	probably benign
R9489:Ldlr	UTSW	9	21,646,626 (GRCm39)	missense	probably damaging	1.00
R9517:Ldlr	UTSW	9	21,655,240 (GRCm39)	missense	possibly damaging	0.90
R9605:Ldlr	UTSW	9	21,646,626 (GRCm39)	missense	probably damaging	1.00
R9709:Ldlr	UTSW	9	21,657,135 (GRCm39)	missense	probably benign	0.00
X0024:Ldlr	UTSW	9	21,651,114 (GRCm39)	missense	probably damaging	1.00
Z1177:Ldlr	UTSW	9	21,651,126 (GRCm39)	missense	probably benign	0.00

Predicted Primers

PCR Primer
(F):5'- AGGCTCCATAGGCTATCTGCTCTTC -3'
(R):5'- AGCTCTTTGGACACTCACCCATGC -3'

Sequencing Primer
(F):5'- ATAGAATCTACTGGTCCGACCTG -3'
(R):5'- CACAGGGTCCACTACGATG -3'

Posted On

2013-07-11