Mutagenetix > Incidental Mutations

Incidental Mutation 'R4697:Gnas'

355754

Institutional Source

Beutler Lab

Gene Symbol

Gnas

Ensembl Gene

ENSMUSG00000027523

Gene Name

GNAS (guanine nucleotide binding protein, alpha stimulating) complex locus

Synonyms

Gnasxl, C130027O20Rik, 5530400H20Rik, Nespl, Nesp, A930027G11Rik, Gs alpha, G alpha s, Gsa, Nesp55, Galphas, Gnas1, P1, Gs-alpha, XLalphas, P3, neuroendocrine-specific Golgi protein p55 isoform 1, Oedsml, P2

MMRRC Submission

041947-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R4697 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

174284320-174346744 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 174298080 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Valine at position 14 (D14V)

Ref Sequence

ENSEMBL: ENSMUSP00000139839 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000080493] [ENSMUST00000087876] [ENSMUST00000087877] [ENSMUST00000109088] [ENSMUST00000109095] [ENSMUST00000109096] [ENSMUST00000130761] [ENSMUST00000130940] [ENSMUST00000180362] [ENSMUST00000186907] [ENSMUST00000185956]

AlphaFold

Q6R0H7

Predicted Effect

silent
Transcript: ENSMUST00000080493

SMART Domains

Protein: ENSMUSP00000079341
Gene: ENSMUSG00000027523

Domain	Start	End	E-Value	Type
low complexity region	19	48	N/A	INTRINSIC
internal_repeat_1	89	166	3.02e-8	PROSPERO
internal_repeat_1	209	276	3.02e-8	PROSPERO
low complexity region	350	365	N/A	INTRINSIC
low complexity region	391	404	N/A	INTRINSIC
low complexity region	459	477	N/A	INTRINSIC
low complexity region	480	498	N/A	INTRINSIC
low complexity region	515	525	N/A	INTRINSIC
low complexity region	535	570	N/A	INTRINSIC
low complexity region	576	626	N/A	INTRINSIC
low complexity region	633	643	N/A	INTRINSIC
low complexity region	659	678	N/A	INTRINSIC
low complexity region	685	696	N/A	INTRINSIC
G_alpha	759	1132	5.01e-185	SMART

Predicted Effect

silent
Transcript: ENSMUST00000087876

SMART Domains

Protein: ENSMUSP00000085184
Gene: ENSMUSG00000027523

Domain	Start	End	E-Value	Type
low complexity region	19	48	N/A	INTRINSIC
internal_repeat_1	89	166	2.42e-8	PROSPERO
internal_repeat_1	209	276	2.42e-8	PROSPERO
low complexity region	350	365	N/A	INTRINSIC
low complexity region	391	404	N/A	INTRINSIC
low complexity region	459	477	N/A	INTRINSIC
low complexity region	480	498	N/A	INTRINSIC
low complexity region	515	525	N/A	INTRINSIC
low complexity region	535	570	N/A	INTRINSIC
low complexity region	576	626	N/A	INTRINSIC
low complexity region	633	643	N/A	INTRINSIC
low complexity region	659	678	N/A	INTRINSIC
low complexity region	685	696	N/A	INTRINSIC
G_alpha	759	1118	8.32e-191	SMART

Predicted Effect

silent
Transcript: ENSMUST00000087877

SMART Domains

Protein: ENSMUSP00000085185
Gene: ENSMUSG00000027523

Domain	Start	End	E-Value	Type
low complexity region	19	48	N/A	INTRINSIC
internal_repeat_1	89	166	1.1e-8	PROSPERO
internal_repeat_1	209	276	1.1e-8	PROSPERO
low complexity region	350	365	N/A	INTRINSIC
low complexity region	391	404	N/A	INTRINSIC
low complexity region	459	477	N/A	INTRINSIC
low complexity region	480	498	N/A	INTRINSIC
low complexity region	515	525	N/A	INTRINSIC
low complexity region	535	570	N/A	INTRINSIC
low complexity region	576	626	N/A	INTRINSIC
low complexity region	633	643	N/A	INTRINSIC
low complexity region	659	678	N/A	INTRINSIC
low complexity region	685	696	N/A	INTRINSIC
Blast:G_alpha	759	799	2e-14	BLAST
low complexity region	802	816	N/A	INTRINSIC
low complexity region	847	859	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000109088
AA Change: D14V

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000104716
Gene: ENSMUSG00000027523
AA Change: D14V

