Mutagenetix > Incidental Mutation

Incidental Mutation 'R1839:Robo3'

205605

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

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R1839 (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 37422327 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 696 (V696A)

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: V674A

PolyPhen 2 Score 0.005 (Sensitivity: 0.97; Specificity: 0.74)

SMART Domains

Protein: ENSMUSP00000034643
Gene: ENSMUSG00000032128
AA Change: V674A

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: V696A

PolyPhen 2 Score 0.005 (Sensitivity: 0.97; Specificity: 0.74)

SMART Domains

Protein: ENSMUSP00000110690
Gene: ENSMUSG00000032128
AA Change: V696A

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: V674A

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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000171467

Meta Mutation Damage Score

0.0842

Coding Region Coverage

1x: 97.4%
3x: 96.7%
10x: 94.7%
20x: 90.6%

Validation Efficiency

98% (90/92)

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: 84 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700006A11Rik	T	C	3: 124,409,720	T403A	probably damaging	Het
Acat3	T	A	17: 12,928,606	R175*	probably null	Het
Adam1b	C	A	5: 121,501,041	C647F	probably damaging	Het
Adam28	T	C	14: 68,639,210	N197S	possibly damaging	Het
Adcy2	C	T	13: 68,689,261		probably null	Het
Adcy5	A	T	16: 35,248,940	N426I	probably damaging	Het
Adgre1	T	C	17: 57,441,299	S500P	probably benign	Het
Aloxe3	A	G	11: 69,130,085	Y212C	probably damaging	Het
Ap3d1	A	G	10: 80,727,108	S180P	probably damaging	Het
Arhgap20	C	T	9: 51,849,326	R790W	probably damaging	Het
Atp8b4	C	A	2: 126,361,782	A757S	possibly damaging	Het
Begain	G	A	12: 109,035,323		probably benign	Het
Ccdc141	T	C	2: 77,011,665	E1474G	probably benign	Het
Ccdc88b	A	G	19: 6,854,109		probably benign	Het
Ccnk	A	G	12: 108,195,074	T195A	probably damaging	Het
Cd55b	C	A	1: 130,414,105	C265F	probably damaging	Het
Celsr3	A	G	9: 108,829,906	H1196R	probably benign	Het
Cenpt	T	C	8: 105,849,014	S190G	possibly damaging	Het
Chd8	T	C	14: 52,204,883	S2077G	probably benign	Het
Col6a5	G	A	9: 105,864,833	H2296Y	probably benign	Het
Cxxc4	C	A	3: 134,240,653	H332N	probably damaging	Het
Cyp24a1	T	C	2: 170,496,741	I12V	probably benign	Het
Cyp3a57	T	A	5: 145,381,301	L364Q	probably damaging	Het
Ddi2	T	C	4: 141,713,526	I47V	probably benign	Het
Ddx5	A	T	11: 106,784,897	D322E	probably benign	Het
Dhx40	A	G	11: 86,789,297	C405R	possibly damaging	Het
Emc1	T	C	4: 139,360,485	F100S	probably damaging	Het
Exoc2	T	C	13: 30,906,497		probably benign	Het
Gm10110	A	T	14: 89,897,836		noncoding transcript	Het
Gm17332	T	C	11: 31,182,386	H26R	possibly damaging	Het
Gna12	T	C	5: 140,762,612	N183S	probably benign	Het
Gpx6	A	G	13: 21,312,327	N24D	probably benign	Het
Gsdma3	C	T	11: 98,629,858	A105V	probably benign	Het
Hsd3b5	T	C	3: 98,619,728	Y134C	probably benign	Het
