Incidental Mutation 'P0012:Arhgap1'
ID7567
Institutional Source Beutler Lab
Gene Symbol Arhgap1
Ensembl Gene ENSMUSG00000027247
Gene NameRho GTPase activating protein 1
SynonymsCdc42GAP, p50rhoGAP, B230365D05Rik
MMRRC Submission 038266-MU
Accession Numbers

NCBI RefSeq: NM_001145902.1; NM_146124.4; MGI: 2445003

Is this an essential gene? Possibly non essential (E-score: 0.278) question?
Stock #P0012 (G1)
Quality Score
Status Validated
Chromosome2
Chromosomal Location91649860-91672326 bp(+) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) T to C at 91670263 bp
ZygosityHeterozygous
Amino Acid Change Valine to Alanine at position 379 (V379A)
Ref Sequence ENSEMBL: ENSMUSP00000106963 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000028678] [ENSMUST00000076803] [ENSMUST00000090614] [ENSMUST00000111329] [ENSMUST00000111330] [ENSMUST00000111331]
Predicted Effect probably benign
Transcript: ENSMUST00000028678
SMART Domains Protein: ENSMUSP00000028678
Gene: ENSMUSG00000027244

DomainStartEndE-ValueType
Pfam:ATG13 77 195 1.5e-10 PFAM
low complexity region 252 269 N/A INTRINSIC
low complexity region 423 442 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000076803
SMART Domains Protein: ENSMUSP00000076081
Gene: ENSMUSG00000027244

DomainStartEndE-ValueType
Pfam:ATG13 17 195 1.1e-35 PFAM
low complexity region 386 405 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000090614
AA Change: V339A

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
SMART Domains Protein: ENSMUSP00000088105
Gene: ENSMUSG00000027247
AA Change: V339A

DomainStartEndE-ValueType
low complexity region 4 18 N/A INTRINSIC
low complexity region 42 52 N/A INTRINSIC
SEC14 64 215 5.08e-25 SMART
low complexity region 224 238 N/A INTRINSIC
RhoGAP 257 428 1.06e-61 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000111329
AA Change: V339A

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
SMART Domains Protein: ENSMUSP00000106961
Gene: ENSMUSG00000027247
AA Change: V339A

DomainStartEndE-ValueType
low complexity region 4 18 N/A INTRINSIC
low complexity region 42 52 N/A INTRINSIC
SEC14 64 215 5.08e-25 SMART
low complexity region 224 238 N/A INTRINSIC
RhoGAP 257 428 1.06e-61 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000111330
AA Change: V339A

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
SMART Domains Protein: ENSMUSP00000106962
Gene: ENSMUSG00000027247
AA Change: V339A

DomainStartEndE-ValueType
low complexity region 4 18 N/A INTRINSIC
low complexity region 42 52 N/A INTRINSIC
SEC14 64 215 5.08e-25 SMART
low complexity region 224 238 N/A INTRINSIC
RhoGAP 257 428 1.06e-61 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000111331
AA Change: V379A

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)
SMART Domains Protein: ENSMUSP00000106963
Gene: ENSMUSG00000027247
AA Change: V379A

DomainStartEndE-ValueType
low complexity region 44 58 N/A INTRINSIC
low complexity region 82 92 N/A INTRINSIC
SEC14 104 255 5.08e-25 SMART
low complexity region 264 278 N/A INTRINSIC
RhoGAP 297 468 1.06e-61 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000123702
Predicted Effect noncoding transcript
Transcript: ENSMUST00000141012
Predicted Effect noncoding transcript
Transcript: ENSMUST00000149426
Meta Mutation Damage Score 0.106 question?
Coding Region Coverage
  • 1x: 85.5%
  • 3x: 81.0%
  • 10x: 67.7%
  • 20x: 52.2%
Validation Efficiency 85% (579/685)
MGI Phenotype Strain: 3606252
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of a large family of proteins that activate Rho-type guanosine triphosphate (GTP) metabolizing enzymes. The encoded protein contains a SRC homology 3 domain and interacts with Bcl-2-associated protein family members. [provided by RefSeq, Aug 2012]
PHENOTYPE: Homozygous null mice display incomplete penetrance of postnatal lethality, increased apoptosis, and growth retardation. [provided by MGI curators]
Allele List at MGI

