Incidental Mutation 'R1677:Robo3'
ID 188193
Institutional Source Beutler Lab
Gene Symbol Robo3
Ensembl Gene ENSMUSG00000032128
Gene Name roundabout guidance receptor 3
Synonyms Robo3a, Rbig1, Rig1, Rig-1, Robo3b
MMRRC Submission 039713-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R1677 (G1)
Quality Score 225
Status Validated
Chromosome 9
Chromosomal Location 37327341-37344730 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 37329005 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Arginine to Glycine at position 1238 (R1238G)
Ref Sequence ENSEMBL: ENSMUSP00000150639 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000034643] [ENSMUST00000102895] [ENSMUST00000115038] [ENSMUST00000115046] [ENSMUST00000115048] [ENSMUST00000156972] [ENSMUST00000170512] [ENSMUST00000214185]
AlphaFold no structure available at present
Predicted Effect possibly damaging
Transcript: ENSMUST00000034643
AA Change: R1238G

PolyPhen 2 Score 0.629 (Sensitivity: 0.87; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000034643
Gene: ENSMUSG00000032128
AA Change: R1238G

DomainStartEndE-ValueType
IGc2 54 128 9.7e-11 SMART
IGc2 156 221 1.44e-4 SMART
IGc2 248 311 1.89e-13 SMART
IGc2 337 409 9.84e-12 SMART
IGc2 441 506 2.09e-15 SMART
FN3 534 616 4.24e-14 SMART
FN3 648 731 3.06e0 SMART
FN3 747 832 1.97e-9 SMART
low complexity region 870 890 N/A INTRINSIC
low complexity region 1055 1082 N/A INTRINSIC
low complexity region 1131 1149 N/A INTRINSIC
low complexity region 1155 1169 N/A INTRINSIC
low complexity region 1193 1206 N/A INTRINSIC
low complexity region 1245 1256 N/A INTRINSIC
low complexity region 1268 1281 N/A INTRINSIC
low complexity region 1336 1376 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000102895
SMART Domains Protein: ENSMUSP00000099959
Gene: ENSMUSG00000032125

DomainStartEndE-ValueType
signal peptide 1 37 N/A INTRINSIC
IG 48 144 2.51e0 SMART
IGc2 160 225 6.86e-11 SMART
FN3 263 343 2.05e0 SMART
FN3 358 440 1.27e-3 SMART
low complexity region 488 494 N/A INTRINSIC
low complexity region 544 562 N/A INTRINSIC
low complexity region 720 733 N/A INTRINSIC
low complexity region 748 762 N/A INTRINSIC
low complexity region 775 799 N/A INTRINSIC
low complexity region 855 866 N/A INTRINSIC
low complexity region 871 880 N/A INTRINSIC
Predicted Effect possibly damaging
Transcript: ENSMUST00000115038
AA Change: R1260G

PolyPhen 2 Score 0.629 (Sensitivity: 0.87; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000110690
Gene: ENSMUSG00000032128
AA Change: R1260G

DomainStartEndE-ValueType
low complexity region 34 47 N/A INTRINSIC
IGc2 76 150 9.7e-11 SMART
IGc2 178 243 1.44e-4 SMART
IGc2 270 333 1.89e-13 SMART
IGc2 359 431 9.84e-12 SMART
IGc2 463 528 2.09e-15 SMART
FN3 556 638 4.24e-14 SMART
FN3 670 753 3.06e0 SMART
FN3 769 854 1.97e-9 SMART
low complexity region 892 912 N/A INTRINSIC
low complexity region 1077 1104 N/A INTRINSIC
low complexity region 1153 1171 N/A INTRINSIC
