Mutagenetix > Incidental Mutation

Incidental Mutation 'R0390:Robo3'

31611

Institutional Source

Beutler Lab

Gene Symbol

Robo3

Ensembl Gene

ENSMUSG00000032128

Gene Name

roundabout guidance receptor 3

Synonyms

Rig1, Rig-1, Robo3b, Robo3a, Rbig1

MMRRC Submission

038596-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0390 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

37415669-37433246 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 37422177 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 746 (V746A)

Ref Sequence

ENSEMBL: ENSMUSP00000110690 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000034643] [ENSMUST00000115038] [ENSMUST00000170512]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000034643
AA Change: V724A

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000034643
Gene: ENSMUSG00000032128
AA Change: V724A

Domain	Start	End	E-Value	Type
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: ENSMUST00000115038
AA Change: V746A

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000110690
Gene: ENSMUSG00000032128
AA Change: V746A

Domain	Start	End	E-Value	Type
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 benign
Transcript: ENSMUST00000170512
AA Change: V724A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000171467

Meta Mutation Damage Score

0.0898

Coding Region Coverage

1x: 99.1%
3x: 98.1%
10x: 95.9%
20x: 92.0%

Validation Efficiency

98% (110/112)

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: 110 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A730017C20Rik	T	A	18: 59,075,688	V136E	probably damaging	Het
Adam18	C	T	8: 24,674,054	G38R	probably benign	Het
Ap2m1	T	C	16: 20,541,099	M183T	probably damaging	Het
Apob	A	T	12: 7,988,678	I364F	probably damaging	Het
Arl6	A	T	16: 59,622,421		probably benign	Het
Cand2	A	G	6: 115,774,653	M15V	possibly damaging	Het
Cbl	A	G	9: 44,201,005	F131S	probably damaging	Het
Ccdc151	T	A	9: 21,991,708	H442L	probably benign	Het
Ccdc74a	A	G	16: 17,650,476	S321G	probably benign	Het
Cdc14b	T	C	13: 64,210,192		probably benign	Het
Cep152	T	C	2: 125,576,869		probably benign	Het
Cep290	A	G	10: 100,508,758	E479G	probably benign	Het
Chrm2	T	G	6: 36,524,111	I301R	probably benign	Het
Clec2e	A	G	6: 129,093,468	W197R	probably damaging	Het
Cnot10	G	T	9: 114,629,150	S96*	probably null	Het
Col19a1	A	G	1: 24,289,655		probably benign	Het
Csmd2	T	C	4: 128,133,673		probably benign	Het
Cthrc1	A	T	15: 39,086,764	*172L	probably null	Het
Cul9	A	T	17: 46,528,589	I821N	probably benign	Het
Daam1	G	C	12: 71,975,304		probably benign	Het
Dhx58	A	T	11: 100,699,264	I398N	probably damaging	Het
Dip2b	T	A	15: 100,193,913	H844Q	probably damaging	Het
Dmac2	A	G	7: 25,621,029	D50G	probably damaging	Het
Dmxl1	C	A	18: 49,879,362	Q1529K	probably benign	Het
Dtna	C	T	18: 23,597,501	P315L	probably damaging	Het
Ep300	T	C	15: 81,640,116	S1382P	unknown	Het
Fat2	A	T	11: 55,310,777	N490K	probably damaging	Het
Flg2	T	A	3: 93,200,355		probably benign	Het
Gm13084	T	A	4: 143,811,699	D234V	probably benign	Het
Gpatch1	T	C	7: 35,281,381		probably benign	Het
Grin2a	C	A	16: 9,579,585	K879N	possibly damaging	Het
Hacd3	A	C	9: 65,001,022	I164S	possibly damaging	Het
Hinfp	A	C	9: 44,298,948	C197G	probably damaging	Het
Hsd17b12	T	C	2: 94,114,990		probably benign	Het
Hsd3b1	A	T	3: 98,853,039	L212Q	probably damaging	Het
Ifrd1	C	T	12: 40,214,094		probably null	Het
Igf2bp2	A	G	16: 22,081,801	F129L	possibly damaging	Het
Kirrel3	T	A	9: 35,020,163	I409N	probably damaging	Het
Klhdc10	T	C	6: 30,447,412	I204T	probably damaging	Het
