Mutagenetix > Incidental Mutations

Incidental Mutation 'R0062:Rttn'

16252

Institutional Source

Beutler Lab

Gene Symbol

Rttn

Ensembl Gene

ENSMUSG00000023066

Gene Name

rotatin

Synonyms

C530033I08Rik, 4921538A15Rik

MMRRC Submission

038354-MU

Accession Numbers

Ncbi RefSeq: NM_175542.3; MGI:2179288

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R0062 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

88971790-89131013 bp(+) (GRCm38)

Type of Mutation

critical splice donor site (2 bp from exon)

DNA Base Change (assembly)

T to C at 89010966 bp

Zygosity

Heterozygous

Amino Acid Change

Ref Sequence

ENSEMBL: ENSMUSP00000023828 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000023828]

Predicted Effect

probably null
Transcript: ENSMUST00000023828

SMART Domains

Protein: ENSMUSP00000023828
Gene: ENSMUSG00000023066

Domain	Start	End	E-Value	Type
Pfam:RTTN_N	16	112	1.2e-36	PFAM
low complexity region	188	199	N/A	INTRINSIC
Blast:ARM	216	261	9e-18	BLAST
low complexity region	302	319	N/A	INTRINSIC
low complexity region	335	341	N/A	INTRINSIC
SCOP:d1gw5a_	515	952	9e-3	SMART
Blast:ARM	863	910	4e-8	BLAST
low complexity region	972	985	N/A	INTRINSIC
low complexity region	1165	1176	N/A	INTRINSIC
low complexity region	1213	1222	N/A	INTRINSIC
low complexity region	1680	1698	N/A	INTRINSIC
low complexity region	1861	1879	N/A	INTRINSIC
Blast:ARM	2088	2129	1e-10	BLAST

Meta Mutation Damage Score

0.544

Coding Region Coverage

1x: 90.3%
3x: 88.1%
10x: 83.4%
20x: 77.5%

Validation Efficiency

91% (72/79)

MGI Phenotype

Strain: 2674124
Lethality: E9-E12
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a large protein whose specific function is unknown. Absence of the orthologous protein in mouse results in embryonic lethality with deficient axial rotation, abnormal differentiation of the neural tube, and randomized looping of the heart tube during development. In human, mutations in this gene are associated with polymicrogyria with seizures. In human fibroblasts this protein localizes at the ciliary basal bodies. Given the intracellular localization of this protein and the phenotypic effects of mutations, this gene is suspected of playing a role in the maintenance of normal ciliary structure which in turn effects the developmental process of left-right organ specification, axial rotation, and perhaps notochord development. [provided by RefSeq, Jan 2013]
PHENOTYPE: Mice homozygous for an insertional mutation exhibit embryonic lethality and neurulation defects resulting in the arrest of gastrulation movements and abnormal left-right specification in the heart. [provided by MGI curators]

Allele List at MGI

All alleles(15) : Targeted(2) Gene trapped(12) Transgenic(1)

