Incidental Mutation 'D4216:Ric8b'
ID236
Institutional Source Beutler Lab
Gene Symbol Ric8b
Ensembl Gene ENSMUSG00000035620
Gene NameRIC8 guanine nucleotide exchange factor B
SynonymsRic-8b, Ric-8
Accession Numbers

Genbank: NM_001013441, NM_183172; MGI: 2682307

Is this an essential gene? Essential (E-score: 1.000) question?
Stock #D4216 (G3) of strain honey
Quality Score
Status Validated
Chromosome10
Chromosomal Location84917616-85018337 bp(+) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) T to C at 85015141 bp
ZygosityHeterozygous
Amino Acid Change Leucine to Proline at position 546 (L546P)
Ref Sequence ENSEMBL: ENSMUSP00000046981 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000038523] [ENSMUST00000095385]
Predicted Effect probably damaging
Transcript: ENSMUST00000038523
AA Change: L546P

PolyPhen 2 Score 0.988 (Sensitivity: 0.73; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000046981
Gene: ENSMUSG00000035620
AA Change: L546P

DomainStartEndE-ValueType
Pfam:Ric8 66 538 8.1e-125 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000095385
AA Change: L506P

PolyPhen 2 Score 0.974 (Sensitivity: 0.76; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000093032
Gene: ENSMUSG00000035620
AA Change: L506P

DomainStartEndE-ValueType
Pfam:Ric8 66 486 1.2e-111 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000214820
Predicted Effect noncoding transcript
Transcript: ENSMUST00000217175
Meta Mutation Damage Score 0.4248 question?
Coding Region Coverage
  • 1x: 58.2%
  • 3x: 22.7%
Validation Efficiency 68% (27/40)
Allele List at MGI

All alleles(24) : Targeted, other(4) Gene trapped(20)

Other mutations in this stock
Total: 9 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Fbxo33 A T 12: 59,206,050 V221E probably benign Het
Frmpd2 T A 14: 33,552,057 F1085L probably damaging Homo
Kcnrg T G 14: 61,611,793 Y234* probably null Homo
Mrgpra6 T A 7: 47,188,756 L231F probably damaging Het
Naca T C 10: 128,044,240 S1714P possibly damaging Homo
Rapgef6 T C 11: 54,668,746 probably benign Homo
Slc34a2 A G 5: 53,065,497 T310A probably benign Homo
Ssc5d C T 7: 4,943,983 T1112I possibly damaging Homo
Stau1 A G 2: 166,949,750 V489A probably benign Homo
Other mutations in Ric8b
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL02254:Ric8b APN 10 84980136 missense probably damaging 1.00
IGL02388:Ric8b APN 10 84992271 unclassified probably benign
IGL02435:Ric8b APN 10 84980076 missense probably benign 0.06
IGL02890:Ric8b APN 10 85001867 missense possibly damaging 0.80
IGL03163:Ric8b APN 10 85001822 missense probably damaging 1.00
IGL03211:Ric8b APN 10 85001793 missense probably damaging 1.00
R0491:Ric8b UTSW 10 84992222 missense probably damaging 1.00
R0612:Ric8b UTSW 10 85001881 missense probably damaging 1.00
R1077:Ric8b UTSW 10 84970717 splice site probably benign
R1448:Ric8b UTSW 10 84947671 missense possibly damaging 0.93
R1565:Ric8b UTSW 10 84980099 missense probably benign 0.01
R1617:Ric8b UTSW 10 84947611 missense probably damaging 0.98
R1634:Ric8b UTSW 10 84970748 missense probably damaging 1.00
R1983:Ric8b UTSW 10 85001838 missense probably damaging 0.99
R2339:Ric8b UTSW 10 84970024 missense probably benign 0.00
R2897:Ric8b UTSW 10 84947897 missense probably benign 0.01
R2898:Ric8b UTSW 10 84947897 missense probably benign 0.01
R4657:Ric8b UTSW 10 84992137 missense probably damaging 1.00
R4747:Ric8b UTSW 10 84917764 missense probably benign 0.36
R4953:Ric8b UTSW 10 84958082 missense possibly damaging 0.92
R5277:Ric8b UTSW 10 84947652 missense probably damaging 0.99
R5308:Ric8b UTSW 10 84947747 missense probably benign
R5326:Ric8b UTSW 10 84992212 missense probably damaging 1.00
R6248:Ric8b UTSW 10 84947845 missense probably damaging 1.00
R6782:Ric8b UTSW 10 84947527 missense probably damaging 1.00
R7548:Ric8b UTSW 10 84947872 missense probably damaging 1.00
R8123:Ric8b UTSW 10 84969873 missense probably damaging 1.00
Z1176:Ric8b UTSW 10 84947544 missense probably benign 0.04
Nature of Mutation

DNA sequencing using the SOLiD technique identified a T to C transition at position 1763 of the Ric8b transcript using Genbank record NM_183172 in exon 10 of 10 total exons. Two transcripts of the Ric8b gene are displayed on Ensembl. The mutated nucleotide causes a leucine to proline substitution at amino acid 546 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

 
Protein Function and Prediction
Tthe Ric8b gene encodes two isoforms of a guanine nucleotide exchange factor (GEF), which can activate some, but not all, G-alpha proteins by exchanging bound GDP for free GTP. The protein, which is known as Synembryn-B, is able to potentiate G(olf)-alpha-dependent cAMP accumulation suggesting that it may be an important component for odorant signal transduction. Synembryn-B localizes to the cell cortex, and is predominantly expressed in the mature olfactory sensory neurons and also in a few regions in the brain. Isoform 1 contains 560 amino acids (Uniprot Q80XE1).
 
The L546F change is predicted to be benign by the PolyPhen program.
Posted On2010-06-23