Mutagenetix > Incidental Mutation

Incidental Mutation 'R5935:Lrp8'

462158

Institutional Source

Beutler Lab

Gene Symbol

Lrp8

Ensembl Gene

ENSMUSG00000028613

Gene Name

low density lipoprotein receptor-related protein 8, apolipoprotein e receptor

Synonyms

4932703M08Rik, Lr8b, apoER2

MMRRC Submission

044129-MU

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.477) question?

Stock #

R5935 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

107659337-107734037 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to A at 107714493 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Glutamine at position 622 (H622Q)

Ref Sequence

ENSEMBL: ENSMUSP00000102344 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000030356] [ENSMUST00000106732] [ENSMUST00000106733] [ENSMUST00000126573] [ENSMUST00000143601]

AlphaFold

Q924X6

Predicted Effect

probably damaging
Transcript: ENSMUST00000030356
AA Change: H622Q

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000030356
Gene: ENSMUSG00000028613
AA Change: H622Q

Domain	Start	End	E-Value	Type
signal peptide	1	27	N/A	INTRINSIC
LDLa	40	77	3.24e-13	SMART
EGF_like	79	117	3.29e1	SMART
LDLa	79	118	2.45e-13	SMART
LDLa	120	159	1.19e-11	SMART
LDLa	160	197	3.52e-14	SMART
LDLa	199	239	8.09e-14	SMART
LDLa	250	288	4.05e-14	SMART
LDLa	290	327	4.58e-13	SMART
EGF	331	367	2.83e-5	SMART
EGF_CA	368	407	9.91e-10	SMART
LY	434	476	8.44e-4	SMART
LY	481	523	2.29e-14	SMART
LY	524	567	5.96e-13	SMART
LY	568	610	4.21e-13	SMART
LY	612	654	7.24e-3	SMART
EGF	681	727	1.56e1	SMART
low complexity region	729	745	N/A	INTRINSIC
low complexity region	783	798	N/A	INTRINSIC
transmembrane domain	818	840	N/A	INTRINSIC
low complexity region	863	869	N/A	INTRINSIC

Predicted Effect

unknown
Transcript: ENSMUST00000106731
AA Change: H424Q

SMART Domains

Protein: ENSMUSP00000102342
Gene: ENSMUSG00000028613
AA Change: H424Q

Domain	Start	End	E-Value	Type
EGF_like	9	47	3.29e1	SMART
LDLa	9	48	2.45e-13	SMART
LDLa	50	89	1.19e-11	SMART
LDLa	93	130	4.58e-13	SMART
EGF	134	170	2.83e-5	SMART
EGF_CA	171	210	9.91e-10	SMART
LY	237	279	8.44e-4	SMART
LY	284	326	2.29e-14	SMART
LY	327	370	5.96e-13	SMART
LY	371	413	4.21e-13	SMART
LY	415	457	7.24e-3	SMART
EGF	484	530	1.56e1	SMART
low complexity region	532	548	N/A	INTRINSIC
low complexity region	586	601	N/A	INTRINSIC
transmembrane domain	621	643	N/A	INTRINSIC
low complexity region	666	672	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000106732
AA Change: H537Q

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000102343
Gene: ENSMUSG00000028613
AA Change: H537Q

Domain	Start	End	E-Value	Type
signal peptide	1	27	N/A	INTRINSIC
LDLa	40	77	3.24e-13	SMART
EGF_like	79	117	3.29e1	SMART
LDLa	79	118	2.45e-13	SMART
LDLa	120	159	1.19e-11	SMART
LDLa	164	201	4.58e-13	SMART
LDLa	204	244	1.4e-8	SMART
EGF	246	282	2.83e-5	SMART
EGF_CA	283	322	9.91e-10	SMART
LY	349	391	8.44e-4	SMART
LY	396	438	2.29e-14	SMART
LY	439	482	5.96e-13	SMART
LY	483	525	4.21e-13	SMART
LY	527	569	7.24e-3	SMART
EGF	596	642	1.56e1	SMART
low complexity region	644	660	N/A	INTRINSIC
low complexity region	698	713	N/A	INTRINSIC
transmembrane domain	733	755	N/A	INTRINSIC
low complexity region	778	784	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000106733
AA Change: H622Q

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000102344
Gene: ENSMUSG00000028613
AA Change: H622Q

