SOS1 (SOS Ras/Rac guanine nucleotide exchange factor 1)

Gene

• Entrez ID: 6654
• Gene name: SOS Ras/Rac guanine nucleotide exchange factor 1
• Gene symbol: SOS1
• Synonyms: GF1, GGF1, GINGF, HGF, NS4, SOS-1
• Chromosome: 2
• Chromosome location: 2p22.1
• Summary: 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]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs137852812	G>T	Pathogenic	Coding sequence variant, missense variant
rs137852813	A>C,G	Pathogenic	Coding sequence variant, missense variant
rs137852814	T>A,C	Likely-pathogenic, pathogenic-likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs138459502	G>A,C	Uncertain-significance, likely-benign, likely-pathogenic	Coding sequence variant, synonymous variant, missense variant
rs139290271	A>G	Benign, conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs141594736	G>A,C,T	Conflicting-interpretations-of-pathogenicity, uncertain-significance, likely-benign	Coding sequence variant, synonymous variant, missense variant
rs143962515	T>C	Benign, conflicting-interpretations-of-pathogenicity, uncertain-significance	Coding sequence variant, missense variant
rs188849286	G>A	Uncertain-significance, conflicting-interpretations-of-pathogenicity	3 prime UTR variant
rs200786705	G>C	Likely-benign, conflicting-interpretations-of-pathogenicity, benign	Coding sequence variant, missense variant
rs201085754	A>C	Likely-benign, conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs201982464	T>C	Uncertain-significance, conflicting-interpretations-of-pathogenicity, benign	Intron variant
rs202043599	C>G,T	Likely-benign, conflicting-interpretations-of-pathogenicity, uncertain-significance	Coding sequence variant, missense variant
rs267607079	C>A,G	Pathogenic	Coding sequence variant, missense variant
rs267607080	A>G	Pathogenic	Coding sequence variant, missense variant
rs369277679	C>G	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, missense variant
rs387906518	->G	Pathogenic	Coding sequence variant, frameshift variant
rs397517146	T>C	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs397517147	C>T	Pathogenic	Coding sequence variant, missense variant
rs397517148	C>G,T	Pathogenic	Coding sequence variant, missense variant
rs397517149	T>G	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs397517150	A>C,G	Pathogenic	Coding sequence variant, missense variant
rs397517153	A>C,G	Pathogenic	Coding sequence variant, missense variant
rs397517154	C>A,G,T	Uncertain-significance, likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs397517156	T>A	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs397517159	C>T	Pathogenic	Coding sequence variant, missense variant
rs397517163	A>G	Likely-pathogenic	Coding sequence variant, missense variant
rs397517164	C>T	Pathogenic	Coding sequence variant, missense variant
rs397517166	G>C	Likely-pathogenic	Coding sequence variant, missense variant
rs397517172	T>C	Pathogenic	Coding sequence variant, missense variant
rs397517174	A>C,G	Uncertain-significance, likely-pathogenic	Coding sequence variant, missense variant
rs397517177	A>C	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs397517180	C>A	Pathogenic	Coding sequence variant, missense variant
rs574088829	T>A,G	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs727503436	AAAAA>-,AAA,AAAA,AAAAAA	Benign, likely-benign, conflicting-interpretations-of-pathogenicity	Intron variant
rs727504295	C>T	Pathogenic	Missense variant, coding sequence variant
rs727505093	A>C,T	Pathogenic, likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs727505381	A>G	Pathogenic	Missense variant, coding sequence variant
rs730881034	G>A	Conflicting-interpretations-of-pathogenicity, likely-benign, uncertain-significance	Missense variant, coding sequence variant
rs730881043	A>T	Likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs730881044	T>C	Pathogenic	Missense variant, coding sequence variant
rs730881045	A>T	Pathogenic	Missense variant, coding sequence variant
rs730881046	G>T	Likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs730881048	CC>TT	Pathogenic	Missense variant, coding sequence variant
rs730881054	A>C,G,T	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs772823827	G>A	Conflicting-interpretations-of-pathogenicity	Intron variant, coding sequence variant, synonymous variant
rs786205522	T>A	Likely-pathogenic	Coding sequence variant, missense variant
rs886041923	T>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1057517861	T>C,G	Likely-pathogenic	Missense variant, coding sequence variant
rs1057517918	T>C	Likely-pathogenic	Missense variant, coding sequence variant
rs1057519963	T>A	Likely-pathogenic	Missense variant, coding sequence variant
rs1553353452	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1553354396	A>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1553356111	G>A,C	Uncertain-significance, likely-pathogenic	Coding sequence variant, missense variant
rs1553362937	G>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1558474706	G>T	Uncertain-significance, likely-pathogenic	Coding sequence variant, missense variant
rs1572830219	CTT>-	Likely-pathogenic	Coding sequence variant, inframe deletion
rs1572830693	AA>TC	Likely-pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT046240	hsa-miR-23b-3p	CLASH	23622248
MIRT088625	hsa-miR-4325	HITS-CLIP	23313552
MIRT236646	hsa-miR-4789-5p	HITS-CLIP	23313552
MIRT236655	hsa-miR-5011-5p	HITS-CLIP	23313552
MIRT437439	hsa-miR-124-3p	Luciferase reporter assay, qRT-PCR, Western blot	23817964
MIRT494975	hsa-miR-3157-5p	PAR-CLIP	23708386
MIRT494976	hsa-miR-6715a-3p	PAR-CLIP	23708386
MIRT494977	hsa-miR-4691-3p	PAR-CLIP	23708386
MIRT494978	hsa-miR-5571-5p	PAR-CLIP	23708386
MIRT699002	hsa-miR-5089-3p	HITS-CLIP	23313552
MIRT699003	hsa-miR-466	HITS-CLIP	23313552
MIRT699004	hsa-miR-4643	HITS-CLIP	23313552
MIRT699005	hsa-miR-4789-3p	HITS-CLIP	23313552
MIRT699006	hsa-miR-4801	HITS-CLIP	23313552
MIRT699007	hsa-miR-4731-3p	HITS-CLIP	23313552
MIRT699008	hsa-miR-548an	HITS-CLIP	23313552
MIRT699009	hsa-miR-1178-3p	HITS-CLIP	23313552
MIRT699010	hsa-miR-196b-3p	HITS-CLIP	23313552
MIRT699011	hsa-miR-3613-3p	HITS-CLIP	23313552
MIRT699012	hsa-miR-433-5p	HITS-CLIP	23313552
MIRT699013	hsa-miR-216a-3p	HITS-CLIP	23313552
MIRT699014	hsa-miR-3681-3p	HITS-CLIP	23313552
MIRT699015	hsa-miR-128-3p	HITS-CLIP	23313552
MIRT699016	hsa-miR-27b-3p	HITS-CLIP	23313552
MIRT699017	hsa-miR-27a-3p	HITS-CLIP	23313552
MIRT731133	hsa-miR-146a-5p	Western blot, Luciferase reporter assay	25469565