low complexity region 1177 1191 N/A INTRINSIC
low complexity region 1215 1228 N/A INTRINSIC
low complexity region 1267 1278 N/A INTRINSIC
low complexity region 1290 1303 N/A INTRINSIC
low complexity region 1358 1398 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000115046
SMART Domains Protein: ENSMUSP00000110698
Gene: ENSMUSG00000032125

DomainStartEndE-ValueType
signal peptide 1 37 N/A INTRINSIC
IG 48 144 2.51e0 SMART
IGc2 160 225 6.86e-11 SMART
FN3 263 343 2.05e0 SMART
FN3 358 440 1.27e-3 SMART
low complexity region 484 500 N/A INTRINSIC
low complexity region 540 546 N/A INTRINSIC
low complexity region 596 614 N/A INTRINSIC
low complexity region 747 756 N/A INTRINSIC
low complexity region 779 792 N/A INTRINSIC
low complexity region 807 821 N/A INTRINSIC
low complexity region 834 858 N/A INTRINSIC
low complexity region 914 925 N/A INTRINSIC
low complexity region 930 939 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000115048
SMART Domains Protein: ENSMUSP00000110700
Gene: ENSMUSG00000032125

DomainStartEndE-ValueType
signal peptide 1 37 N/A INTRINSIC
IG 48 144 2.51e0 SMART
IGc2 160 225 6.86e-11 SMART
FN3 263 343 2.05e0 SMART
FN3 358 440 1.27e-3 SMART
low complexity region 488 494 N/A INTRINSIC
low complexity region 544 562 N/A INTRINSIC
low complexity region 695 704 N/A INTRINSIC
low complexity region 727 740 N/A INTRINSIC
low complexity region 755 769 N/A INTRINSIC
low complexity region 782 806 N/A INTRINSIC
low complexity region 862 873 N/A INTRINSIC
low complexity region 878 887 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000156972
Predicted Effect noncoding transcript
Transcript: ENSMUST00000167089
Predicted Effect noncoding transcript
Transcript: ENSMUST00000171467
Predicted Effect possibly damaging
Transcript: ENSMUST00000170512
AA Change: R1238G

PolyPhen 2 Score 0.745 (Sensitivity: 0.85; Specificity: 0.92)
Predicted Effect noncoding transcript
Transcript: ENSMUST00000167216
Predicted Effect noncoding transcript
Transcript: ENSMUST00000215777
Predicted Effect probably benign
Transcript: ENSMUST00000214185
Meta Mutation Damage Score 0.0944 question?
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.3%
  • 10x: 96.3%
  • 20x: 92.6%
Validation Efficiency 100% (95/95)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is a member of the Roundabout (ROBO) gene family that controls neurite outgrowth, growth cone guidance, and axon fasciculation. ROBO proteins are a subfamily of the immunoglobulin transmembrane receptor superfamily. SLIT proteins 1-3, a family of secreted chemorepellants, are ligands for ROBO proteins and SLIT/ROBO interactions regulate myogenesis, leukocyte migration, kidney morphogenesis, angiogenesis, and vasculogenesis in addition to neurogenesis. This gene, ROBO3, has a putative extracellular domain with five immunoglobulin (Ig)-like loops and three fibronectin (Fn) type III motifs, a transmembrane segment, and a cytoplasmic tail with three conserved signaling