Incidental Mutation 'R4260:Grb2'
ID 322625
Institutional Source Beutler Lab
Gene Symbol Grb2
Ensembl Gene ENSMUSG00000059923
Gene Name growth factor receptor bound protein 2
Synonyms
MMRRC Submission 041073-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R4260 (G1)
Quality Score 225
Status Validated
Chromosome 11
Chromosomal Location 115534871-115599423 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 115540642 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Threonine at position 85 (I85T)
Ref Sequence ENSEMBL: ENSMUSP00000102104 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000021090] [ENSMUST00000106495] [ENSMUST00000106497] [ENSMUST00000106499] [ENSMUST00000135065]
AlphaFold Q60631
Predicted Effect possibly damaging
Transcript: ENSMUST00000021090
AA Change: I85T

PolyPhen 2 Score 0.938 (Sensitivity: 0.80; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000021090
Gene: ENSMUSG00000059923
AA Change: I85T

DomainStartEndE-ValueType
SH3 1 57 2.31e-21 SMART
SH2 58 141 2.97e-35 SMART
SH3 159 214 5.55e-24 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000106495
AA Change: I85T

PolyPhen 2 Score 0.960 (Sensitivity: 0.78; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000102104
Gene: ENSMUSG00000059923
AA Change: I85T

DomainStartEndE-ValueType
SH3 1 57 2.31e-21 SMART
SH2 58 141 2.97e-35 SMART
SH3 143 200 2.08e-14 SMART
Predicted Effect possibly damaging
Transcript: ENSMUST00000106497
AA Change: I85T

PolyPhen 2 Score 0.938 (Sensitivity: 0.80; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000102106
Gene: ENSMUSG00000059923
AA Change: I85T

DomainStartEndE-ValueType
SH3 1 57 2.31e-21 SMART
SH2 58 141 2.97e-35 SMART
SH3 159 214 5.55e-24 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000106499
SMART Domains Protein: ENSMUSP00000102108
Gene: ENSMUSG00000059923

DomainStartEndE-ValueType
SH3 1 57 2.31e-21 SMART
SH2 16 100 1.36e0 SMART
SH3 118 173 5.55e-24 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000135065
SMART Domains Protein: ENSMUSP00000117539
Gene: ENSMUSG00000059923