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000165	Process	MAPK cascade	TAS
GO:0001782	Process	B cell homeostasis	IEA
GO:0001942	Process	Hair follicle development	IEA
GO:0003209	Process	Cardiac atrium morphogenesis	IEA
GO:0003344	Process	Pericardium morphogenesis	IEA
GO:0003677	Function	DNA binding	IEA
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	EXP	7731718
GO:0005096	Function	GTPase activator activity	TAS	9790532
GO:0005515	Function	Protein binding	IPI	7527391, 7629138, 7773779, 9020117, 9447984, 9544989, 9569023, 9690470, 10026169, 10206341, 12029088, 12482578, 12577067, 12628188, 14679214, 15507210, 16520382, 17084389, 17141806, 17474147, 17515907, 18454158, 19141281, 19323566, 19380743, 19464300, 20133692, 20473329, 21706016, 21
GO:0005737	Component	Cytoplasm	IDA	17515907
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	TAS
GO:0007165	Process	Signal transduction	NAS	8493579
GO:0007173	Process	Epidermal growth factor receptor signaling pathway	TAS
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS
GO:0007265	Process	Ras protein signal transduction	TAS
GO:0007296	Process	Vitellogenesis	IEA
GO:0007411	Process	Axon guidance	TAS
GO:0008286	Process	Insulin receptor signaling pathway	TAS
GO:0014069	Component	Postsynaptic density	IEA
GO:0017124	Function	SH3 domain binding	IEA
GO:0019221	Process	Cytokine-mediated signaling pathway	TAS
GO:0033081	Process	Regulation of T cell differentiation in thymus	IEA
GO:0035264	Process	Multicellular organism growth	IEA
GO:0038095	Process	Fc-epsilon receptor signaling pathway	TAS
GO:0038128	Process	ERBB2 signaling pathway	TAS
GO:0042129	Process	Regulation of T cell proliferation	IEA
GO:0043025	Component	Neuronal cell body	IEA
GO:0043065	Process	Positive regulation of apoptotic process	TAS
GO:0043547	Process	Positive regulation of GTPase activity	IEA
GO:0045742	Process	Positive regulation of epidermal growth factor receptor signaling pathway	IEA
GO:0046982	Function	Protein heterodimerization activity	IEA
GO:0048011	Process	Neurotrophin TRK receptor signaling pathway	TAS
GO:0048514	Process	Blood vessel morphogenesis	IEA
GO:0050900	Process	Leukocyte migration	TAS
GO:0051056	Process	Regulation of small GTPase mediated signal transduction	TAS
GO:0051057	Process	Positive regulation of small GTPase mediated signal transduction	IEA
GO:0060021	Process	Roof of mouth development	IEA
GO:0061029	Process	Eyelid development in camera-type eye	IEA
GO:0061384	Process	Heart trabecula morphogenesis	IEA
GO:1904693	Process	Midbrain morphogenesis	IEA
GO:2000973	Process	Regulation of pro-B cell differentiation	IEA