motifs: CC0, CC2, and CC3 (CC for conserved cytoplasmic). Unlike other ROBO family members, ROBO3 lacks motif CC1. The ROBO3 gene regulates axonal navigation at the ventral midline of the neural tube. In mouse, loss of Robo3 results in a complete failure of commissural axons to cross the midline throughout the spinal cord and the hindbrain. Mutations ROBO3 result in horizontal gaze palsy with progressive scoliosis (HGPPS); an autosomal recessive disorder characterized by congenital absence of horizontal gaze, progressive scoliosis, and failure of the corticospinal and somatosensory axon tracts to cross the midline in the medulla. Alternative transcript variants have been described but have not been experimentally validated. [provided by RefSeq, Dec 2009]
PHENOTYPE: Homozygous mutants display perinatal lethality, abnormal commissural axon growth, and fragile floor plates. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 90 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700093K21Rik A T 11: 23,467,357 (GRCm39) M92K probably benign Het
4931406C07Rik T C 9: 15,212,660 (GRCm39) probably null Het
A430005L14Rik G A 4: 154,045,357 (GRCm39) V129M probably damaging Het
Actg2 T C 6: 83,499,801 (GRCm39) T150A possibly damaging Het
Actn1 A T 12: 80,306,806 (GRCm39) D20E probably benign Het
Alcam C T 16: 52,091,136 (GRCm39) E461K probably damaging Het
Anapc1 G A 2: 128,518,128 (GRCm39) P242L probably benign Het
Ankrd49 A T 9: 14,692,674 (GRCm39) D163E probably benign Het
Atp8b5 G A 4: 43,372,903 (GRCm39) R1149Q possibly damaging Het
Cacnb3 G T 15: 98,540,455 (GRCm39) V328F probably damaging Het
Camk4 T C 18: 33,309,275 (GRCm39) I226T probably damaging Het
Ccdc148 T C 2: 58,892,176 (GRCm39) D172G probably damaging Het
Cdh12 A G 15: 21,520,491 (GRCm39) I319V probably damaging Het
Cenpc1 T C 5: 86,209,857 (GRCm39) probably benign Het
Cfap69 A C 5: 5,632,457 (GRCm39) N15K probably damaging Het
Ckap2l A C 2: 129,127,087 (GRCm39) S364A possibly damaging Het
Clic6 G A 16: 92,324,972 (GRCm39) G36R probably damaging Het
Col6a3 T C 1: 90,749,583 (GRCm39) Y417C probably benign Het
Cstf3 T A 2: 104,494,623 (GRCm39) probably benign Het
Cyp4f39 G A 17: 32,711,304 (GRCm39) A484T probably benign Het
Dnah3 T C 7: 119,527,963 (GRCm39) N3829D probably damaging Het
Dntt C A 19: 41,017,923 (GRCm39) P16T probably benign Het
Dym T A 18: 75,258,583 (GRCm39) I447N probably damaging Het
Elmo1 T C 13: 20,773,841 (GRCm39) V617A probably benign Het
Elovl7 G A 13: 108,419,160 (GRCm39) G264D probably damaging Het
Epha7 T A 4: 28,947,571 (GRCm39) Y610* probably null Het
Fn1 T C 1: 71,636,814 (GRCm39) I178V probably benign Het
Fndc9 T C 11: 46,129,152 (GRCm39) Y224H probably benign Het
Gad1 T C 2: 70,404,521 (GRCm39) V137A probably damaging Het
Gapvd1 A G 2: 34,590,773 (GRCm39) probably null Het
Gbp11 C T 5: 105,475,277 (GRCm39) C357Y probably damaging Het
Gcc1 G A 6: 28,419,163 (GRCm39) A390V probably benign Het