DomainStartEndE-ValueType
SH3 1 57 1.4e-23 SMART
Meta Mutation Damage Score 0.9397 question?
Coding Region Coverage
  • 1x: 99.3%
  • 3x: 98.7%
  • 10x: 97.5%
  • 20x: 95.7%
Validation Efficiency 98% (50/51)
MGI Phenotype FUNCTION: The protein encoded by this gene binds the epidermal growth factor receptor and contains one SH2 domain and two SH3 domains. Its two SH3 domains direct complex formation with proline-rich regions of other proteins, and its SH2 domain binds tyrosine phosphorylated sequences. This gene is similar to the Sem5 gene of C.elegans, which is involved in the signal transduction pathway. Three alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Sep 2015]
PHENOTYPE: Embryos homozygous for a targeted null mutation lack expanded inner cell masses, show only a few endodermal cells, and die by embryonic day 7.5. Heterozygotes have defective T cell signaling and lack the cardiac hypertrophy response to pressure overload. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 42 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adnp2 G A 18: 80,180,742 (GRCm39) S52L possibly damaging Het
Best3 A T 10: 116,860,131 (GRCm39) M464L probably benign Het
Ccdc83 T G 7: 89,877,599 (GRCm39) D281A possibly damaging Het
Ccnf G A 17: 24,445,741 (GRCm39) P502S probably damaging Het
Cd109 T A 9: 78,543,745 (GRCm39) S96R possibly damaging Het
Cep290 A C 10: 100,350,354 (GRCm39) E649D probably damaging Het
Cntnap5a G T 1: 116,374,325 (GRCm39) A946S probably benign Het
Csnk2a2 A T 8: 96,184,027 (GRCm39) D177E probably benign Het
Cyld T C 8: 89,468,019 (GRCm39) S551P probably damaging Het
Degs1 A T 1: 182,106,806 (GRCm39) I151N probably benign Het
Dnah12 A G 14: 26,520,883 (GRCm39) I1901V probably benign Het
Eif2ak3 G A 6: 70,866,497 (GRCm39) R597H probably damaging Het
Epg5 A T 18: 78,002,336 (GRCm39) H585L possibly damaging Het
Epg5 G C 18: 78,058,914 (GRCm39) W1889C probably damaging Het
Fam220a G C 5: 143,548,762 (GRCm39) R58P possibly damaging Het
Gemin5 G A 11: 58,059,185 (GRCm39) A32V probably damaging Het
Gm11189 A C 11: 53,091,703 (GRCm39) noncoding transcript Het
Herc1 CTGAGGACTCTTTG CTG 9: 66,355,630 (GRCm39) probably null Het
Ide A C 19: 37,306,585 (GRCm39) S63A unknown Het
Kel A T 6: 41,663,357 (GRCm39) probably benign Het
Kifap3 C A 1: 163,689,597 (GRCm39) T527K probably damaging Het
Klra10 A G 6: 130,249,644 (GRCm39) W214R probably damaging Het
Luc7l3 A T 11: 94,186,876 (GRCm39) probably benign Het
Mrpl4 A G 9: 20,918,988 (GRCm39) E211G possibly damaging Het
Or4k39 T A 2: 111,238,850 (GRCm39) noncoding transcript Het
Or52n5 A C 7: 104,587,803 (GRCm39) E23D probably damaging Het
Pbld2 T C 10: 62,860,186 (GRCm39) probably benign Het
Plcg1 T C 2: 160,593,627 (GRCm39) probably null Het
Ppcs A G 4: 119,279,106 (GRCm39) F149L probably damaging Het
Ptpdc1 A G 13: 48,733,234 (GRCm39) M802T probably benign Het
Ptprf A G 4: 118,083,280 (GRCm39) F909S possibly damaging Het
Raph1 A T 1: 60,542,124 (GRCm39) M330K possibly damaging Het
Rprd1a G A 18: 24,621,352 (GRCm39) R276C possibly damaging Het
Scg3 A G 9: 75,558,979 (GRCm39) Y406H probably damaging Het
Setdb1 G A 3: 95,234,808 (GRCm39) S965F probably damaging Het
Sgo2b A T 8: 64,381,330 (GRCm39) F501I probably benign Het
Slc38a4 A G 15: 96,896,374 (GRCm39) Y498H probably damaging Het
Slc5a4b A G 10: 75,939,686 (GRCm39) L150P probably damaging Het
Spata17 T A 1: 186,780,677 (GRCm39) T357S possibly damaging Het
Tmt1a A G 15: 100,210,951 (GRCm39) D141G probably benign Het
Zap70 T A 1: 36,818,189 (GRCm39) probably benign Het
Zfp985 G A 4: 147,668,029 (GRCm39) C299Y probably damaging Het
Other mutations in Grb2
AlleleSourceChrCoordTypePredicted EffectPPH Score
Hill_country UTSW 11 115,536,698 (GRCm39) missense probably benign 0.06
ANU74:Grb2 UTSW 11 115,536,733 (GRCm39) missense probably benign
R0003:Grb2 UTSW 11 115,546,251 (GRCm39) missense probably damaging 0.97
R2077:Grb2 UTSW 11 115,536,651 (GRCm39) missense probably damaging 1.00
R5796:Grb2 UTSW 11 115,536,698 (GRCm39) missense probably benign 0.06
Predicted Primers PCR Primer
(F):5'- TGCTACAACTAGGCCTTAGAGC -3'
(R):5'- AAGCTCCATCTCTCAGGAAGG -3'

Sequencing Primer
(F):5'- GGCCTTAGAGCAAACACTAGGATTTC -3'
(R):5'- TAAGAGCCCCAGGGAGCCTTAG -3'
Posted On 2015-06-20