Domain	Start	End	E-Value	Type
signal peptide	1	27	N/A	INTRINSIC
LDLa	40	77	3.24e-13	SMART
EGF_like	79	117	3.29e1	SMART
LDLa	79	118	2.45e-13	SMART
LDLa	120	159	1.19e-11	SMART
LDLa	160	197	3.52e-14	SMART
LDLa	199	239	8.09e-14	SMART
LDLa	250	288	4.05e-14	SMART
LDLa	290	327	4.58e-13	SMART
EGF	331	367	2.83e-5	SMART
EGF_CA	368	407	9.91e-10	SMART
LY	434	476	8.44e-4	SMART
LY	481	523	2.29e-14	SMART
LY	524	567	5.96e-13	SMART
LY	568	610	4.21e-13	SMART
LY	612	654	7.24e-3	SMART
EGF	681	727	1.56e1	SMART
low complexity region	729	745	N/A	INTRINSIC
low complexity region	783	798	N/A	INTRINSIC
transmembrane domain	818	840	N/A	INTRINSIC
low complexity region	863	869	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000123140

Predicted Effect

probably damaging
Transcript: ENSMUST00000126573
AA Change: H495Q

PolyPhen 2 Score 0.974 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000118020
Gene: ENSMUSG00000028613
AA Change: H495Q

Domain	Start	End	E-Value	Type
signal peptide	1	27	N/A	INTRINSIC
LDLa	40	77	3.24e-13	SMART
EGF_like	79	117	3.29e1	SMART
LDLa	79	118	2.45e-13	SMART
LDLa	120	159	1.19e-11	SMART
LDLa	163	200	4.58e-13	SMART
EGF	204	240	2.83e-5	SMART
EGF_CA	241	280	9.91e-10	SMART
LY	307	349	8.44e-4	SMART
LY	354	396	2.29e-14	SMART
LY	397	440	5.96e-13	SMART
LY	441	483	4.21e-13	SMART
LY	485	527	7.24e-3	SMART
EGF	554	600	1.56e1	SMART
transmembrane domain	616	638	N/A	INTRINSIC
low complexity region	661	667	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000135022

Predicted Effect

probably damaging
Transcript: ENSMUST00000143601
AA Change: H663Q

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000115854
Gene: ENSMUSG00000028613
AA Change: H663Q

Domain	Start	End	E-Value	Type
signal peptide	1	27	N/A	INTRINSIC
LDLa	40	77	3.24e-13	SMART
EGF_like	79	117	3.29e1	SMART
LDLa	79	118	2.45e-13	SMART
LDLa	120	159	1.19e-11	SMART
LDLa	160	197	3.52e-14	SMART
LDLa	199	239	8.09e-14	SMART
LDLa	250	288	4.05e-14	SMART
LDLa	290	327	4.58e-13	SMART
LDLa	330	370	1.4e-8	SMART
EGF	372	408	2.83e-5	SMART
EGF_CA	409	448	9.91e-10	SMART
LY	475	517	8.44e-4	SMART
LY	522	564	2.29e-14	SMART
LY	565	608	5.96e-13	SMART
LY	609	651	4.21e-13	SMART
LY	653	695	7.24e-3	SMART
EGF	722	768	1.56e1	SMART
low complexity region	770	786	N/A	INTRINSIC
low complexity region	824	839	N/A	INTRINSIC
transmembrane domain	859	881	N/A	INTRINSIC
low complexity region	904	910	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000146552

