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

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R8931 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

21723483-21749919 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 21731812 bp (GRCm38)

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: 12,928,518	P204R	probably damaging	Het
Aldh3b1	A	G	19: 3,918,803	I250T	possibly damaging	Het
Ankrd11	C	T	8: 122,895,979	R378K	probably damaging	Het
Arap1	G	A	7: 101,408,117	R1355Q	possibly damaging	Het
Arhgef19	T	C	4: 141,249,292	V455A	probably damaging	Het
BC051019	T	C	7: 109,716,079	E323G	probably damaging	Het
BC051142	T	C	17: 34,440,354		probably benign	Het
Bzw2	T	C	12: 36,134,944	N2S	possibly damaging	Het
Calm3	G	C	7: 16,917,473	F66L	probably damaging	Het
Carmil1	T	A	13: 24,154,721	T191S	probably benign	Het
Cbwd1	T	G	19: 24,955,416	K84N	probably damaging	Het
Cep170	A	T	1: 176,769,811	C389S	probably benign	Het
Clhc1	C	T	11: 29,560,533	Q195*	probably null	Het
Cttnbp2	A	G	6: 18,434,809	L350P	probably benign	Het
Cyp7a1	T	C	4: 6,271,238	E306G	possibly damaging	Het
Ddx25	T	C	9: 35,554,568	N119S	possibly damaging	Het
Ephx2	G	T	14: 66,084,992		probably benign	Het
Ern2	C	T	7: 122,170,140	A888T	probably benign	Het
Fbln2	A	T	6: 91,269,090	I973F	probably damaging	Het
Fbn1	T	C	2: 125,360,175	I1259M	probably damaging	Het
Glis1	A	G	4: 107,563,863	H92R	probably benign	Het
Gm13283	A	C	4: 88,761,279	D169A	probably benign	Het
Gm14085	C	A	2: 122,518,502	P303Q		Het
Gm8882	G	A	6: 132,361,934	P107L		Het
Gpr61	A	G	3: 108,150,154	L397P	probably benign	Het
Hip1	A	T	5: 135,431,443		probably benign	Het
Hist1h4j	T	A	13: 21,735,199	I35N	probably damaging	Het
Hmgcs2	C	T	3: 98,296,241	A222V	probably damaging	Het
Ifna2	G	A	4: 88,683,475	T102I	probably benign	Het
Kat6b	T	C	14: 21,624,927	S387P	probably damaging	Het
Mc3r	A	T	2: 172,249,595	I246F	possibly damaging	Het
Mug1	G	C	6: 121,884,337	A1306P	probably benign	Het
Myo15	A	G	11: 60,477,194	E260G	probably benign	Het
Naa16	A	G	14: 79,344,955	Y565H	probably damaging	Het
Ndufaf7	A	G	17: 78,937,521	Y23C	possibly damaging	Het
Nop58	G	A	1: 59,692,390		probably null	Het
Olfr794	A	T	10: 129,570,681	T9S	probably benign	Het
Olfr820	A	T	10: 130,017,900	T180S	possibly damaging	Het
Olfr832	T	A	9: 18,944,624		probably benign	Het
Pcdh8	G	A	14: 79,769,531	Q531*	probably null	Het
Pik3c2g	A	G	6: 139,875,367	T297A	probably benign	Het
Poc1b	T	C	10: 99,192,999		probably null	Het
Prokr2	A	G	2: 132,374,076	V155A	possibly damaging	Het
Rce1	C	T	19: 4,624,066		probably benign	Het
Rnf148	A	T	6: 23,654,705	N97K	possibly damaging	Het
Setbp1	A	G	18: 78,856,508	S1315P	probably benign	Het
Sgcz	A	G	8: 37,639,986	V124A	probably damaging	Het
Slc25a2	C	A	18: 37,638,036	G147C	probably damaging	Het
Sod2	T	C	17: 13,008,306	L49P	probably damaging	Het
Tbc1d12	T	C	19: 38,865,654	V260A	probably benign	Het
Tcte2	C	A	17: 13,713,148		probably benign	Het
Tenm3	T	C	8: 48,235,602	T2317A	probably damaging	Het
Tfcp2	T	C	15: 100,504,417	I500V	possibly damaging	Het
Tmem2	T	A	19: 21,792,959	S104T	probably benign	Het
Trav14-3	C	A	14: 53,763,655	Q108K	probably damaging	Het
Trbv14	T	C	6: 41,135,430	Y54H	probably damaging	Het
Trpm3	T	A	19: 22,766,670	V337E	probably damaging	Het
Uox	A	T	3: 146,612,292	I14F	probably damaging	Het
Wdfy3	A	G	5: 101,917,555	V1249A	probably benign	Het
Zfp511	T	C	7: 140,037,281	Y97H	probably damaging	Het
Zfp536	G	T	7: 37,569,296	Q232K	probably benign	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
R0586:Ldlr	UTSW	9	21739744	missense	probably benign	0.00
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
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'- TGCTGGGTACATTTGTCACC -3'
(R):5'- GCCTTCTTCTAACTCACGAATGG -3'

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

Posted On

2021-08-31