Mutagenetix > Incidental Mutation

Incidental Mutation 'R1968:Gnas'

219178

Institutional Source

Beutler Lab

Gene Symbol

Gnas

Ensembl Gene

ENSMUSG00000027523

Gene Name

GNAS complex locus

Synonyms

P2, Gnasxl, Gnas1, Nesp, neuroendocrine-specific Golgi protein p55 isoform 1, XLalphas, Gsa, Oedsml, Gs alpha, Nesp55, Galphas, Nespl, SCG6, Gs-alpha, P1, P3, G alpha s

MMRRC Submission

039981-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1968 (G1)

Quality Score

120

Status

Not validated

Chromosome

Chromosomal Location

174126113-174188537 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 174140526 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 232 (S232P)

Ref Sequence

ENSEMBL: ENSMUSP00000139839 (fasta)

Gene Model

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

AlphaFold

Q6R0H7

Predicted Effect

unknown
Transcript: ENSMUST00000080493
AA Change: V291A

SMART Domains

Protein: ENSMUSP00000079341
Gene: ENSMUSG00000027523
AA Change: V291A

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: V291A

SMART Domains

Protein: ENSMUSP00000085184
Gene: ENSMUSG00000027523
AA Change: V291A

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: V291A

SMART Domains

Protein: ENSMUSP00000085185
Gene: ENSMUSG00000027523
AA Change: V291A

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: S232P

PolyPhen 2 Score 0.958 (Sensitivity: 0.78; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000104716
Gene: ENSMUSG00000027523
AA Change: S232P

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 damaging
Transcript: ENSMUST00000186907
AA Change: S232P

PolyPhen 2 Score 0.958 (Sensitivity: 0.78; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000139839
Gene: ENSMUSG00000027523
AA Change: S232P