Meta Mutation Damage Score

0.8387

Coding Region Coverage

1x: 99.9%
3x: 99.6%
10x: 98.2%
20x: 94.8%

Validation Efficiency

96% (92/96)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the low density lipoprotein receptor (LDLR) family. Low density lipoprotein receptors are cell surface proteins that play roles in both signal transduction and receptor-mediated endocytosis of specific ligands for lysosomal degradation. The encoded protein plays a critical role in the migration of neurons during development by mediating Reelin signaling, and also functions as a receptor for the cholesterol transport protein apolipoprotein E. Expression of this gene may be a marker for major depressive disorder. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jun 2011]
PHENOTYPE: Homozygotes for a targeted null mutation exhibit impaired granule cell migration, radial glial scaffold formation, contextual fear conditioning, and long-term potentiation. Mutant males have abnormal sperm and are sterile. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 87 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adam26b	C	G	8: 43,974,335 (GRCm39)	M222I	probably benign	Het
Ahnak	T	C	19: 8,992,546 (GRCm39)	V4610A	possibly damaging	Het
Ankrd13c	C	T	3: 157,653,220 (GRCm39)		silent	Het
Cables2	A	G	2: 179,903,841 (GRCm39)		probably benign	Het
Cabp2	C	A	19: 4,136,497 (GRCm39)	A181D	probably damaging	Het
Camsap3	A	G	8: 3,651,999 (GRCm39)	D265G	probably damaging	Het
Cbs	G	T	17: 31,851,853 (GRCm39)	T50N	probably damaging	Het
Cenpa	A	T	5: 30,830,381 (GRCm39)	Q83L	possibly damaging	Het
Cit	A	T	5: 116,063,598 (GRCm39)		probably benign	Het
Ckap5	A	G	2: 91,445,445 (GRCm39)	E1694G	possibly damaging	Het
Copz1	A	T	15: 103,203,197 (GRCm39)	M104L	probably benign	Het
Crot	T	A	5: 9,024,192 (GRCm39)	M335L	probably benign	Het
Ctnna2	T	C	6: 77,120,904 (GRCm39)	D373G	probably benign	Het
Ctu2	G	A	8: 123,203,693 (GRCm39)		probably benign	Het
Cyp3a59	T	A	5: 146,027,455 (GRCm39)	Y75*	probably null	Het
Dbi	A	G	1: 120,048,583 (GRCm39)	I21T	probably benign	Het
Dcun1d3	A	G	7: 119,458,799 (GRCm39)	S79P	probably benign	Het
Dock10	T	A	1: 80,483,304 (GRCm39)		probably benign	Het
Dstyk	T	A	1: 132,381,875 (GRCm39)	I543N	probably damaging	Het
Epx	G	T	11: 87,756,318 (GRCm39)	A621E	probably damaging	Het
Farp2	G	A	1: 93,548,367 (GRCm39)		probably null	Het
Gm11992	C	T	11: 9,002,711 (GRCm39)	P25S	probably damaging	Het
Grik5	A	T	7: 24,758,502 (GRCm39)	M307K	possibly damaging	Het
Hnf1b	A	T	11: 83,773,503 (GRCm39)	N234I	probably damaging	Het
Htr2a	A	G	14: 74,882,530 (GRCm39)	D172G	probably damaging	Het
Ifit1bl2	T	C	19: 34,597,128 (GRCm39)	T163A	probably benign	Het
Igsf10	A	T	3: 59,235,578 (GRCm39)	D1534E	probably benign	Het
Il3ra	T	G	14: 14,350,799 (GRCm38)	V178G	probably damaging	Het
Itgb1	A	T	8: 129,439,718 (GRCm39)	K136*	probably null	Het
Itprid1	A	T	6: 55,874,754 (GRCm39)	R235*	probably null	Het
Lama2	T	A	10: 26,891,494 (GRCm39)	I2540F	probably benign	Het
Lrrc2	T	A	9: 110,795,629 (GRCm39)	M138K	probably benign	Het
Lrrk2	C	A	15: 91,630,034 (GRCm39)	H1242N	probably benign	Het
Lsm11	G	C	11: 45,835,445 (GRCm39)	R99G	probably benign	Het
Mif4gd	C	T	11: 115,500,439 (GRCm39)	V40M	probably benign	Het
