Incidental Mutation 'R6235:Robo3'
ID 504876
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 044433-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R6235 (G1)
Quality Score 106.008
Status Validated
Chromosome 9
Chromosomal Location 37327341-37344730 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to G at 37332225 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Tyrosine to Serine at position 891 (Y891S)
Ref Sequence ENSEMBL: ENSMUSP00000150639 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000034643] [ENSMUST00000115038] [ENSMUST00000170512]
AlphaFold no structure available at present
Predicted Effect probably damaging
Transcript: ENSMUST00000034643
AA Change: Y891S

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000034643
Gene: ENSMUSG00000032128
AA Change: Y891S

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 damaging
Transcript: ENSMUST00000115038
AA Change: Y913S

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000110690
Gene: ENSMUSG00000032128
AA Change: Y913S

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 noncoding transcript
Transcript: ENSMUST00000167089
Predicted Effect noncoding transcript
Transcript: ENSMUST00000167216
Predicted Effect probably damaging
Transcript: ENSMUST00000170512
AA Change: Y891S

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
Predicted Effect noncoding transcript
Transcript: ENSMUST00000171467
Meta Mutation Damage Score 0.3105 question?
Coding Region Coverage
  • 1x: 99.9%
  • 3x: 99.7%
  • 10x: 98.4%
  • 20x: 95.4%
Validation Efficiency 95% (73/77)
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: 77 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adam34l T G 8: 44,078,949 (GRCm39) N425T probably benign Het
Adam6b T C 12: 113,455,330 (GRCm39) F716L probably benign Het
Akip1 A G 7: 109,306,620 (GRCm39) M106V probably benign Het
Aldh1l1 A T 6: 90,541,439 (GRCm39) I278F probably benign Het
Aplnr A G 2: 84,967,970 (GRCm39) T332A probably benign Het
Aqp4 A G 18: 15,531,170 (GRCm39) V197A probably damaging Het
Arid4a A T 12: 71,116,546 (GRCm39) probably null Het
Baiap2 A T 11: 119,872,234 (GRCm39) N99Y probably damaging Het
Ceacam1 A T 7: 25,171,217 (GRCm39) probably null Het
Cep78 T C 19: 15,953,850 (GRCm39) probably null Het
Cldn3 T C 5: 135,015,573 (GRCm39) F92S possibly damaging Het
Clec16a C A 16: 10,512,499 (GRCm39) P812Q probably damaging Het
Cnga4 T G 7: 105,056,906 (GRCm39) Y336* probably null Het
Copg2 A G 6: 30,793,006 (GRCm39) I443T probably damaging Het
Crhbp C A 13: 95,580,358 (GRCm39) A81S probably damaging Het
Csad A T 15: 102,087,041 (GRCm39) V410D probably damaging Het
Ctps1 G A 4: 120,416,003 (GRCm39) L207F probably benign Het
Dab2ip A G 2: 35,613,099 (GRCm39) E1003G probably damaging Het
Ddx31 C G 2: 28,734,854 (GRCm39) A5G probably benign Het
Dnah12 A T 14: 26,576,761 (GRCm39) I3004F probably damaging Het
Fbxo15 A G 18: 84,999,029 (GRCm39) probably benign Het
Fbxw28 C A 9: 109,155,258 (GRCm39) W356C probably damaging Het
Gimap6 G T 6: 48,679,391 (GRCm39) T215K probably benign Het
Hspa4 C T 11: 53,153,766 (GRCm39) E702K probably benign Het
Hunk A G 16: 90,229,594 (GRCm39) I152V probably damaging Het
Itk T C 11: 46,227,255 (GRCm39) E456G probably benign Het
Krt40 G A 11: 99,433,920 (GRCm39) A22V possibly damaging Het
