Incidental Mutation 'R7541:Gnas'
ID 583877
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 045613-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R7541 (G1)
Quality Score 225.009
Status Validated
Chromosome 2
Chromosomal Location 174284320-174346744 bp(+) (GRCm38)
Type of Mutation missense
DNA Base Change (assembly) T to A at 174298099 bp (GRCm38)
Zygosity Heterozygous
Amino Acid Change Serine to Threonine at position 80 (S80T)
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: S80T
SMART Domains Protein: ENSMUSP00000079341
Gene: ENSMUSG00000027523
AA Change: S80T

DomainStartEndE-ValueType
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: S80T
SMART Domains Protein: ENSMUSP00000085184
Gene: ENSMUSG00000027523
AA Change: S80T

DomainStartEndE-ValueType
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: S80T
SMART Domains Protein: ENSMUSP00000085185
Gene: ENSMUSG00000027523
AA Change: S80T

DomainStartEndE-ValueType
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: N20K

PolyPhen 2 Score 0.976 (Sensitivity: 0.76; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000104716
Gene: ENSMUSG00000027523
AA Change: N20K

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
Pfam:NESP55 1 253 1.2e-157 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000109096
SMART Domains Protein: ENSMUSP00000104724
Gene: ENSMUSG00000027523

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
Pfam:NESP55 1 59 1.6e-30 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000180362
SMART Domains Protein: ENSMUSP00000136180
Gene: ENSMUSG00000027523

DomainStartEndE-ValueType
Pfam:NESP55 1 253 1.2e-157 PFAM
Predicted Effect unknown
Transcript: ENSMUST00000185956
AA Change: S80T
SMART Domains Protein: ENSMUSP00000140174
Gene: ENSMUSG00000027523
AA Change: S80T

DomainStartEndE-ValueType
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 probably damaging
Transcript: ENSMUST00000186907
AA Change: N20K

PolyPhen 2 Score 0.976 (Sensitivity: 0.76; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000139839
Gene: ENSMUSG00000027523
AA Change: N20K

