Incidental Mutation 'D4043:Adgrg1'
ID252
Institutional Source Beutler Lab
Gene Symbol Adgrg1
Ensembl Gene ENSMUSG00000031785
Gene Nameadhesion G protein-coupled receptor G1
SynonymsCyt28, Gpr56
Accession Numbers
Is this an essential gene? Non essential (E-score: 0.000) question?
Stock #D4043 (G3) of strain 483
Quality Score
Status Validated
Chromosome8
Chromosomal Location94974751-95014217 bp(+) (GRCm38)
Type of Mutationunclassified (2 bp from exon)
DNA Base Change (assembly) T to C at 95005229 bp
ZygosityHomozygous
Amino Acid Change
Ref Sequence ENSEMBL: ENSMUSP00000148304 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000093271] [ENSMUST00000179619] [ENSMUST00000211944] [ENSMUST00000211984] [ENSMUST00000212118] [ENSMUST00000212141] [ENSMUST00000212531] [ENSMUST00000212581] [ENSMUST00000212660] [ENSMUST00000212799] [ENSMUST00000212956] [ENSMUST00000212976] [ENSMUST00000212995]
Predicted Effect probably benign
Transcript: ENSMUST00000093271
AA Change: V168A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000090959
Gene: ENSMUSG00000031785
AA Change: V168A

DomainStartEndE-ValueType
signal peptide 1 25 N/A INTRINSIC
GPS 342 394 1.42e-12 SMART
Pfam:7tm_2 400 648 8.1e-32 PFAM
low complexity region 678 685 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000179619
AA Change: V168A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000137520
Gene: ENSMUSG00000031785
AA Change: V168A

DomainStartEndE-ValueType
signal peptide 1 25 N/A INTRINSIC
GPS 342 394 1.42e-12 SMART
Pfam:7tm_2 400 648 3.4e-31 PFAM
low complexity region 678 685 N/A INTRINSIC
Predicted Effect noncoding transcript
Transcript: ENSMUST00000211806
Predicted Effect noncoding transcript
Transcript: ENSMUST00000211850
Predicted Effect noncoding transcript
Transcript: ENSMUST00000211911
Predicted Effect probably benign
Transcript: ENSMUST00000211944
Predicted Effect probably benign
Transcript: ENSMUST00000211984
AA Change: V168A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
Predicted Effect probably null
Transcript: ENSMUST00000212118
Predicted Effect probably benign
Transcript: ENSMUST00000212141
AA Change: V168A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
Predicted Effect probably benign
Transcript: ENSMUST00000212531
Predicted Effect probably benign
Transcript: ENSMUST00000212581
Predicted Effect probably benign
Transcript: ENSMUST00000212660
AA Change: V168A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
Predicted Effect probably benign
Transcript: ENSMUST00000212799
Predicted Effect probably benign
Transcript: ENSMUST00000212956
Predicted Effect probably benign
Transcript: ENSMUST00000212976
AA Change: V173A