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: V291A

SMART Domains

Protein: ENSMUSP00000140174
Gene: ENSMUSG00000027523
AA Change: V291A

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: ENSMUST00000154658

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000184327

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000183673

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000151472

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000150276

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

probably benign
Transcript: ENSMUST00000130940

SMART Domains

Protein: ENSMUSP00000118210
Gene: ENSMUSG00000027523

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

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 96.8%
20x: 94.2%

Validation Efficiency

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: 95 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aadacl4fm4	A	G	4: 144,397,193 (GRCm39)	Y180H	possibly damaging	Het
Abcc10	A	T	17: 46,633,125 (GRCm39)	L528Q	probably damaging	Het
Adam18	T	A	8: 25,136,463 (GRCm39)	T353S	probably benign	Het
Aldh1a3	A	G	7: 66,061,248 (GRCm39)		probably null	Het
Aldh3b2	T	A	19: 4,030,705 (GRCm39)	M390K	probably benign	Het
Arhgap45	T	C	10: 79,863,536 (GRCm39)	I793T	probably damaging	Het
Arsb	A	G	13: 93,944,067 (GRCm39)	M253V	probably benign	Het
Atcay	T	C	10: 81,048,312 (GRCm39)	D258G	possibly damaging	Het
Atf1	G	T	15: 100,152,395 (GRCm39)		probably null	Het
Atp1a4	C	T	1: 172,067,731 (GRCm39)	E511K	probably benign	Het
Atp8a1	A	G	5: 67,825,000 (GRCm39)	V777A	probably benign	Het
Baz1a	T	C	12: 54,947,122 (GRCm39)	T1173A	possibly damaging	Het
Bdh2	A	T	3: 134,991,370 (GRCm39)	D15V	probably benign	Het
Cacna1e	T	C	1: 154,576,240 (GRCm39)	Y69C	probably damaging	Het
Caskin2	A	G	11: 115,694,440 (GRCm39)	L387P	probably benign	Het
Cat	T	C	2: 103,315,334 (GRCm39)	E17G	probably benign	Het
Ccdc15	T	C	9: 37,259,091 (GRCm39)	I54M	probably benign	Het
Ccn1	T	C	3: 145,353,965 (GRCm39)	Y275C	probably damaging	Het
Cdhr1	T	G	14: 36,801,682 (GRCm39)	I754L	probably benign	Het
Cep120	G	A	18: 53,856,313 (GRCm39)	T368I	probably benign	Het
Cep126	C	A	9: 8,100,909 (GRCm39)	D542Y	probably damaging	Het
Cep135	T	C	5: 76,772,594 (GRCm39)	S660P	possibly damaging	Het
Cfap70	A	T	14: 20,470,879 (GRCm39)	S455R	possibly damaging	Het
Chd8	A	G	14: 52,458,450 (GRCm39)	M886T	probably damaging	Het
Ckap5	T	C	2: 91,416,688 (GRCm39)	S1098P	probably benign	Het
Clec4e	A	T	6: 123,260,533 (GRCm39)	I204N	probably damaging	Het
Cntnap5c	G	A	17: 58,666,291 (GRCm39)	R1107H	probably damaging	Het
Cramp1	T	C	17: 25,183,913 (GRCm39)	D1234G	probably damaging	Het
Csf1r	A	T	18: 61,245,867 (GRCm39)	I275L	probably benign	Het
Cyp27a1	A	G	1: 74,776,435 (GRCm39)	E457G	probably benign	Het
Cyp2d11	T	C	15: 82,273,749 (GRCm39)	T410A	probably benign	Het
Cyp2d22	G	C	15: 82,257,373 (GRCm39)	T264S	probably benign	Het
Daam2	G	A	17: 49,790,088 (GRCm39)	R390W	probably damaging	Het
Decr2	T	C	17: 26,302,053 (GRCm39)	S226G	probably benign	Het
Dennd6b	T	C	15: 89,074,544 (GRCm39)	D91G	possibly damaging	Het
Dglucy	T	C	12: 100,825,903 (GRCm39)	V515A	possibly damaging	Het
Dlg5	A	T	14: 24,214,187 (GRCm39)	L734*	probably null	Het
Dop1b	A	G	16: 93,579,307 (GRCm39)	N1690D	probably damaging	Het
Exoc5	A	G	14: 49,272,347 (GRCm39)	Y356H	probably benign	Het
Fut7	T	A	2: 25,315,738 (GRCm39)	V332D	probably benign	Het