DomainStartEndE-ValueType
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: 100.0%
  • 10x: 99.7%
  • 20x: 99.2%
Validation Efficiency 96% (51/53)
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: 53 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700020D05Rik G A 19: 5,503,411 (GRCm38) P114L probably benign Het
4930539E08Rik G A 17: 28,905,324 (GRCm38) R335W probably damaging Het
9530053A07Rik T A 7: 28,144,256 (GRCm38) C856* probably null Het
Acss2 G A 2: 155,574,690 (GRCm38) probably null Het
Adamts10 G A 17: 33,531,616 (GRCm38) R210H probably benign Het
Als2 T C 1: 59,167,616 (GRCm38) probably null Het
Aplp2 A T 9: 31,152,356 (GRCm38) M652K possibly damaging Het
Atrn A G 2: 130,961,571 (GRCm38) I560M possibly damaging Het
Bicc1 T C 10: 70,946,604 (GRCm38) D602G possibly damaging Het
Cdh4 A G 2: 179,444,810 (GRCm38) probably null Het
Clasp1 T A 1: 118,542,997 (GRCm38) probably null Het
Col6a6 A G 9: 105,767,324 (GRCm38) I1255T probably damaging Het
Comp G T 8: 70,381,350 (GRCm38) V672L probably damaging Het
Dbnl T G 11: 5,795,486 (GRCm38) D122E probably damaging Het
Dgkz G A 2: 91,942,675 (GRCm38) R346C probably damaging Het
Dnhd1 C T 7: 105,678,309 (GRCm38) R54C probably damaging Het
Elmo3 T C 8: 105,306,714 (GRCm38) I121T probably damaging Het
Fam184b A G 5: 45,542,232 (GRCm38) L614P probably damaging Het
Fbxo18 T C 2: 11,749,537 (GRCm38) R797G probably benign Het
Gata6 A G 18: 11,059,108 (GRCm38) T392A probably damaging Het
Gm17783 T A 16: 45,528,492 (GRCm38) T106S possibly damaging Het
Gm21731 A T 13: 120,240,979 (GRCm38) M104L probably benign Het
Gm29609 A G 5: 31,154,232 (GRCm38) F855S probably benign Het
Gm3424 T C 14: 5,829,330 (GRCm38) N88D possibly damaging Het
Hsd17b14 C A 7: 45,566,146 (GRCm38) P190Q probably damaging Het
Iqch C T 9: 63,445,521 (GRCm38) V955I possibly damaging Het
Kcnt2 T C 1: 140,376,384 (GRCm38) V164A probably benign Het
Krt87 A G 15: 101,438,634 (GRCm38) L46P probably damaging Het
Lef1 A G 3: 131,191,099 (GRCm38) M237V probably benign Het
Lmbr1l A T 15: 98,909,386 (GRCm38) probably null Het
Lrrc49 T C 9: 60,610,403 (GRCm38) I408V probably damaging Het
Luc7l3 T C 11: 94,295,965 (GRCm38) S365G unknown Het
March2 A T 17: 33,703,058 (GRCm38) C109* probably null Het
Metrnl T A 11: 121,715,970 (GRCm38) C284S probably damaging Het
Mmachc G A 4: 116,705,885 (GRCm38) T91I probably benign Het
Mrps7 T G 11: 115,606,870 (GRCm38) M187R probably damaging Het
Ncapd3 A G 9: 27,067,040 (GRCm38) E845G probably damaging Het
Olfr1393 T A 11: 49,280,333 (GRCm38) F62I probably damaging Het
Olfr272 A T 4: 52,911,376 (GRCm38) D139E probably benign Het
Ooep T A 9: 78,378,065 (GRCm38) T90S possibly damaging Het
Pcdhb18 A T 18: 37,491,609 (GRCm38) D664V probably damaging Het
Pigz T C 16: 31,945,131 (GRCm38) S336P probably benign Het
Pou2f2 A T 7: 25,116,128 (GRCm38) D71E probably benign Het
Reep6 G T 10: 80,335,199 (GRCm38) R303L possibly damaging Het
Rmdn2 A T 17: 79,627,868 (GRCm38) S137C Het
Rnf220 A T 4: 117,489,930 (GRCm38) L95H probably damaging Het
Rsf1 CGGCGGCGG CGGCGGCGGGGGCGGCGG 7: 97,579,911 (GRCm38) probably benign Het
Stxbp1 A T 2: 32,818,505 (GRCm38) S83T probably damaging Het
Trappc11 T C 8: 47,505,582 (GRCm38) probably null Het
Ttn G T 2: 76,791,301 (GRCm38) D15598E probably damaging Het
Vav2 T A 2: 27,275,002 (GRCm38) R645W probably damaging Het
