Mutagenetix > Incidental Mutation

Incidental Mutation 'R1398:Ldlr'

160237

Institutional Source

Beutler Lab

Gene Symbol

Ldlr

Ensembl Gene

ENSMUSG00000032193

Gene Name

low density lipoprotein receptor

Synonyms

MMRRC Submission

039460-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R1398 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

21634872-21661215 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 21650838 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glutamine to Leucine at position 449 (Q449L)

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: Q449L

PolyPhen 2 Score 0.006 (Sensitivity: 0.97; Specificity: 0.75)

SMART Domains

Protein: ENSMUSP00000034713
Gene: ENSMUSG00000032193
AA Change: Q449L

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: Q449L

PolyPhen 2 Score 0.005 (Sensitivity: 0.97; Specificity: 0.74)

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

0.5083

Coding Region Coverage

1x: 99.0%
3x: 98.1%
10x: 95.6%
20x: 90.7%

Validation Efficiency

96% (75/78)

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: 74 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca17	T	C	17: 24,547,511 (GRCm39)	K288E	probably damaging	Het
Aldh3a2	T	C	11: 61,147,562 (GRCm39)		probably null	Het
Anks1b	A	G	10: 89,885,891 (GRCm39)	T196A	probably damaging	Het
Anks6	T	A	4: 47,044,926 (GRCm39)	T327S	possibly damaging	Het
Bdh2	T	C	3: 135,001,057 (GRCm39)		probably benign	Het
C4b	T	A	17: 34,949,693 (GRCm39)		probably benign	Het
Cacna2d1	G	A	5: 16,562,764 (GRCm39)	V847I	possibly damaging	Het
Cadps	G	T	14: 12,449,822 (GRCm38)	T1129K	probably damaging	Het
Cdc45	A	G	16: 18,600,721 (GRCm39)		probably benign	Het
Cep63	A	T	9: 102,480,285 (GRCm39)		probably benign	Het
Chil4	T	A	3: 106,126,825 (GRCm39)		probably null	Het
Cnot11	A	G	1: 39,584,261 (GRCm39)	R478G	probably damaging	Het
Cyp2c67	A	G	19: 39,627,069 (GRCm39)	S254P	probably damaging	Het
Dnah11	T	A	12: 118,020,841 (GRCm39)	K87*	probably null	Het
Dpy19l2	T	A	9: 24,492,559 (GRCm39)		probably benign	Het
Dsc1	A	T	18: 20,221,393 (GRCm39)	I694N	probably damaging	Het
Ehd4	A	T	2: 119,958,081 (GRCm39)	I168K	probably benign	Het
Eif4e	A	T	3: 138,252,136 (GRCm39)	N25Y	probably damaging	Het
Elapor2	A	G	5: 9,430,297 (GRCm39)	Y69C	probably damaging	Het
Eme2	G	A	17: 25,111,892 (GRCm39)	S263F	probably damaging	Het
Fgfrl1	T	A	5: 108,854,147 (GRCm39)		probably benign	Het
Fhip2a	T	A	19: 57,361,358 (GRCm39)		probably benign	Het
Gm3159	T	A	14: 4,398,586 (GRCm38)	Y92*	probably null	Het
Gm4922	T	A	10: 18,659,496 (GRCm39)	S409C	possibly damaging	Het
Gmcl1	G	A	6: 86,691,244 (GRCm39)		probably benign	Het
Grsf1	A	G	5: 88,813,706 (GRCm39)	Y231H	probably benign	Het
Heatr4	T	A	12: 84,014,395 (GRCm39)	H614L	possibly damaging	Het
Hoxa13	C	G	6: 52,260,647 (GRCm38)		probably benign	Het
Hoxa13	G	C	6: 52,260,648 (GRCm38)		probably benign	Het