Mpp3	A	T	11: 101,916,241 (GRCm39)	V37D	probably damaging	Het
Mre11a	T	A	9: 14,698,258 (GRCm39)	D35E	probably damaging	Het
Mroh4	C	A	15: 74,493,003 (GRCm39)	V233F	probably damaging	Het
Npy2r	A	T	3: 82,448,068 (GRCm39)	S123T	possibly damaging	Het
Nrip2	A	G	6: 128,385,361 (GRCm39)	Y264C	possibly damaging	Het
Obscn	A	G	11: 58,897,639 (GRCm39)	S6639P	unknown	Het
Or10d4	C	T	9: 39,580,386 (GRCm39)	T11I	probably benign	Het
Or51t4	T	A	7: 102,598,017 (GRCm39)	F105Y	probably benign	Het
Osbpl5	C	T	7: 143,310,695 (GRCm39)		probably benign	Het
Panx1	A	T	9: 14,921,513 (GRCm39)	Y121N	probably damaging	Het
Pcdhb8	A	G	18: 37,489,243 (GRCm39)	D307G	probably damaging	Het
Pde1b	A	G	15: 103,429,866 (GRCm39)	K120E	possibly damaging	Het
Pdzrn4	T	C	15: 92,295,255 (GRCm39)	S154P	probably benign	Het
Ppp1r13b	T	C	12: 111,796,876 (GRCm39)	K889R	probably benign	Het
Ppp4r3a	T	A	12: 101,017,872 (GRCm39)	D439V	probably damaging	Het
Ptk2b	A	G	14: 66,411,328 (GRCm39)	I401T	probably damaging	Het
Rab24	T	C	13: 55,468,343 (GRCm39)	T153A	probably damaging	Het
Rarb	C	A	14: 16,434,264 (GRCm38)	A305S	probably damaging	Het
Rc3h2	GCC	GCCC	2: 37,304,745 (GRCm39)		probably null	Het
Scn10a	G	A	9: 119,456,237 (GRCm39)	T1194I	probably damaging	Het
Scn3a	G	T	2: 65,295,180 (GRCm39)	N1514K	probably damaging	Het
Serpinb3d	T	C	1: 107,011,105 (GRCm39)	T36A	probably benign	Het
Shisa5	T	A	9: 108,885,751 (GRCm39)	M229K	possibly damaging	Het
Sik2	C	T	9: 50,828,431 (GRCm39)	G204R	probably damaging	Het
Sla	C	T	15: 66,665,554 (GRCm39)	G46E	probably damaging	Het
Slc35g3	A	T	11: 69,652,509 (GRCm39)	M1K	probably null	Het
Slc5a7	A	T	17: 54,583,972 (GRCm39)	Y439*	probably null	Het
Slc9a1	T	C	4: 133,147,176 (GRCm39)		probably benign	Het
Slitrk6	T	G	14: 110,987,305 (GRCm39)	T801P	probably benign	Het
Spata31d1c	T	C	13: 65,184,894 (GRCm39)	V812A	possibly damaging	Het
Spata31g1	T	C	4: 42,971,465 (GRCm39)	L230P	probably benign	Het
Spef1l	G	A	7: 139,556,526 (GRCm39)	H154Y	probably benign	Het
Sphkap	A	C	1: 83,317,320 (GRCm39)	L59R	probably damaging	Het
Spmip8	A	T	8: 96,046,620 (GRCm39)	T98S	possibly damaging	Het
Srsf10	C	A	4: 135,583,553 (GRCm39)	R6S	probably damaging	Het
Supt5	T	A	7: 28,028,900 (GRCm39)	R131S	probably benign	Het
Syne1	T	C	10: 5,310,706 (GRCm39)		probably null	Het
Tet2	T	A	3: 133,194,296 (GRCm39)	H46L	possibly damaging	Het
Tnfsf4	T	A	1: 161,244,819 (GRCm39)	N169K	probably damaging	Het
Tprg1	A	T	16: 25,136,011 (GRCm39)	M1L	possibly damaging	Het
Tsen2	A	G	6: 115,536,556 (GRCm39)	Y104C	probably damaging	Het
Ttc6	A	G	12: 57,720,590 (GRCm39)	Y952C	probably damaging	Het
Umod	A	T	7: 119,070,650 (GRCm39)	I414N	probably damaging	Het
Usp10	G	T	8: 120,673,828 (GRCm39)	V398L	possibly damaging	Het
Vmn2r23	A	T	6: 123,718,854 (GRCm39)	I736F	possibly damaging	Het
Vmn2r65	C	A	7: 84,592,869 (GRCm39)	G446V	probably benign	Het
Wbp1l	C	T	19: 46,642,619 (GRCm39)	R191*	probably null	Het
Yars2	A	G	16: 16,127,335 (GRCm39)	I467V	probably benign	Het
Ykt6	A	G	11: 5,909,338 (GRCm39)	E49G	possibly damaging	Het
Zan	T	A	5: 137,442,192 (GRCm39)	M1907L	unknown	Het
Zdhhc2	T	C	8: 40,917,277 (GRCm39)	S225P	probably damaging	Het
Zfc3h1	A	T	10: 115,267,262 (GRCm39)		probably benign	Het

