Incidental Mutation 'R8886:Robo3'
ID 677337
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 068691-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R8886 (G1)
Quality Score 225.009
Status Validated
Chromosome 9
Chromosomal Location 37327341-37344730 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 37328768 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Glutamic Acid to Glycine at position 1276 (E1276G)
Ref Sequence ENSEMBL: ENSMUSP00000110690 (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 probably damaging
Transcript: ENSMUST00000034643
AA Change: E1254G

PolyPhen 2 Score 0.980 (Sensitivity: 0.75; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000034643
Gene: ENSMUSG00000032128
AA Change: E1254G

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 probably damaging
Transcript: ENSMUST00000115038
AA Change: E1276G

PolyPhen 2 Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000110690
Gene: ENSMUSG00000032128
AA Change: E1276G

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 probably damaging
Transcript: ENSMUST00000170512
AA Change: E1254G

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
Predicted Effect probably benign
Transcript: ENSMUST00000214185
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.6%
  • 20x: 98.8%
Validation Efficiency 99% (72/73)
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: 71 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700025G04Rik T A 1: 151,882,349 (GRCm39) N14I possibly damaging Het
1700066M21Rik T A 1: 57,422,008 (GRCm39) I128N probably damaging Het
4930407I10Rik G T 15: 81,950,051 (GRCm39) S1316I probably damaging Het
Abcc9 T C 6: 142,546,420 (GRCm39) probably benign Het
Adgrb3 A G 1: 25,150,928 (GRCm39) S1102P probably damaging Het
BC061237 A C 14: 44,741,691 (GRCm39) I145L probably benign Het
Birc7 A T 2: 180,574,786 (GRCm39) probably benign Het
Boc C T 16: 44,319,806 (GRCm39) G393S Het
Ccdc112 C T 18: 46,444,826 (GRCm39) G18R unknown Het
Cryzl1 T A 16: 91,492,188 (GRCm39) T213S possibly damaging Het
Cttnbp2 T C 6: 18,414,298 (GRCm39) N916D probably benign Het
Cyp4v3 A T 8: 45,774,785 (GRCm39) L123* probably null Het
Dmpk C A 7: 18,825,886 (GRCm39) probably benign Het
Dnah9 A T 11: 65,943,840 (GRCm39) V1932E probably damaging Het
Ect2 T C 3: 27,200,126 (GRCm39) probably benign Het
Eif4a3 A G 11: 119,179,705 (GRCm39) Y361H probably damaging Het
Fkbp10 A G 11: 100,312,862 (GRCm39) E336G probably damaging Het
Gnptg T C 17: 25,453,628 (GRCm39) S305G probably benign Het
Greb1l A T 18: 10,553,843 (GRCm39) I1615F probably benign Het
Gse1 G A 8: 121,297,470 (GRCm39) R561Q unknown Het
Igkv9-129 T A 6: 67,817,221 (GRCm39) Y108* probably null Het
Igsf10 T A 3: 59,237,410 (GRCm39) T924S probably benign Het
Itgb6 A T 2: 60,458,324 (GRCm39) C476* probably null Het
Itih4 C T 14: 30,617,482 (GRCm39) Q601* probably null Het
Itpk1 G A 12: 102,550,604 (GRCm39) probably benign Het
Itpr3 G A 17: 27,337,651 (GRCm39) probably benign Het
Jakmip3 G A 7: 138,609,171 (GRCm39) E92K probably benign Het
Klhl29 A T 12: 5,187,542 (GRCm39) L274H possibly damaging Het