Isg20l2	C	A	3: 87,846,061 (GRCm39)	L325I	probably benign	Het
Kalrn	A	G	16: 34,033,190 (GRCm39)	Y879H	probably damaging	Het
Kcnk10	C	A	12: 98,402,485 (GRCm39)	W318L	probably damaging	Het
Kctd1	T	C	18: 15,195,654 (GRCm39)	E323G	possibly damaging	Het
Kif4	G	T	X: 99,732,703 (GRCm39)	A492S	probably benign	Het
Krtap4-1	T	C	11: 99,518,558 (GRCm39)	T151A	unknown	Het
Lepr	T	A	4: 101,649,216 (GRCm39)	D872E	probably damaging	Het
Lgals12	C	T	19: 7,581,322 (GRCm39)		probably benign	Het
Lrig3	C	T	10: 125,838,957 (GRCm39)	P488L	probably benign	Het
Lrrc4b	A	C	7: 44,111,876 (GRCm39)	I583L	probably benign	Het
Lyst	T	C	13: 13,915,121 (GRCm39)	S3272P	possibly damaging	Het
Marchf2	T	C	17: 33,915,096 (GRCm39)	H166R	probably damaging	Het
Mtbp	C	A	15: 55,440,933 (GRCm39)	Y373*	probably null	Het
Myh2	C	T	11: 67,076,113 (GRCm39)	H767Y	probably benign	Het
Ncam1	G	A	9: 49,428,889 (GRCm39)		probably benign	Het
Neb	T	A	2: 52,179,658 (GRCm39)	N1282Y	probably damaging	Het
Nectin3	A	G	16: 46,269,119 (GRCm39)	Y428H	possibly damaging	Het
Nrros	A	T	16: 31,961,962 (GRCm39)	I649N	probably damaging	Het
Nvl	A	T	1: 180,924,691 (GRCm39)		probably benign	Het
Or5p70	T	A	7: 107,994,708 (GRCm39)	V127E	probably damaging	Het
Pms1	A	T	1: 53,246,435 (GRCm39)	V368E	possibly damaging	Het
Polq	T	A	16: 36,882,857 (GRCm39)	S1674T	possibly damaging	Het
Ppp1r21	T	C	17: 88,850,307 (GRCm39)	V31A	probably damaging	Het
Rev3l	T	A	10: 39,697,579 (GRCm39)	V692E	probably benign	Het
Robo4	T	C	9: 37,319,372 (GRCm39)		probably null	Het
Rps6kc1	T	C	1: 190,532,212 (GRCm39)	I597V	probably damaging	Het
Rtel1	T	A	2: 180,977,658 (GRCm39)		probably null	Het
Scn9a	A	G	2: 66,314,930 (GRCm39)	M1587T	probably benign	Het
Sec31b	T	A	19: 44,512,104 (GRCm39)	I597F	probably benign	Het
Skint5	T	C	4: 113,636,268 (GRCm39)	N650S	unknown	Het
Slc22a28	G	T	19: 8,107,566 (GRCm39)	S167*	probably null	Het
Slfn1	T	A	11: 83,011,968 (GRCm39)	M28K	probably damaging	Het
Smc6	T	C	12: 11,321,880 (GRCm39)		probably benign	Het
Sox8	T	C	17: 25,786,857 (GRCm39)	H282R	probably benign	Het
Spata31e2	G	T	1: 26,724,422 (GRCm39)	Q253K	possibly damaging	Het
Syngr3	C	A	17: 24,905,414 (GRCm39)	V161L	probably benign	Het
Trak1	C	T	9: 121,283,425 (GRCm39)	S397F	probably damaging	Het
Uso1	C	T	5: 92,329,327 (GRCm39)	A405V	probably benign	Het
Uvrag	G	T	7: 98,715,027 (GRCm39)	Y190*	probably null	Het
Vps13d	A	T	4: 144,826,553 (GRCm39)	L1726Q	probably null	Het
Vwf	A	T	6: 125,580,420 (GRCm39)	Q556L	probably benign	Het
Wdr70	T	A	15: 8,065,325 (GRCm39)	M246L	probably benign	Het
Yipf3	T	C	17: 46,562,372 (GRCm39)	F285S	probably damaging	Het
Zdhhc13	G	A	7: 48,476,621 (GRCm39)	G579R	probably damaging	Het
Zdhhc18	G	C	4: 133,354,608 (GRCm39)	F125L	probably benign	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
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'- ATAGGCTATCTGCTCTTCACCAAC -3'
(R):5'- TGGTGTCAGCCACAGATACG -3'

Posted On

2014-03-14