Kpna6	A	T	4: 129,657,804	S65R	possibly damaging	Het
Lama3	A	T	18: 12,407,563	D308V	probably benign	Het
Larp4b	T	A	13: 9,158,107		probably null	Het
Lgr6	C	T	1: 134,994,010	A199T	probably damaging	Het
Lyzl1	A	T	18: 4,169,175	T11S	probably benign	Het
Man1c1	A	G	4: 134,578,315	L366P	probably damaging	Het
Mef2a	A	G	7: 67,251,724	M100T	probably damaging	Het
Mettl13	G	A	1: 162,538,889	H474Y	possibly damaging	Het
Mmp3	A	G	9: 7,451,320	D352G	probably benign	Het
Mns1	T	C	9: 72,452,804	I412T	probably damaging	Het
Mon2	T	C	10: 123,007,021	D1501G	probably null	Het
Mylk	G	T	16: 34,875,620	G242W	probably damaging	Het
Nav1	T	C	1: 135,449,966	D1715G	possibly damaging	Het
Nckap1l	T	C	15: 103,453,883	S2P	probably damaging	Het
Nek3	A	T	8: 22,128,729		probably benign	Het
Nfrkb	A	G	9: 31,388,897		probably benign	Het
Nlrp4d	T	C	7: 10,388,778	D53G	probably benign	Het
Nol8	T	C	13: 49,662,152	S561P	probably damaging	Het
Nuf2	A	C	1: 169,525,297		probably benign	Het
Ofcc1	T	A	13: 40,015,313	D866V	possibly damaging	Het
Olfr195	A	G	16: 59,149,299	I150V	probably benign	Het
Optn	A	G	2: 5,046,195	L125P	probably benign	Het
Otoa	T	A	7: 121,131,341	F588Y	probably benign	Het
Pappa	T	A	4: 65,351,613		probably null	Het
Pde5a	T	G	3: 122,835,583	C635W	probably damaging	Het
Pdgfb	A	T	15: 80,003,419		probably null	Het
Pih1d2	T	A	9: 50,621,046	C135S	probably damaging	Het
Plcg1	G	T	2: 160,752,366	C361F	probably damaging	Het
Ppp4r4	T	C	12: 103,601,360		probably benign	Het
Prdm10	G	A	9: 31,349,268		probably null	Het
Prex2	T	A	1: 11,089,706		probably null	Het
Prss56	T	G	1: 87,184,730		probably null	Het
Prtg	A	G	9: 72,844,958	K209E	probably benign	Het
Ptprc	G	A	1: 138,122,575	T36I	possibly damaging	Het
Rasgrp4	A	G	7: 29,145,860	Y302C	probably damaging	Het
Rb1cc1	T	A	1: 6,248,634	M759K	probably damaging	Het
Rbm15b	T	A	9: 106,885,998	M324L	probably benign	Het
Rcbtb2	T	C	14: 73,178,547	V500A	probably damaging	Het
Rgs6	A	G	12: 83,133,677	K434R	probably damaging	Het
Rims1	C	T	1: 22,596,526	A125T	possibly damaging	Het
Rtl1	C	T	12: 109,591,386	E1340K	unknown	Het
Sacs	G	A	14: 61,205,640	D1712N	possibly damaging	Het
Samd4b	G	A	7: 28,403,977	P19S	probably benign	Het
Samhd1	T	C	2: 157,114,231	Y347C	probably damaging	Het
Sema6d	T	A	2: 124,658,490	I393N	probably damaging	Het
Sigmar1	C	T	4: 41,741,243	A4T	probably benign	Het
Skint9	C	A	4: 112,389,179	L245F	probably benign	Het
Slc35f5	T	C	1: 125,585,095	L372P	probably damaging	Het
Smc1b	A	T	15: 85,066,277	I1182N	probably damaging	Het
Smyd3	A	G	1: 178,957,573		probably benign	Het
Sptlc1	T	C	13: 53,337,612	D417G	probably benign	Het
Sv2c	T	C	13: 96,088,708	N31S	probably benign	Het
Tjp1	T	C	7: 65,314,990	D811G	probably damaging	Het
Top2b	A	G	14: 16,418,442	T1221A	probably benign	Het
Tph2	T	C	10: 115,174,109	D182G	probably damaging	Het
Traf6	C	T	2: 101,688,588	Q141*	probably null	Het
Ttn	T	C	2: 76,756,931	D21574G	probably damaging	Het
Uba2	T	A	7: 34,151,021	N367I	probably benign	Het
Ube2b	T	C	11: 51,988,602		probably benign	Het
Ubr5	G	T	15: 38,030,672	L426I	probably benign	Het
Ugt2a2	T	A	5: 87,464,148	H301L	probably benign	Het
Upf2	T	A	2: 6,018,894		probably benign	Het
Utrn	T	C	10: 12,710,060	D991G	probably benign	Het
Vmn2r25	T	C	6: 123,823,181	D734G	probably damaging	Het
Vmn2r68	T	A	7: 85,233,249		probably benign	Het
Vmn2r68	C	G	7: 85,233,258		probably null	Het
Vwf	T	A	6: 125,626,361	Y891*	probably null	Het
Wwox	C	T	8: 114,706,278	T228I	probably benign	Het
Zer1	C	T	2: 30,108,213		probably benign	Het
Zfp180	C	T	7: 24,104,707	H184Y	possibly damaging	Het
Zfp68	A	T	5: 138,607,225	Y279N	probably benign	Het