Gramd4	A	G	15: 86,017,106 (GRCm39)	E522G	probably damaging	Het
Gys1	A	G	7: 45,092,970 (GRCm39)	T297A	probably damaging	Het
Herc4	T	C	10: 63,109,304 (GRCm39)	S180P	probably benign	Het
Hivep3	C	T	4: 119,953,435 (GRCm39)	P584S	possibly damaging	Het
Irag2	T	A	6: 145,115,499 (GRCm39)	S310T	probably damaging	Het
Itpk1	G	T	12: 102,641,729 (GRCm39)		probably null	Het
Jmjd1c	A	T	10: 67,061,219 (GRCm39)	S1191C	probably damaging	Het
Lima1	T	C	15: 99,717,565 (GRCm39)	N147S	probably benign	Het
Map4k5	G	A	12: 69,865,266 (GRCm39)	T506I	probably damaging	Het
Mat1a	A	T	14: 40,832,991 (GRCm39)	E58V	probably damaging	Het
Mfsd13a	T	C	19: 46,360,492 (GRCm39)	L348P	probably damaging	Het
Mon2	A	G	10: 122,845,470 (GRCm39)	Y1413H	probably damaging	Het
Mpp3	C	A	11: 101,909,378 (GRCm39)		probably benign	Het
Mpp4	T	A	1: 59,183,961 (GRCm39)	I260F	probably damaging	Het
Myocd	C	A	11: 65,091,733 (GRCm39)	G70C	probably damaging	Het
Nckap1	C	T	2: 80,348,286 (GRCm39)	S889N	probably benign	Het
Nckap5	T	A	1: 125,942,367 (GRCm39)	D209V	probably damaging	Het
Nlrp9a	A	G	7: 26,264,366 (GRCm39)	K707R	probably benign	Het
Npr3	A	G	15: 11,905,055 (GRCm39)	L224S	probably benign	Het
Or5m9b	T	A	2: 85,905,549 (GRCm39)	L155Q	probably damaging	Het
Or5w20	T	A	2: 87,727,383 (GRCm39)	V280E	probably damaging	Het
Or6c74	A	G	10: 129,869,602 (GRCm39)	S36G	probably damaging	Het
Otof	C	T	5: 30,545,998 (GRCm39)	D467N	probably damaging	Het
Paxx	T	C	2: 25,350,640 (GRCm39)		probably benign	Het
Pcmt1	G	A	10: 7,516,474 (GRCm39)	R179*	probably null	Het
Phkb	T	A	8: 86,697,580 (GRCm39)	V463D	probably benign	Het
Prkcq	T	C	2: 11,250,208 (GRCm39)	V175A	probably damaging	Het
Rasl11b	T	G	5: 74,356,797 (GRCm39)	I58S	probably damaging	Het
Rb1cc1	A	T	1: 6,318,419 (GRCm39)		probably null	Het
Reck	T	A	4: 43,913,771 (GRCm39)		probably null	Het
Riox1	G	T	12: 83,998,156 (GRCm39)	D231Y	probably damaging	Het
Rlf	T	A	4: 121,005,617 (GRCm39)	N1231I	probably damaging	Het
Rpn1	A	G	6: 88,072,530 (GRCm39)	D291G	possibly damaging	Het
Samsn1	C	T	16: 75,742,461 (GRCm39)		noncoding transcript	Het
Scara5	T	C	14: 65,927,249 (GRCm39)	C49R	possibly damaging	Het
Serpini1	A	G	3: 75,521,785 (GRCm39)	D92G	probably benign	Het
Setdb2	A	T	14: 59,656,858 (GRCm39)	L153Q	probably damaging	Het
Sh3rf3	C	T	10: 58,649,809 (GRCm39)	T138M	probably benign	Het
Shkbp1	C	T	7: 27,054,825 (GRCm39)		probably null	Het
Slc22a29	G	A	19: 8,195,707 (GRCm39)	P111S	probably benign	Het
Smarca1	A	G	X: 46,941,564 (GRCm39)	V618A	probably damaging	Het
Spef2	T	A	15: 9,609,602 (GRCm39)	M1308L	probably damaging	Het
Spink5	A	G	18: 44,123,775 (GRCm39)	N354S	probably benign	Het
Srrm2	T	C	17: 24,040,465 (GRCm39)	S2370P	probably damaging	Het
Ssxb3	A	T	X: 8,454,905 (GRCm39)	I28N	probably damaging	Het
Sucla2	A	G	14: 73,831,119 (GRCm39)	T411A	probably damaging	Het
Tex38	A	C	4: 115,637,537 (GRCm39)	S89A	probably benign	Het
Tjp2	A	T	19: 24,088,437 (GRCm39)	D723E	probably damaging	Het
Tln2	A	T	9: 67,163,183 (GRCm39)	N1121K	probably damaging	Het
Tti1	T	C	2: 157,850,966 (GRCm39)	E91G	possibly damaging	Het
Wbp2	A	T	11: 115,973,191 (GRCm39)	M72K	possibly damaging	Het
Wdfy4	C	A	14: 32,828,001 (GRCm39)	C1062F	possibly damaging	Het
Wiz	A	G	17: 32,578,346 (GRCm39)	Y389H	probably damaging	Het
Zcchc3	T	C	2: 152,256,012 (GRCm39)	K229R	probably damaging	Het
Zmat3	C	A	3: 32,415,131 (GRCm39)	D60Y	probably damaging	Het

