Mutagenetix > Incidental Mutation

Incidental Mutation 'R0555:Gnas'

45435

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

038747-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0555 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

174284320-174346744 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 174298511 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Alanine at position 158 (T158A)

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

unknown
Transcript: ENSMUST00000080493
AA Change: D217G

SMART Domains

Protein: ENSMUSP00000079341
Gene: ENSMUSG00000027523
AA Change: D217G

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

unknown
Transcript: ENSMUST00000087876
AA Change: D217G

SMART Domains

Protein: ENSMUSP00000085184
Gene: ENSMUSG00000027523
AA Change: D217G

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

unknown
Transcript: ENSMUST00000087877
AA Change: D217G

SMART Domains

Protein: ENSMUSP00000085185
Gene: ENSMUSG00000027523
AA Change: D217G

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

possibly damaging
Transcript: ENSMUST00000109088
AA Change: T158A

PolyPhen 2 Score 0.784 (Sensitivity: 0.85; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000104716
Gene: ENSMUSG00000027523
AA Change: T158A

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

possibly damaging
Transcript: ENSMUST00000186907
AA Change: T158A

PolyPhen 2 Score 0.784 (Sensitivity: 0.85; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000139839
Gene: ENSMUSG00000027523
AA Change: T158A

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

unknown
Transcript: ENSMUST00000185956
AA Change: D217G

SMART Domains

Protein: ENSMUSP00000140174
Gene: ENSMUSG00000027523
AA Change: D217G

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

noncoding transcript
Transcript: ENSMUST00000184327

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000183673

Meta Mutation Damage Score

0.1795

Coding Region Coverage

1x: 99.6%
3x: 98.8%
10x: 96.9%
20x: 93.8%

Validation Efficiency

100% (98/98)