Vmn1r169 T A 7: 23,577,987 (GRCm38) V268D probably benign Het
Zp2 A T 7: 120,136,056 (GRCm38) C365S probably damaging Het
Other mutations in Gnas
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00565:Gnas APN 2 174,341,711 (GRCm38) splice site probably benign
IGL00928:Gnas APN 2 174,297,953 (GRCm38) nonsense probably null
IGL01014:Gnas APN 2 174,297,974 (GRCm38) utr 5 prime probably benign
IGL01743:Gnas APN 2 174,298,332 (GRCm38) nonsense probably null
IGL01808:Gnas APN 2 174,298,697 (GRCm38) missense probably damaging 0.96
IGL02559:Gnas APN 2 174,341,936 (GRCm38) splice site probably benign
R0555:Gnas UTSW 2 174,298,511 (GRCm38) missense possibly damaging 0.78
R0627:Gnas UTSW 2 174,298,135 (GRCm38) intron probably benign
R1418:Gnas UTSW 2 174,345,214 (GRCm38) splice site probably benign
R1706:Gnas UTSW 2 174,299,975 (GRCm38) missense possibly damaging 0.90
R1751:Gnas UTSW 2 174,297,894 (GRCm38) utr 5 prime probably benign
R1968:Gnas UTSW 2 174,298,733 (GRCm38) missense probably damaging 0.96
R2290:Gnas UTSW 2 174,300,010 (GRCm38) missense probably benign 0.09
R4125:Gnas UTSW 2 174,300,165 (GRCm38) missense possibly damaging 0.94
R4128:Gnas UTSW 2 174,300,165 (GRCm38) missense possibly damaging 0.94
R4697:Gnas UTSW 2 174,298,080 (GRCm38) missense probably damaging 1.00
R4888:Gnas UTSW 2 174,298,089 (GRCm38) missense possibly damaging 0.94
R5458:Gnas UTSW 2 174,298,331 (GRCm38) missense probably benign 0.41
R5640:Gnas UTSW 2 174,284,971 (GRCm38) missense probably benign 0.44
R5696:Gnas UTSW 2 174,299,675 (GRCm38) intron probably benign
R5757:Gnas UTSW 2 174,345,247 (GRCm38) missense probably damaging 1.00
R6053:Gnas UTSW 2 174,299,852 (GRCm38) missense possibly damaging 0.89
R6083:Gnas UTSW 2 174,297,862 (GRCm38) start codon destroyed probably null
R6736:Gnas UTSW 2 174,334,251 (GRCm38) missense probably damaging 0.98
R7074:Gnas UTSW 2 174,285,049 (GRCm38) missense probably damaging 1.00
R7239:Gnas UTSW 2 174,298,615 (GRCm38) missense unknown
R7679:Gnas UTSW 2 174,284,831 (GRCm38) missense probably damaging 0.99
R7694:Gnas UTSW 2 174,300,212 (GRCm38) missense probably damaging 1.00
R7713:Gnas UTSW 2 174,299,027 (GRCm38) missense unknown
R7834:Gnas UTSW 2 174,298,990 (GRCm38) nonsense probably null
R8138:Gnas UTSW 2 174,298,386 (GRCm38) missense probably benign 0.06
R8459:Gnas UTSW 2 174,284,939 (GRCm38) missense probably benign 0.05
R8537:Gnas UTSW 2 174,298,601 (GRCm38) missense possibly damaging 0.83
R8731:Gnas UTSW 2 174,284,906 (GRCm38) missense probably benign 0.01
R8924:Gnas UTSW 2 174,299,484 (GRCm38) missense unknown
R9431:Gnas UTSW 2 174,298,033 (GRCm38) missense unknown
R9513:Gnas UTSW 2 174,343,296 (GRCm38) missense probably damaging 0.98
R9617:Gnas UTSW 2 174,300,195 (GRCm38) missense possibly damaging 0.90
R9710:Gnas UTSW 2 174,299,339 (GRCm38) missense unknown
R9711:Gnas UTSW 2 174,299,599 (GRCm38) missense unknown
R9762:Gnas UTSW 2 174,298,846 (GRCm38) nonsense probably null
X0022:Gnas UTSW 2 174,299,744 (GRCm38) missense probably benign 0.33
Z1088:Gnas UTSW 2 174,298,373 (GRCm38) missense probably benign 0.27
Z1176:Gnas UTSW 2 174,298,606 (GRCm38) missense unknown
Z1177:Gnas UTSW 2 174,284,887 (GRCm38) missense unknown
Predicted Primers PCR Primer
(F):5'- CACGGCAATAATATGTCAGGACAAC -3'
(R):5'- CCAAAATCGCTGGGTTGAAGG -3'

Sequencing Primer
(F):5'- TATGTCAGGACAACACGATATCC -3'
(R):5'- GCTTGGAGGCCTGATGG -3'
Posted On 2019-10-17