Mutagenetix > Incidental Mutation

Incidental Mutation 'R9710:Gnas'

730043

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

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R9710 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

174126113-174188537 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 174141132 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Methionine at position 493 (T493M)

Ref Sequence

ENSEMBL: ENSMUSP00000079341 (fasta)

Gene Model

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

AlphaFold

Q6R0H7

Predicted Effect

unknown
Transcript: ENSMUST00000080493
AA Change: T493M

SMART Domains

Protein: ENSMUSP00000079341
Gene: ENSMUSG00000027523
AA Change: T493M

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: T493M

SMART Domains

Protein: ENSMUSP00000085184
Gene: ENSMUSG00000027523
AA Change: T493M

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

probably damaging
Transcript: ENSMUST00000087877
AA Change: T493M

PolyPhen 2 Score 0.974 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000085185
Gene: ENSMUSG00000027523
AA Change: T493M

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

unknown
Transcript: ENSMUST00000109088
AA Change: R434W

SMART Domains

Protein: ENSMUSP00000104716
Gene: ENSMUSG00000027523
AA Change: R434W

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

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

unknown
Transcript: ENSMUST00000185956
AA Change: T493M

SMART Domains

Protein: ENSMUSP00000140174
Gene: ENSMUSG00000027523
AA Change: T493M

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: ENSMUST00000186907
AA Change: R434W

