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

21723483-21749919 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 21739744 bp (GRCm38)

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
9530053A07Rik	T	A	7: 28,137,091	V145D	probably damaging	Het
Abca1	A	T	4: 53,092,860	V308E	probably benign	Het
Amy1	A	G	3: 113,562,769		probably benign	Het
Astn2	C	T	4: 66,185,142	V345M	unknown	Het
Brwd1	T	C	16: 96,043,086	E756G	probably damaging	Het
Ccpg1	C	T	9: 73,001,821	L135F	probably benign	Het
Cecr2	C	T	6: 120,757,884	H694Y	probably damaging	Het
Cfh	G	A	1: 140,183,182	T14I	probably damaging	Het
Cfhr2	G	A	1: 139,813,434	R268*	probably null	Het
Clca1	T	A	3: 145,032,589	I53L	probably benign	Het
Clcn6	A	G	4: 148,038,749		probably benign	Het
Cnfn	C	T	7: 25,367,831	V98I	probably benign	Het
Cntnap1	C	T	11: 101,187,014	R1122W	probably damaging	Het
Cpne9	A	T	6: 113,295,063	E384V	probably damaging	Het
Ctr9	T	C	7: 111,049,498		probably benign	Het
Ctsj	T	A	13: 61,003,701		probably benign	Het
Cyp2c39	A	C	19: 39,513,490		probably benign	Het
Dock5	A	C	14: 67,809,032	I767S	probably damaging	Het
Eftud2	T	C	11: 102,846,620	T552A	probably damaging	Het
Epdr1	A	G	13: 19,594,545	I25T	probably damaging	Het
Fam160a2	T	C	7: 105,389,447	E195G	probably damaging	Het
Fam208b	A	G	13: 3,590,321	L272P	probably damaging	Het
Fcgbp	A	T	7: 28,089,713	D568V	probably damaging	Het
Frem2	T	A	3: 53,647,921	T1732S	probably damaging	Het
Fuz	T	C	7: 44,898,558	V183A	possibly damaging	Het
Grb7	T	C	11: 98,453,220	S284P	probably damaging	Het
Hoxb4	G	T	11: 96,318,887	G40C	probably damaging	Het
Kcnn1	T	C	8: 70,863,869		probably benign	Het
Kmt2d	C	A	15: 98,835,207		probably benign	Het
L3mbtl3	A	G	10: 26,327,834	V366A	unknown	Het
Lnpep	A	T	17: 17,575,396		probably benign	Het
Mical3	A	T	6: 121,029,641		probably benign	Het
Myh15	T	C	16: 49,171,887		probably benign	Het
Nup155	T	A	15: 8,130,232	H542Q	probably benign	Het
Olfr1100	T	C	2: 86,978,782	N5D	probably damaging	Het
Olfr1240	T	A	2: 89,439,354	R308S	possibly damaging	Het
Olfr53	T	C	7: 140,652,063	F28S	probably benign	Het
Olfr780	A	G	10: 129,322,047	I141M	probably benign	Het
Olfr967	A	T	9: 39,751,118	H244L	probably damaging	Het
Opn4	A	G	14: 34,598,973		probably benign	Het
Pak3	TTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTC	TTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTC	X: 143,743,893		probably benign	Het
Parp14	T	C	16: 35,841,012	K1522R	probably benign	Het
Pkhd1	A	T	1: 20,524,111	D1259E	probably benign	Het
Pogz	C	T	3: 94,879,353	A1084V	probably damaging	Het
Popdc3	G	A	10: 45,315,263	V157M	probably benign	Het
Prrt4	T	C	6: 29,171,184	Y423C	probably damaging	Het
Qrich1	C	T	9: 108,534,520	H415Y	probably damaging	Het
Rabgap1	A	G	2: 37,543,223	N801D	probably benign	Het
Rb1	A	G	14: 73,287,684		probably benign	Het
Rp1	A	T	1: 4,347,837	N1017K	possibly damaging	Het
Ryr2	T	C	13: 11,635,559	D356G	probably null	Het
Skint8	C	G	4: 111,936,929	P172R	probably damaging	Het
Slc12a8	T	G	16: 33,658,230	M643R	possibly damaging	Het
Sult1c1	A	T	17: 53,964,085		probably benign	Het
Tcaf1	T	A	6: 42,673,539	M869L	probably damaging	Het
Tecpr1	T	C	5: 144,217,401	N78S	probably damaging	Het
Tectb	A	T	19: 55,181,924	Y69F	probably damaging	Het
Them4	A	T	3: 94,329,794	N187I	possibly damaging	Het
Tm9sf3	A	G	19: 41,256,143		probably null	Het
Tnik	G	T	3: 28,577,361		probably benign	Het
Tns2	G	T	15: 102,109,585		probably benign	Het
Tnxb	A	G	17: 34,672,144	D487G	probably damaging	Het
Trim33	T	A	3: 103,310,344	C202S	probably damaging	Het
Trpm2	T	A	10: 77,923,516	I1145F	probably damaging	Het
Trpv2	A	G	11: 62,592,770	T478A	probably benign	Het
Ube2e3	T	C	2: 78,919,990	Y187H	probably benign	Het
Ubxn11	A	G	4: 134,109,652	R64G	possibly damaging	Het
Wwtr1	T	C	3: 57,459,066	T407A	probably damaging	Het
Zfyve26	A	T	12: 79,268,728	S1325T	possibly damaging	Het

