Mutagenetix > Incidental Mutation

Incidental Mutation 'R4087:Sos1'

317440

Institutional Source

Beutler Lab

Gene Symbol

Sos1

Ensembl Gene

ENSMUSG00000024241

Gene Name

SOS Ras/Rac guanine nucleotide exchange factor 1

Synonyms

4430401P03Rik

MMRRC Submission

040980-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4087 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

80701181-80787882 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 80756781 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 257 (V257A)

Ref Sequence

ENSEMBL: ENSMUSP00000067786 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000068714]

AlphaFold

Q62245

PDB Structure

CRK SH3 DOMAIN COMPLEXED WITH PEPTOID INHIBITOR [X-RAY DIFFRACTION]
SOLUTION NMR STRUCTURE OF THE GRB2 N-TERMINAL SH3 DOMAIN COMPLEXED WITH A TEN-RESIDUE PEPTIDE DERIVED FROM SOS DIRECT REFINEMENT AGAINST NOES, J-COUPLINGS, AND 1H AND 13C CHEMICAL SHIFTS, MINIMIZED AVERAGE STRUCTURE [SOLUTION NMR]
PLECKSTRIN HOMOLOGY DOMAIN OF SON OF SEVENLESS 1 (SOS1) WITH GLYCINE-SERINE ADDED TO THE N-TERMINUS, NMR, 20 STRUCTURES [SOLUTION NMR]
SOLUTION NMR STRUCTURE OF THE GRB2 N-TERMINAL SH3 DOMAIN COMPLEXED WITH A TEN-RESIDUE PEPTIDE DERIVED FROM SOS DIRECT REFINEMENT AGAINST NOES, J-COUPLINGS, AND 1H AND 13C CHEMICAL SHIFTS, 15 STRUCTURES [SOLUTION NMR]
SOLUTION NMR STRUCTURE OF THE GRB2 N-TERMINAL SH3 DOMAIN COMPLEXED WITH A TEN-RESIDUE PEPTIDE DERIVED FROM SOS DIRECT REFINEMENT AGAINST NOES, J-COUPLINGS, AND 1H AND 13C CHEMICAL SHIFTS, MINIMIZED AVERAGE STRUCTURE [SOLUTION NMR]
SOLUTION NMR STRUCTURE OF THE GRB2 N-TERMINAL SH3 DOMAIN COMPLEXED WITH A TEN-RESIDUE PEPTIDE DERIVED FROM SOS DIRECT REFINEMENT AGAINST NOES, J-COUPLINGS, AND 1H AND 13C CHEMICAL SHIFTS, 15 STRUCTURES [SOLUTION NMR]

Predicted Effect

probably benign
Transcript: ENSMUST00000068714
AA Change: V257A

PolyPhen 2 Score 0.059 (Sensitivity: 0.94; Specificity: 0.84)

SMART Domains

Protein: ENSMUSP00000067786
Gene: ENSMUSG00000024241
AA Change: V257A

Domain	Start	End	E-Value	Type
Pfam:Histone	40	169	6.8e-16	PFAM
RhoGEF	204	389	8.5e-35	SMART
PH	444	548	2.44e-17	SMART
RasGEFN	596	741	2.18e-56	SMART
RasGEF	776	1020	4.44e-102	SMART
low complexity region	1079	1093	N/A	INTRINSIC
low complexity region	1116	1127	N/A	INTRINSIC
low complexity region	1132	1154	N/A	INTRINSIC
Blast:RasGEF	1155	1306	1e-51	BLAST

Meta Mutation Damage Score

0.1452

Coding Region Coverage

1x: 99.2%
3x: 98.7%
10x: 97.7%
20x: 96.3%

Validation Efficiency

96% (50/52)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a protein that is a guanine nucleotide exchange factor for RAS proteins, membrane proteins that bind guanine nucleotides and participate in signal transduction pathways. GTP binding activates and GTP hydrolysis inactivates RAS proteins. The product of this gene may regulate RAS proteins by facilitating the exchange of GTP for GDP. Mutations in this gene are associated with gingival fibromatosis 1 and Noonan syndrome type 4. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous null mutant embryos exhibit placental and cardiovascular defects resulting in death around mid-gestation. When heterozygous, these mutations enhance the eye defects of homozygous mutants of the epidermal growth factor receptor gene. [provided by MGI curators]

