Incidental Mutation 'P0005:Rpgrip1l'
| ID |
7603 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Rpgrip1l
|
| Ensembl Gene |
ENSMUSG00000033282 |
| Gene Name |
Rpgrip1-like |
| Synonyms |
Nphp8, 1700047E16Rik, Ftm, fantom |
| MMRRC Submission |
038262-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
P0005 (G1)
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
8 |
| Chromosomal Location |
91943658-92039890 bp(-) (GRCm39) |
| Type of Mutation |
splice site |
| DNA Base Change (assembly) |
A to T
at 92025853 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000118230
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000047783]
[ENSMUST00000139113]
|
| AlphaFold |
Q8CG73 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000047783
|
| SMART Domains |
Protein: ENSMUSP00000042702
Gene: ENSMUSG00000033282
| Domain | Start | End | E-Value | Type |
|---|
|
coiled coil region
|
56 |
143 |
N/A |
INTRINSIC |
|
coiled coil region
|
196 |
268 |
N/A |
INTRINSIC |
|
coiled coil region
|
299 |
371 |
N/A |
INTRINSIC |
|
coiled coil region
|
395 |
454 |
N/A |
INTRINSIC |
|
coiled coil region
|
520 |
556 |
N/A |
INTRINSIC |
|
Pfam:C2-C2_1
|
597 |
738 |
5.8e-61 |
PFAM |
|
low complexity region
|
769 |
778 |
N/A |
INTRINSIC |
|
C2
|
791 |
896 |
1.06e-5 |
SMART |
|
low complexity region
|
989 |
1000 |
N/A |
INTRINSIC |
|
low complexity region
|
1057 |
1080 |
N/A |
INTRINSIC |
|
Blast:C2
|
1098 |
1223 |
3e-20 |
BLAST |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000139113
|
| SMART Domains |
Protein: ENSMUSP00000118230
Gene: ENSMUSG00000033282
| Domain | Start | End | E-Value | Type |
|---|
|
coiled coil region
|
56 |
143 |
N/A |
INTRINSIC |
|
| Coding Region Coverage |
- 1x: 85.5%
- 3x: 80.5%
- 10x: 66.1%
- 20x: 49.6%
|
| Validation Efficiency |
95% (104/109) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene can localize to the basal body-centrosome complex or to primary cilia and centrosomes in ciliated cells. The encoded protein has been found to interact with nephrocystin-4. Defects in this gene are a cause of Joubert syndrome type 7 (JBTS7) and Meckel syndrome type 5 (MKS5). [provided by RefSeq, Jun 2016]
PHENOTYPE: Mice homozygous for a knock-out allele do not survive after birth and show exencephaly, polydactyly, laterality defects, abnormal floor plate induction and neural tube patterning, cleft lip, micro- and anophthalmia, and variable cerebral, renal, and hepatic defects due to primary cilium dysfuntion. [provided by MGI curators]
|
| Allele List at MGI |
All alleles(4) : Targeted(3) Gene trapped(1)
|
| Other mutations in this stock |
Total: 20 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Atp13a1 |
T |
C |
8: 70,256,397 (GRCm39) |
V845A |
possibly damaging |
Het |
| Casp6 |
T |
C |
3: 129,705,792 (GRCm39) |
V153A |
probably benign |
Het |
| Col6a1 |
A |
G |
10: 76,553,163 (GRCm39) |
|
probably benign |
Het |
| Dars2 |
A |
G |
1: 160,881,509 (GRCm39) |
|
probably null |
Het |
| Hmgcll1 |
T |
A |
9: 75,982,041 (GRCm39) |
M162K |
possibly damaging |
Het |
| Hydin |
A |
T |
8: 111,220,921 (GRCm39) |
|
probably null |
Het |
| Ift74 |
A |
G |
4: 94,550,813 (GRCm39) |
|
probably benign |
Het |
| Itpr1 |
A |
T |
6: 108,358,218 (GRCm39) |
I595F |
probably damaging |
Het |
| Mgat4f |
T |
A |
1: 134,315,646 (GRCm39) |
M15K |
probably benign |
Het |
| Mmp17 |
T |
C |
5: 129,673,695 (GRCm39) |
V258A |
probably benign |
Het |
| Nek6 |
T |
C |
2: 38,459,749 (GRCm39) |
|
probably null |
Het |
| Nomo1 |
A |
T |
7: 45,686,981 (GRCm39) |
|
probably null |
Het |
| Nudt3 |
A |
G |
17: 27,815,689 (GRCm39) |
|
probably benign |
Het |
| Pramel32 |