Lars2 T C 9: 123,240,945 (GRCm39) V204A probably damaging Het
Lipo3 A G 19: 33,760,963 (GRCm39) Y140H probably damaging Het
Lrp1 G A 10: 127,424,046 (GRCm39) R809W probably damaging Het
Magi3 C T 3: 103,923,384 (GRCm39) G1111D probably damaging Het
Mis18bp1 A T 12: 65,205,182 (GRCm39) V47E probably damaging Het
Mpdz T C 4: 81,303,518 (GRCm39) E140G probably damaging Het
Myo1d T C 11: 80,583,770 (GRCm39) I81V probably benign Het
Nek10 T A 14: 14,821,113 (GRCm38) Y26* probably null Het
Ntng2 C A 2: 29,117,991 (GRCm39) E152D probably damaging Het
Or10w1 C A 19: 13,632,145 (GRCm39) C117* probably null Het
Or5m9b T C 2: 85,905,510 (GRCm39) L142P possibly damaging Het
Otud3 A T 4: 138,629,212 (GRCm39) V185D probably damaging Het
Parp6 C T 9: 59,538,098 (GRCm39) R248W probably benign Het
Pcdhga7 A G 18: 37,849,483 (GRCm39) T497A probably benign Het
Ppp1r18 A G 17: 36,184,769 (GRCm39) E140G probably damaging Het
Prl3b1 T C 13: 27,431,928 (GRCm39) L151P probably damaging Het
Pth1r C T 9: 110,551,384 (GRCm39) E572K possibly damaging Het
Ptprq T A 10: 107,471,199 (GRCm39) T1401S possibly damaging Het
Rad51ap2 A G 12: 11,507,517 (GRCm39) T480A possibly damaging Het
Rax T A 18: 66,068,232 (GRCm39) Q291L unknown Het
Reck T C 4: 43,937,450 (GRCm39) L734P probably damaging Het
Rgmb A G 17: 16,041,081 (GRCm39) F169L probably damaging Het
Rhobtb3 T C 13: 76,041,029 (GRCm39) I426M probably damaging Het
Ring1 C A 17: 34,242,280 (GRCm39) A76S probably damaging Het
Rpusd2 A G 2: 118,865,338 (GRCm39) I12V probably benign Het
Rragd T C 4: 32,995,985 (GRCm39) V165A possibly damaging Het
Rsf1 G GACGGCGGCT 7: 97,229,116 (GRCm39) probably benign Homo
Ryr1 G T 7: 28,815,606 (GRCm39) Q95K probably benign Het
S1pr4 T A 10: 81,334,716 (GRCm39) N253Y possibly damaging Het
Scn3a A C 2: 65,291,679 (GRCm39) V1689G probably damaging Het
Sdhb A G 4: 140,700,984 (GRCm39) N147D probably damaging Het
Sdk1 A T 5: 142,020,181 (GRCm39) H913L possibly damaging Het
Serpina3i T A 12: 104,232,791 (GRCm39) M232K probably damaging Het
Sipa1l2 A T 8: 126,201,610 (GRCm39) V646E probably damaging Het
Slc38a1 A T 15: 96,476,673 (GRCm39) I396N probably benign Het
Slc6a13 A T 6: 121,279,753 (GRCm39) E42D probably benign Het
Stard9 G A 2: 120,544,027 (GRCm39) V4442M probably damaging Het
Sumo3 T A 10: 77,452,071 (GRCm39) probably benign Het
Syngap1 A G 17: 27,177,104 (GRCm39) I356V probably benign Het
Tcam1 C T 11: 106,174,880 (GRCm39) Q112* probably null Het
Tdp2 T A 13: 25,024,378 (GRCm39) L225* probably null Het
Tmprss7 A G 16: 45,478,485 (GRCm39) V747A probably benign Het
Ugt2b34 T A 5: 87,054,223 (GRCm39) Y186F probably benign Het
Usp37 G T 1: 74,514,292 (GRCm39) S293* probably null Het
Vmn1r36 A G 6: 66,693,230 (GRCm39) I109T probably benign Het
Vsig10l T A 7: 43,118,396 (GRCm39) V798E probably benign Het
Zfp36l1 G T 12: 80,159,596 (GRCm39) C18* probably null Het
Zfp959 T C 17: 56,204,427 (GRCm39) Y152H probably damaging Het
Zfyve26 A T 12: 79,296,373 (GRCm39) C1949S probably damaging Het
Zswim9 T A 7: 12,995,529 (GRCm39) E209V 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
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'- GAACTGCCCTCTCACTTCCAAG -3'
(R):5'- AGATCTGGAATGACGCTGTCC -3'

Sequencing Primer
(F):5'- AAGCTTGCTTTCCTCGCTTAG -3'
(R):5'- AATGACGCTGTCCGAGCC -3'
Posted On 2018-02-28