Other mutations in Robo3

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00927:Robo3	APN	9	37427754	critical splice donor site	probably null
IGL01023:Robo3	APN	9	37429551	missense	probably damaging	1.00
IGL01431:Robo3	APN	9	37419111	unclassified	probably benign
IGL01993:Robo3	APN	9	37424653	missense	probably damaging	1.00
IGL02256:Robo3	APN	9	37425353	missense	probably damaging	1.00
IGL02323:Robo3	APN	9	37422201	missense	probably benign	0.05
IGL02561:Robo3	APN	9	37427091	missense	possibly damaging	0.84
IGL02866:Robo3	APN	9	37422306	missense	possibly damaging	0.89
IGL02897:Robo3	APN	9	37427502	nonsense	probably null
IGL03003:Robo3	APN	9	37419291	missense	probably damaging	1.00
IGL03307:Robo3	APN	9	37422564	missense	probably damaging	0.96
IGL03097:Robo3	UTSW	9	37422528	critical splice donor site	probably null
R0137:Robo3	UTSW	9	37425344	missense	probably benign	0.00
R0266:Robo3	UTSW	9	37422640	missense	probably damaging	0.96
R0505:Robo3	UTSW	9	37416759	unclassified	probably benign
R0815:Robo3	UTSW	9	37422183	missense	probably damaging	1.00
R0924:Robo3	UTSW	9	37429482	splice site	probably benign
R1167:Robo3	UTSW	9	37423907	nonsense	probably null
R1203:Robo3	UTSW	9	37418682	missense	probably damaging	1.00
R1451:Robo3	UTSW	9	37417711	missense	probably benign	0.01
R1575:Robo3	UTSW	9	37429661	missense	probably damaging	1.00
R1596:Robo3	UTSW	9	37424632	critical splice donor site	probably null
R1660:Robo3	UTSW	9	37429144	missense	probably damaging	1.00
R1677:Robo3	UTSW	9	37417709	missense	possibly damaging	0.75
R1839:Robo3	UTSW	9	37422327	missense	probably benign	0.00
R1878:Robo3	UTSW	9	37422165	missense	probably damaging	1.00
R1891:Robo3	UTSW	9	37428055	missense	probably damaging	1.00
R2040:Robo3	UTSW	9	37427464	missense	probably damaging	1.00
R2859:Robo3	UTSW	9	37428104	nonsense	probably null
R3786:Robo3	UTSW	9	37422225	missense	probably damaging	1.00
R3886:Robo3	UTSW	9	37422181	nonsense	probably null
R3888:Robo3	UTSW	9	37422181	nonsense	probably null
R3910:Robo3	UTSW	9	37419295	missense	probably damaging	1.00
R4212:Robo3	UTSW	9	37421898	missense	probably damaging	1.00
R4213:Robo3	UTSW	9	37421898	missense	probably damaging	1.00
R4691:Robo3	UTSW	9	37425218	missense	probably damaging	0.99
R4979:Robo3	UTSW	9	37423344	missense	probably damaging	1.00