Ifi213	T	C	1: 173,589,600	I415M	probably damaging	Het
Ints9	C	A	14: 65,016,530	P278T	probably damaging	Het
Krt79	C	T	15: 101,937,938	E192K	possibly damaging	Het
Lrrk2	A	G	15: 91,683,134	N132S	probably benign	Het
Ltn1	T	A	16: 87,416,264	K470*	probably null	Het
Magi2	A	T	5: 20,465,827	T163S	probably damaging	Het
Mcm9	A	G	10: 53,541,553	M18T	probably damaging	Het
Med12l	A	G	3: 59,068,319	T212A	probably benign	Het
Mfhas1	T	C	8: 35,590,858	L829P	possibly damaging	Het
Mgme1	T	A	2: 144,279,487	C288S	probably benign	Het
Muc4	G	C	16: 32,753,919	R1265P	probably benign	Het
Myh7	T	C	14: 54,973,180	N1725S	possibly damaging	Het
Nat6	G	A	9: 107,583,017	R37H	possibly damaging	Het
Nme4	A	T	17: 26,092,097	W165R	probably damaging	Het
Nup205	T	A	6: 35,219,714	D1128E	probably benign	Het
Olfr291	T	C	7: 84,856,548	Y60H	probably damaging	Het
Olfr330	A	T	11: 58,529,373	Y204*	probably null	Het
Pcdh1	T	C	18: 38,199,485	D155G	possibly damaging	Het
Pex12	A	T	11: 83,297,822	S116T	probably damaging	Het
Plekhh1	C	T	12: 79,078,957		probably benign	Het
Plekhh3	A	G	11: 101,163,600		probably benign	Het
Pnpt1	T	C	11: 29,154,342	M572T	possibly damaging	Het
Ppp1r12b	T	C	1: 134,837,981	R667G	probably benign	Het
Rbpms2	ACTGCTGCTGCTGCTGC	ACTGCTGCTGCTGCTGCTGC	9: 65,651,666		probably benign	Het
Rgs14	T	C	13: 55,382,838		probably benign	Het
Rhbdf2	A	T	11: 116,600,191	V645E	possibly damaging	Het
Sall1	A	G	8: 89,028,716	F1212L	possibly damaging	Het
Sdc4	T	C	2: 164,429,012	E109G	probably benign	Het
Serpind1	G	T	16: 17,342,992	R462L	probably damaging	Het
Smad9	CTTT	CTT	3: 54,789,179		probably benign	Het
Sstr4	C	A	2: 148,395,533	N21K	probably benign	Het
Tap1	C	T	17: 34,188,109	A77V	possibly damaging	Het
Thap4	T	C	1: 93,750,287	E259G	probably benign	Het
Thra	A	G	11: 98,756,143	N30S	probably benign	Het
Tmem207	A	T	16: 26,524,821	V27E	possibly damaging	Het
Top3a	A	G	11: 60,753,888	V305A	probably damaging	Het
Trim59	A	T	3: 69,037,638	I123K	probably damaging	Het
Ttn	T	C	2: 76,861,495		probably benign	Het
Ubac1	T	A	2: 26,007,738	E290V	possibly damaging	Het
Unc13b	T	C	4: 43,258,308		probably benign	Het
Uri1	A	T	7: 37,967,389	D206E	probably benign	Het
Utp4	A	G	8: 106,913,454	H465R	probably benign	Het
Uvssa	T	C	5: 33,389,752	S221P	probably benign	Het
Vmn1r39	T	C	6: 66,805,233		probably null	Het
Vps39	A	T	2: 120,325,397	L514H	probably damaging	Het
Vps72	G	A	3: 95,119,218	R158Q	possibly damaging	Het
Wdr59	T	C	8: 111,485,340	D366G	probably benign	Het
Zfp366	C	A	13: 99,228,492	Q54K	probably damaging	Het
Zfp523	T	A	17: 28,194,993	I34N	probably damaging	Het
Zfp974	G	A	7: 27,910,356	P648L	possibly damaging	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
R0390:Robo3	UTSW	9	37422177	missense	probably benign	0.00
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
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'- ATCCTTACCCTCCTCAGGAATG -3'
(R):5'- CGGTTAGAAATGGCATGGCG -3'

Sequencing Primer
(F):5'- CTGGTCACAAAAGGGCTTTC -3'
(R):5'- TTAGAAATGGCATGGCGATGGG -3'

Posted On

2014-06-23