Other mutations in this stock

Total: 55 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4921513I03Rik	G	T	10: 120,778,606		probably benign	Het
Abi2	T	A	1: 60,453,725	N182K	probably benign	Het
Adam25	A	T	8: 40,754,792	H365L	probably damaging	Het
Ankfy1	T	A	11: 72,712,204	Y20N	probably damaging	Het
Arhgef28	A	T	13: 97,956,642	I977N	possibly damaging	Het
Armc4	T	A	18: 7,129,593		probably benign	Het
Cacna1b	A	G	2: 24,758,331	Y161H	probably damaging	Het
Cacna1c	T	C	6: 118,602,237	D1480G	probably damaging	Het
Chl1	A	T	6: 103,749,652	Y1143F	unknown	Het
Clk3	A	G	9: 57,752,166	M533T	probably damaging	Het
Clstn1	G	A	4: 149,634,796	V361M	probably damaging	Het
Cnbd1	A	G	4: 18,860,504	I414T	possibly damaging	Het
Commd3	A	T	2: 18,674,703		probably null	Het
Dnah8	T	A	17: 30,765,711	F3128I	probably damaging	Het
Dock1	A	G	7: 134,777,495		probably null	Het
Dpysl3	C	T	18: 43,333,876		probably null	Het
Ebf2	T	A	14: 67,238,540		probably benign	Het
F830045P16Rik	T	C	2: 129,463,704	E250G	possibly damaging	Het
Fmn2	A	T	1: 174,608,449		probably benign	Het
Fryl	T	C	5: 73,022,278	I2929V	probably benign	Het
Gm11232	T	A	4: 71,756,875	Q130L	possibly damaging	Het
Gna15	A	G	10: 81,512,405		probably null	Het
Gtf3c5	T	C	2: 28,572,186		probably benign	Het
Irs2	G	A	8: 11,005,723	T903I	possibly damaging	Het
Itga2	G	A	13: 114,870,496	S432L	possibly damaging	Het
Izumo1	A	G	7: 45,627,197	T395A	probably benign	Het
Kcnd2	G	A	6: 21,727,226	V593M	possibly damaging	Het
Kprp	T	C	3: 92,824,682	S354G	probably damaging	Het
Krt72	T	C	15: 101,786,008	K151E	probably damaging	Het
Letm2	A	T	8: 25,587,448		probably benign	Het
Lipe	A	G	7: 25,398,449	V23A	possibly damaging	Het
Mcc	C	G	18: 44,519,516		probably benign	Het
Mthfd1	G	A	12: 76,297,589		probably benign	Het
Nbeal1	C	A	1: 60,247,717	N899K	probably benign	Het
Olfr1223	T	C	2: 89,144,622	I134V	possibly damaging	Het
Olfr1338	T	C	4: 118,753,903	I212V	probably benign	Het
Pcdha1	T	A	18: 37,006,628	W437R	probably benign	Het
Pcdhga11	T	G	18: 37,808,475	I643S	probably benign	Het
Pik3r6	T	A	11: 68,528,809	Y149N	probably damaging	Het
Pja2	C	A	17: 64,308,971	V310L	probably damaging	Het
Ripor3	A	G	2: 167,984,438		probably benign	Het
Rpa2	C	A	4: 132,777,814	N251K	probably damaging	Het
Ryr2	C	T	13: 11,869,116		probably null	Het
Scara3	T	C	14: 65,930,968	N400S	probably damaging	Het
Slc8b1	T	A	5: 120,521,863		probably null	Het
Slco1a4	G	A	6: 141,819,479	Q346*	probably null	Het
Stk32b	A	G	5: 37,461,448	S229P	probably damaging	Het
Syde2	A	G	3: 145,998,753	R487G	probably benign	Het
Tbc1d2b	T	C	9: 90,222,302		probably benign	Het
Ticrr	T	C	7: 79,667,906	V396A	probably benign	Het
Trrap	T	C	5: 144,782,193		probably benign	Het
Vps13a	A	T	19: 16,668,690	H1994Q	probably damaging	Het
Wdr36	T	G	18: 32,864,749	V820G	possibly damaging	Het
Wdr83	G	A	8: 85,079,827	T114I	possibly damaging	Het
Zfc3h1	A	G	10: 115,416,753	K1324E	probably benign	Het