Other IDs

• MIM: 182530
• HGNC: 11187
• e!Ensembl: ENSG00000115904

Protein

• UniProt ID: Q07889
• Protein name: Son of sevenless homolog 1 (SOS-1)
• Protein function: Promotes the exchange of Ras-bound GDP by GTP (PubMed:8493579). Probably by promoting Ras activation, regulates phosphorylation of MAP kinase MAPK3 in response to EGF (PubMed:17339331). Catalytic component of a trimeric complex that participates in transduction of signals from Ras to Rac by promoting the Rac-specific guanine nucleotide exchange factor (GEF) activity (By similarity).
• PDB: 1AWE, 1BKD, 1DBH, 1NVU, 1NVV, 1NVW, 1NVX, 1Q9C, 1XD2, 1XD4, 1XDV, 2II0, 3KSY, 4NYI, 4NYJ, 4NYM, 4URU, 4URV, 4URW, 4URX, 4URY, 4URZ, 4US0, 4US1, 4US2, 5OVD, 5OVE, 5OVF, 5OVG, 5OVH, 5OVI, 5WFO, 5WFP, 5WFQ, 5WFR, 6BVI, 6BVJ, 6BVK, 6BVL, 6BVM, 6CUO, 6CUP, 6CUR, 6D55, 6D56, 6D59, 6D5E, 6D5G, 6D5H, 6D5J, 6D5L
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00125	Histone	40 → 169	Core histone H2A/H2B/H3/H4	Domain
  PF00621	RhoGEF	211 → 388	RhoGEF domain	Domain
  PF00169	PH	428 → 546	PH domain	Domain
  PF00618	RasGEF_N	600 → 717	RasGEF N-terminal motif	Domain
  PF00617	RasGEF	783 → 962	RasGEF domain	Family

• Sequence:

  MQAQQLPYEFFSEENAPKWRGLLVPALKKVQGQVHPTLESNDDALQYVEELILQLLNMLC
  QAQPRSASDVEERVQKSFPHPIDKWAIADAQSAIEKRKRRNPLSLPVEKIHPLLKEVLGY
  KIDHQVSVYIVAVLEYISADILKLVGNYVRNIRHYEITKQDIKVAMCADKVLMDMFHQDV
  EDINILSLTDEEPSTSGEQTYYDLVKAFMAEIRQYIRELNLIIKVFREPFVSNSKLFSAN
  DVENIFSRIVDIHELSVKLLGHIEDTVEMTDEGSPHPLVGSCFEDLAEELAFDPYESYAR
  DILRPGFHDRFLSQLSKPGAALYLQSIGEGFKEAVQYVLPRLLLAPVYHCLHYFELLKQL
  EEKSEDQEDKECLKQAITALLNVQSGMEKICSKSLAKRRLSESACRFYSQQMKGKQLAIK
  KMNEIQKNIDGWEGKDIGQCCNEFIMEGTLTRVGAKHERHIFLFDGLMICCKSNHGQPRL
  PGASNAEYRLKEKFFMRKVQINDKDDTNEYKHAFEIILKDENSVIFSAKSAEEKNNWMAA
  LISLQYRSTLERMLDVTMLQEEKEEQMRLPSADVYRFAEPDSEENIIFEENMQPKAGIPI
  IKAGTVIKLIERLTYHMYADPNFVRTFLTTYRSFCKPQELLSLIIERFEIPEPEPTEADR
  IAIENGDQPLSAELKRFRKEYIQPVQLRVLNVCRHWVEHHFYDFERDAYLLQRMEEFIGT
  VRGKAMKKWVESITKIIQRKKIARDNGPGHNITFQSSPPTVEWHISRPGHIETFDLLTLH
  PIEIARQLTLLESDLYRAVQPSELVGSVWTKEDKEINSPNLLKMIRHTTNLTLWFEKCIV
  ETENLEERVAVVSRIIEILQVFQELNNFNGVLEVVSAMNSSPVYRLDHTFEQIPSRQKKI
  LEEAHELSEDHYKKYLAKLRSINPPCVPFFGIYLTNILKTEEGNPEVLKRHGKELINFSK
  RRKVAEITGEIQQYQNQPYCLRVESDIKRFFENLNPMGNSMEKEFTDYLFNKSLEIEPRN
  PKPLPRFPKKYSYPLKSPGVRPSNPRPGTMRHPTPLQQEPRKISYSRIPESETESTASAP
  NSPRTPLTPPPASGASSTTDVCSVFDSDHSSPFHSSNDTVFIQVTLPHGPRSASVSSISL
  TKGTDEVPVPPPVPPRRRPESAPAESSPSKIMSKHLDSPPAIPPRQPTSKAYSPRYSISD
  RTSISDPPESPPLLPPREPVRTPDVFSSSPLHLQPPPLGKKSDHGNAFFPNSPSPFTPPP
  PQTPSPHGTRRHLPSPPLTQEVDLHSIAGPPVPPRQSTSQHIPKLPPKTYKREHTHPSMH
  RDGPPLLENAHSS

• Sequence length: 1333