Other mutations in Gnas

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00565:Gnas	APN	2	174,183,504 (GRCm39)	splice site	probably benign
IGL00928:Gnas	APN	2	174,139,746 (GRCm39)	nonsense	probably null
IGL01014:Gnas	APN	2	174,139,767 (GRCm39)	utr 5 prime	probably benign
IGL01743:Gnas	APN	2	174,140,125 (GRCm39)	nonsense	probably null
IGL01808:Gnas	APN	2	174,140,490 (GRCm39)	missense	probably damaging	0.96
IGL02559:Gnas	APN	2	174,183,729 (GRCm39)	splice site	probably benign
R0555:Gnas	UTSW	2	174,140,304 (GRCm39)	missense	possibly damaging	0.78
R0627:Gnas	UTSW	2	174,139,928 (GRCm39)	intron	probably benign
R1418:Gnas	UTSW	2	174,187,007 (GRCm39)	splice site	probably benign
R1706:Gnas	UTSW	2	174,141,768 (GRCm39)	missense	possibly damaging	0.90
R1751:Gnas	UTSW	2	174,139,687 (GRCm39)	utr 5 prime	probably benign
R2290:Gnas	UTSW	2	174,141,803 (GRCm39)	missense	probably benign	0.09
R4125:Gnas	UTSW	2	174,141,958 (GRCm39)	missense	possibly damaging	0.94
R4128:Gnas	UTSW	2	174,141,958 (GRCm39)	missense	possibly damaging	0.94
R4697:Gnas	UTSW	2	174,139,873 (GRCm39)	missense	probably damaging	1.00
R4888:Gnas	UTSW	2	174,139,882 (GRCm39)	missense	possibly damaging	0.94
R5458:Gnas	UTSW	2	174,140,124 (GRCm39)	missense	probably benign	0.41
R5640:Gnas	UTSW	2	174,126,764 (GRCm39)	missense	probably benign	0.44
R5696:Gnas	UTSW	2	174,141,468 (GRCm39)	intron	probably benign
R5757:Gnas	UTSW	2	174,187,040 (GRCm39)	missense	probably damaging	1.00
R6053:Gnas	UTSW	2	174,141,645 (GRCm39)	missense	possibly damaging	0.89
R6083:Gnas	UTSW	2	174,139,655 (GRCm39)	start codon destroyed	probably null
R6736:Gnas	UTSW	2	174,176,044 (GRCm39)	missense	probably damaging	0.98
R7074:Gnas	UTSW	2	174,126,842 (GRCm39)	missense	probably damaging	1.00
R7239:Gnas	UTSW	2	174,140,408 (GRCm39)	missense	unknown
R7541:Gnas	UTSW	2	174,139,892 (GRCm39)	missense	unknown
R7679:Gnas	UTSW	2	174,126,624 (GRCm39)	missense	probably damaging	0.99
R7694:Gnas	UTSW	2	174,142,005 (GRCm39)	missense	probably damaging	1.00
R7713:Gnas	UTSW	2	174,140,820 (GRCm39)	missense	unknown
R7834:Gnas	UTSW	2	174,140,783 (GRCm39)	nonsense	probably null
R8138:Gnas	UTSW	2	174,140,179 (GRCm39)	missense	probably benign	0.06
R8459:Gnas	UTSW	2	174,126,732 (GRCm39)	missense	probably benign	0.05
R8537:Gnas	UTSW	2	174,140,394 (GRCm39)	missense	possibly damaging	0.83
R8731:Gnas	UTSW	2	174,126,699 (GRCm39)	missense	probably benign	0.01
R8924:Gnas	UTSW	2	174,141,277 (GRCm39)	missense	unknown
R9431:Gnas	UTSW	2	174,139,826 (GRCm39)	missense	unknown
R9513:Gnas	UTSW	2	174,185,089 (GRCm39)	missense	probably damaging	0.98
R9617:Gnas	UTSW	2	174,141,988 (GRCm39)	missense	possibly damaging	0.90
R9710:Gnas	UTSW	2	174,141,132 (GRCm39)	missense	unknown
R9711:Gnas	UTSW	2	174,141,392 (GRCm39)	missense	unknown
R9762:Gnas	UTSW	2	174,140,639 (GRCm39)	nonsense	probably null
X0022:Gnas	UTSW	2	174,141,537 (GRCm39)	missense	probably benign	0.33
Z1088:Gnas	UTSW	2	174,140,166 (GRCm39)	missense	probably benign	0.27
Z1176:Gnas	UTSW	2	174,140,399 (GRCm39)	missense	unknown
Z1177:Gnas	UTSW	2	174,126,680 (GRCm39)	missense	unknown

Predicted Primers

PCR Primer
(F):5'- TCAGGTCGGTGGAGAAGAATTC -3'
(R):5'- GAGGGGACTTTTCCTTCCAC -3'

Sequencing Primer
(F):5'- TGGAGAAGAATTCGGGGGC -3'
(R):5'- GCACTCGCTCTTATCTGGGG -3'

Posted On

2014-08-25