R5238:Robo3	UTSW	9	37416879	missense	probably damaging	0.99
R5570:Robo3	UTSW	9	37425275	missense	possibly damaging	0.81
R5629:Robo3	UTSW	9	37419211	nonsense	probably null
R5770:Robo3	UTSW	9	37419201	missense	possibly damaging	0.87
R5837:Robo3	UTSW	9	37429816	critical splice acceptor site	probably null
R6021:Robo3	UTSW	9	37422533	nonsense	probably null
R6129:Robo3	UTSW	9	37423293	missense	probably benign
R6232:Robo3	UTSW	9	37420929	missense	probably damaging	1.00
R6233:Robo3	UTSW	9	37420929	missense	probably damaging	1.00
R6235:Robo3	UTSW	9	37420929	missense	probably damaging	1.00
R6326:Robo3	UTSW	9	37427027	missense	probably damaging	1.00
R6354:Robo3	UTSW	9	37417217	unclassified	probably benign
R6355:Robo3	UTSW	9	37418939	missense	possibly damaging	0.71
R6475:Robo3	UTSW	9	37423290	missense	probably damaging	0.99
R6937:Robo3	UTSW	9	37429880	missense	probably benign	0.16
R7201:Robo3	UTSW	9	37424330	nonsense	probably null
R7208:Robo3	UTSW	9	37424724	missense	probably damaging	0.99
R7249:Robo3	UTSW	9	37424833	missense	probably benign
R7376:Robo3	UTSW	9	37432916	missense	probably damaging	1.00
R7380:Robo3	UTSW	9	37418556	missense	probably damaging	1.00
R7448:Robo3	UTSW	9	37424815	missense	possibly damaging	0.89
R7475:Robo3	UTSW	9	37425378	missense	probably benign	0.01
R7496:Robo3	UTSW	9	37427825	missense	probably damaging	1.00
R7587:Robo3	UTSW	9	37429646	missense	probably damaging	1.00
R7694:Robo3	UTSW	9	37418520	missense	probably benign	0.14
R8381:Robo3	UTSW	9	37429760	missense	probably damaging	1.00
R8464:Robo3	UTSW	9	37421430	missense	probably damaging	1.00
R8495:Robo3	UTSW	9	37425368	missense	probably damaging	1.00
R8886:Robo3	UTSW	9	37417472	missense	probably damaging	0.99
R9422:Robo3	UTSW	9	37418493	missense	probably benign	0.03
R9563:Robo3	UTSW	9	37429604	missense	probably damaging	1.00
R9564:Robo3	UTSW	9	37429604	missense	probably damaging	1.00
R9681:Robo3	UTSW	9	37423262	missense	possibly damaging	0.75
R9681:Robo3	UTSW	9	37427791	missense	probably benign	0.45
X0024:Robo3	UTSW	9	37427855	missense	probably damaging	1.00
X0027:Robo3	UTSW	9	37427825	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- AAGCGGCCTCAAGTTTCATCCTC -3'
(R):5'- TTGCTCAGCAGACAGCAGCCTATC -3'

Sequencing Primer
(F):5'- TCCCAGTTCTTACATGACAGAACATC -3'
(R):5'- AATGCAGGAGCCCACTGTC -3'

Posted On

2013-04-24