Mutagenetix > Incidental Mutation

Incidental Mutation 'R6805:Lrp8'

533520

Institutional Source

Beutler Lab

Gene Symbol

Lrp8

Ensembl Gene

ENSMUSG00000028613

Gene Name

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

Synonyms

Lr8b, 4932703M08Rik, apoER2

MMRRC Submission

Accession Numbers

Is this an essential gene?

Possibly non essential (E-score: 0.377) question?

Stock #

R6805 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

107802261-107876840 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 107854320 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Histidine at position 307 (Y307H)

Ref Sequence

ENSEMBL: ENSMUSP00000118020 (fasta)

Gene Model

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

AlphaFold

Q924X6

Predicted Effect

probably benign
Transcript: ENSMUST00000030356
AA Change: Y434H

PolyPhen 2 Score 0.112 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000030356
Gene: ENSMUSG00000028613
AA Change: Y434H

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

SMART Domains

Protein: ENSMUSP00000102342
Gene: ENSMUSG00000028613
AA Change: Y236H

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

possibly damaging
Transcript: ENSMUST00000106732
AA Change: Y349H

PolyPhen 2 Score 0.528 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000102343
Gene: ENSMUSG00000028613
AA Change: Y349H

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 benign
Transcript: ENSMUST00000106733
AA Change: Y434H

PolyPhen 2 Score 0.112 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000102344
Gene: ENSMUSG00000028613
AA Change: Y434H

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

probably damaging
Transcript: ENSMUST00000126573
AA Change: Y307H

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000118020
Gene: ENSMUSG00000028613
AA Change: Y307H

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

probably benign
Transcript: ENSMUST00000143601
AA Change: Y475H

PolyPhen 2 Score 0.089 (Sensitivity: 0.93; Specificity: 0.85)

SMART Domains

Protein: ENSMUSP00000115854
Gene: ENSMUSG00000028613
AA Change: Y475H

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

Coding Region Coverage

1x: 99.9%
3x: 99.7%
10x: 98.8%
20x: 97.1%

Validation Efficiency

98% (62/63)

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: 62 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2410089E03Rik	T	C	15: 8,244,306	V2591A	probably benign	Het
4930407I10Rik	A	G	15: 82,062,543	T214A	possibly damaging	Het
A930009A15Rik	G	T	10: 115,579,905		probably benign	Het
Aadac	A	C	3: 60,037,336	D143A	probably benign	Het
Acot10	T	G	15: 20,665,366	T430P	probably benign	Het
Adgrb3	T	C	1: 25,826,172	T197A	possibly damaging	Het
B230118H07Rik	T	C	2: 101,566,459	K192E	probably benign	Het
Bbs1	A	G	19: 4,900,615	I200T	probably damaging	Het
C1ra	G	A	6: 124,517,725	E316K	probably benign	Het
Cadps	G	A	14: 12,467,103	A943V	probably damaging	Het
Cc2d2a	A	G	5: 43,681,331	E48G	probably damaging	Het
Clca1	A	T	3: 145,018,667	C211S	probably damaging	Het
Col18a1	A	G	10: 77,054,239	L1429P	probably damaging	Het
Cul2	T	G	18: 3,421,263	Y196D	probably damaging	Het
D630023F18Rik	T	C	1: 65,117,206	S43G	probably benign	Het
Ddx39	G	A	8: 83,723,137	R427Q	probably damaging	Het
Def6	A	G	17: 28,223,717	T285A	probably damaging	Het
Defb21	T	A	2: 152,574,869	D88E	probably benign	Het
Defb6	A	G	8: 19,228,101	K63R	probably benign	Het
Dnph1	T	C	17: 46,498,744	S112P	probably damaging	Het
Dock10	T	A	1: 80,586,690	I467L	probably benign	Het
Dspp	C	A	5: 104,175,850	H286Q	probably benign	Het
Eya1	T	A	1: 14,183,277	T459S	probably benign	Het
Faf1	T	C	4: 109,861,852	L385P	probably damaging	Het
Fbxw21	C	A	9: 109,157,565	R82L	probably damaging	Het
Fryl	A	G	5: 73,065,094	V2048A	probably benign	Het
Galnt5	A	T	2: 58,035,299	D864V	possibly damaging	Het
Gata6	T	G	18: 11,054,460	S130A	possibly damaging	Het
Gbf1	G	T	19: 46,262,507	R434L	probably damaging	Het
Gga3	A	G	11: 115,585,762	F709L	probably damaging	Het
Hcar1	A	G	5: 123,879,130	V166A	probably benign	Het
Hexa	T	A	9: 59,563,937	N491K	possibly damaging	Het
Hpse2	A	T	19: 43,294,321	C164*	probably null	Het
Ifi202b	T	C	1: 173,974,989	Y93C	probably damaging	Het
Iscu	T	A	5: 113,775,243	I79N	probably damaging	Het
Jmjd7	T	A	2: 120,031,323	Y182*	probably null	Het
Jup	A	T	11: 100,383,458	D135E	probably benign	Het
Kit	T	A	5: 75,652,808	I881N	probably damaging	Het
Llgl1	T	A	11: 60,702,865	S55T	probably benign	Het
Lonp2	G	A	8: 86,709,096	M653I	probably benign	Het
Med13	A	T	11: 86,278,796	M1914K	possibly damaging	Het
Ms4a1	A	G	19: 11,253,173		probably null	Het
Naip1	A	G	13: 100,427,341	S439P	probably benign	Het
Nrg1	T	C	8: 31,821,264	R476G	probably damaging	Het
Olfr1129	T	A	2: 87,574,918		probably null	Het
Olfr835	G	T	9: 19,035,301	M59I	probably damaging	Het
Pds5b	T	A	5: 150,805,561		probably null	Het
Phf12	G	A	11: 78,027,373	G804R	probably damaging	Het
Pou6f2	T	C	13: 18,239,489	T234A		Het
Prune2	A	T	19: 17,120,590	I1153L	probably benign	Het
Ptprc	C	T	1: 138,067,885		probably null	Het
Qpctl	T	C	7: 19,149,154	Q11R	probably benign	Het
Rfx4	A	G	10: 84,840,228	K103E	possibly damaging	Het
Srcin1	T	A	11: 97,551,980		probably null	Het
St6galnac1	G	T	11: 116,768,944	A181D	probably damaging	Het
Stk36	T	C	1: 74,622,239	V475A	probably benign	Het
Tbc1d21	T	C	9: 58,361,288	T263A	possibly damaging	Het
Tex24	A	T	8: 27,345,000	K185N	probably damaging	Het
Tnxb	T	A	17: 34,698,153	V2174E	possibly damaging	Het
Tollip	A	G	7: 141,890,845	S57P	probably benign	Het
Zbtb49	A	G	5: 38,213,241		probably benign	Het
Zfp758	A	G	17: 22,361,669	T30A	probably benign	Het

