Incidental Mutation 'R0039:Arhgap5'
| ID |
15518 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Arhgap5
|
| Ensembl Gene |
ENSMUSG00000035133 |
| Gene Name |
Rho GTPase activating protein 5 |
| Synonyms |
p190B, p190-B |
| MMRRC Submission |
038333-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R0039 (G1)
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
12 |
| Chromosomal Location |
52550755-52618758 bp(+) (GRCm39) |
| Type of Mutation |
nonsense |
| DNA Base Change (assembly) |
C to T
at 52565518 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Glutamine to Stop codon
at position 830
(Q830*)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000151809
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000110725]
[ENSMUST00000217820]
[ENSMUST00000219443]
|
| AlphaFold |
no structure available at present |
| Predicted Effect |
probably null
Transcript: ENSMUST00000110725
AA Change: Q830*
|
| SMART Domains |
Protein: ENSMUSP00000106353
Gene: ENSMUSG00000035133
AA Change: Q830*
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Ras
|
142 |
248 |
5.3e-7 |
PFAM |
|
FF
|
269 |
325 |
6.03e-12 |
SMART |
|
FF
|
367 |
420 |
4.61e-8 |
SMART |
|
FF
|
427 |
482 |
2.22e-10 |
SMART |
|
FF
|
483 |
537 |
3.89e-6 |
SMART |
|
low complexity region
|
1035 |
1053 |
N/A |
INTRINSIC |
|
low complexity region
|
1224 |
1247 |
N/A |
INTRINSIC |
|
RhoGAP
|
1273 |
1447 |
1.03e-73 |
SMART |
|
low complexity region
|
1479 |
1496 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000217820
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000218755
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000218869
|
| Predicted Effect |
probably null
Transcript: ENSMUST00000219443
AA Change: Q830*
|
| Meta Mutation Damage Score |
0.9755 |
| Coding Region Coverage |
- 1x: 82.5%
- 3x: 74.4%
- 10x: 54.3%
- 20x: 37.4%
|
| Validation Efficiency |
95% (60/63) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Rho GTPase activating protein 5 negatively regulates RHO GTPases, a family which may mediate cytoskeleton changes by stimulating the hydrolysis of bound GTP. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygotes die at birth, are 30% smaller, do not inflate their lungs, and show a small thymus, abnormal adipocyte differentiation and brain defects in the corpus callosum, anterior commissure and lateral ventricles. Mutant MEFs show impaired adipogenesis but undergo myogenesis in response to IGF-1. [provided by MGI curators]
|
| Allele List at MGI |
All alleles(4) : Targeted, knock-out(1) Gene trapped(3)
|
| Other mutations in this stock |
Total: 29 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Atic |
A |
T |
1: 71,617,009 (GRCm39) |
E523V |
possibly damaging |
Het |
| Cass4 |
T |
A |
2: 172,268,900 (GRCm39) |
F329L |
probably damaging |
Het |
| Cdk17 |
A |
T |
10: 93,062,640 (GRCm39) |
|
probably benign |
Het |
| Cep120 |
C |
T |
18: 53,819,033 (GRCm39) |
R886H |
probably benign |
Het |
| Cep170 |
A |
C |
1: 176,610,061 (GRCm39) |
|
probably null |
Het |
| Dsg3 |
A |
G |
18: 20,654,541 (GRCm39) |
K82E |
probably benign |
Het |
| Dtd1 |
C |
T |
2: 144,588,896 (GRCm39) |
R185W |
probably damaging |
Het |
| Glt6d1 |
C |
A |
2: 25,684,739 (GRCm39) |
|
probably null |
Het |
| Hectd1 |
T |
G |
12: 51,800,608 (GRCm39) |
E2070A |
possibly damaging |
Het |
| Ifit1bl2 |
T |
A |
19: 34,596,846 (GRCm39) |
K257* |
probably null |
Het |
| Ighv8-5 |
T |
A |
12: 115,031,207 (GRCm39) |
T111S |
possibly damaging |
Het |
| Lmtk2 |
