Mutagenetix > Incidental Mutation

Incidental Mutation 'R1587:Ldlr'

177578

Institutional Source

Beutler Lab

Gene Symbol

Ldlr

Ensembl Gene

ENSMUSG00000032193

Gene Name

low density lipoprotein receptor

Synonyms

MMRRC Submission

039624-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R1587 (G1)

Quality Score

206

Status

Not validated

Chromosome

Chromosomal Location

21634872-21661215 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 21649209 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Leucine at position 328 (H328L)

Ref Sequence

ENSEMBL: ENSMUSP00000149431 (fasta)

Gene Model

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

AlphaFold

P35951

Predicted Effect

probably damaging
Transcript: ENSMUST00000034713
AA Change: H328L

PolyPhen 2 Score 0.972 (Sensitivity: 0.77; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000034713
Gene: ENSMUSG00000032193
AA Change: H328L

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 damaging
Transcript: ENSMUST00000213114
AA Change: H328L

PolyPhen 2 Score 0.987 (Sensitivity: 0.73; Specificity: 0.96)

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000214359

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000215917

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000217111

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000217613

Coding Region Coverage

1x: 99.0%
3x: 98.0%
10x: 95.2%
20x: 88.9%

Validation Efficiency

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: 59 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A530064D06Rik	A	T	17: 48,473,585 (GRCm39)	S111T	probably benign	Het
Abhd2	A	T	7: 79,003,758 (GRCm39)	H279L	probably benign	Het
Ablim1	C	T	19: 57,071,979 (GRCm39)	M1I	probably null	Het
Agrn	T	C	4: 156,263,897 (GRCm39)	Q122R	probably damaging	Het
Arfgef1	A	T	1: 10,230,184 (GRCm39)	F1218I	probably damaging	Het
Bud13	C	T	9: 46,201,513 (GRCm39)	P395S	probably damaging	Het
Ccdc110	G	A	8: 46,394,783 (GRCm39)	V225M	probably benign	Het
Ccdc30	A	T	4: 119,210,373 (GRCm39)	S248T	probably damaging	Het
Cdh20	C	A	1: 110,027,757 (GRCm39)	Q501K	probably damaging	Het
Cwc27	T	C	13: 104,929,145 (GRCm39)	D266G	probably benign	Het
Cyp2d40	T	A	15: 82,645,334 (GRCm39)		probably null	Het
Cyp4a32	T	G	4: 115,467,731 (GRCm39)	N238K	probably benign	Het
Ddx11	T	C	17: 66,456,251 (GRCm39)	L770P	probably damaging	Het
Dgcr8	C	T	16: 18,098,155 (GRCm39)	G412E	probably damaging	Het
Disp2	C	A	2: 118,622,064 (GRCm39)	A932D	probably damaging	Het
Dlg4	T	A	11: 69,922,572 (GRCm39)	N291K	possibly damaging	Het
Dnajc7	A	G	11: 100,492,556 (GRCm39)	I39T	probably damaging	Het
Elp1	G	A	4: 56,786,666 (GRCm39)	Q426*	probably null	Het
Eno3	T	C	11: 70,552,296 (GRCm39)	V316A	probably damaging	Het
Ep400	G	A	5: 110,874,768 (GRCm39)	T944I	probably benign	Het
Ezh2	T	G	6: 47,529,424 (GRCm39)		probably null	Het
F7	A	T	8: 13,084,783 (GRCm39)	I270F	possibly damaging	Het
Fancc	A	G	13: 63,488,246 (GRCm39)	F245L	probably benign	Het
Fzd7	G	A	1: 59,522,165 (GRCm39)	C16Y	possibly damaging	Het
Gm29394	A	G	15: 57,892,008 (GRCm39)	*200Q	probably null	Het
Ints8	A	G	4: 11,245,722 (GRCm39)		probably null	Het
Krt36	A	T	11: 99,993,128 (GRCm39)	I449N	probably damaging	Het
Limk2	T	C	11: 3,303,455 (GRCm39)	N101S	possibly damaging	Het
Lrp4	A	G	2: 91,306,650 (GRCm39)	N321S	probably benign	Het
Mafk	T	C	5: 139,785,900 (GRCm39)	S33P	probably damaging	Het
Mbtps1	T	C	8: 120,244,958 (GRCm39)	Y831C	probably damaging	Het
Mfge8	T	A	7: 78,784,513 (GRCm39)	I344F	probably damaging	Het
Myo5b	T	C	18: 74,867,061 (GRCm39)	V1430A	probably benign	Het
Nbas	G	A	12: 13,608,686 (GRCm39)	R2154H	probably benign	Het
Nlrp6	G	A	7: 140,502,959 (GRCm39)	R355H	probably damaging	Het
Noc4l	T	C	5: 110,800,889 (GRCm39)	T76A	probably benign	Het
Nrp1	T	A	8: 129,202,763 (GRCm39)	C583S	probably damaging	Het
Or2w4	C	T	13: 21,796,083 (GRCm39)	D19N	probably benign	Het
Or5d35	T	A	2: 87,855,477 (GRCm39)	M137K	probably damaging	Het
Pgm5	T	A	19: 24,793,113 (GRCm39)	I318F	probably damaging	Het
Phf1	T	A	17: 27,156,466 (GRCm39)	V536D	probably damaging	Het
Prpf4b	C	A	13: 35,076,133 (GRCm39)	A641D	probably benign	Het
Ptpro	T	A	6: 137,420,592 (GRCm39)	V1007D	probably damaging	Het
Rbm47	A	G	5: 66,182,334 (GRCm39)	I433T	probably benign	Het
Resf1	G	T	6: 149,228,018 (GRCm39)	V355F	probably damaging	Het
S100a3	G	A	3: 90,509,618 (GRCm39)	E88K	probably benign	Het
Sesn1	A	G	10: 41,687,108 (GRCm39)	I31V	probably benign	Het
Son	T	A	16: 91,456,606 (GRCm39)	S1784R	probably damaging	Het
Srbd1	G	T	17: 86,292,865 (GRCm39)	D901E	probably damaging	Het
St8sia6	C	T	2: 13,677,416 (GRCm39)	D134N	possibly damaging	Het
Synpo2	T	A	3: 122,908,047 (GRCm39)	D423V	probably damaging	Het
Vmn2r108	A	G	17: 20,692,383 (GRCm39)	S158P	probably damaging	Het
Vmn2r109	A	T	17: 20,761,002 (GRCm39)	V785E	probably damaging	Het
Zfp143	A	G	7: 109,673,275 (GRCm39)	D124G	probably benign	Het
Zfp251	A	G	15: 76,754,484 (GRCm39)	L54P	probably damaging	Het
Zfp324	G	T	7: 12,704,570 (GRCm39)	S253I	possibly damaging	Het
Zfp59	A	G	7: 27,553,559 (GRCm39)	E337G	possibly damaging	Het
Zfp663	G	T	2: 165,195,437 (GRCm39)	Q261K	probably benign	Het
Zhx3	T	C	2: 160,623,613 (GRCm39)		probably null	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
R0586:Ldlr	UTSW	9	21,651,040 (GRCm39)	missense	probably benign	0.00
R1398:Ldlr	UTSW	9	21,650,838 (GRCm39)	missense	probably benign	0.01
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'- GCTCGCTGTGCATCATAGATGTGAC -3'
(R):5'- TGTTCACCCCTGGAACTCTCCTAAG -3'

Sequencing Primer
(F):5'- cacatgcagacacgcttatac -3'
(R):5'- cctaagagccctaagcagtg -3'

Posted On

2014-04-24