Domain	Start	End	E-Value	Type
low complexity region	192	209	N/A	INTRINSIC
low complexity region	336	352	N/A	INTRINSIC
low complexity region	402	415	N/A	INTRINSIC
low complexity region	421	446	N/A	INTRINSIC
low complexity region	459	481	N/A	INTRINSIC
low complexity region	493	510	N/A	INTRINSIC
low complexity region	529	599	N/A	INTRINSIC
low complexity region	643	658	N/A	INTRINSIC
low complexity region	700	716	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000109095

SMART Domains

Protein: ENSMUSP00000104723
Gene: ENSMUSG00000027523

Domain	Start	End	E-Value	Type
Pfam:NESP55	1	253	1.2e-157	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000109096

SMART Domains

Protein: ENSMUSP00000104724
Gene: ENSMUSG00000027523

Domain	Start	End	E-Value	Type
Pfam:NESP55	1	253	1.2e-157	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000130761

Predicted Effect

probably benign
Transcript: ENSMUST00000130940

SMART Domains

Protein: ENSMUSP00000118210
Gene: ENSMUSG00000027523

Domain	Start	End	E-Value	Type
Pfam:NESP55	1	59	1.6e-30	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000150276

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000151472

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000154658

Predicted Effect

probably benign
Transcript: ENSMUST00000180362

SMART Domains

Protein: ENSMUSP00000136180
Gene: ENSMUSG00000027523

Domain	Start	End	E-Value	Type
Pfam:NESP55	1	253	1.2e-157	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000183673

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000184327

Predicted Effect

probably damaging
Transcript: ENSMUST00000186907
AA Change: D14V

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000139839
Gene: ENSMUSG00000027523
AA Change: D14V

Domain	Start	End	E-Value	Type
low complexity region	192	209	N/A	INTRINSIC
low complexity region	336	352	N/A	INTRINSIC
low complexity region	402	415	N/A	INTRINSIC
low complexity region	421	446	N/A	INTRINSIC
low complexity region	459	481	N/A	INTRINSIC
low complexity region	493	510	N/A	INTRINSIC
low complexity region	529	599	N/A	INTRINSIC
low complexity region	643	658	N/A	INTRINSIC
low complexity region	700	716	N/A	INTRINSIC

Predicted Effect

silent
Transcript: ENSMUST00000185956

SMART Domains

Protein: ENSMUSP00000140174
Gene: ENSMUSG00000027523

Domain	Start	End	E-Value	Type
low complexity region	19	48	N/A	INTRINSIC
internal_repeat_1	89	166	3.02e-8	PROSPERO
internal_repeat_1	209	276	3.02e-8	PROSPERO
low complexity region	350	365	N/A	INTRINSIC
low complexity region	391	404	N/A	INTRINSIC
low complexity region	459	477	N/A	INTRINSIC
low complexity region	480	498	N/A	INTRINSIC
low complexity region	515	525	N/A	INTRINSIC
low complexity region	535	570	N/A	INTRINSIC
low complexity region	576	626	N/A	INTRINSIC
low complexity region	633	643	N/A	INTRINSIC
low complexity region	659	678	N/A	INTRINSIC
low complexity region	685	696	N/A	INTRINSIC
G_alpha	759	1132	5.01e-185	SMART

Meta Mutation Damage Score

0.0737

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 97.0%
20x: 94.5%

Validation Efficiency

96% (75/78)