A |
G |
4: 88,546,187 (GRCm39) |
L385P |
probably damaging |
Het |
| Prkg2 |
A |
C |
5: 99,117,806 (GRCm39) |
F512V |
probably damaging |
Het |
| Ptp4a3 |
T |
A |
15: 73,627,160 (GRCm39) |
D72E |
possibly damaging |
Het |
| Rrp9 |
G |
A |
9: 106,358,376 (GRCm39) |
R101H |
probably benign |
Het |
| Slc7a6os |
T |
C |
8: 106,931,154 (GRCm39) |
I161V |
probably benign |
Het |
| Tex15 |
T |
C |
8: 34,060,896 (GRCm39) |
F109L |
probably benign |
Het |
| Tns2 |
A |
G |
15: 102,022,491 (GRCm39) |
Q1188R |
probably damaging |
Het |
|
| Other mutations in Rpgrip1l |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00419:Rpgrip1l
|
APN |
8 |
91,990,202 (GRCm39) |
missense |
possibly damaging |
0.52 |
|
IGL00932:Rpgrip1l
|
APN |
8 |
92,002,265 (GRCm39) |
missense |
probably benign |
0.33 |
|
IGL01113:Rpgrip1l
|
APN |
8 |
91,987,367 (GRCm39) |
intron |
probably benign |
|
|
IGL01151:Rpgrip1l
|
APN |
8 |
92,001,777 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01321:Rpgrip1l
|
APN |
8 |
91,987,501 (GRCm39) |
nonsense |
probably null |
|
|
IGL01384:Rpgrip1l
|
APN |
8 |
92,000,268 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL01634:Rpgrip1l
|
APN |
8 |
91,979,172 (GRCm39) |
missense |
probably benign |
0.25 |
|
IGL01634:Rpgrip1l
|
APN |
8 |
91,979,171 (GRCm39) |
missense |
probably benign |
|
|
IGL01781:Rpgrip1l
|
APN |
8 |
91,996,846 (GRCm39) |
missense |
probably benign |
0.16 |
|
IGL01784:Rpgrip1l
|
APN |
8 |
91,997,089 (GRCm39) |
missense |
possibly damaging |
0.56 |
|
IGL02034:Rpgrip1l
|
APN |
8 |
91,977,776 (GRCm39) |
critical splice donor site |
probably null |
|
|
IGL02250:Rpgrip1l
|
APN |
8 |
91,959,489 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL02285:Rpgrip1l
|
APN |
8 |
91,959,535 (GRCm39) |
missense |
possibly damaging |
0.92 |
|
IGL02634:Rpgrip1l
|
APN |
8 |
91,951,972 (GRCm39) |
splice site |
probably benign |
|
|
IGL02736:Rpgrip1l
|
APN |
8 |
91,990,219 (GRCm39) |
missense |
possibly damaging |
0.91 |
|
IGL02825:Rpgrip1l
|
APN |
8 |
92,031,433 (GRCm39) |
missense |
possibly damaging |
0.67 |
|
IGL02962:Rpgrip1l
|
APN |
8 |
91,996,990 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
IGL03031:Rpgrip1l
|
APN |
8 |
91,987,411 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL03184:Rpgrip1l
|
APN |
8 |
92,027,437 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0118:Rpgrip1l
|
UTSW |
8 |
91,996,750 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0490:Rpgrip1l
|
UTSW |
8 |
92,026,473 (GRCm39) |
splice site |
probably benign |
|
|
R0599:Rpgrip1l
|
UTSW |
8 |
92,031,628 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1514:Rpgrip1l
|
UTSW |
8 |
91,987,378 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1648:Rpgrip1l
|
UTSW |
8 |
91,979,517 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1914:Rpgrip1l
|
UTSW |
8 |
91,959,552 (GRCm39) |
missense |
probably benign |
0.13 |
|
R1915:Rpgrip1l
|
UTSW |
8 |
91,959,552 (GRCm39) |
missense |
probably benign |
0.13 |
|
R2093:Rpgrip1l
|
UTSW |
8 |
91,996,760 (GRCm39) |
missense |
possibly damaging |
0.87 |
|
R2225:Rpgrip1l
|
UTSW |
8 |
91,948,095 (GRCm39) |
missense |
probably benign |
0.45 |
|
R2504:Rpgrip1l
|
UTSW |
8 |
92,007,344 (GRCm39) |
critical splice donor site |
probably null |
|
|
R3859:Rpgrip1l
|
UTSW |
8 |
91,990,286 (GRCm39) |
missense |
probably benign |
0.00 |
|
R4118:Rpgrip1l
|
UTSW |
8 |
91,979,535 (GRCm39) |
missense |
probably benign |
|
|
R4801:Rpgrip1l
|
UTSW |
8 |
91,996,805 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4802:Rpgrip1l
|
UTSW |
8 |
91,996,805 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4921:Rpgrip1l
|