G |
T |
5: 144,103,205 (GRCm39) |
L321F |
probably damaging |
Het |
| Mcoln2 |
C |
T |
3: 145,889,316 (GRCm39) |
T374M |
probably damaging |
Het |
| Mfn1 |
T |
C |
3: 32,592,416 (GRCm39) |
|
probably benign |
Het |
| Miox |
C |
T |
15: 89,220,477 (GRCm39) |
L189F |
possibly damaging |
Het |
| Mroh8 |
T |
C |
2: 157,071,849 (GRCm39) |
H552R |
possibly damaging |
Het |
| Myh2 |
T |
A |
11: 67,069,103 (GRCm39) |
L304Q |
probably damaging |
Het |
| Prune1 |
T |
A |
3: 95,169,678 (GRCm39) |
T175S |
probably damaging |
Het |
| Rdh10 |
C |
T |
1: 16,199,508 (GRCm39) |
T238I |
probably damaging |
Het |
| Rlf |
T |
A |
4: 121,004,039 (GRCm39) |
H1647L |
possibly damaging |
Het |
| Rreb1 |
C |
T |
13: 38,083,613 (GRCm39) |
T92M |
probably damaging |
Het |
| Scn9a |
A |
T |
2: 66,392,788 (GRCm39) |
M268K |
probably damaging |
Het |
| Sec16a |
A |
G |
2: 26,313,926 (GRCm39) |
V1893A |
probably benign |
Het |
| Snd1 |
T |
A |
6: 28,745,209 (GRCm39) |
L518Q |
probably damaging |
Het |
| Stat1 |
T |
A |
1: 52,179,819 (GRCm39) |
V343D |
probably damaging |
Het |
| Topors |
A |
G |
4: 40,262,772 (GRCm39) |
S171P |
probably damaging |
Het |
| Tubd1 |
C |
T |
11: 86,440,221 (GRCm39) |
Q82* |
probably null |
Het |
| Unc13c |
A |
G |
9: 73,576,847 (GRCm39) |
|
probably benign |
Het |
| Wdr43 |
G |
T |
17: 71,960,487 (GRCm39) |
G590* |
probably null |
Het |
|
| Other mutations in Arhgap5 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00679:Arhgap5
|
APN |
12 |
52,564,064 (GRCm39) |
missense |
probably damaging |
0.98 |
|
IGL00823:Arhgap5
|
APN |
12 |
52,565,525 (GRCm39) |
missense |
possibly damaging |
0.84 |
|
IGL01161:Arhgap5
|
APN |
12 |
52,563,643 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01360:Arhgap5
|
APN |
12 |
52,565,023 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01910:Arhgap5
|
APN |
12 |
52,563,644 (GRCm39) |
missense |
probably benign |
0.33 |
|
IGL02417:Arhgap5
|
APN |
12 |
52,565,136 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL02448:Arhgap5
|
APN |
12 |
52,609,123 (GRCm39) |
missense |
probably damaging |
0.97 |
|
IGL02813:Arhgap5
|
APN |
12 |
52,563,748 (GRCm39) |
missense |
probably benign |
0.20 |
|
IGL03398:Arhgap5
|
APN |
12 |
52,564,094 (GRCm39) |
missense |
probably damaging |
0.99 |
|
Decline
|
UTSW |
12 |
52,563,365 (GRCm39) |
nonsense |
probably null |
|
|
Pass
|
UTSW |
12 |
52,563,290 (GRCm39) |
missense |
possibly damaging |
0.82 |
|
3-1:Arhgap5
|
UTSW |
12 |
52,565,665 (GRCm39) |
missense |
possibly damaging |
0.54 |
|
R0088:Arhgap5
|
UTSW |
12 |
52,563,331 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0104:Arhgap5
|
UTSW |
12 |
52,563,500 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0111:Arhgap5
|
UTSW |
12 |
52,606,743 (GRCm39) |
splice site |
probably benign |
|
|
R0356:Arhgap5
|
UTSW |
12 |
52,563,091 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0616:Arhgap5
|
UTSW |
12 |
52,563,848 (GRCm39) |
missense |
possibly damaging |
0.79 |
|
R0707:Arhgap5
|
UTSW |
12 |
52,564,951 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0718:Arhgap5
|
UTSW |
12 |
52,563,290 (GRCm39) |
missense |
possibly damaging |
0.82 |
|
R0849:Arhgap5
|
UTSW |
12 |
52,566,406 (GRCm39) |
missense |
probably benign |
0.01 |
|
R0975:Arhgap5
|
UTSW |
12 |
52,563,927 (GRCm39) |
missense |
possibly damaging |
0.61 |
|
R1326:Arhgap5
|
UTSW |
12 |
52,565,153 (GRCm39) |
missense |
possibly damaging |
0.80 |
|
R1421:Arhgap5
|
UTSW |
12 |
52,563,631 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1422:Arhgap5