All alleles(28) : Targeted(1) Gene trapped(27)

Other mutations in this stock
Total: 9 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adamtsl3 A C 7: 82,574,257 N156T probably benign Het
Akap3 T C 6: 126,864,601 F61S possibly damaging Het
Ces1h T C 8: 93,353,510 K459E unknown Het
Fbn1 T C 2: 125,369,321 probably benign Het
Hrh2 T C 13: 54,214,428 F141S probably benign Het
Igkv3-4 A T 6: 70,672,247 N77Y probably benign Het
Nup205 T C 6: 35,196,543 M496T possibly damaging Het
Tas2r124 T C 6: 132,755,540 Y271H possibly damaging Het
Tnfrsf11b A G 15: 54,259,798 probably benign Het
Other mutations in Arhgap1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01876:Arhgap1 APN 2 91650219 unclassified probably null
IGL02283:Arhgap1 APN 2 91670776 missense probably damaging 1.00
IGL02540:Arhgap1 APN 2 91670239 missense probably damaging 1.00
P0041:Arhgap1 UTSW 2 91669393 missense probably benign 0.03
R0049:Arhgap1 UTSW 2 91670169 missense probably damaging 1.00
R0049:Arhgap1 UTSW 2 91670169 missense probably damaging 1.00
R1385:Arhgap1 UTSW 2 91670831 missense probably damaging 1.00
R4386:Arhgap1 UTSW 2 91668237 missense probably damaging 1.00
R5774:Arhgap1 UTSW 2 91654108 missense possibly damaging 0.91
R6985:Arhgap1 UTSW 2 91668198 missense probably damaging 1.00
Protein Function and Prediction

RHO GTPase-activating protein 1 [Arhgap1; alternatively, RhoGAP1 (1), Cdc42GAP (2), or p50RhoGAP (3)] is a member of the RhoGAP family of proteins, negative regulators of Rho GTPases (4).  RhoGAP1 stimulates the GTPase activity of p21-Rho, a member of the Rho family of GTP-binding proteins that can modulate cytoskeletal changes [OMIM *602732; (1)].  In addition, RhoGAP1 inactivates Cdc42 via GTP hydrolysis stimulation to regulate cytoskeletal rearrangements needed for cell division (2;3).  Studies in yeast have shown that Cdc42 is also necessary for survival, growth, and development (5).

Expression/Localization

RhoGAP1 is ubiquitously expressed in the mouse (4).

Background

Arhgap1tm1Yizh/ tm1Yizh; MGI:3606252

involves: 129S6/SvEvTac

Approximatley 93% of pups die before weaning (4).  Also, the embryos are 25-40% smaller than wild-type animals; animals that that survive past weaning are about 30% smaller but are fertile (4).  Embryonic fibroblasts, the embryonic liver, and embryonic brain from this model exhibit increased apoptosis; cell proliferation and cell cycle are normal (4).

 

Arhgap1tm1Yizh/ tm1Yizh; MGI:3606252

involves: 129S6/SvEvTac * C57BL/6

In this genetic background, the majority of mutants die during the neonatal period; approximately 7% survive when placed under foster care (6).  Those that survive to adulthood, have a premature lifespan (~12 months) (6). The animals also have premature aging-like phenotypes, including reduction in body mass, loss of subdermal adipose tissue, severe lordokyphosis (i.e., poor posture), muscle atrophy, osteoporosis, and reduction of reepithelialization ability in wound healing (6). Embryonic fibroblasts from this model have reduced DNA damage repair activity after DNA-damaging agent treatment (6). Also, the animals develop anemia and have reduced cellularity in the spleen, bone marrow, kidney, and liver (6).  The T and B cell containing white pulp regions in the spleen are reduced in 12 month old mutants (6).

References
Posted On2012-10-04
Science WriterAnne Murray