UTSW |
8 |
91,987,637 (GRCm39) |
missense |
probably benign |
0.05 |
|
R4976:Rpgrip1l
|
UTSW |
8 |
92,007,444 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5092:Rpgrip1l
|
UTSW |
8 |
91,948,012 (GRCm39) |
nonsense |
probably null |
|
|
R5099:Rpgrip1l
|
UTSW |
8 |
91,975,350 (GRCm39) |
missense |
probably benign |
0.20 |
|
R5119:Rpgrip1l
|
UTSW |
8 |
92,007,444 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5141:Rpgrip1l
|
UTSW |
8 |
91,987,546 (GRCm39) |
missense |
probably benign |
0.29 |
|
R5793:Rpgrip1l
|
UTSW |
8 |
91,987,400 (GRCm39) |
missense |
probably benign |
0.06 |
|
R5847:Rpgrip1l
|
UTSW |
8 |
92,031,613 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5871:Rpgrip1l
|
UTSW |
8 |
91,948,014 (GRCm39) |
missense |
possibly damaging |
0.89 |
|
R5916:Rpgrip1l
|
UTSW |
8 |
91,979,541 (GRCm39) |
missense |
possibly damaging |
0.93 |
|
R6619:Rpgrip1l
|
UTSW |
8 |
91,959,499 (GRCm39) |
missense |
possibly damaging |
0.69 |
|
R6654:Rpgrip1l
|
UTSW |
8 |
91,946,833 (GRCm39) |
missense |
probably benign |
0.36 |
|
R6956:Rpgrip1l
|
UTSW |
8 |
92,012,941 (GRCm39) |
splice site |
probably null |
|
|
R6984:Rpgrip1l
|
UTSW |
8 |
91,987,426 (GRCm39) |
missense |
probably benign |
0.03 |
|
R7064:Rpgrip1l
|
UTSW |
8 |
91,990,148 (GRCm39) |
nonsense |
probably null |
|
|
R7145:Rpgrip1l
|
UTSW |
8 |
91,959,434 (GRCm39) |
critical splice donor site |
probably null |
|
|
R7243:Rpgrip1l
|
UTSW |
8 |
91,996,751 (GRCm39) |
missense |
probably benign |
0.00 |
|
R7673:Rpgrip1l
|
UTSW |
8 |
92,027,415 (GRCm39) |
missense |
possibly damaging |
0.89 |
|
R7796:Rpgrip1l
|
UTSW |
8 |
91,996,865 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8684:Rpgrip1l
|
UTSW |
8 |
92,000,329 (GRCm39) |
missense |
probably benign |
0.00 |
|
R8769:Rpgrip1l
|
UTSW |
8 |
91,979,212 (GRCm39) |
splice site |
probably benign |
|
|
R8955:Rpgrip1l
|
UTSW |
8 |
92,007,456 (GRCm39) |
missense |
possibly damaging |
0.67 |
|
R9006:Rpgrip1l
|
UTSW |
8 |
92,007,436 (GRCm39) |
missense |
probably benign |
|
|
R9085:Rpgrip1l
|
UTSW |
8 |
92,014,303 (GRCm39) |
missense |
possibly damaging |
0.68 |
|
R9188:Rpgrip1l
|
UTSW |
8 |
92,031,638 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9258:Rpgrip1l
|
UTSW |
8 |
91,987,614 (GRCm39) |
nonsense |
probably null |
|
|
R9268:Rpgrip1l
|
UTSW |
8 |
92,007,355 (GRCm39) |
missense |
probably benign |
|
|
R9366:Rpgrip1l
|
UTSW |
8 |
91,996,809 (GRCm39) |
nonsense |
probably null |
|
|
R9547:Rpgrip1l
|
UTSW |
8 |
91,977,873 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9565:Rpgrip1l
|
UTSW |
8 |
92,031,516 (GRCm39) |
missense |
probably benign |
0.05 |
|
R9582:Rpgrip1l
|
UTSW |
8 |
91,996,886 (GRCm39) |
missense |
probably benign |
0.03 |
|
R9604:Rpgrip1l
|
UTSW |
8 |
92,031,433 (GRCm39) |
missense |
possibly damaging |
0.67 |
|
R9614:Rpgrip1l
|
UTSW |
8 |
91,987,434 (GRCm39) |
missense |
possibly damaging |
0.79 |
|
R9697:Rpgrip1l
|
UTSW |
8 |
91,987,391 (GRCm39) |
missense |
possibly damaging |
0.49 |
|
Z1088:Rpgrip1l
|
UTSW |
8 |
91,996,748 (GRCm39) |
missense |
possibly damaging |
0.89 |
|
Z1088:Rpgrip1l
|
UTSW |
8 |
91,987,603 (GRCm39) |
missense |
possibly damaging |
0.96 |
|
Z1088:Rpgrip1l
|
UTSW |
8 |
91,946,807 (GRCm39) |
makesense |
probably null |
|
|
| Protein Function and Prediction |
RPGRIP1L is a primary cilia protein essential for left-right asymmetry and patterning of the neural tube and limbs [reviewed in (1)]. It is also propsed to be involved in the Hedgehog signaling pathway [(2); reviewed in (1)]. Mutations in RPGRIP1L can alter its interaction with nephrocystin-4, a protein involved in nephronophthisis (3).
