Mutagenetix > Incidental Mutation

Incidental Mutation 'R8931:Ldlr'

680316

Institutional Source

Beutler Lab

Gene Symbol

Ldlr

Ensembl Gene

ENSMUSG00000032193

Gene Name

low density lipoprotein receptor

Synonyms

MMRRC Submission

068775-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R8931 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

21634872-21661215 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 21643108 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Methionine at position 45 (V45M)

Ref Sequence

ENSEMBL: ENSMUSP00000034713 (fasta)

Gene Model

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

AlphaFold

P35951

Predicted Effect

probably damaging
Transcript: ENSMUST00000034713
AA Change: V45M

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000034713
Gene: ENSMUSG00000032193
AA Change: V45M

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: V45M

PolyPhen 2 Score 0.960 (Sensitivity: 0.78; Specificity: 0.95)

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.8%

Validation Efficiency

100% (58/58)

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: 61 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acat3	G	C	17: 13,147,405 (GRCm39)	P204R	probably damaging	Het
Aldh3b1	A	G	19: 3,968,803 (GRCm39)	I250T	possibly damaging	Het
Ankrd11	C	T	8: 123,622,718 (GRCm39)	R378K	probably damaging	Het
Arap1	G	A	7: 101,057,324 (GRCm39)	R1355Q	possibly damaging	Het
Arhgef19	T	C	4: 140,976,603 (GRCm39)	V455A	probably damaging	Het
BC051019	T	C	7: 109,315,286 (GRCm39)	E323G	probably damaging	Het
Bzw2	T	C	12: 36,184,943 (GRCm39)	N2S	possibly damaging	Het
Calm3	G	C	7: 16,651,398 (GRCm39)	F66L	probably damaging	Het
Carmil1	T	A	13: 24,338,704 (GRCm39)	T191S	probably benign	Het
Cemip2	T	A	19: 21,770,323 (GRCm39)	S104T	probably benign	Het
Cep170	A	T	1: 176,597,377 (GRCm39)	C389S	probably benign	Het
Clhc1	C	T	11: 29,510,533 (GRCm39)	Q195*	probably null	Het
Cttnbp2	A	G	6: 18,434,808 (GRCm39)	L350P	probably benign	Het
Cyp7a1	T	C	4: 6,271,238 (GRCm39)	E306G	possibly damaging	Het
Ddx25	T	C	9: 35,465,864 (GRCm39)	N119S	possibly damaging	Het
Ephx2	G	T	14: 66,322,441 (GRCm39)		probably benign	Het
Ern2	C	T	7: 121,769,363 (GRCm39)	A888T	probably benign	Het
Fbln2	A	T	6: 91,246,072 (GRCm39)	I973F	probably damaging	Het
Fbn1	T	C	2: 125,202,095 (GRCm39)	I1259M	probably damaging	Het
Glis1	A	G	4: 107,421,060 (GRCm39)	H92R	probably benign	Het
Gm13283	A	C	4: 88,679,516 (GRCm39)	D169A	probably benign	Het
Gpr61	A	G	3: 108,057,470 (GRCm39)	L397P	probably benign	Het
H4c11	T	A	13: 21,919,369 (GRCm39)	I35N	probably damaging	Het
Hip1	A	T	5: 135,460,297 (GRCm39)		probably benign	Het
Hmgcs2	C	T	3: 98,203,557 (GRCm39)	A222V	probably damaging	Het
Ifna2	G	A	4: 88,601,712 (GRCm39)	T102I	probably benign	Het
Kat6b	T	C	14: 21,674,995 (GRCm39)	S387P	probably damaging	Het
Mc3r	A	T	2: 172,091,515 (GRCm39)	I246F	possibly damaging	Het
Mug1	G	C	6: 121,861,296 (GRCm39)	A1306P	probably benign	Het
Myo15a	A	G	11: 60,368,020 (GRCm39)	E260G	probably benign	Het
Naa16	A	G	14: 79,582,395 (GRCm39)	Y565H	probably damaging	Het
Ndufaf7	A	G	17: 79,244,950 (GRCm39)	Y23C	possibly damaging	Het
Nop58	G	A	1: 59,731,549 (GRCm39)		probably null	Het
Or6c33	A	T	10: 129,853,769 (GRCm39)	T180S	possibly damaging	Het
Or6c88	A	T	10: 129,406,550 (GRCm39)	T9S	probably benign	Het
Or7g19	T	A	9: 18,855,920 (GRCm39)		probably benign	Het
Pcdh8	G	A	14: 80,006,971 (GRCm39)	Q531*	probably null	Het
Pik3c2g	A	G	6: 139,821,093 (GRCm39)	T297A	probably benign	Het
Poc1b	T	C	10: 99,028,861 (GRCm39)		probably null	Het
Prb1c	G	A	6: 132,338,897 (GRCm39)	P107L		Het
Prokr2	A	G	2: 132,215,996 (GRCm39)	V155A	possibly damaging	Het
Rce1	C	T	19: 4,674,094 (GRCm39)		probably benign	Het
Rnf148	A	T	6: 23,654,704 (GRCm39)	N97K	possibly damaging	Het
Setbp1	A	G	18: 78,899,723 (GRCm39)	S1315P	probably benign	Het
Sgcz	A	G	8: 38,107,140 (GRCm39)	V124A	probably damaging	Het
Slc25a2	C	A	18: 37,771,089 (GRCm39)	G147C	probably damaging	Het
Slc28a2b	C	A	2: 122,348,983 (GRCm39)	P303Q		Het
Sod2	T	C	17: 13,227,193 (GRCm39)	L49P	probably damaging	Het
Tbc1d12	T	C	19: 38,854,098 (GRCm39)	V260A	probably benign	Het
Tcte2	C	A	17: 13,933,410 (GRCm39)		probably benign	Het
Tenm3	T	C	8: 48,688,637 (GRCm39)	T2317A	probably damaging	Het
Tfcp2	T	C	15: 100,402,298 (GRCm39)	I500V	possibly damaging	Het
Trav14-3	C	A	14: 54,001,112 (GRCm39)	Q108K	probably damaging	Het
Trbv14	T	C	6: 41,112,364 (GRCm39)	Y54H	probably damaging	Het
Trpm3	T	A	19: 22,744,034 (GRCm39)	V337E	probably damaging	Het
Tsbp1	T	C	17: 34,659,328 (GRCm39)		probably benign	Het
Uox	A	T	3: 146,318,047 (GRCm39)	I14F	probably damaging	Het
Wdfy3	A	G	5: 102,065,421 (GRCm39)	V1249A	probably benign	Het
Zfp511	T	C	7: 139,617,194 (GRCm39)	Y97H	probably damaging	Het
Zfp536	G	T	7: 37,268,721 (GRCm39)	Q232K	probably benign	Het
Zng1	T	G	19: 24,932,780 (GRCm39)	K84N	probably 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
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
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
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'- TGCTGGGTACATTTGTCACC -3'
(R):5'- GCCTTCTTCTAACTCACGAATGG -3'

Sequencing Primer
(F):5'- GGGTACATTTGTCACCTCTGTTGC -3'
(R):5'- TCTTGGCACAGCAGTAGAGC -3'

Posted On

2021-08-31