Other mutations in Rttn

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00595:Rttn	APN	18	88974340	missense	probably benign	0.00
IGL00788:Rttn	APN	18	88972509	missense	probably benign	0.00
IGL00929:Rttn	APN	18	89028935	missense	probably damaging	1.00
IGL01392:Rttn	APN	18	88995613	missense	probably benign	0.03
IGL01395:Rttn	APN	18	89129770	missense	possibly damaging	0.89
IGL01701:Rttn	APN	18	89064215	missense	probably damaging	1.00
IGL02136:Rttn	APN	18	89046128	missense	possibly damaging	0.87
IGL02151:Rttn	APN	18	89020205	missense	probably damaging	1.00
IGL02165:Rttn	APN	18	89043041	missense	probably benign
IGL02228:Rttn	APN	18	89042231	missense	probably damaging	1.00
IGL02276:Rttn	APN	18	89048454	missense	possibly damaging	0.94
IGL02612:Rttn	APN	18	88973626	missense	probably damaging	1.00
IGL02645:Rttn	APN	18	89110686	missense	probably benign	0.04
IGL02716:Rttn	APN	18	89048417	missense	possibly damaging	0.77
IGL02820:Rttn	APN	18	89028998	missense	probably damaging	1.00
IGL02961:Rttn	APN	18	89053573	missense	probably damaging	1.00
IGL02973:Rttn	APN	18	88972494	missense	probably damaging	1.00
IGL03027:Rttn	APN	18	88979690	missense	probably damaging	1.00
IGL03082:Rttn	APN	18	88983948	missense	probably damaging	1.00
IGL03121:Rttn	APN	18	88975751	missense	probably damaging	1.00
IGL03135:Rttn	APN	18	89015150	missense	probably damaging	1.00
IGL03328:Rttn	APN	18	89043028	missense	probably benign	0.19
R0062:Rttn	UTSW	18	89010966	critical splice donor site	probably null
R0310:Rttn	UTSW	18	89009460	splice site	probably benign
R0330:Rttn	UTSW	18	88986080	splice site	probably null
R0363:Rttn	UTSW	18	89010955	missense	probably damaging	1.00
R0485:Rttn	UTSW	18	89090419	splice site	probably benign
R0590:Rttn	UTSW	18	88979635	missense	probably damaging	1.00
R0601:Rttn	UTSW	18	89042966	missense	probably benign	0.00
R0604:Rttn	UTSW	18	88977758	missense	probably damaging	1.00
R0631:Rttn	UTSW	18	88989546	missense	probably benign	0.00
R0882:Rttn	UTSW	18	88973689	nonsense	probably null
R0885:Rttn	UTSW	18	88983810	missense	probably benign	0.03
R0900:Rttn	UTSW	18	89101691	missense	probably benign	0.13
R1077:Rttn	UTSW	18	89064249	missense	probably damaging	1.00
R1444:Rttn	UTSW	18	89042867	missense	probably benign	0.04
R1460:Rttn	UTSW	18	89109357	splice site	probably benign
R1517:Rttn	UTSW	18	89113350	missense	probably benign	0.01
R1630:Rttn	UTSW	18	89042954	missense	probably benign	0.02
R1632:Rttn	UTSW	18	89009336	missense	probably benign	0.18
R1722:Rttn	UTSW	18	88973531	missense	probably benign	0.34
R1755:Rttn	UTSW	18	89009317	missense	probably damaging	1.00
R1881:Rttn	UTSW	18	89015212	missense	probably damaging	0.96
R1971:Rttn	UTSW	18	89090433	missense	probably benign
R2035:Rttn	UTSW	18	89020216	missense	probably damaging	1.00
R2109:Rttn	UTSW	18	88986073	missense	possibly damaging	0.93
R2191:Rttn	UTSW	18	89095648	critical splice donor site	probably null
R2201:Rttn	UTSW	18	89010943	missense	possibly damaging	0.88
R2266:Rttn	UTSW	18	89064171	missense	probably benign	0.05
R3014:Rttn	UTSW	18	89014620	missense	probably damaging	1.00
R3052:Rttn	UTSW	18	89015246	splice site	probably benign
R3427:Rttn	UTSW	18	89095651	splice site	probably null
R3431:Rttn	UTSW	18	89095571	missense	probably benign	0.04
R3786:Rttn	UTSW	18	89037894	missense	probably benign	0.00
R3803:Rttn	UTSW	18	88977707	missense	probably damaging	0.96
R3980:Rttn	UTSW	18	89017275	missense	probably benign	0.12
R4035:Rttn	UTSW	18	88995653	missense	probably benign	0.03
R4170:Rttn	UTSW	18	88975723	missense	probably damaging	1.00
R4223:Rttn	UTSW	18	89095584	missense	probably damaging	1.00
R4273:Rttn	UTSW	18	89091896	missense	probably benign
R4517:Rttn	UTSW	18	89028973	missense	probably damaging	0.99
R4674:Rttn	UTSW	18	89011011	intron	probably null
R4837:Rttn	UTSW	18	89090415	splice site	probably null
R4869:Rttn	UTSW	18	89043014	nonsense	probably null
R4881:Rttn	UTSW	18	89101685	missense	probably damaging	1.00
R4959:Rttn	UTSW	18	89042168	missense	probably damaging	1.00
R4973:Rttn	UTSW	18	89042168	missense	probably damaging	1.00
R4975:Rttn	UTSW	18	89064085	intron	probably null
R5166:Rttn	UTSW	18	89013094	missense	possibly damaging	0.48
R5243:Rttn	UTSW	18	89108063	missense	possibly damaging	0.74
R5594:Rttn	UTSW	18	89090436	missense	possibly damaging	0.95
R5654:Rttn	UTSW	18	89048432	missense	probably benign
R5794:Rttn	UTSW	18	88995569	missense	probably benign	0.18
R5799:Rttn	UTSW	18	89037946	missense	probably damaging	0.99
R5955:Rttn	UTSW	18	89121009	missense	probably damaging	0.99
R5963:Rttn	UTSW	18	89073695	missense	probably benign	0.01
R5989:Rttn	UTSW	18	88973626	missense	probably damaging	1.00
R6004:Rttn	UTSW	18	89021692	missense	probably damaging	0.96
R6132:Rttn	UTSW	18	89115646	critical splice donor site	probably null
R6430:Rttn	UTSW	18	89021685	missense	probably null	0.18
R6436:Rttn	UTSW	18	89110729	missense	probably damaging	1.00
R6681:Rttn	UTSW	18	89014611	missense	probably damaging	1.00
R6994:Rttn	UTSW	18	89028899	missense	probably damaging	1.00
R7049:Rttn	UTSW	18	89064216	missense	probably damaging	1.00
R7078:Rttn	UTSW	18	89009422	missense	probably benign	0.03
R7083:Rttn	UTSW	18	89090598	missense	probably damaging	1.00
R7250:Rttn	UTSW	18	88989523	missense	probably benign	0.03
R7402:Rttn	UTSW	18	88985911	missense	possibly damaging	0.92
R7565:Rttn	UTSW	18	89060479	missense	probably damaging	1.00
X0017:Rttn	UTSW	18	89113402	missense	probably benign	0.01
X0022:Rttn	UTSW	18	88973667	nonsense	probably null