|
| Expression/Localization |
There is ubiquitous RPGRIP1L expression in human embryonic and fetal tissues, including brain, forelimbs, and kidney, confirming its importance in early development (4). RT-PCR detected strong expression of RPGRIP1L in ubiquitous RPGRIP1L expression in adult human testis and kidney and fetal eye, brain, and kidney (5). RPGRIP1L is localized to primary cilia and centrosomes (4;5).
|
| Background |
Mutations in RPGRIP1L have been found in cases of COACH syndrome (OMIM: 216360), Joubert syndrome 7 (OMIM: 611560), and Meckel syndrome 5 (OMIM: 611561). COACH syndrome and Joubert syndrome are characterized by mental retardation and ataxia (4-6). Patients with Meckel syndrome have anencephaly, occipital encephalocele, postaxial polydactyly, cleft lip and palate, microphthalmia, severe cystic kidney disease, and hepatic bile duct proliferation, and bowing of the long bones (4).
Rpgrip1ltm1Urt/tm1Urt; MGI:3716208
involves: 129S1/Sv * 129X1/SvJ
This model has complete perinatal lethality with embryos or mice perishing around the time of birth (2;4). The mice also display inverted tail turning and less celia in the neural tube at around E11 (2). The embryos have heterotaxia in organ development and the embryos develop only two symmetrical lung lobes (2). The animals also have polydactyly, execencephaly, and microphtalmia (2;4). The brains of the animals are affected due to the loss of Rpgrip1l expression: they have reduced or absent pituitary diverticulum, corpus callosum, and olfactory bulb (4).
|
| References |
2. Vierkotten, J., Dildrop, R., Peters, T., Wang, B., and Ruther, U. (2007) Ftm is a Novel Basal Body Protein of Cilia Involved in Shh Signalling. Development. 134, 2569-2577.
3. Roepman, R., Letteboer, S. J., Arts, H. H., van Beersum, S. E., Lu, X., Krieger, E., Ferreira, P. A., and Cremers, F. P. (2005) Interaction of Nephrocystin-4 and RPGRIP1 is Disrupted by Nephronophthisis Or Leber Congenital Amaurosis-Associated Mutations. Proc Natl Acad Sci U S A. 102, 18520-18525.
4. Delous, M., Baala, L., Salomon, R., Laclef, C., Vierkotten, J., Tory, K., Golzio, C., Lacoste, T., Besse, L., Ozilou, C., Moutkine, I., Hellman, N. E., Anselme, I., Silbermann, F., Vesque, C., Gerhardt, C., Rattenberry, E., Wolf, M. T., Gubler, M. C., Martinovic, J., Encha-Razavi, F., Boddaert, N., Gonzales, M., Macher, M. A., Nivet, H., Champion, G., Bertheleme, J. P., Niaudet, P., McDonald, F., Hildebrandt, F., Johnson, C. A., Vekemans, M., Antignac, C., Ruther, U., Schneider-Maunoury, S., Attie-Bitach, T., and Saunier, S. (2007) The Ciliary Gene RPGRIP1L is Mutated in Cerebello-Oculo-Renal Syndrome (Joubert Syndrome Type B) and Meckel Syndrome. Nat Genet. 39, 875-881.
5. Arts, H. H., Doherty, D., van Beersum, S. E., Parisi, M. A., Letteboer, S. J., Gorden, N. T., Peters, T. A., Marker, T., Voesenek, K., Kartono, A., Ozyurek, H., Farin, F. M., Kroes, H. Y., Wolfrum, U., Brunner, H. G., Cremers, F. P., Glass, I. A., Knoers, N. V., and Roepman, R. (2007) Mutations in the Gene Encoding the Basal Body Protein RPGRIP1L, a Nephrocystin-4 Interactor, Cause Joubert Syndrome. Nat Genet. 39, 882-888.
6. Brancati, F., Travaglini, L., Zablocka, D., Boltshauser, E., Accorsi, P., Montagna, G., Silhavy, J. L., Barrano, G., Bertini, E., Emma, F., Rigoli, L., International JSRD Study Group, Dallapiccola, B., Gleeson, J. G., and Valente, E. M. (2008) RPGRIP1L Mutations are mainly Associated with the Cerebello-Renal Phenotype of Joubert Syndrome-Related Disorders. Clin Genet. 74, 164-170. |
| Posted On |
2012-10-05 |
| Science Writer |
Anne Murray |
Incidental Mutation