Mutagenetix > Incidental Mutations

Incidental Mutation 'R0373:Sos1'

65628

Institutional Source

Beutler Lab

Gene Symbol

Sos1

Ensembl Gene

ENSMUSG00000024241

Gene Name

SOS Ras/Rac guanine nucleotide exchange factor 1

Synonyms

4430401P03Rik

MMRRC Submission

038579-MU

Accession Numbers

Genbank: NM_009231.2; Ensembl: ENSMUST00000068714

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R0373 (G1)

Quality Score

137

Status

Not validated

Chromosome

Chromosomal Location

80393752-80480453 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 80453763 bp

Zygosity

Heterozygous

Amino Acid Change

Alanine to Aspartic acid at position 168 (A168D)

Ref Sequence

ENSEMBL: ENSMUSP00000067786 (fasta)

Gene Model

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

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 damaging
Transcript: ENSMUST00000068714
AA Change: A168D

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000067786
Gene: ENSMUSG00000024241
AA Change: A168D

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

Coding Region Coverage

1x: 99.1%
3x: 98.1%
10x: 95.8%
20x: 91.5%

Validation Efficiency

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: 93 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930579F01Rik	A	T	3: 138,173,582	L235Q	probably damaging	Het
Adam6b	T	A	12: 113,490,655	V364D	probably benign	Het
Akap13	T	C	7: 75,609,929	L767P	probably benign	Het
Akap13	T	A	7: 75,730,500	S2193T	probably damaging	Het
Anapc11	T	C	11: 120,605,377	V69A	probably benign	Het
Ankmy1	C	T	1: 92,896,190	R118Q	probably damaging	Het
Ankrd27	T	C	7: 35,638,053	S931P	probably benign	Het
Atp6v1c2	G	A	12: 17,288,168	R280C	probably damaging	Het
Bbs10	T	A	10: 111,300,052	I342N	probably damaging	Het
Calhm2	T	C	19: 47,132,950	D260G	possibly damaging	Het
Camk2a	A	G	18: 60,958,238	E264G	probably damaging	Het
Ccdc146	T	A	5: 21,319,545	M270L	probably benign	Het
Cdc16	A	G	8: 13,779,264	T517A	probably benign	Het
Ces1g	T	C	8: 93,331,193	H160R	probably benign	Het
Chst4	T	C	8: 110,030,394	N196S	probably damaging	Het
Ciz1	A	T	2: 32,367,467	N175Y	probably damaging	Het
Cyb5r4	G	A	9: 87,027,040	V57I	probably damaging	Het
Cyth3	A	G	5: 143,684,426		probably benign	Het
Def6	A	G	17: 28,220,180	E255G	probably damaging	Het
Dhtkd1	T	G	2: 5,911,870	Q665P	probably damaging	Het
Dsg3	A	C	18: 20,539,747	D825A	probably damaging	Het
Eif3m	T	C	2: 105,005,000	T242A	probably benign	Het
Emilin3	A	G	2: 160,909,817	F101L	probably benign	Het
Epha7	A	G	4: 28,935,700		probably null	Het
Fam205a1	T	C	4: 42,851,161	I332V	probably benign	Het
Fbxo45	A	T	16: 32,238,405	Y224N	probably damaging	Het
Fhod3	A	T	18: 25,090,104	M836L	possibly damaging	Het
Fut4	C	A	9: 14,751,210	V263F	probably damaging	Het
Ggt1	C	T	10: 75,579,270	T206M	probably benign	Het
Gls	T	C	1: 52,188,699	R79G	probably damaging	Het
Gm436	A	T	4: 144,686,220	M50K	possibly damaging	Het
Grhl1	T	C	12: 24,581,515	S156P	probably benign	Het
Ipo8	C	T	6: 148,775,042	S983N	probably benign	Het
Kcna7	C	T	7: 45,409,444	A385V	probably damaging	Het