Other mutations in Ldlr

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00501:Ldlr	APN	9	21735361	critical splice donor site	probably null
IGL01975:Ldlr	APN	9	21733697	missense	probably benign	0.05
IGL02043:Ldlr	APN	9	21733499	missense	probably benign	0.03
IGL02524:Ldlr	APN	9	21733681	missense	probably damaging	1.00
IGL03049:Ldlr	APN	9	21745819	missense	probably benign	0.00
IGL03113:Ldlr	APN	9	21739828	missense	possibly damaging	0.85
R0240:Ldlr	UTSW	9	21737999	splice site	probably benign
R1398:Ldlr	UTSW	9	21739542	missense	probably benign	0.01
R1587:Ldlr	UTSW	9	21737913	missense	probably damaging	0.99
R2198:Ldlr	UTSW	9	21732402	missense	probably damaging	1.00
R3730:Ldlr	UTSW	9	21731801	missense	probably benign	0.09
R4422:Ldlr	UTSW	9	21737952	missense	probably damaging	1.00
R5044:Ldlr	UTSW	9	21735242	missense	probably benign	0.00
R5046:Ldlr	UTSW	9	21745907	critical splice donor site	probably null
R6186:Ldlr	UTSW	9	21723759	start gained	probably benign
R6195:Ldlr	UTSW	9	21731781	nonsense	probably null
R6523:Ldlr	UTSW	9	21737253	missense	probably damaging	1.00
R6682:Ldlr	UTSW	9	21732375	missense	probably benign
R7256:Ldlr	UTSW	9	21745744	missense	probably benign	0.01
R7384:Ldlr	UTSW	9	21739794	missense	probably benign	0.07
R7823:Ldlr	UTSW	9	21742306	critical splice donor site	probably null
R8065:Ldlr	UTSW	9	21737945	missense	probably damaging	1.00
R8223:Ldlr	UTSW	9	21747250	missense	probably damaging	1.00
R8732:Ldlr	UTSW	9	21739689	missense	probably benign	0.00
R8931:Ldlr	UTSW	9	21731812	missense	probably damaging	0.99
R8954:Ldlr	UTSW	9	21739532	missense	possibly damaging	0.87
R9315:Ldlr	UTSW	9	21733486	splice site	probably benign
R9489:Ldlr	UTSW	9	21735330	missense	probably damaging	1.00
R9517:Ldlr	UTSW	9	21743944	missense	possibly damaging	0.90
R9605:Ldlr	UTSW	9	21735330	missense	probably damaging	1.00
R9709:Ldlr	UTSW	9	21745839	missense	probably benign	0.00
X0024:Ldlr	UTSW	9	21739818	missense	probably damaging	1.00
Z1177:Ldlr	UTSW	9	21739830	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