Klk1b5 T A 7: 43,869,192 (GRCm39) M122K probably damaging Het
Krt84 A G 15: 101,437,221 (GRCm39) I314T possibly damaging Het
Lama2 A T 10: 27,245,157 (GRCm39) probably benign Het
Lmntd1 T C 6: 145,363,152 (GRCm39) T270A probably damaging Het
Mindy4 T C 6: 55,255,223 (GRCm39) L567P probably benign Het
Mt2 A T 8: 94,899,476 (GRCm39) M1L probably damaging Het
Myct1 C T 10: 5,554,208 (GRCm39) T25I probably damaging Het
Myh11 A G 16: 14,052,278 (GRCm39) I396T Het
Naprt T C 15: 75,765,433 (GRCm39) T136A probably damaging Het
Nbea T C 3: 55,966,148 (GRCm39) N438S probably damaging Het
Nckap1 C A 2: 80,339,055 (GRCm39) probably null Het
Nop56 G T 2: 130,117,902 (GRCm39) R126L probably damaging Het
Nts C T 10: 102,320,868 (GRCm39) A74T probably benign Het
Ogfr GGCCAGAGGACCCCAAAAGCCAGGTGGAGCCAGAGGACCCCAAAAGCCAGGTGGAGCCAGAGGACCCCAAAAGCCAGGTGGAGCCAGAGGACCCCAAAAGCCAGGTGGGGCCAGAGGACCCCCAAAGCCAGGTGG GGCCAGAGGACCCCAAAAGCCAGGTGGAGCCAGAGGACCCCAAAAGCCAGGTGGAGCCAGAGGACCCCAAAAGCCAGGTGGGGCCAGAGGACCCCCAAAGCCAGGTGG 2: 180,237,059 (GRCm39) probably benign Het
Or8b49 T G 9: 38,506,446 (GRCm39) F310V possibly damaging Het
Pcp2 A G 8: 3,675,208 (GRCm39) probably null Het
Pdgfra T C 5: 75,343,734 (GRCm39) S752P probably benign Het
Pign C T 1: 105,512,779 (GRCm39) V635I probably benign Het
Plekhg3 C A 12: 76,611,748 (GRCm39) H342Q possibly damaging Het
Ppp4c A T 7: 126,386,466 (GRCm39) I177N probably damaging Het
Psmd5 A G 2: 34,747,755 (GRCm39) F301L possibly damaging Het
Rad52 C T 6: 119,890,041 (GRCm39) R56C probably damaging Het
Rbm20 A T 19: 53,801,767 (GRCm39) I92L probably benign Het
Rnf213 A G 11: 119,364,264 (GRCm39) D4522G Het
Rxrb T C 17: 34,256,428 (GRCm39) F500L probably damaging Het
Sar1a A T 10: 61,522,172 (GRCm39) N88I possibly damaging Het
Scd3 A G 19: 44,230,276 (GRCm39) D353G probably damaging Het
Sh2d4b T C 14: 40,595,946 (GRCm39) probably benign Het
Ski A T 4: 155,244,016 (GRCm39) L498Q probably null Het
Spocd1 T A 4: 129,845,631 (GRCm39) M497K Het
Sspo A G 6: 48,458,201 (GRCm39) E3299G possibly damaging Het
St14 C A 9: 31,008,420 (GRCm39) V507F possibly damaging Het
Tcf24 G A 1: 10,037,388 (GRCm39) T108I probably benign Het
Tecta T C 9: 42,278,359 (GRCm39) T1050A probably benign Het
Ttc17 T C 2: 94,205,473 (GRCm39) D291G probably benign Het
Tubgcp2 G T 7: 139,584,882 (GRCm39) R518S probably benign Het
Ugt2a3 T C 5: 87,484,358 (GRCm39) Y222C probably damaging Het
Unc5c C G 3: 141,509,581 (GRCm39) A687G probably benign Het
Usp42 T C 5: 143,700,714 (GRCm39) D1103G probably damaging Het
Vmn1r83 A C 7: 12,055,843 (GRCm39) D71E probably benign Het
Vmn2r3 T A 3: 64,194,892 (GRCm39) I9F possibly damaging Het
Zfand1 T C 3: 10,409,862 (GRCm39) Q160R probably null Het
Zhx3 T C 2: 160,623,216 (GRCm39) N317S 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
R1677:Robo3 UTSW 9 37,329,005 (GRCm39) missense possibly damaging 0.75
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
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'- TTGGGACTTCTGCAAGCCTC -3'
(R):5'- TACAGAAGGGAGCACAGTCC -3'

Sequencing Primer
(F):5'- GACTTCTGCAAGCCTCCAGTC -3'
(R):5'- AACCCTAGGCCTGGGAGATG -3'
Posted On 2021-08-02