Kpnb1	A	T	11: 97,185,090	L40Q	probably damaging	Het
Matn1	A	T	4: 130,950,106	S209C	probably damaging	Het
Mcc	A	G	18: 44,475,222	I501T	probably benign	Het
Mdp1	A	T	14: 55,659,375	F104L	probably damaging	Het
Mib2	A	T	4: 155,656,288	N626K	probably damaging	Het
Mrgprh	T	C	17: 12,876,956	S28P	possibly damaging	Het
Mup-ps23	T	A	4: 61,856,149		noncoding transcript	Het
Myh15	A	G	16: 49,182,959	T1794A	possibly damaging	Het
Myo18a	C	G	11: 77,821,042	P680A	probably benign	Het
Myom2	G	T	8: 15,098,419	D532Y	possibly damaging	Het
Ndufaf5	A	G	2: 140,170,881	N57S	probably benign	Het
Nectin3	C	T	16: 46,458,187	V282M	probably damaging	Het
Nup188	G	T	2: 30,330,988	D997Y	probably damaging	Het
Olfm3	T	C	3: 115,122,805	V462A	probably damaging	Het
Olfr1044	A	C	2: 86,171,706	F37C	probably damaging	Het
Olfr1225	A	T	2: 89,170,413	F266L	probably benign	Het
Olfr305	A	T	7: 86,363,805	C177*	probably null	Het
Opcml	A	G	9: 28,813,398	H164R	possibly damaging	Het
Pacrg	A	G	17: 10,403,418	I209T	probably damaging	Het
Pcf11	T	C	7: 92,661,215	M522V	probably benign	Het
Pck1	T	A	2: 173,153,390	M1K	probably null	Het
Pcm1	G	T	8: 41,276,111	E707*	probably null	Het
Pcsk5	G	A	19: 17,654,849	R318W	probably damaging	Het
Phf11d	A	T	14: 59,353,344	M188K	possibly damaging	Het
Ppip5k2	A	T	1: 97,740,537	C615*	probably null	Het
Prkdc	T	A	16: 15,791,927	S3132T	probably damaging	Het
Prl2c5	A	T	13: 13,183,024		probably benign	Het
Prpsap2	A	G	11: 61,741,000	I177T	possibly damaging	Het
Rad50	A	G	11: 53,650,519	S1297P	probably damaging	Het
Rasip1	T	A	7: 45,635,244	N678K	possibly damaging	Het
Rubcn	A	G	16: 32,835,980	S544P	probably damaging	Het
Rwdd2a	A	T	9: 86,574,400	T210S	possibly damaging	Het
Scd2	A	G	19: 44,303,040	D306G	probably damaging	Het
Sema3b	T	C	9: 107,602,918	N207S	probably benign	Het
Sf3b2	C	T	19: 5,274,824	D845N	probably damaging	Het
Sipa1l2	C	A	8: 125,464,410	C947F	probably damaging	Het
Slc12a1	A	T	2: 125,226,031	T1013S	probably damaging	Het
Slc18a2	A	T	19: 59,287,367	I461L	probably benign	Het
Slc1a6	C	A	10: 78,801,922	Y427*	probably null	Het
Slc30a4	A	T	2: 122,689,399	I231K	probably damaging	Het
Sptb	T	C	12: 76,621,371	S651G	probably benign	Het
Stk36	T	C	1: 74,633,620	L1007P	probably damaging	Het
Tek	A	T	4: 94,804,341	N229Y	probably damaging	Het
Tep1	A	G	14: 50,836,768	F1887L	possibly damaging	Het
Tet1	A	T	10: 62,878,209	C602*	probably null	Het
Tnfrsf19	A	G	14: 60,972,036	S262P	possibly damaging	Het
Trim5	T	C	7: 104,265,684	I393V	probably benign	Het
Trpm6	A	G	19: 18,853,587	E1272G	probably benign	Het
Ttc21b	A	T	2: 66,188,326	Y1246N	probably damaging	Het
Ttll3	T	A	6: 113,398,777	L151H	probably damaging	Het
U2surp	C	T	9: 95,484,443	V470I	probably benign	Het
Ubr1	A	T	2: 120,946,657	Y276N	probably benign	Het
Uggt1	A	G	1: 36,179,670	S59P	probably benign	Het
Unc45a	T	C	7: 80,326,344	T796A	probably damaging	Het
Unc5b	C	A	10: 60,778,940	V193F	possibly damaging	Het
Upp1	G	T	11: 9,129,590	M50I	probably benign	Het
Vps18	C	T	2: 119,293,905	R438C	probably damaging	Het
Zfp715	T	C	7: 43,299,336	Y400C	possibly damaging	Het
Zfp955b	T	C	17: 33,302,522	Y322H	probably benign	Het

