Mutagenetix > Incidental Mutation

Incidental Mutation 'D4043:Adgrg1'

252

Institutional Source

Beutler Lab

Gene Symbol

Adgrg1

Ensembl Gene

ENSMUSG00000031785

Gene Name

adhesion G protein-coupled receptor G1

Synonyms

Cyt28, Gpr56

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.169) question?

Stock #

D4043 (G3) of strain 483

Quality Score

Status

Validated

Chromosome

Chromosomal Location

95701379-95740845 bp(+) (GRCm39)

Type of Mutation

splice site (2 bp from exon)

DNA Base Change (assembly)

T to C at 95731857 bp (GRCm39)

Zygosity

Homozygous

Amino Acid Change

Ref Sequence

ENSEMBL: ENSMUSP00000148304 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000093271] [ENSMUST00000179619] [ENSMUST00000211944] [ENSMUST00000211984] [ENSMUST00000212976] [ENSMUST00000212141] [ENSMUST00000212660] [ENSMUST00000212956] [ENSMUST00000212118] [ENSMUST00000212995] [ENSMUST00000212799] [ENSMUST00000212581] [ENSMUST00000212531]

AlphaFold

Q8K209

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

Domain	Start	End	E-Value	Type
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

Domain	Start	End	E-Value	Type
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 benign
Transcript: ENSMUST00000212976
AA Change: V173A

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

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: ENSMUST00000212660
AA Change: V168A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

Predicted Effect

probably benign
Transcript: ENSMUST00000212956

Predicted Effect

probably null
Transcript: ENSMUST00000212118

Predicted Effect

probably benign
Transcript: ENSMUST00000212995

Predicted Effect

probably benign
Transcript: ENSMUST00000212799

Predicted Effect

probably benign
Transcript: ENSMUST00000212581

Predicted Effect

probably benign
Transcript: ENSMUST00000212531

Meta Mutation Damage Score

0.9755

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
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adam29	A	T	8: 56,325,496 (GRCm39)	C319*	probably null	Het
Ago3	A	T	4: 126,244,796 (GRCm39)	V630E	probably damaging	Het
Armc8	G	T	9: 99,366,029 (GRCm39)	N628K	probably benign	Het
Cfap96	A	G	8: 46,409,440 (GRCm39)	V293A	probably damaging	Het
Chd7	A	G	4: 8,862,650 (GRCm39)	D2579G	probably damaging	Het
Duox1	G	A	2: 122,175,276 (GRCm39)	C1358Y	probably benign	Het
Ftsj3	C	A	11: 106,145,634 (GRCm39)	M66I	possibly damaging	Homo
Iqub	C	T	6: 24,505,750 (GRCm39)	E53K	possibly damaging	Het
Kirrel1	T	A	3: 86,990,510 (GRCm39)	T771S	probably benign	Het
Lrrc66	A	T	5: 73,764,869 (GRCm39)	S725T	probably benign	Het
Mael	T	C	1: 166,064,455 (GRCm39)	I104M	probably benign	Homo
Mkks	C	T	2: 136,716,530 (GRCm39)	V457I	probably benign	Het
Nadk2	T	A	15: 9,103,473 (GRCm39)		probably benign	Homo
Npas1	T	C	7: 16,197,169 (GRCm39)		probably null	Het
Ocrl	T	C	X: 47,025,200 (GRCm39)	V359A	probably benign	Homo
Or8k27	G	A	2: 86,275,564 (GRCm39)	T254M	probably damaging	Het
Pde6b	C	T	5: 108,573,222 (GRCm39)	R531*	probably null	Het
Polr1a	G	A	6: 71,918,401 (GRCm39)	C653Y	possibly damaging	Het
Rbm26	A	G	14: 105,389,976 (GRCm39)	V216A	possibly damaging	Het
Rin2	C	A	2: 145,664,283 (GRCm39)	H52Q	possibly damaging	Het
Ssc5d	C	T	7: 4,946,982 (GRCm39)	T1112I	possibly damaging	Het
Sv2c	C	T	13: 96,224,989 (GRCm39)	V107M	probably benign	Het
Tasor	A	G	14: 27,193,949 (GRCm39)	I1050V	probably benign	Het
Tulp3	G	A	6: 128,301,113 (GRCm39)	S366L	probably benign	Het
Zfp831	T	A	2: 174,487,059 (GRCm39)	V578E	probably benign	Homo

Other mutations in Adgrg1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00983:Adgrg1	APN	8	95,731,871 (GRCm39)	missense	probably damaging	1.00
IGL01138:Adgrg1	APN	8	95,730,085 (GRCm39)	missense	probably damaging	1.00
IGL01806:Adgrg1	APN	8	95,739,559 (GRCm39)	missense	probably damaging	1.00
IGL02229:Adgrg1	APN	8	95,730,139 (GRCm39)	missense	probably damaging	1.00
IGL03109:Adgrg1	APN	8	95,734,304 (GRCm39)	unclassified	probably benign
R0383:Adgrg1	UTSW	8	95,738,370 (GRCm39)	missense	probably damaging	1.00
R1155:Adgrg1	UTSW	8	95,733,468 (GRCm39)	missense	possibly damaging	0.92
R1656:Adgrg1	UTSW	8	95,738,438 (GRCm39)	nonsense	probably null
R1944:Adgrg1	UTSW	8	95,733,928 (GRCm39)	missense	probably damaging	0.99
R1952:Adgrg1	UTSW	8	95,735,119 (GRCm39)	critical splice donor site	probably null
R2408:Adgrg1	UTSW	8	95,730,121 (GRCm39)	missense	probably null	1.00
R3776:Adgrg1	UTSW	8	95,736,283 (GRCm39)	missense	probably damaging	0.99
R3813:Adgrg1	UTSW	8	95,738,193 (GRCm39)	missense	probably benign	0.34
R4254:Adgrg1	UTSW	8	95,732,530 (GRCm39)	splice site	probably null
R4255:Adgrg1	UTSW	8	95,732,530 (GRCm39)	splice site	probably null
R4951:Adgrg1	UTSW	8	95,731,874 (GRCm39)	missense	probably damaging	1.00
R4997:Adgrg1	UTSW	8	95,736,148 (GRCm39)	missense	probably damaging	1.00
R5152:Adgrg1	UTSW	8	95,736,373 (GRCm39)	missense	probably damaging	1.00
R6122:Adgrg1	UTSW	8	95,729,129 (GRCm39)	missense	probably benign	0.45
R6897:Adgrg1	UTSW	8	95,729,126 (GRCm39)	missense	probably benign
R7446:Adgrg1	UTSW	8	95,738,412 (GRCm39)	missense	probably damaging	1.00
R7736:Adgrg1	UTSW	8	95,731,965 (GRCm39)	missense	probably benign
R7784:Adgrg1	UTSW	8	95,739,510 (GRCm39)	nonsense	probably null
R8187:Adgrg1	UTSW	8	95,732,446 (GRCm39)	missense	probably benign	0.01
R8425:Adgrg1	UTSW	8	95,735,035 (GRCm39)	missense	probably damaging	1.00
R8474:Adgrg1	UTSW	8	95,729,936 (GRCm39)	missense	probably damaging	1.00
R8674:Adgrg1	UTSW	8	95,727,526 (GRCm39)	intron	probably benign
R8683:Adgrg1	UTSW	8	95,736,276 (GRCm39)	missense	probably damaging	1.00
Z1177:Adgrg1	UTSW	8	95,734,258 (GRCm39)	missense	probably damaging	1.00

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 On

2010-08-09