Allele List at MGI

All alleles(25) : Targeted, knock-out(2) Targeted, other(2) Gene trapped(21)

Other mutations in this stock

Total: 43 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A530064D06Rik	A	G	17: 48,473,678 (GRCm39)	S80P	probably damaging	Het
Acss3	T	G	10: 106,889,313 (GRCm39)	Y169S	probably damaging	Het
Cep250	G	A	2: 155,834,552 (GRCm39)	R2159K	probably damaging	Het
Cldn34c4	A	T	X: 126,629,011 (GRCm39)	V153E	probably damaging	Het
Col4a4	T	A	1: 82,501,643 (GRCm39)	Y370F	unknown	Het
Col6a6	A	T	9: 105,661,155 (GRCm39)	I318N	possibly damaging	Het
Csmd1	T	A	8: 16,042,738 (GRCm39)	I2332F	probably damaging	Het
Dnajc28	G	A	16: 91,413,755 (GRCm39)	T187M	probably damaging	Het
Dym	T	A	18: 75,363,172 (GRCm39)	Y559N	probably damaging	Het
Eif3g	A	G	9: 20,809,248 (GRCm39)	V59A	possibly damaging	Het
Fam171a1	G	A	2: 3,227,333 (GRCm39)	R697Q	probably damaging	Het
Fermt3	T	A	19: 6,980,945 (GRCm39)		probably null	Het
Git2	A	G	5: 114,902,466 (GRCm39)	Y189H	probably damaging	Het
Gkn3	C	T	6: 87,360,507 (GRCm39)	A163T	probably damaging	Het
Gm7713	C	T	15: 59,866,258 (GRCm39)		noncoding transcript	Het
Gpr108	A	G	17: 57,544,925 (GRCm39)	Y313H	probably damaging	Het
Itprid2	C	T	2: 79,488,691 (GRCm39)	Q925*	probably null	Het
Kcnh8	T	C	17: 53,110,428 (GRCm39)	I213T	possibly damaging	Het
Lpgat1	A	T	1: 191,495,728 (GRCm39)	I306F	possibly damaging	Het
Mapk8	T	C	14: 33,112,205 (GRCm39)	T228A	probably benign	Het
Med12l	T	C	3: 59,205,342 (GRCm39)	V2101A	probably benign	Het
Mettl13	T	C	1: 162,375,771 (GRCm39)	K19E	possibly damaging	Het
Mta1	A	G	12: 113,075,802 (GRCm39)	Y22C	probably damaging	Het
Notch3	T	C	17: 32,377,087 (GRCm39)	T273A	possibly damaging	Het
Notch4	T	C	17: 34,803,409 (GRCm39)	W1443R	probably damaging	Het
Npy5r	T	A	8: 67,134,697 (GRCm39)	D32V	probably damaging	Het
Or8k36-ps1	C	A	2: 86,437,297 (GRCm39)	*206L	probably null	Het
Rbm47	A	G	5: 66,180,080 (GRCm39)	M409T	probably benign	Het
Rnf144a	C	T	12: 26,377,591 (GRCm39)	V51I	probably damaging	Het
Rxfp1	T	A	3: 79,552,256 (GRCm39)	T682S	probably damaging	Het
Sertad2	GCCCC	GCCCCC	11: 20,598,664 (GRCm39)		probably null	Het
Tdrd9	C	T	12: 111,979,920 (GRCm39)	Q256*	probably null	Het
Tmprss11d	A	T	5: 86,457,138 (GRCm39)	S174T	probably damaging	Het
Tor1b	T	A	2: 30,846,531 (GRCm39)	I238N	probably damaging	Het
Tppp2	T	C	14: 52,156,957 (GRCm39)		probably null	Het
Traf3ip3	A	G	1: 192,863,628 (GRCm39)	V414A	probably damaging	Het
Trim14	T	A	4: 46,523,709 (GRCm39)	T110S	probably benign	Het
Trim30d	T	C	7: 104,137,007 (GRCm39)	N66D	probably damaging	Het
Usp48	A	G	4: 137,350,651 (GRCm39)	N46S	possibly damaging	Het
Vmn2r115	A	C	17: 23,565,358 (GRCm39)	Q415P	probably benign	Het
Wbp2nl	A	G	15: 82,192,762 (GRCm39)	M149V	probably benign	Het
Zfp106	T	C	2: 120,357,380 (GRCm39)		probably null	Het
Zfp281	T	A	1: 136,553,859 (GRCm39)	I279N	probably damaging	Het