MGI Phenotype

FUNCTION: This locus has a highly complex imprinted expression pattern. It gives rise to maternally, paternally, and biallelically expressed transcripts that are derived from four alternative promoters and 5' exons. Some transcripts contain a differentially methylated region (DMR) at their 5' exons, which is commonly found in imprinted genes and correlates with transcript expression. This gene has an antisense transcript. One of the transcripts produced from this locus, and the antisense transcript, are both paternally expressed noncoding RNAs, and may regulate imprinting in this region. In addition, one of the transcripts contains a second overlapping ORF, which encodes a structurally unrelated protein - Alex. Alternative splicing of downstream exons is also observed, which results in different forms of the stimulatory G-protein alpha subunit, a key element of the classical signal transduction pathway linking receptor-ligand interactions with the activation of adenylyl cyclase and a variety of cellular reponses. Additional transcript variants have been found for this gene, but the full-length nature and/or biological validity of some variants have not been determined. [provided by RefSeq, Jun 2015]
PHENOTYPE: Mutant homozygotes stop developing normally by embryonic day 10.5 and die prenatally. On some backgrounds heterozygotes show imprinted phenotypes, including differences in body shape/weight, locomotor activity, metabolism, and developmental anomalies. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 66 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
9030624J02Rik	T	A	7: 118,791,448	I455N	probably damaging	Het
A2m	T	C	6: 121,638,284	M1T	probably null	Het
Aatf	T	A	11: 84,449,138	D449V	probably damaging	Het
Acbd3	T	A	1: 180,721,944		probably benign	Het
BC005561	A	G	5: 104,522,240	K1543E	probably benign	Het
Bicc1	T	A	10: 70,953,484	I366F	possibly damaging	Het
Ccdc74a	T	C	16: 17,649,749	S184P	possibly damaging	Het
Cntn4	T	C	6: 106,525,485	V401A	probably damaging	Het
Cux2	T	C	5: 121,873,753	T540A	probably damaging	Het
Disp2	G	T	2: 118,791,684	E966*	probably null	Het
Dpp7	A	G	2: 25,354,919	Y209H	probably benign	Het
Dstyk	T	A	1: 132,449,487	F277Y	probably damaging	Het
Dtx1	A	T	5: 120,694,408		probably null	Het
Ear-ps2	G	A	14: 44,047,060		noncoding transcript	Het
Ednra	T	C	8: 77,664,995	H422R	probably benign	Het
Erlec1	T	A	11: 30,952,640	I67F	probably benign	Het
Fam161b	G	A	12: 84,348,558		probably benign	Het
Gata5	A	T	2: 180,327,379	C345*	probably null	Het
Glmp	T	C	3: 88,328,274	V47A	probably damaging	Het
Gm9762	T	A	3: 78,966,550		noncoding transcript	Het
Gnl3	T	C	14: 31,017,329	S53G	probably damaging	Het
Grhl3	C	T	4: 135,548,466	V527M	probably damaging	Het
Hoxd10	T	A	2: 74,694,187	L281*	probably null	Het
Kif16b	T	G	2: 142,690,694	Y1175S	probably benign	Het
Kif2b	A	G	11: 91,576,846	S204P	probably benign	Het
Klhl40	T	A	9: 121,778,734	I320N	probably damaging	Het
Ksr2	G	A	5: 117,708,147	R693Q	probably damaging	Het
Mis12	A	G	11: 71,025,326	K62E	possibly damaging	Het
Mlc1	A	G	15: 88,974,777	C102R	probably damaging	Het
Muc5b	T	C	7: 141,857,361	I1348T	unknown	Het
Myh7b	A	G	2: 155,629,322	E1130G	probably damaging	Het
Nat8f4	T	C	6: 85,901,386	T52A	probably benign	Het
Nxpe2	C	A	9: 48,320,521	V379L	probably benign	Het
Olfr1231	C	A	2: 89,302,902	S230I	possibly damaging	Het
Olfr1231	T	A	2: 89,302,903	S230C	probably damaging	Het
Olfr1448	C	T	19: 12,919,934	C125Y	probably damaging	Het
Olfr1465	A	T	19: 13,313,717	D189E	probably benign	Het
Olfr288	G	A	15: 98,186,868	R310W	probably damaging	Het
Pcdhga7	A	T	18: 37,717,208	Y756F	probably damaging	Het
Pcsk6	T	A	7: 65,959,241	Y284N	probably damaging	Het
Pdcd11	T	C	19: 47,126,347	V1367A	possibly damaging	Het
Postn	T	A	3: 54,375,071	N484K	probably damaging	Het
Prkd3	C	T	17: 78,961,171	V572I	probably benign	Het
Qser1	T	C	2: 104,787,183	S1005G	probably benign	Het
Radil	G	T	5: 142,486,801	D951E	probably benign	Het
Ripk1	C	T	13: 34,027,942	R352*	probably null	Het
Sacs	T	C	14: 61,212,747	F4081L	probably benign	Het
Sbf1	A	G	15: 89,315,085	V11A	possibly damaging	Het
Sgip1	T	A	4: 102,934,587	F536I	probably damaging	Het
Slc45a1	A	G	4: 150,638,284	L381P	probably damaging	Het
Smarcad1	C	T	6: 65,052,641	P71L	probably benign	Het
Spns1	T	A	7: 126,377,037	D14V	probably damaging	Het
Sv2c	T	A	13: 95,986,018	I417F	possibly damaging	Het
Tas2r113	T	A	6: 132,893,516	M169K	probably benign	Het
Tgm1	A	T	14: 55,705,681	N567K	probably benign	Het
Tln2	C	T	9: 67,395,461	R76Q	probably damaging	Het
Trpm6	T	C	19: 18,853,791	V1340A	probably benign	Het
Tspan18	A	T	2: 93,312,030		probably null	Het
Txndc11	C	T	16: 11,084,314	V679I	probably damaging	Het
Usf1	G	T	1: 171,416,964	G144V	possibly damaging	Het
Vmn1r59	T	C	7: 5,454,452	Y103C	probably damaging	Het
Vmn2r23	A	T	6: 123,741,826	I713F	probably damaging	Het
Vmn2r79	A	T	7: 87,037,960	I850F	probably damaging	Het
Wdr90	C	T	17: 25,855,363	R676H	probably benign	Het
Zfp867	G	A	11: 59,463,661	R281W	probably damaging	Het
Zfp939	T	C	7: 39,472,942		noncoding transcript	Het