|
UTSW |
12 |
52,566,297 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1625:Arhgap5
|
UTSW |
12 |
52,564,159 (GRCm39) |
missense |
probably benign |
|
|
R1711:Arhgap5
|
UTSW |
12 |
52,566,128 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1970:Arhgap5
|
UTSW |
12 |
52,589,376 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2004:Arhgap5
|
UTSW |
12 |
52,564,817 (GRCm39) |
missense |
probably benign |
0.05 |
|
R2356:Arhgap5
|
UTSW |
12 |
52,565,930 (GRCm39) |
missense |
probably benign |
0.00 |
|
R3792:Arhgap5
|
UTSW |
12 |
52,566,671 (GRCm39) |
missense |
probably benign |
0.21 |
|
R3808:Arhgap5
|
UTSW |
12 |
52,613,970 (GRCm39) |
missense |
possibly damaging |
0.72 |
|
R4458:Arhgap5
|
UTSW |
12 |
52,564,740 (GRCm39) |
missense |
probably benign |
|
|
R4703:Arhgap5
|
UTSW |
12 |
52,564,366 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R4736:Arhgap5
|
UTSW |
12 |
52,565,860 (GRCm39) |
missense |
probably benign |
0.00 |
|
R4737:Arhgap5
|
UTSW |
12 |
52,565,860 (GRCm39) |
missense |
probably benign |
0.00 |
|
R4740:Arhgap5
|
UTSW |
12 |
52,565,860 (GRCm39) |
missense |
probably benign |
0.00 |
|
R4768:Arhgap5
|
UTSW |
12 |
52,604,275 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4806:Arhgap5
|
UTSW |
12 |
52,565,486 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R4817:Arhgap5
|
UTSW |
12 |
52,565,992 (GRCm39) |
missense |
possibly damaging |
0.71 |
|
R5586:Arhgap5
|
UTSW |
12 |
52,566,695 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
R5681:Arhgap5
|
UTSW |
12 |
52,566,562 (GRCm39) |
missense |
probably benign |
0.21 |
|
R5683:Arhgap5
|
UTSW |
12 |
52,566,369 (GRCm39) |
missense |
probably benign |
|
|
R5911:Arhgap5
|
UTSW |
12 |
52,565,525 (GRCm39) |
missense |
possibly damaging |
0.84 |
|
R6448:Arhgap5
|
UTSW |
12 |
52,564,446 (GRCm39) |
missense |
probably benign |
0.11 |
|
R6887:Arhgap5
|
UTSW |
12 |
52,565,927 (GRCm39) |
missense |
probably benign |
|
|
R6988:Arhgap5
|
UTSW |
12 |
52,564,908 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R7009:Arhgap5
|
UTSW |
12 |
52,566,422 (GRCm39) |
missense |
probably benign |
0.03 |
|
R7013:Arhgap5
|
UTSW |
12 |
52,565,109 (GRCm39) |
missense |
probably benign |
0.05 |
|
R7239:Arhgap5
|
UTSW |
12 |
52,564,159 (GRCm39) |
missense |
probably benign |
|
|
R7310:Arhgap5
|
UTSW |
12 |
52,589,270 (GRCm39) |
critical splice acceptor site |
probably null |
|
|
R7339:Arhgap5
|
UTSW |
12 |
52,564,481 (GRCm39) |
missense |
possibly damaging |
0.64 |
|
R7375:Arhgap5
|
UTSW |
12 |
52,563,365 (GRCm39) |
nonsense |
probably null |
|
|
R7421:Arhgap5
|
UTSW |
12 |
52,564,783 (GRCm39) |
missense |
probably benign |
0.42 |
|
R7442:Arhgap5
|
UTSW |
12 |
52,563,739 (GRCm39) |
missense |
probably benign |
0.25 |
|
R7842:Arhgap5
|
UTSW |
12 |
52,565,480 (GRCm39) |
missense |
possibly damaging |
0.78 |
|
R8079:Arhgap5
|
UTSW |
12 |
52,613,988 (GRCm39) |
missense |
probably benign |
|
|
R8241:Arhgap5
|
UTSW |
12 |
52,565,098 (GRCm39) |
missense |
probably benign |
0.00 |
|
R8419:Arhgap5
|
UTSW |
12 |
52,565,572 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9138:Arhgap5
|
UTSW |
12 |
52,609,146 (GRCm39) |
missense |
probably benign |
0.05 |
|
X0018:Arhgap5
|
UTSW |
12 |
52,565,180 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Z1176:Arhgap5
|
UTSW |
12 |
52,565,246 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
| Nature of Mutation |
Two transcripts of the Arhgap5 gene are displayed on Ensembl.