Other mutations in Sos1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00805:Sos1	APN	17	80,705,953 (GRCm39)	missense	possibly damaging	0.94
IGL00915:Sos1	APN	17	80,741,367 (GRCm39)	missense	probably benign	0.00
IGL00929:Sos1	APN	17	80,716,025 (GRCm39)	missense	probably damaging	1.00
IGL01073:Sos1	APN	17	80,730,176 (GRCm39)	missense	probably damaging	1.00
IGL01116:Sos1	APN	17	80,752,929 (GRCm39)	missense	probably damaging	1.00
IGL01533:Sos1	APN	17	80,722,511 (GRCm39)	missense	probably damaging	0.97
IGL01546:Sos1	APN	17	80,716,040 (GRCm39)	missense	probably damaging	1.00
IGL01583:Sos1	APN	17	80,741,329 (GRCm39)	missense	probably benign	0.11
IGL01628:Sos1	APN	17	80,730,106 (GRCm39)	splice site	probably benign
IGL01837:Sos1	APN	17	80,730,157 (GRCm39)	missense	probably damaging	1.00
IGL02170:Sos1	APN	17	80,705,719 (GRCm39)	missense	probably damaging	0.99
IGL02426:Sos1	APN	17	80,742,372 (GRCm39)	missense	possibly damaging	0.82
IGL02992:Sos1	APN	17	80,726,445 (GRCm39)	missense	probably benign	0.01
IGL03037:Sos1	APN	17	80,727,758 (GRCm39)	missense	probably damaging	0.98
1mM(1):Sos1	UTSW	17	80,762,486 (GRCm39)	missense	possibly damaging	0.46
BB007:Sos1	UTSW	17	80,714,267 (GRCm39)	missense	probably benign	0.00
BB017:Sos1	UTSW	17	80,714,267 (GRCm39)	missense	probably benign	0.00
PIT4354001:Sos1	UTSW	17	80,756,785 (GRCm39)	missense	possibly damaging	0.52
R0056:Sos1	UTSW	17	80,721,050 (GRCm39)	missense	probably damaging	1.00
R0348:Sos1	UTSW	17	80,715,740 (GRCm39)	missense	probably benign
R0373:Sos1	UTSW	17	80,761,192 (GRCm39)	missense	probably damaging	1.00
R0477:Sos1	UTSW	17	80,742,363 (GRCm39)	missense	possibly damaging	0.92
R0621:Sos1	UTSW	17	80,759,408 (GRCm39)	critical splice donor site	probably null
R0839:Sos1	UTSW	17	80,741,159 (GRCm39)	missense	probably damaging	1.00
R1174:Sos1	UTSW	17	80,753,037 (GRCm39)	nonsense	probably null
R1490:Sos1	UTSW	17	80,721,104 (GRCm39)	missense	probably benign	0.11
R1566:Sos1	UTSW	17	80,761,345 (GRCm39)	missense	probably damaging	0.99
R1635:Sos1	UTSW	17	80,730,108 (GRCm39)	splice site	probably null
R3412:Sos1	UTSW	17	80,714,146 (GRCm39)	missense	probably benign
R3770:Sos1	UTSW	17	80,705,737 (GRCm39)	missense	probably damaging	0.97
R3951:Sos1	UTSW	17	80,731,610 (GRCm39)	missense	probably damaging	1.00
R3964:Sos1	UTSW	17	80,762,608 (GRCm39)	missense	probably damaging	1.00
R3966:Sos1	UTSW	17	80,762,608 (GRCm39)	missense	probably damaging	1.00
R4086:Sos1	UTSW	17	80,756,781 (GRCm39)	missense	probably benign	0.06