Gm6811 A G 17: 21,314,185 (GRCm39) noncoding transcript Het
Htt A T 5: 34,985,918 (GRCm39) D1063V probably damaging Het
Igfn1 C T 1: 135,898,839 (GRCm39) A576T probably damaging Het
Il12rb2 T C 6: 67,280,485 (GRCm39) Y240C probably damaging Het
Itga3 T C 11: 94,946,585 (GRCm39) D747G probably damaging Het
Kcnip2 A C 19: 45,782,979 (GRCm39) D134E probably damaging Het
Kif2b C A 11: 91,466,798 (GRCm39) R495I probably damaging Het
Lef1 T C 3: 130,993,938 (GRCm39) probably benign Het
Lias C T 5: 65,548,981 (GRCm39) R4C probably damaging Het
Lpcat2 T C 8: 93,591,560 (GRCm39) V68A probably benign Het
Lrrc37 A T 11: 103,505,768 (GRCm39) S2067T probably benign Het
Lrrc8e A T 8: 4,284,190 (GRCm39) K138N probably damaging Het
Map4k5 G A 12: 69,852,082 (GRCm39) H767Y probably benign Het
Mga C A 2: 119,791,333 (GRCm39) T2406K possibly damaging Het
Mtx1 A T 3: 89,116,648 (GRCm39) S418T probably benign Het
Myh7 C T 14: 55,224,973 (GRCm39) M531I probably benign Het
Myorg C T 4: 41,497,947 (GRCm39) R561H probably benign Het
Ncaph2 T A 15: 89,255,427 (GRCm39) M555K probably damaging Het
Nckap1 C T 2: 80,348,286 (GRCm39) S889N probably benign Het
Ncoa6 T C 2: 155,244,584 (GRCm39) probably benign Het
Nrp2 A G 1: 62,822,479 (GRCm39) S691G probably benign Het
Odad2 T C 18: 7,222,554 (GRCm39) T572A probably benign Het
Odf2l A T 3: 144,845,543 (GRCm39) probably null Het
Or5aq6 T A 2: 86,923,081 (GRCm39) H220L probably benign Het
Pcdh20 A G 14: 88,705,410 (GRCm39) V630A probably damaging Het
Pebp4 T C 14: 70,285,923 (GRCm39) probably null Het
Ppfia3 T A 7: 45,006,090 (GRCm39) M301L probably benign Het
Ppp1r21 C A 17: 88,858,097 (GRCm39) Q203K probably benign Het
Prr23a1 T C 9: 98,725,406 (GRCm39) V256A probably benign Het
Rbfox1 A G 16: 7,110,091 (GRCm39) R150G possibly damaging Het
Rnps1-ps A T 6: 7,982,943 (GRCm39) noncoding transcript Het
Rp9 T G 9: 22,365,097 (GRCm39) Q35P probably damaging Het
Rsrc1 C A 3: 67,262,808 (GRCm39) A254E probably damaging Het
Shtn1 T A 19: 58,998,222 (GRCm39) K390N probably damaging Het
Sidt2 C T 9: 45,864,517 (GRCm39) V71I probably benign Het
Sirt7 A G 11: 120,515,365 (GRCm39) V97A possibly damaging Het
Slc14a2 A G 18: 78,206,419 (GRCm39) S466P probably benign Het
Slc2a10 T A 2: 165,357,361 (GRCm39) D340E probably benign Het
Slc36a2 A C 11: 55,075,735 (GRCm39) N17K probably benign Het
Slc4a10 A C 2: 62,155,071 (GRCm39) N1086T probably benign Het
Sptb T C 12: 76,676,423 (GRCm39) D177G probably damaging Het
Srpk2 A T 5: 23,730,748 (GRCm39) probably null Het
Sucla2 T G 14: 73,830,121 (GRCm39) V386G probably damaging Het
Susd1 G T 4: 59,424,089 (GRCm39) N45K possibly damaging Het
Tbxas1 T C 6: 38,994,822 (GRCm39) probably benign Het
Topors C T 4: 40,261,776 (GRCm39) E503K probably damaging Het
Trpv5 T C 6: 41,634,731 (GRCm39) R533G probably benign Het
Tshr A G 12: 91,504,115 (GRCm39) H351R possibly damaging Het
Ube2f G A 1: 91,203,037 (GRCm39) V94M probably damaging Het
Ugdh A G 5: 65,580,521 (GRCm39) S216P probably damaging Het