Other mutations in Sos1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00805:Sos1	APN	17	80398524	missense	possibly damaging	0.94
IGL00915:Sos1	APN	17	80433938	missense	probably benign	0.00
IGL00929:Sos1	APN	17	80408596	missense	probably damaging	1.00
IGL01073:Sos1	APN	17	80422747	missense	probably damaging	1.00
IGL01116:Sos1	APN	17	80445500	missense	probably damaging	1.00
IGL01533:Sos1	APN	17	80415082	missense	probably damaging	0.97
IGL01546:Sos1	APN	17	80408611	missense	probably damaging	1.00
IGL01583:Sos1	APN	17	80433900	missense	probably benign	0.11
IGL01628:Sos1	APN	17	80422677	splice site	probably benign
IGL01837:Sos1	APN	17	80422728	missense	probably damaging	1.00
IGL02170:Sos1	APN	17	80398290	missense	probably damaging	0.99
IGL02426:Sos1	APN	17	80434943	missense	possibly damaging	0.82
IGL02992:Sos1	APN	17	80419016	missense	probably benign	0.01
IGL03037:Sos1	APN	17	80420329	missense	probably damaging	0.98
1mM(1):Sos1	UTSW	17	80455057	missense	possibly damaging	0.46
PIT4354001:Sos1	UTSW	17	80449356	missense	possibly damaging	0.52
R0056:Sos1	UTSW	17	80413621	missense	probably damaging	1.00
R0348:Sos1	UTSW	17	80408311	missense	probably benign
R0477:Sos1	UTSW	17	80434934	missense	possibly damaging	0.92
R0621:Sos1	UTSW	17	80451979	critical splice donor site	probably null
R0839:Sos1	UTSW	17	80433730	missense	probably damaging	1.00
R1174:Sos1	UTSW	17	80445608	nonsense	probably null
R1490:Sos1	UTSW	17	80413675	missense	probably benign	0.11
R1566:Sos1	UTSW	17	80453916	missense	probably damaging	0.99
R1635:Sos1	UTSW	17	80422679	splice site	probably null
R3412:Sos1	UTSW	17	80406717	missense	probably benign
R3770:Sos1	UTSW	17	80398308	missense	probably damaging	0.97
R3951:Sos1	UTSW	17	80424181	missense	probably damaging	1.00
R3964:Sos1	UTSW	17	80455179	missense	probably damaging	1.00
R3966:Sos1	UTSW	17	80455179	missense	probably damaging	1.00
R4086:Sos1	UTSW	17	80449352	missense	probably benign	0.06
R4087:Sos1	UTSW	17	80449352	missense	probably benign	0.06
R4089:Sos1	UTSW	17	80449352	missense	probably benign	0.06
R4194:Sos1	UTSW	17	80398584	missense	probably benign	0.02
R4468:Sos1	UTSW	17	80453811	missense	probably damaging	1.00
R4469:Sos1	UTSW	17	80453811	missense	probably damaging	1.00
R4597:Sos1	UTSW	17	80433826	missense	probably benign	0.05
R4773:Sos1	UTSW	17	80398231	missense	probably damaging	0.99
R4923:Sos1	UTSW	17	80434952	missense	probably benign	0.10
R5120:Sos1	UTSW	17	80408248	missense	probably damaging	0.98
R5478:Sos1	UTSW	17	80433847	missense	probably damaging	1.00
R5566:Sos1	UTSW	17	80453890	missense	possibly damaging	0.91
R5984:Sos1	UTSW	17	80452132	missense	possibly damaging	0.68
R6053:Sos1	UTSW	17	80415034	missense	possibly damaging	0.94
R6153:Sos1	UTSW	17	80449335	missense	probably benign	0.01
R6567:Sos1	UTSW	17	80433503	missense	probably damaging	1.00
R7392:Sos1	UTSW	17	80424200	missense	probably damaging	1.00
R7623:Sos1	UTSW	17	80479894	missense	probably benign	0.28
R7763:Sos1	UTSW	17	80413713	missense	probably benign
X0020:Sos1	UTSW	17	80449277	missense	probably damaging	1.00
Z1177:Sos1	UTSW	17	80453918	missense	probably benign	0.05

Predicted Primers

PCR Primer
(F):5'- ACCTGGATGTATGCTATGAGGTTACTGG -3'
(R):5'- GAGACGATTCTGCTTCCCTCTGTG -3'

Sequencing Primer
(F):5'- GCTATGAGGTTACTGGAAATCTCTCC -3'
(R):5'- tgtgtgtgtgtgtTTCTCATGAATG -3'

Posted On

2013-08-08