Other mutations in Lrp8

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01308:Lrp8	APN	4	107864076	missense	probably benign	0.04
IGL01514:Lrp8	APN	4	107855684	missense	probably damaging	1.00
IGL02058:Lrp8	APN	4	107870109	missense	probably benign	0.25
IGL02398:Lrp8	APN	4	107847494	missense	probably damaging	0.97
IGL02398:Lrp8	APN	4	107869048	missense	probably damaging	1.00
IGL02706:Lrp8	APN	4	107803319	nonsense	probably null
IGL02754:Lrp8	APN	4	107834755	splice site	probably null
IGL02967:Lrp8	APN	4	107861234	missense	probably benign	0.21
IGL03080:Lrp8	APN	4	107855799	missense	probably damaging	1.00
IGL02837:Lrp8	UTSW	4	107861281	missense	probably benign	0.01
R0312:Lrp8	UTSW	4	107806855	intron	probably benign
R0440:Lrp8	UTSW	4	107869098	missense	probably damaging	0.99
R0598:Lrp8	UTSW	4	107857237	missense	possibly damaging	0.73
R1627:Lrp8	UTSW	4	107854416	missense	probably damaging	0.99
R1967:Lrp8	UTSW	4	107859971	missense	probably damaging	1.00
R2183:Lrp8	UTSW	4	107803265	missense	probably damaging	1.00
R2208:Lrp8	UTSW	4	107855790	missense	probably damaging	1.00
R2325:Lrp8	UTSW	4	107864009	missense	probably benign	0.03
R3712:Lrp8	UTSW	4	107848302	missense	probably benign	0.08
R4093:Lrp8	UTSW	4	107843271	nonsense	probably null
R4706:Lrp8	UTSW	4	107861273	missense	probably benign	0.00
R4765:Lrp8	UTSW	4	107854395	missense	probably damaging	1.00
R4840:Lrp8	UTSW	4	107870037	missense	possibly damaging	0.79
R4900:Lrp8	UTSW	4	107806809	intron	probably benign
R5033:Lrp8	UTSW	4	107834755	splice site	probably null
R5280:Lrp8	UTSW	4	107854321	missense	probably damaging	1.00
R5381:Lrp8	UTSW	4	107869110	missense	probably damaging	1.00
R5935:Lrp8	UTSW	4	107857296	missense	probably damaging	1.00
R5972:Lrp8	UTSW	4	107869070	missense	probably damaging	1.00
R6076:Lrp8	UTSW	4	107847459	missense	possibly damaging	0.81
R6343:Lrp8	UTSW	4	107869156	splice site	probably null
R7100:Lrp8	UTSW	4	107802450	missense	possibly damaging	0.93
R7262:Lrp8	UTSW	4	107847464	missense	probably benign
R7717:Lrp8	UTSW	4	107834743	missense	probably benign	0.00
R7949:Lrp8	UTSW	4	107803327	missense	probably damaging	1.00
R8350:Lrp8	UTSW	4	107847464	missense	probably benign
R8371:Lrp8	UTSW	4	107869071	missense	probably damaging	1.00
R9272:Lrp8	UTSW	4	107859961	missense	probably benign	0.19
R9461:Lrp8	UTSW	4	107843318	missense	possibly damaging	0.93
R9567:Lrp8	UTSW	4	107854272	missense	probably damaging	0.99
Z1177:Lrp8	UTSW	4	107843332	missense	probably benign	0.02

Predicted Primers

PCR Primer
(F):5'- TTCTAGCCTGTGAGGTAGGGAC -3'
(R):5'- GATTCCATGTCCCCTGTCAAG -3'

Sequencing Primer
(F):5'- GGACCATCATCCCCACTTCATAGG -3'
(R):5'- TGTCAAGCCCAACTGCC -3'

Posted On

2018-09-12