Incidental Mutation 'R6076:Lrp8'
ID 482733
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 044237-MU
Accession Numbers
Essential gene? Possibly non essential (E-score: 0.477) question?
Stock # R6076 (G1)
Quality Score 225.009
Status Not validated
Chromosome 4
Chromosomal Location 107659337-107734037 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to T at 107704656 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Arginine to Leucine at position 292 (R292L)
Ref Sequence ENSEMBL: ENSMUSP00000030356 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000030356] [ENSMUST00000106732] [ENSMUST00000106733] [ENSMUST00000126573] [ENSMUST00000143601]
AlphaFold Q924X6
Predicted Effect possibly damaging
Transcript: ENSMUST00000030356
AA Change: R292L

PolyPhen 2 Score 0.812 (Sensitivity: 0.84; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000030356
Gene: ENSMUSG00000028613
AA Change: R292L

DomainStartEndE-ValueType
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: R94L
SMART Domains Protein: ENSMUSP00000102342
Gene: ENSMUSG00000028613
AA Change: R94L

DomainStartEndE-ValueType
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 benign
Transcript: ENSMUST00000106732
AA Change: R166L

PolyPhen 2 Score 0.220 (Sensitivity: 0.91; Specificity: 0.88)
SMART Domains Protein: ENSMUSP00000102343
Gene: ENSMUSG00000028613
AA Change: R166L

DomainStartEndE-ValueType
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: R292L

PolyPhen 2 Score 0.152 (Sensitivity: 0.92; Specificity: 0.87)
SMART Domains Protein: ENSMUSP00000102344
Gene: ENSMUSG00000028613
AA Change: R292L

DomainStartEndE-ValueType
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 benign
Transcript: ENSMUST00000126573
AA Change: R165L

PolyPhen 2 Score 0.282 (Sensitivity: 0.91; Specificity: 0.88)
SMART Domains Protein: ENSMUSP00000118020
Gene: ENSMUSG00000028613
AA Change: R165L

DomainStartEndE-ValueType
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 benign
Transcript: ENSMUST00000143601
AA Change: R292L

PolyPhen 2 Score 0.011 (Sensitivity: 0.96; Specificity: 0.78)
SMART Domains Protein: ENSMUSP00000115854
Gene: ENSMUSG00000028613
AA Change: R292L

DomainStartEndE-ValueType
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: ENSMUST00000147319
Predicted Effect noncoding transcript
Transcript: ENSMUST00000135591
Predicted Effect noncoding transcript
Transcript: ENSMUST00000146552
Coding Region Coverage
  • 1x: 99.9%
  • 3x: 99.6%
  • 10x: 98.3%
  • 20x: 95.2%
Validation Efficiency
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: 46 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Ank3 G A 10: 69,838,395 (GRCm39) R1566K possibly damaging Het
Atp6v0a1 T A 11: 100,945,886 (GRCm39) I723N probably damaging Het
C530025M09Rik T C 2: 149,672,670 (GRCm39) probably benign Het
Cdkn1a A G 17: 29,318,332 (GRCm39) K149E probably damaging Het
Cep70 T A 9: 99,180,558 (GRCm39) I571N probably damaging Het
Cimip4 T C 15: 78,270,427 (GRCm39) R114G possibly damaging Het
Col9a1 A T 1: 24,234,457 (GRCm39) probably benign Het
Csde1 G A 3: 102,948,545 (GRCm39) D132N possibly damaging Het
Dlk1 A G 12: 109,425,895 (GRCm39) Q256R probably damaging Het
Epha6 A T 16: 60,026,073 (GRCm39) D456E probably damaging Het
Ephx2 A G 14: 66,330,297 (GRCm39) V354A probably damaging Het
Fpr-rs4 A G 17: 18,242,317 (GRCm39) N108S probably damaging Het
Gimap1 C T 6: 48,719,521 (GRCm39) Q116* probably null Het
Gm10784 T C 13: 50,099,310 (GRCm39) noncoding transcript Het
Grid2ip G C 5: 143,373,130 (GRCm39) S736T probably benign Het
Hic1 T C 11: 75,058,154 (GRCm39) D245G probably damaging Het
Hpcal4 C A 4: 123,084,514 (GRCm39) Q148K probably benign Het
Hspa14 C T 2: 3,512,109 (GRCm39) S55N probably benign Het
Hspa1b G A 17: 35,176,473 (GRCm39) T504I probably damaging Het
Jchain G T 5: 88,675,631 (GRCm39) T3N probably benign Het
Kl C G 5: 150,876,466 (GRCm39) F95L probably damaging Het
Kndc1 A G 7: 139,481,954 (GRCm39) T115A probably damaging Het
Lrrc15 T A 16: 30,091,806 (GRCm39) D511V probably benign Het
Mapk8 A G 14: 33,112,250 (GRCm39) C213R probably damaging Het
Mcph1 C T 8: 18,682,015 (GRCm39) P384L probably benign Het
Mrps7 T C 11: 115,495,713 (GRCm39) S84P probably damaging Het
Nceh1 A C 3: 27,333,344 (GRCm39) I147L probably benign Het
Noxa1 A T 2: 24,975,821 (GRCm39) I409N probably damaging Het
Or1p1c T C 11: 74,161,088 (GRCm39) I291T probably damaging Het
Pkd1 G A 17: 24,800,004 (GRCm39) G2975R probably benign Het
Ppip5k1 T C 2: 121,167,591 (GRCm39) D17G probably null Het
Prex2 T A 1: 11,256,174 (GRCm39) Y1182N probably benign Het
Rasa2 T C 9: 96,427,699 (GRCm39) N722S probably benign Het
Rcc1l A G 5: 134,198,167 (GRCm39) V155A possibly damaging Het
Rest A G 5: 77,430,821 (GRCm39) E1080G unknown Het
Sacs A T 14: 61,441,985 (GRCm39) K1344* probably null Het
Sec16a C T 2: 26,313,954 (GRCm39) E1884K probably damaging Het
Secisbp2 C A 13: 51,833,813 (GRCm39) T651K probably damaging Het
Sema3e A G 5: 14,291,100 (GRCm39) D620G probably benign Het
Slc6a17 A G 3: 107,379,387 (GRCm39) S553P possibly damaging Het
Smpd5 C A 15: 76,179,092 (GRCm39) N153K probably damaging Het
Ube2d4 T A 15: 58,718,992 (GRCm39) noncoding transcript Het
Vps13c A G 9: 67,818,884 (GRCm39) I1102V probably damaging Het
Wdr36 C A 18: 32,979,998 (GRCm39) S241Y probably damaging Het
Wdr7 T A 18: 63,872,348 (GRCm39) D427E probably damaging Het
Zfp945 G A 17: 23,070,432 (GRCm39) P489L probably damaging Het
Other mutations in Lrp8
AlleleSourceChrCoordTypePredicted EffectPPH 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
R5935:Lrp8 UTSW 4 107,714,493 (GRCm39) missense probably damaging 1.00
R5972:Lrp8 UTSW 4 107,726,267 (GRCm39) missense probably damaging 1.00
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'- AAAGCTCGTGTCTGTGCTGAG -3'
(R):5'- TGTGGAAGGGATCATCTCAGAG -3'

Sequencing Primer
(F):5'- AAACTGGAGTGCTGTGTGACC -3'
(R):5'- TCATCTCAGAGTTAGAGGGAGG -3'
Posted On 2017-07-14