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: 96 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adam10	T	A	9: 70,754,234	I363N	probably damaging	Het
Ahcyl2	T	C	6: 29,890,671		probably benign	Het
Asap1	A	G	15: 64,094,364	L941P	probably damaging	Het
Aurka	G	A	2: 172,367,147	R23C	probably benign	Het
Cacna1c	C	T	6: 118,612,625	R1446H	probably damaging	Het
Casp8ap2	T	A	4: 32,640,381	H478Q	probably damaging	Het
Clcn4	C	T	7: 7,290,504	A418T	possibly damaging	Het
Cpxm2	A	T	7: 132,044,043	Y715*	probably null	Het
Csmd1	T	C	8: 16,185,273	M1179V	probably benign	Het
Ddx21	A	T	10: 62,587,528	F632I	probably damaging	Het
Dnaic1	C	A	4: 41,625,335	T433K	possibly damaging	Het
Dpyd	G	A	3: 119,431,542	G988D	probably damaging	Het
Dync1i2	AAAAGAAGAGGAAAGAAGAGGAAAG	AAAAGAAGAGGAAAG	2: 71,214,518		probably null	Het
Dync1li2	A	T	8: 104,420,665	S466T	probably benign	Het
Ears2	T	C	7: 122,048,444	T206A	probably benign	Het
Elmod1	A	T	9: 53,931,592		probably benign	Het
Eps8l3	C	A	3: 107,892,345	D590E	probably benign	Het
Etfdh	A	T	3: 79,605,805	H370Q	probably benign	Het
Fam83g	C	A	11: 61,707,663	A792E	probably benign	Het
Ffar3	G	T	7: 30,855,537	Y119*	probably null	Het
Fosb	G	T	7: 19,307,213	S118R	possibly damaging	Het
Foxn4	G	A	5: 114,263,114	L3F	probably damaging	Het
Foxo4	A	G	X: 101,255,178	K65E	probably damaging	Het
Frem2	A	G	3: 53,516,860	L3052P	probably damaging	Het
Fubp3	G	A	2: 31,608,137	R101H	probably damaging	Het
Gba2	C	A	4: 43,569,927	G429C	probably damaging	Het
Gimap1	T	C	6: 48,741,429		probably benign	Het
Gm17657	A	T	17: 29,519,571	F74I	probably benign	Het
Gpc5	T	C	14: 115,552,328	V538A	probably damaging	Het
Greb1l	T	C	18: 10,458,781		probably benign	Het
H2-M10.5	G	A	17: 36,774,728	G260R	probably damaging	Het
Hbs1l	A	C	10: 21,349,323	Q412H	probably benign	Het
Hecw1	G	T	13: 14,236,941	T1058N	probably damaging	Het
Heph	A	T	X: 96,558,084	T1027S	probably damaging	Het
Hoga1	A	C	19: 42,046,075	E53A	possibly damaging	Het
Insrr	T	G	3: 87,814,437		probably benign	Het
Ipo11	A	T	13: 106,892,461	V328D	probably damaging	Het
Jakmip1	T	C	5: 37,118,873	V509A	probably damaging	Het
Jmjd1c	T	C	10: 67,225,789	V1307A	probably benign	Het
Kmt2a	T	A	9: 44,847,571	S1027C	probably damaging	Het
Kprp	G	C	3: 92,824,357	P462R	unknown	Het
Lman1l	T	C	9: 57,614,101	T193A	probably benign	Het
Lrit3	A	T	3: 129,791,296	V271D	probably damaging	Het
Map4	T	A	9: 109,979,103		probably benign	Het
Mark4	A	C	7: 19,448,673		probably benign	Het
Mfsd14b	A	G	13: 65,078,445	V142A	probably benign	Het
Mis18bp1	A	T	12: 65,161,453	I162N	possibly damaging	Het
Mrpl43	A	T	19: 45,005,952		probably benign	Het
Mrpl47	A	G	3: 32,736,693	F16S	probably benign	Het
Myh2	G	T	11: 67,178,967	G380C	probably damaging	Het
Myo15	T	C	11: 60,521,638	Y3284H	probably damaging	Het
Nectin2	A	G	7: 19,733,223		probably benign	Het
Neu3	A	G	7: 99,814,183	V111A	probably damaging	Het
Nol4l	T	C	2: 153,417,684		probably null	Het
Nphp3	C	A	9: 104,023,434	H510Q	probably damaging	Het
Nprl3	T	A	11: 32,233,118		probably null	Het
Olfr292	A	G	7: 86,695,308	N284S	probably damaging	Het
Olfr48	T	C	2: 89,844,443	T177A	probably benign	Het
Olfr598	T	C	7: 103,328,963	V159A	probably benign	Het
Olfr791	T	C	10: 129,526,896	I223T	possibly damaging	Het
Pex1	A	G	5: 3,606,130	E319G	possibly damaging	Het
Phtf1	C	A	3: 104,004,469	T709K	probably damaging	Het
Plek2	A	T	12: 78,892,172	L271Q	probably damaging	Het
Plekhg5	T	A	4: 152,107,469	C421*	probably null	Het
Polk	A	C	13: 96,484,179	C525W	probably damaging	Het
Ppfibp2	T	C	7: 107,729,174	S471P	probably damaging	Het
Prickle2	A	T	6: 92,458,565	F74L	probably benign	Het
Prl7d1	A	T	13: 27,712,055	V113D	probably benign	Het
Prr14	C	T	7: 127,472,095		probably benign	Het
Ptpro	T	A	6: 137,443,594	V1007D	probably damaging	Het
Ret	A	G	6: 118,178,610	V375A	probably damaging	Het
Rora	T	C	9: 69,361,746	F41S	probably damaging	Het
Sall1	T	C	8: 89,031,758	T573A	probably benign	Het
Shb	A	G	4: 45,458,321	V281A	possibly damaging	Het
Slc25a26	A	T	6: 94,592,410		probably null	Het
Sltm	T	C	9: 70,586,081	F769L	probably damaging	Het
Snx9	T	A	17: 5,918,413	M328K	probably damaging	Het
Stk25	G	T	1: 93,624,591	Q356K	probably benign	Het
Svep1	T	A	4: 58,128,858	Y613F	possibly damaging	Het
Syne4	G	A	7: 30,316,744	A195T	probably damaging	Het
Tmem8	T	C	17: 26,117,114	L130S	probably benign	Het
Trcg1	C	T	9: 57,242,333	T396M	probably damaging	Het
Trim30b	A	G	7: 104,357,298	V117A	possibly damaging	Het
Trpc4	T	C	3: 54,302,090		probably benign	Het
Ttll4	A	G	1: 74,688,280	H827R	probably damaging	Het
Urgcp	T	C	11: 5,717,477	E287G	probably damaging	Het
Usp2	G	T	9: 44,092,784	L319F	probably damaging	Het
Vmn1r167	A	T	7: 23,505,087	V168D	probably damaging	Het
Vmn2r100	C	A	17: 19,522,120	P252Q	possibly damaging	Het
Vmn2r61	A	T	7: 42,266,018	I130F	probably benign	Het
Vmn2r63	A	T	7: 42,928,528	Y195*	probably null	Het
Vmn2r81	T	C	10: 79,293,449	S725P	probably damaging	Het
Wnt10b	A	G	15: 98,772,937		probably benign	Het
Zcchc6	A	G	13: 59,800,317	V328A	probably benign	Het
Zfp292	T	C	4: 34,807,194	E1950G	probably damaging	Het
Zfyve16	A	G	13: 92,516,520		probably benign	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
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
R4697:Gnas	UTSW	2	174298080	missense	probably damaging	1.00
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
R9431:Gnas	UTSW	2	174298033	missense	unknown
R9513:Gnas	UTSW	2	174343296	missense	probably damaging	0.98
R9617:Gnas	UTSW	2	174300195	missense	possibly damaging	0.90
R9710:Gnas	UTSW	2	174299339	missense	unknown
R9711:Gnas	UTSW	2	174299599	missense	unknown
R9762:Gnas	UTSW	2	174298846	nonsense	probably null
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'- AGGAAGCCATGCCATTCGAGAC -3'
(R):5'- CAATGGAGGCTCTGCCAATCTCAAG -3'

Sequencing Primer
(F):5'- AACCCAGCGATTTTGGAGC -3'
(R):5'- TCTGCCAATCTCAAGCAGGG -3'

Posted On

2013-06-11