Incidental Mutation 'R6233:Robo3'
ID 504760
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 044361-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R6233 (G1)
Quality Score 203.009
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: 98.2%
  • 20x: 94.8%
Validation Efficiency 98% (79/81)
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: 79 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Acvr1 T A 2: 58,338,411 (GRCm39) N437I probably benign Het
Adam34l T G 8: 44,078,949 (GRCm39) N425T probably benign Het
Adgrg7 T A 16: 56,599,005 (GRCm39) T57S possibly damaging Het
Agbl2 T A 2: 90,643,657 (GRCm39) D792E probably benign Het
Ankrd9 A T 12: 110,943,554 (GRCm39) I160N probably damaging Het
Aoc1l2 A G 6: 48,907,899 (GRCm39) T300A probably benign Het
Baz2b T A 2: 59,737,855 (GRCm39) Q1818L possibly damaging Het
Bod1 A G 11: 31,616,740 (GRCm39) *174Q probably null Het
Cacna1a A G 8: 85,315,382 (GRCm39) Y1539C probably damaging Het
Clmn A C 12: 104,751,714 (GRCm39) L247R probably damaging Het
Cyp1b1 G T 17: 80,021,695 (GRCm39) L16M probably damaging Het
Dhrs7l T C 12: 72,666,341 (GRCm39) Y110C probably damaging Het
Dhx29 T A 13: 113,101,071 (GRCm39) S1205T probably benign Het
Dmkn C A 7: 30,479,104 (GRCm39) A280E probably damaging Het
Dnah7b G A 1: 46,243,429 (GRCm39) D1578N probably damaging Het
Dnase1l1 C T X: 73,320,644 (GRCm39) probably null Homo
Dsc3 C T 18: 20,098,852 (GRCm39) G776R possibly damaging Het
Eefsec A G 6: 88,335,526 (GRCm39) probably null Het
Efhb A G 17: 53,769,580 (GRCm39) F243S possibly damaging Het
Eif2ak2 A T 17: 79,178,662 (GRCm39) Y137* probably null Het
Eny2 A G 15: 44,297,056 (GRCm39) probably null Het
F2rl3 A G 8: 73,489,513 (GRCm39) T247A probably benign Het
Fan1 A T 7: 64,004,119 (GRCm39) H782Q probably damaging Het
Fbxo28 A G 1: 182,169,073 (GRCm39) S22P unknown Het
Fcgbpl1 T C 7: 27,830,885 (GRCm39) C33R probably damaging Het
Fcrlb A G 1: 170,736,458 (GRCm39) I106T probably damaging Het
Fer1l5 T C 1: 36,414,367 (GRCm39) probably null Het
Fgfbp1 T C 5: 44,136,704 (GRCm39) D196G possibly damaging Het
Gab1 A T 8: 81,606,161 (GRCm39) Y24* probably null Het
Gcc2 T C 10: 58,106,806 (GRCm39) S681P probably damaging Het
Git2 T C 5: 114,905,175 (GRCm39) N94S probably benign Het
Gm5799 T G 14: 43,782,088 (GRCm39) L87V probably damaging Het
Gna12 A G 5: 140,746,447 (GRCm39) F333L possibly damaging Het
Gria2 A G 3: 80,614,510 (GRCm39) I510T probably damaging Het
Hace1 T A 10: 45,546,539 (GRCm39) I391N possibly damaging Het
Il1rap A G 16: 26,529,256 (GRCm39) T310A probably benign Het
Itpr3 T C 17: 27,305,934 (GRCm39) I164T probably damaging Het
Kcnk4 T C 19: 6,905,697 (GRCm39) N90S probably benign Het
Krt40 G A 11: 99,433,920 (GRCm39) A22V possibly damaging Het
Lamc1 A T 1: 153,099,412 (GRCm39) D1520E probably benign Het
Lrrc37 A T 11: 103,504,214 (GRCm39) L2585I probably damaging Het
Mipep T A 14: 61,109,554 (GRCm39) W644R probably damaging Het
Mycl A G 4: 122,893,713 (GRCm39) D171G probably damaging Het
Myh7b C T 2: 155,473,719 (GRCm39) A1584V possibly damaging Het
Nf1 A G 11: 79,456,801 (GRCm39) Y629C probably damaging Het
Obscn T A 11: 58,888,033 (GRCm39) E2164V probably damaging Het
Or52h1 A T 7: 103,828,961 (GRCm39) V218D possibly damaging Het
Or5b118 T C 19: 13,449,104 (GRCm39) Y257H probably damaging Het
Or5w19 T C 2: 87,698,904 (GRCm39) S190P possibly damaging Het
Or6c209 T C 10: 129,483,165 (GRCm39) M56T probably benign Het
Or8k25 T C 2: 86,243,551 (GRCm39) I282V probably damaging Het
Pcdh20 T C 14: 88,705,488 (GRCm39) E604G probably benign Het
Pilra T C 5: 137,821,763 (GRCm39) T291A possibly damaging Het
Ppp1r9a G T 6: 5,077,610 (GRCm39) D630Y probably damaging Het
Pros1 A C 16: 62,719,284 (GRCm39) Q102P possibly damaging Het
Rad21l T C 2: 151,495,462 (GRCm39) D407G probably benign Het
Rapgef5 G A 12: 117,703,453 (GRCm39) probably null Het
Rbm25 G A 12: 83,706,200 (GRCm39) A182T probably benign Het
Rnf13 A G 3: 57,740,391 (GRCm39) E236G possibly damaging Het
Rsrp1 T A 4: 134,654,113 (GRCm39) I255K probably damaging Het
Scn1a T A 2: 66,107,962 (GRCm39) Y1588F possibly damaging Het
Sdr16c6 T A 4: 4,069,984 (GRCm39) I119F probably damaging Het
Shoc1 T A 4: 59,076,245 (GRCm39) D566V possibly damaging Het
Slc12a7 T C 13: 73,953,590 (GRCm39) S767P possibly damaging Het
Slc23a1 A G 18: 35,757,497 (GRCm39) I258T probably damaging Het
Spata13 G A 14: 60,929,456 (GRCm39) R338H probably benign Het
Sufu G A 19: 46,464,071 (GRCm39) G428R probably damaging Het
Sult2a1 T C 7: 13,566,600 (GRCm39) D125G probably damaging Het
Tapbp T C 17: 34,138,956 (GRCm39) L41P probably damaging Het
Tbc1d16 T A 11: 119,101,391 (GRCm39) K40* probably null Het
Tdrd6 A G 17: 43,940,643 (GRCm39) V135A probably damaging Het
Tenm3 A C 8: 48,870,094 (GRCm39) V233G probably damaging Het
Tmem87a A T 2: 120,222,656 (GRCm39) probably null Het
Tspan11 T C 6: 127,915,227 (GRCm39) Y114H probably damaging Het
Ttn T A 2: 76,567,997 (GRCm39) Y27632F probably benign Het
Usp44 G A 10: 93,686,202 (GRCm39) C539Y probably damaging Het
Vmn2r73 G A 7: 85,519,099 (GRCm39) P508S probably benign Het
Zfp831 A G 2: 174,488,490 (GRCm39) D1055G possibly damaging Het
Zfp871 CCACAC CC 17: 32,994,494 (GRCm39) probably null 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
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'- GAACTGCCCTCTCACTTCCAAG -3'
(R):5'- AGATCTGGAATGACGCTGTCC -3'

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