R4089:Sos1	UTSW	17	80,756,781 (GRCm39)	missense	probably benign	0.06
R4194:Sos1	UTSW	17	80,706,013 (GRCm39)	missense	probably benign	0.02
R4468:Sos1	UTSW	17	80,761,240 (GRCm39)	missense	probably damaging	1.00
R4469:Sos1	UTSW	17	80,761,240 (GRCm39)	missense	probably damaging	1.00
R4597:Sos1	UTSW	17	80,741,255 (GRCm39)	missense	probably benign	0.05
R4773:Sos1	UTSW	17	80,705,660 (GRCm39)	missense	probably damaging	0.99
R4923:Sos1	UTSW	17	80,742,381 (GRCm39)	missense	probably benign	0.10
R5120:Sos1	UTSW	17	80,715,677 (GRCm39)	missense	probably damaging	0.98
R5478:Sos1	UTSW	17	80,741,276 (GRCm39)	missense	probably damaging	1.00
R5566:Sos1	UTSW	17	80,761,319 (GRCm39)	missense	possibly damaging	0.91
R5984:Sos1	UTSW	17	80,759,561 (GRCm39)	missense	possibly damaging	0.68
R6053:Sos1	UTSW	17	80,722,463 (GRCm39)	missense	possibly damaging	0.94
R6153:Sos1	UTSW	17	80,756,764 (GRCm39)	missense	probably benign	0.01
R6567:Sos1	UTSW	17	80,740,932 (GRCm39)	missense	probably damaging	1.00
R7392:Sos1	UTSW	17	80,731,629 (GRCm39)	missense	probably damaging	1.00
R7623:Sos1	UTSW	17	80,787,323 (GRCm39)	missense	probably benign	0.28
R7763:Sos1	UTSW	17	80,721,142 (GRCm39)	missense	probably benign
R7930:Sos1	UTSW	17	80,714,267 (GRCm39)	missense	probably benign	0.00
R8132:Sos1	UTSW	17	80,716,031 (GRCm39)	missense	probably damaging	1.00
R8236:Sos1	UTSW	17	80,715,712 (GRCm39)	missense	probably benign	0.41
R8322:Sos1	UTSW	17	80,715,728 (GRCm39)	missense	probably damaging	0.96
R8348:Sos1	UTSW	17	80,741,548 (GRCm39)	missense	probably benign	0.00
R8448:Sos1	UTSW	17	80,741,548 (GRCm39)	missense	probably benign	0.00
R8554:Sos1	UTSW	17	80,705,842 (GRCm39)	missense	probably damaging	0.99
R8850:Sos1	UTSW	17	80,741,405 (GRCm39)	missense	probably damaging	1.00
R8966:Sos1	UTSW	17	80,705,879 (GRCm39)	missense	possibly damaging	0.87
R9051:Sos1	UTSW	17	80,715,723 (GRCm39)	missense	probably benign
R9355:Sos1	UTSW	17	80,722,479 (GRCm39)	missense	possibly damaging	0.71
R9378:Sos1	UTSW	17	80,761,239 (GRCm39)	missense	probably damaging	1.00
R9576:Sos1	UTSW	17	80,742,367 (GRCm39)	missense	probably benign	0.11
X0020:Sos1	UTSW	17	80,756,706 (GRCm39)	missense	probably damaging	1.00
Z1177:Sos1	UTSW	17	80,761,347 (GRCm39)	missense	probably benign	0.05

Predicted Primers

PCR Primer
(F):5'- TGTGACTTGAGCTGGAAATAGG -3'
(R):5'- CGCCATCCTTATTCCCAGAAAG -3'

Sequencing Primer
(F):5'- CTGGAAATAGGAATTATGAACCCC -3'
(R):5'- TGTTCTCCAGCCACAACAGACTG -3'

Posted On

2015-05-15