Protein Function and Prediction

Rttn encodes rotatin, a novel transmembrane protein that is required for axial rotation, left-right specification, and notochord development in embryos (1). Additional studies indicate that rotatin is required for the maintenance of normal ciliary structure (2).

Expression/Localization

Rttn is expressed from embryonic day (E) 7.5 through embryonic development (1). At E8.5, Rttn is expressed in the telencephalon, mesoderm, somites, and notochord (1). At E9.5, Rttn expression persists in the somites with expression extending to the forelimb bud, basal forebrain, and first branchial arch (1). At E11.5 and E12.5, Rttn expression was detected in the heart primordium and the expression in the branchial arches was increased (1). The Rttn protein colocalizes with basal bodes at the primary cilium in human fibroblasts (2). In the embryonic mouse brain, rotatin localized to the marginal zone of the developing mouse cortex and in the upper cortical layers (2).

Background

Mutations in RTTN are linked to polymicrogyria with seizures [OMIM: 614833; (2)]. Patients with this disorder had microcephaly, moderate to severe mental retardation, poor speech, dysarthria, and seizures (2).

Rttn^{Gt(pGT1.8geo)7Pgr/ Gt(pGT1.8geo)7Pgr}; MGI:2674124

involves: 129S1/Sv * 129X1/SvJ * NMRI

Homozygotes with this gene-trapped allele exhibit embryonic lethality during organogenesis (E9.5-E11.5), randomized heart looping, pericardial effusion, abnormal axial rotation, abnormal somite development, abnormal neural tube morphology/development, and decreased embryo size (1).

References

1. Faisst, A. M., Alvarez-Bolado, G., Treichel, D., and Gruss, P. (2002) Rotatin is a Novel Gene Required for Axial Rotation and Left-Right Specification in Mouse Embryos. Mech Dev. 113, 15-28.

2. Kheradmand Kia, S., Verbeek, E., Engelen, E., Schot, R., Poot, R. A., de Coo, I. F., Lequin, M. H., Poulton, C. J., Pourfarzad, F., Grosveld, F. G., Brehm, A., de Wit, M. C., Oegema, R., Dobyns, W. B., Verheijen, F. W., and Mancini, G. M. (2012) RTTN Mutations Link Primary Cilia Function to Organization of the Human Cerebral Cortex. Am J Hum Genet. 91, 533-540.

Posted On

2013-01-20

Science Writer

Anne Murray