Other mutations in Lrp8

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01308:Lrp8	APN	4	107,721,273 (GRCm39)	missense	probably benign	0.04
IGL01514:Lrp8	APN	4	107,712,881 (GRCm39)	missense	probably damaging	1.00
IGL02058:Lrp8	APN	4	107,727,306 (GRCm39)	missense	probably benign	0.25
IGL02398:Lrp8	APN	4	107,726,245 (GRCm39)	missense	probably damaging	1.00
IGL02398:Lrp8	APN	4	107,704,691 (GRCm39)	missense	probably damaging	0.97
IGL02706:Lrp8	APN	4	107,660,516 (GRCm39)	nonsense	probably null
IGL02754:Lrp8	APN	4	107,691,952 (GRCm39)	splice site	probably null
IGL02967:Lrp8	APN	4	107,718,431 (GRCm39)	missense	probably benign	0.21
IGL03080:Lrp8	APN	4	107,712,996 (GRCm39)	missense	probably damaging	1.00
IGL02837:Lrp8	UTSW	4	107,718,478 (GRCm39)	missense	probably benign	0.01
R0312:Lrp8	UTSW	4	107,664,052 (GRCm39)	intron	probably benign
R0440:Lrp8	UTSW	4	107,726,295 (GRCm39)	missense	probably damaging	0.99
R0598:Lrp8	UTSW	4	107,714,434 (GRCm39)	missense	possibly damaging	0.73
R1627:Lrp8	UTSW	4	107,711,613 (GRCm39)	missense	probably damaging	0.99
R1967:Lrp8	UTSW	4	107,717,168 (GRCm39)	missense	probably damaging	1.00
R2183:Lrp8	UTSW	4	107,660,462 (GRCm39)	missense	probably damaging	1.00
R2208:Lrp8	UTSW	4	107,712,987 (GRCm39)	missense	probably damaging	1.00
R2325:Lrp8	UTSW	4	107,721,206 (GRCm39)	missense	probably benign	0.03
R3712:Lrp8	UTSW	4	107,705,499 (GRCm39)	missense	probably benign	0.08
R4093:Lrp8	UTSW	4	107,700,468 (GRCm39)	nonsense	probably null
R4706:Lrp8	UTSW	4	107,718,470 (GRCm39)	missense	probably benign	0.00
R4765:Lrp8	UTSW	4	107,711,592 (GRCm39)	missense	probably damaging	1.00
R4840:Lrp8	UTSW	4	107,727,234 (GRCm39)	missense	possibly damaging	0.79
R4900:Lrp8	UTSW	4	107,664,006 (GRCm39)	intron	probably benign
R5033:Lrp8	UTSW	4	107,691,952 (GRCm39)	splice site	probably null
R5280:Lrp8	UTSW	4	107,711,518 (GRCm39)	missense	probably damaging	1.00
R5381:Lrp8	UTSW	4	107,726,307 (GRCm39)	missense	probably damaging	1.00
R5972:Lrp8	UTSW	4	107,726,267 (GRCm39)	missense	probably damaging	1.00
R6076:Lrp8	UTSW	4	107,704,656 (GRCm39)	missense	possibly damaging	0.81
R6343:Lrp8	UTSW	4	107,726,353 (GRCm39)	splice site	probably null
R6805:Lrp8	UTSW	4	107,711,517 (GRCm39)	missense	probably damaging	0.99
R7100:Lrp8	UTSW	4	107,659,647 (GRCm39)	missense	possibly damaging	0.93
R7262:Lrp8	UTSW	4	107,704,661 (GRCm39)	missense	probably benign
R7717:Lrp8	UTSW	4	107,691,940 (GRCm39)	missense	probably benign	0.00
R7949:Lrp8	UTSW	4	107,660,524 (GRCm39)	missense	probably damaging	1.00
R8350:Lrp8	UTSW	4	107,704,661 (GRCm39)	missense	probably benign
R8371:Lrp8	UTSW	4	107,726,268 (GRCm39)	missense	probably damaging	1.00
R9272:Lrp8	UTSW	4	107,717,158 (GRCm39)	missense	probably benign	0.19
R9461:Lrp8	UTSW	4	107,700,515 (GRCm39)	missense	possibly damaging	0.93
R9567:Lrp8	UTSW	4	107,711,469 (GRCm39)	missense	probably damaging	0.99
Z1177:Lrp8	UTSW	4	107,700,529 (GRCm39)	missense	probably benign	0.02

Predicted Primers

PCR Primer
(F):5'- TCTTGAGTCAGAGTCCCCTC -3'
(R):5'- GAGGCTGCTCTTGGAGTCTATAC -3'

Sequencing Primer
(F):5'- TCAGAGTCCCCTCGTGGTG -3'
(R):5'- GGAGTCTATACAAACCTGTCAGCTG -3'

Posted On

2017-02-28