SMART Domains

Protein: ENSMUSP00000139839
Gene: ENSMUSG00000027523
AA Change: R434W

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

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.7%

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: 92 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930407I10Rik	T	C	15: 81,946,852 (GRCm39)	S250P	probably benign	Het
Ahcyl1	T	A	3: 107,578,494 (GRCm39)	I248F	possibly damaging	Het
Alpk2	T	A	18: 65,482,646 (GRCm39)	E454V	probably damaging	Het
Ank3	A	T	10: 69,829,070 (GRCm39)	T2580S		Het
Anks1	G	A	17: 28,128,571 (GRCm39)	G46R	possibly damaging	Het
Arhgap45	A	G	10: 79,857,635 (GRCm39)	E322G	probably damaging	Het
Arhgef2	T	C	3: 88,528,576 (GRCm39)	I4T	probably benign	Het
C1qtnf4	T	C	2: 90,720,351 (GRCm39)	I208T	probably damaging	Het
Cachd1	T	A	4: 100,832,092 (GRCm39)	N751K	probably benign	Het
Cacna1a	G	T	8: 85,320,808 (GRCm39)	V1589F	possibly damaging	Het
Cacnb1	T	C	11: 97,902,197 (GRCm39)	H205R	probably benign	Het
Castor1	A	G	11: 4,169,015 (GRCm39)	K61E	probably benign	Het
Ccdc9b	G	T	2: 118,591,077 (GRCm39)	A152E	probably benign	Het
Clvs2	C	A	10: 33,389,307 (GRCm39)	R311L	probably benign	Het
Crim1	G	T	17: 78,610,504 (GRCm39)	G320*	probably null	Het
Crtam	A	T	9: 40,895,671 (GRCm39)	D218E	probably benign	Het
Cwc27	G	A	13: 104,943,158 (GRCm39)	T128I	probably damaging	Het
Cyp4a14	T	A	4: 115,349,347 (GRCm39)	I238F	probably benign	Het
D930020B18Rik	A	C	10: 121,503,563 (GRCm39)	E246A	probably benign	Het
Dsg1c	T	A	18: 20,410,044 (GRCm39)	V504E	probably benign	Het
Enpp6	T	A	8: 47,518,948 (GRCm39)	S239T	probably damaging	Het
Eri2	A	T	7: 119,384,824 (GRCm39)	I559N	probably benign	Het
Fbxo34	T	C	14: 47,768,724 (GRCm39)	Y746H	probably damaging	Het
Galr1	A	T	18: 82,424,103 (GRCm39)	L58Q	probably damaging	Het
Ghdc	A	G	11: 100,658,863 (GRCm39)	V423A	probably benign	Het
Glt28d2	T	C	3: 85,779,059 (GRCm39)	D138G	probably benign	Het
Gm266	A	T	12: 111,451,763 (GRCm39)	C148S	probably benign	Het
Hivep2	T	C	10: 14,015,203 (GRCm39)	I1790T	probably damaging	Het
Impg1	A	G	9: 80,287,276 (GRCm39)	V390A	probably benign	Het
Isy1	A	G	6: 87,796,574 (GRCm39)	F239L	possibly damaging	Het
Itgb5	A	G	16: 33,685,917 (GRCm39)	T86A	probably benign	Het
Itpr1	T	C	6: 108,382,481 (GRCm39)	C1458R	possibly damaging	Het
Krt28	T	C	11: 99,255,921 (GRCm39)	E446G	probably damaging	Het
Lama1	A	T	17: 68,129,404 (GRCm39)	Q3071L		Het
Lasp1	A	G	11: 97,697,593 (GRCm39)		probably benign	Het
Lmf2	T	C	15: 89,237,419 (GRCm39)	K348E	probably benign	Het
Lrch3	G	T	16: 32,796,108 (GRCm39)	E331*	probably null	Het
Lzic	T	A	4: 149,573,141 (GRCm39)	F98I	probably damaging	Het
Map7d1	C	A	4: 126,127,440 (GRCm39)		probably null	Het
Marchf8	C	T	6: 116,378,405 (GRCm39)	T113I	possibly damaging	Het
Mgrn1	A	T	16: 4,745,740 (GRCm39)	K423*	probably null	Het
Muc20	G	A	16: 32,615,266 (GRCm39)	T37I	possibly damaging	Het
Myh15	A	G	16: 48,959,044 (GRCm39)	E972G	probably damaging	Het
Myocd	T	A	11: 65,087,167 (GRCm39)	K253N	probably damaging	Het
Myod1	T	G	7: 46,026,575 (GRCm39)	L160R	probably damaging	Het
Nanog	T	C	6: 122,684,799 (GRCm39)	S20P	probably benign	Het
Nat8f2	A	T	6: 85,844,683 (GRCm39)	Y226*	probably null	Het
Nsmf	A	G	2: 24,949,077 (GRCm39)	K277R	probably null	Het
Nsrp1	C	T	11: 76,967,503 (GRCm39)	G30R	probably damaging	Het
Nsun6	C	A	2: 15,003,009 (GRCm39)	R389L	probably benign	Het
Obscn	G	A	11: 58,943,397 (GRCm39)	R4251C	probably benign	Het
Or10g9	A	T	9: 39,912,172 (GRCm39)	M117K	probably damaging	Het
Or11h4	C	T	14: 50,974,199 (GRCm39)	C140Y	probably benign	Het
Or51h1	A	G	7: 102,308,441 (GRCm39)	T138A	probably damaging	Het
Or5w20	G	A	2: 87,726,902 (GRCm39)	D120N	probably damaging	Het
Pgm1	T	C	4: 99,843,918 (GRCm39)	L567P	probably damaging	Het
Polrmt	G	T	10: 79,576,535 (GRCm39)	H474N	probably benign	Het
Ppfia2	A	G	10: 106,664,885 (GRCm39)	I374V	probably benign	Het
Pramel5	T	A	4: 143,999,545 (GRCm39)	I181F	probably benign	Het
Prpf4b	T	A	13: 35,083,870 (GRCm39)	Y880N	probably damaging	Het
Ptpn3	G	A	4: 57,249,957 (GRCm39)	Q180*	probably null	Het
Ptprc	T	C	1: 138,008,627 (GRCm39)	R687G	probably damaging	Het
Rnaseh2a	T	C	8: 85,684,638 (GRCm39)	T241A	probably damaging	Het
Rnf148	T	A	6: 23,654,802 (GRCm39)	I65F	possibly damaging	Het
Rnf213	A	G	11: 119,331,831 (GRCm39)	I2348V		Het
Rttn	A	G	18: 89,035,334 (GRCm39)	N736S	possibly damaging	Het
Ryr3	A	C	2: 112,633,534 (GRCm39)	V2093G	probably damaging	Het
Selenof	T	A	3: 144,283,370 (GRCm39)	F33L	probably benign	Het
Sh2d3c	C	T	2: 32,635,889 (GRCm39)	R238*	probably null	Het
Slc23a4	T	C	6: 34,923,235 (GRCm39)	K543R	probably benign	Het
Smn1	A	T	13: 100,272,210 (GRCm39)	N278I	possibly damaging	Het
Sox7	G	A	14: 64,185,509 (GRCm39)	A182T	probably benign	Het
Spata31e5	T	A	1: 28,817,120 (GRCm39)	Y304F	probably benign	Het
Sptlc2	A	T	12: 87,359,533 (GRCm39)	I501N	probably benign	Het
Srf	T	C	17: 46,866,271 (GRCm39)	T162A	probably benign	Het
Srm	C	T	4: 148,676,039 (GRCm39)		probably benign	Het
Stim1	CAGCGCCTGACGGAGC	CAGC	7: 102,080,118 (GRCm39)		probably benign	Het
Taar8a	T	C	10: 23,952,714 (GRCm39)	L106P	probably damaging	Het
Tcte1	A	G	17: 45,850,798 (GRCm39)	H358R	possibly damaging	Het
Tmem205	A	G	9: 21,837,587 (GRCm39)	S20P	probably damaging	Het
Trav16	T	A	14: 53,980,910 (GRCm39)	V33E	possibly damaging	Het
Trf	T	A	9: 103,103,217 (GRCm39)	I149F	probably damaging	Het
Trmt2a	C	T	16: 18,070,041 (GRCm39)	Q419*	probably null	Het
Ttc19	A	G	11: 62,203,997 (GRCm39)	I319M	probably benign	Het
Txndc16	T	C	14: 45,400,467 (GRCm39)	I345V	probably benign	Het
Ube3b	T	C	5: 114,553,370 (GRCm39)	I914T	probably benign	Het
Ubr3	T	C	2: 69,727,957 (GRCm39)	F107L	possibly damaging	Het
Vmn1r73	T	C	7: 11,490,407 (GRCm39)	F75S	possibly damaging	Het
Vmn2r54	A	T	7: 12,363,753 (GRCm39)	M380K	possibly damaging	Het
Wdr7	T	A	18: 63,927,317 (GRCm39)	M989K	possibly damaging	Het
Zcchc3	A	G	2: 152,256,385 (GRCm39)	S105P	probably benign	Het
Zfp735	T	A	11: 73,601,806 (GRCm39)	V250E	possibly 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
R1968:Gnas	UTSW	2	174,140,526 (GRCm39)	missense	probably damaging	0.96
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
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'- GAACGCCTTCAGATCTCCAG -3'
(R):5'- AGACCAGTGGACCTGCATAG -3'

Sequencing Primer
(F):5'- AGATCTCCAGTCGGATCCTGAAG -3'
(R):5'- GCAGAGGCTGACATTGCTG -3'

Posted On

2022-10-06