Unc45b T A 11: 82,802,531 (GRCm39) probably null Het
Vmn1r226 A G 17: 20,908,335 (GRCm39) E189G probably damaging Het
Xrcc6 T G 15: 81,913,900 (GRCm39) D75E probably benign Het
Ypel1 A G 16: 16,921,474 (GRCm39) L70P probably damaging Het
Zcwpw1 A T 5: 137,795,022 (GRCm39) R73W probably damaging Het
Zfp219 T C 14: 52,246,512 (GRCm39) E160G probably damaging Het
Zfp804b G T 5: 7,229,533 (GRCm39) probably benign Het
Zscan22 C A 7: 12,640,730 (GRCm39) P325T probably damaging Het
Other mutations in Robo3
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00927:Robo3 APN 9 37,339,050 (GRCm39) critical splice donor site probably null
IGL01023:Robo3 APN 9 37,340,847 (GRCm39) missense probably damaging 1.00
IGL01431:Robo3 APN 9 37,330,407 (GRCm39) unclassified probably benign
IGL01993:Robo3 APN 9 37,335,949 (GRCm39) missense probably damaging 1.00
IGL02256:Robo3 APN 9 37,336,649 (GRCm39) missense probably damaging 1.00
IGL02323:Robo3 APN 9 37,333,497 (GRCm39) missense probably benign 0.05
IGL02561:Robo3 APN 9 37,338,387 (GRCm39) missense possibly damaging 0.84
IGL02866:Robo3 APN 9 37,333,602 (GRCm39) missense possibly damaging 0.89
IGL02897:Robo3 APN 9 37,338,798 (GRCm39) nonsense probably null
IGL03003:Robo3 APN 9 37,330,587 (GRCm39) missense probably damaging 1.00
IGL03307:Robo3 APN 9 37,333,860 (GRCm39) missense probably damaging 0.96
IGL03097:Robo3 UTSW 9 37,333,824 (GRCm39) critical splice donor site probably null
R0137:Robo3 UTSW 9 37,336,640 (GRCm39) missense probably benign 0.00
R0266:Robo3 UTSW 9 37,333,936 (GRCm39) missense probably damaging 0.96
R0390:Robo3 UTSW 9 37,333,473 (GRCm39) missense probably benign 0.00
R0505:Robo3 UTSW 9 37,328,055 (GRCm39) unclassified probably benign
R0815:Robo3 UTSW 9 37,333,479 (GRCm39) missense probably damaging 1.00
R0924:Robo3 UTSW 9 37,340,778 (GRCm39) splice site probably benign
R1167:Robo3 UTSW 9 37,335,203 (GRCm39) nonsense probably null
R1203:Robo3 UTSW 9 37,329,978 (GRCm39) missense probably damaging 1.00
R1451:Robo3 UTSW 9 37,329,007 (GRCm39) missense probably benign 0.01
R1575:Robo3 UTSW 9 37,340,957 (GRCm39) missense probably damaging 1.00
R1596:Robo3 UTSW 9 37,335,928 (GRCm39) critical splice donor site probably null
R1660:Robo3 UTSW 9 37,340,440 (GRCm39) missense probably damaging 1.00
R1839:Robo3 UTSW 9 37,333,623 (GRCm39) missense probably benign 0.00
R1878:Robo3 UTSW 9 37,333,461 (GRCm39) missense probably damaging 1.00
R1891:Robo3 UTSW 9 37,339,351 (GRCm39) missense probably damaging 1.00
R2040:Robo3 UTSW 9 37,338,760 (GRCm39) missense probably damaging 1.00
R2859:Robo3 UTSW 9 37,339,400 (GRCm39) nonsense probably null
R3786:Robo3 UTSW 9 37,333,521 (GRCm39) missense probably damaging 1.00
R3886:Robo3 UTSW 9 37,333,477 (GRCm39) nonsense probably null
R3888:Robo3 UTSW 9 37,333,477 (GRCm39) nonsense probably null
R3910:Robo3 UTSW 9 37,330,591 (GRCm39) missense probably damaging 1.00
R4212:Robo3 UTSW 9 37,333,194 (GRCm39) missense probably damaging 1.00