|
| Protein Function and Prediction |
The Arhgap5 gene encodes a 1503 amino acid GTPase-activating protein for Rho family members. The protein contains 4 FF domains, and a Rho-GAP domain at residues 1261-1448 (Uniprot P97393). Arhgap5 (alternatively, p190B) is a cytosolic Rho family GTPase-activating protein that is co-localized with the alpha 5 beta 1 integrin receptor for fibronectin in fibrillar patterns (1;2). P190B functions to regulate actin stress fiber dynamics through the hydrolysis of Rho-GTP (2-4). Through its function in hydrolyzing Rho-GTP, p190B also regulates cell cycle progression (3).The GAP domain is crucial for the regulation of actin cytoskeletal rearrangements in axonal pathfinding and stability (5-8) and in response to integrin engagement (9;10), growth factor stimulation (4), and v-Src transformation (11). When p190B heterozygous mice mated to a MMTV-Neu breast cancer model, tumor penetrance was reduced and tumor onset was delayed (12). Further studies determined that p190B regulates chromosome segregation and apoptosis in cancer cells (13).
|
| Expression/Localization |
p190B localizes to centrosomes during interphase and mitosis (13).
|
| Background |
Arhgap5tm1Jset/tm1Jset; MGI:2179998
involves: 129S2/SvPas * C57BL/6J
Homozygotes die at birth, are 30% smaller, do not inflate their lungs, and show a small thymus, abnormal adipocyte differentiation and brain defects in the corpus callosum, anterior commissure and lateral ventricles (14). Mutant MEFs show impaired adipogenesis but undergo myogenesis in response to IGF-1 (14). Also depletion in Arhgap5 leads to decreased incidence of mammary ductal morphogenesis (15).
|
| References |
1. Burbelo, P. D., Miyamoto, S., Utani, A., Brill, S., Yamada, K. M., Hall, A., and Yamada, Y. (1995) P190-B, a New Member of the Rho GAP Family, and Rho are Induced to Cluster After Integrin Cross-Linking. J Biol Chem. 270, 30919-30926.
2. Ridley, A. J., Self, A. J., Kasmi, F., Paterson, H. F., Hall, A., Marshall, C. J., and Ellis, C. (1993) Rho Family GTPase Activating Proteins p190, Bcr and rhoGAP show Distinct Specificities in Vitro and in Vivo. EMBO J. 12, 5151-5160.
4. Chang, J. H., Gill, S., Settleman, J., and Parsons, S. J. (1995) C-Src Regulates the Simultaneous Rearrangement of Actin Cytoskeleton, p190RhoGAP, and p120RasGAP Following Epidermal Growth Factor Stimulation. J Cell Biol. 130, 355-368.
5. Brouns, M. R., Matheson, S. F., Hu, K. Q., Delalle, I., Caviness, V. S., Silver, J., Bronson, R. T., and Settleman, J. (2000) The Adhesion Signaling Molecule p190 RhoGAP is Required for Morphogenetic Processes in Neural Development. Development. 127, 4891-4903.
7. Billuart, P., Winter, C. G., Maresh, A., Zhao, X., and Luo, L. (2001) Regulating Axon Branch Stability: The Role of p190 RhoGAP in Repressing a Retraction Signaling Pathway. Cell. 107, 195-207.
10. Nakahara, H., Mueller, S. C., Nomizu, M., Yamada, Y., Yeh, Y., and Chen, W. T. (1998) Activation of beta1 Integrin Signaling Stimulates Tyrosine Phosphorylation of p190RhoGAP and Membrane-Protrusive Activities at Invadopodia. J Biol Chem. 273, 9-12.
12. Heckman-Stoddard, B. M., Vargo-Gogola, T., McHenry, P. R., Jiang, V., Herrick, M. P., Hilsenbeck, S. G., Settleman, J., and Rosen, J. M. (2009) Haploinsufficiency for p190B RhoGAP Inhibits MMTV-Neu Tumor Progression. Breast Cancer Res. 11, R61.
13. Hwang, M., Peddibhotla, S., McHenry, P., Chang, P., Yochum, Z., Park, K. U., Sears, J. C., and Vargo-Gogola, T. (2012) P190B RhoGAP Regulates Chromosome Segregation in Cancer Cells. Cancers (Basel). 4, 475-489.
14. Sordella, R., Classon, M., Hu, K. Q., Matheson, S. F., Brouns, M. R., Fine, B., Zhang, L., Takami, H., Yamada, Y., and Settleman, J. (2002) Modulation of CREB Activity by the Rho GTPase Regulates Cell and Organism Size during Mouse Embryonic Development. Dev Cell. 2, 553-565.
15. Chakravarty, G., Hadsell, D., Buitrago, W., Settleman, J., and Rosen, J. M. (2003) P190-B RhoGAP Regulates Mammary Ductal Morphogenesis. Mol Endocrinol. 17, 1054-1065. |
| Posted On |
2012-12-21 |
| Science Writer |
Anne Murray |
Incidental Mutation