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
Predicted Effect probably benign
Transcript: ENSMUST00000212995
Meta Mutation Damage Score 0.1124 question?
Coding Region Coverage
  • 1x: 88.8%
  • 3x: 72.5%
Validation Efficiency 88% (220/249)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the G protein-coupled receptor family and regulates brain cortical patterning. The encoded protein binds specifically to transglutaminase 2, a component of tissue and tumor stroma implicated as an inhibitor of tumor progression. Mutations in this gene are associated with a brain malformation known as bilateral frontoparietal polymicrogyria. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]
PHENOTYPE: Mice homozygous for a null allele exhibit neuronal ectopias in the frontoparietal cortex due to disruptions in the pial basement membrane. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 25 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1110020G09Rik T A 15: 9,103,385 probably benign Homo
1700029J07Rik A G 8: 45,956,403 V293A probably damaging Het
Adam29 A T 8: 55,872,461 C319* probably null Het
Ago3 A T 4: 126,351,003 V630E probably damaging Het
Armc8 G T 9: 99,483,976 N628K probably benign Het
Chd7 A G 4: 8,862,650 D2579G probably damaging Het
Duox1 G A 2: 122,344,795 C1358Y probably benign Het
Fam208a A G 14: 27,471,992 I1050V probably benign Het
Ftsj3 C A 11: 106,254,808 M66I possibly damaging Homo
Iqub C T 6: 24,505,751 E53K possibly damaging Het
Kirrel T A 3: 87,083,203 T771S probably benign Het
Lrrc66 A T 5: 73,607,526 S725T probably benign Het
Mael T C 1: 166,236,886 I104M probably benign Homo
Mkks C T 2: 136,874,610 V457I probably benign Het
Npas1 T C 7: 16,463,244 probably null Het
Ocrl T C X: 47,936,323 V359A probably benign Homo
Olfr1065 G A 2: 86,445,220 T254M probably damaging Het
Pde6b C T 5: 108,425,356 R531* probably null Het
Polr1a G A 6: 71,941,417 C653Y possibly damaging Het
Rbm26 A G 14: 105,152,540 V216A possibly damaging Het
Rin2 C A 2: 145,822,363 H52Q possibly damaging Het
Ssc5d C T 7: 4,943,983 T1112I possibly damaging Het
Sv2c C T 13: 96,088,481 V107M probably benign Het
Tulp3 G A 6: 128,324,150 S366L probably benign Het
Zfp831 T A 2: 174,645,266 V578E probably benign Homo
Other mutations in Adgrg1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00983:Adgrg1 APN 8 95005243 missense probably damaging 1.00
IGL01138:Adgrg1 APN 8 95003457 missense probably damaging 1.00
IGL01806:Adgrg1 APN 8 95012931 missense probably damaging 1.00
IGL02229:Adgrg1 APN 8 95003511 missense probably damaging 1.00
IGL03109:Adgrg1 APN 8 95007676 unclassified probably benign
R0383:Adgrg1 UTSW 8 95011742 missense probably damaging 1.00
R1155:Adgrg1 UTSW 8 95006840 missense possibly damaging 0.92
R1656:Adgrg1 UTSW 8 95011810 nonsense probably null
R1944:Adgrg1 UTSW 8 95007300 missense probably damaging 0.99
R1952:Adgrg1 UTSW 8 95008491 critical splice donor site probably null
R2408:Adgrg1 UTSW 8 95003493 missense probably null 1.00
R3776:Adgrg1 UTSW 8 95009655 missense probably damaging 0.99
R3813:Adgrg1 UTSW 8 95011565 missense probably benign 0.34
R4254:Adgrg1 UTSW 8 95005902 unclassified probably null
R4255:Adgrg1 UTSW 8 95005902 unclassified probably null
R4951:Adgrg1 UTSW 8 95005246 missense probably damaging 1.00
R4997:Adgrg1 UTSW 8 95009520 missense probably damaging 1.00
R5152:Adgrg1 UTSW 8 95009745 missense probably damaging 1.00
R6122:Adgrg1 UTSW 8 95002501 missense probably benign 0.45
R6897:Adgrg1 UTSW 8 95002498 missense probably benign
Nature of Mutation
DNA sequencing using the SOLiD technique identified a T to C transition at position 569 of the Gpr56 transcript in exon 4 of 14 total exons. The mutated nucleotide causes a valine to alanine substitution at amino acid 168 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function and Prediction
The Gpr56 gene encodes a 687amino acid G-protein coupled receptor (GPCR) that may be involved in cell-cell interactions. All GPCRs are seven-pass membrane proteins and signal through heterotrimic G proteins. The extracellular N-terminal region (aa 26-402) contains a mucin-like domain and a cysteine box (Uniprot Q8K209). Mice homozygous for a null allele exhibit neuronal ectopias in the frontoparietal cortex due to disruptions in the pial basement membrane. Homozygous mutations in humans result in bilateral frontoparietal polymicrogyria (BFPP; OMIM 606854). All of the human missense mutations affected extracellular portions of the protein and were found mostly in the N-terminal region.
 
The V168A change is located in the N-terminal region of the protein, and is predicted to be benign by the PolyPhen program.
Posted On2010-08-09