R4213:Robo3 UTSW 9 37,333,194 (GRCm39) missense probably damaging 1.00
R4691:Robo3 UTSW 9 37,336,514 (GRCm39) missense probably damaging 0.99
R4979:Robo3 UTSW 9 37,334,640 (GRCm39) missense probably damaging 1.00
R5238:Robo3 UTSW 9 37,328,175 (GRCm39) missense probably damaging 0.99
R5570:Robo3 UTSW 9 37,336,571 (GRCm39) missense possibly damaging 0.81
R5629:Robo3 UTSW 9 37,330,507 (GRCm39) nonsense probably null
R5770:Robo3 UTSW 9 37,330,497 (GRCm39) missense possibly damaging 0.87
R5837:Robo3 UTSW 9 37,341,112 (GRCm39) critical splice acceptor site probably null
R6021:Robo3 UTSW 9 37,333,829 (GRCm39) nonsense probably null
R6129:Robo3 UTSW 9 37,334,589 (GRCm39) missense probably benign
R6232:Robo3 UTSW 9 37,332,225 (GRCm39) missense probably damaging 1.00
R6233:Robo3 UTSW 9 37,332,225 (GRCm39) missense probably damaging 1.00
R6235:Robo3 UTSW 9 37,332,225 (GRCm39) missense probably damaging 1.00
R6326:Robo3 UTSW 9 37,338,323 (GRCm39) missense probably damaging 1.00
R6354:Robo3 UTSW 9 37,328,513 (GRCm39) unclassified probably benign
R6355:Robo3 UTSW 9 37,330,235 (GRCm39) missense possibly damaging 0.71
R6475:Robo3 UTSW 9 37,334,586 (GRCm39) missense probably damaging 0.99
R6937:Robo3 UTSW 9 37,341,176 (GRCm39) missense probably benign 0.16
R7201:Robo3 UTSW 9 37,335,626 (GRCm39) nonsense probably null
R7208:Robo3 UTSW 9 37,336,020 (GRCm39) missense probably damaging 0.99
R7249:Robo3 UTSW 9 37,336,129 (GRCm39) missense probably benign
R7376:Robo3 UTSW 9 37,344,212 (GRCm39) missense probably damaging 1.00
R7380:Robo3 UTSW 9 37,329,852 (GRCm39) missense probably damaging 1.00
R7448:Robo3 UTSW 9 37,336,111 (GRCm39) missense possibly damaging 0.89
R7475:Robo3 UTSW 9 37,336,674 (GRCm39) missense probably benign 0.01
R7496:Robo3 UTSW 9 37,339,121 (GRCm39) missense probably damaging 1.00
R7587:Robo3 UTSW 9 37,340,942 (GRCm39) missense probably damaging 1.00
R7694:Robo3 UTSW 9 37,329,816 (GRCm39) missense probably benign 0.14
R8381:Robo3 UTSW 9 37,341,056 (GRCm39) missense probably damaging 1.00
R8464:Robo3 UTSW 9 37,332,726 (GRCm39) missense probably damaging 1.00
R8495:Robo3 UTSW 9 37,336,664 (GRCm39) missense probably damaging 1.00
R8886:Robo3 UTSW 9 37,328,768 (GRCm39) missense probably damaging 0.99
R9422:Robo3 UTSW 9 37,329,789 (GRCm39) missense probably benign 0.03
R9563:Robo3 UTSW 9 37,340,900 (GRCm39) missense probably damaging 1.00
R9564:Robo3 UTSW 9 37,340,900 (GRCm39) missense probably damaging 1.00
R9681:Robo3 UTSW 9 37,339,087 (GRCm39) missense probably benign 0.45
R9681:Robo3 UTSW 9 37,334,558 (GRCm39) missense possibly damaging 0.75
X0024:Robo3 UTSW 9 37,339,151 (GRCm39) missense probably damaging 1.00
X0027:Robo3 UTSW 9 37,339,121 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- GGACTATTGGGACTTCTGCAAGCC -3'
(R):5'- CCGGGTGAGTCTGATGAAATTCAGC -3'

Sequencing Primer
(F):5'- TCTAGGGAAGACATGCTGCC -3'
(R):5'- GATGAAATTCAGCTTGCTTCCAC -3'
Posted On 2014-05-09