Other mutations in Gnas

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00565:Gnas	APN	2	174341711	splice site	probably benign
IGL00928:Gnas	APN	2	174297953	nonsense	probably null
IGL01014:Gnas	APN	2	174297974	utr 5 prime	probably benign
IGL01743:Gnas	APN	2	174298332	nonsense	probably null
IGL01808:Gnas	APN	2	174298697	missense	probably damaging	0.96
IGL02559:Gnas	APN	2	174341936	splice site	probably benign
R0555:Gnas	UTSW	2	174298511	missense	possibly damaging	0.78
R0627:Gnas	UTSW	2	174298135	intron	probably benign
R1418:Gnas	UTSW	2	174345214	splice site	probably benign
R1706:Gnas	UTSW	2	174299975	missense	possibly damaging	0.90
R1751:Gnas	UTSW	2	174297894	utr 5 prime	probably benign
R1968:Gnas	UTSW	2	174298733	missense	probably damaging	0.96
R2290:Gnas	UTSW	2	174300010	missense	probably benign	0.09
R4125:Gnas	UTSW	2	174300165	missense	possibly damaging	0.94
R4128:Gnas	UTSW	2	174300165	missense	possibly damaging	0.94
R4888:Gnas	UTSW	2	174298089	missense	possibly damaging	0.94
R5458:Gnas	UTSW	2	174298331	missense	probably benign	0.41
R5640:Gnas	UTSW	2	174284971	missense	probably benign	0.44
R5696:Gnas	UTSW	2	174299675	intron	probably benign
R5757:Gnas	UTSW	2	174345247	missense	probably damaging	1.00
R6053:Gnas	UTSW	2	174299852	missense	possibly damaging	0.89
R6083:Gnas	UTSW	2	174297862	start codon destroyed	probably null
R6736:Gnas	UTSW	2	174334251	missense	probably damaging	0.98
R7074:Gnas	UTSW	2	174285049	missense	probably damaging	1.00
R7239:Gnas	UTSW	2	174298615	missense	unknown
R7541:Gnas	UTSW	2	174298099	missense	unknown
R7679:Gnas	UTSW	2	174284831	missense	probably damaging	0.99
R7694:Gnas	UTSW	2	174300212	missense	probably damaging	1.00
R7713:Gnas	UTSW	2	174299027	missense	unknown
R7834:Gnas	UTSW	2	174298990	nonsense	probably null
R8138:Gnas	UTSW	2	174298386	missense	probably benign	0.06
R8459:Gnas	UTSW	2	174284939	missense	probably benign	0.05
R8537:Gnas	UTSW	2	174298601	missense	possibly damaging	0.83
R8731:Gnas	UTSW	2	174284906	missense	probably benign	0.01
R8924:Gnas	UTSW	2	174299484	missense	unknown
X0022:Gnas	UTSW	2	174299744	missense	probably benign	0.33
Z1088:Gnas	UTSW	2	174298373	missense	probably benign	0.27
Z1176:Gnas	UTSW	2	174298606	missense	unknown
Z1177:Gnas	UTSW	2	174284887	missense	unknown

Predicted Primers

PCR Primer
(F):5'- CGGCAATAATATGTCAGGACAACAC -3'
(R):5'- AAAATCGCTGGGTTGAAGGC -3'

Sequencing Primer
(F):5'- TATGTCAGGACAACACGATATCC -3'
(R):5'- CTTGGAGGCCTGATGGGGTC -3'

Posted On

2015-10-21