SOS2 (SOS Ras/Rho guanine nucleotide exchange factor 2)

Gene

• Entrez ID: 6655
• Gene name: SOS Ras/Rho guanine nucleotide exchange factor 2
• Gene symbol: SOS2
• Synonyms (NCBI Gene): NS9, SOS-2
• Chromosome: 14
• Chromosome location: 14q21.3
• Summary: This gene encodes a regulatory protein that is involved in the positive regulation of ras proteins. Mutations in this gene are associated with Noonan Syndrome-9. [provided by RefSeq, Jul 2016]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs775506222	AAT>-	Conflicting-interpretations-of-pathogenicity	Inframe deletion, coding sequence variant
rs797045167	A>C,G,T	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs869320687	G>C	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs1594982548	T>A	Likely-pathogenic	Missense variant, coding sequence variant
rs1595001710	G>T	Likely-pathogenic	Missense variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT019010	hsa-miR-335-5p	Microarray	18185580
MIRT023126	hsa-miR-124-3p	Microarray	18668037
MIRT046544	hsa-miR-1-3p	CLASH	23622248
MIRT653244	hsa-miR-148a-3p	HITS-CLIP	23824327
MIRT653243	hsa-miR-148b-3p	HITS-CLIP	23824327
MIRT653242	hsa-miR-152-3p	HITS-CLIP	23824327
MIRT653241	hsa-miR-548e-5p	HITS-CLIP	23824327
MIRT653239	hsa-miR-6835-3p	HITS-CLIP	23824327
MIRT653240	hsa-miR-188-5p	HITS-CLIP	23824327
MIRT653237	hsa-miR-6866-3p	HITS-CLIP	23824327
MIRT653238	hsa-miR-4719	HITS-CLIP	23824327
MIRT653236	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT653235	hsa-miR-513b-5p	HITS-CLIP	23824327
MIRT653234	hsa-miR-4276	HITS-CLIP	23824327
MIRT653233	hsa-miR-204-5p	HITS-CLIP	23824327
MIRT653232	hsa-miR-211-5p	HITS-CLIP	23824327
MIRT653231	hsa-miR-30a-3p	HITS-CLIP	23824327
MIRT653230	hsa-miR-30d-3p	HITS-CLIP	23824327
MIRT653229	hsa-miR-30e-3p	HITS-CLIP	23824327
MIRT653244	hsa-miR-148a-3p	Luciferase reporter assay, qRT-PCR, Western blotting	32667746
MIRT653244	hsa-miR-148a-3p	HITS-CLIP	23824327
MIRT653243	hsa-miR-148b-3p	HITS-CLIP	23824327
MIRT653242	hsa-miR-152-3p	HITS-CLIP	23824327
MIRT653241	hsa-miR-548e-5p	HITS-CLIP	23824327
MIRT653239	hsa-miR-6835-3p	HITS-CLIP	23824327
MIRT653240	hsa-miR-188-5p	HITS-CLIP	23824327
MIRT653237	hsa-miR-6866-3p	HITS-CLIP	23824327
MIRT653238	hsa-miR-4719	HITS-CLIP	23824327
MIRT653236	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT653235	hsa-miR-513b-5p	HITS-CLIP	23824327
MIRT653234	hsa-miR-4276	HITS-CLIP	23824327
MIRT653233	hsa-miR-204-5p	HITS-CLIP	23824327
MIRT653232	hsa-miR-211-5p	HITS-CLIP	23824327
MIRT653231	hsa-miR-30a-3p	HITS-CLIP	23824327
MIRT653230	hsa-miR-30d-3p	HITS-CLIP	23824327
MIRT653229	hsa-miR-30e-3p	HITS-CLIP	23824327
MIRT1379986	hsa-miR-1179	CLIP-seq
MIRT1379987	hsa-miR-1185	CLIP-seq
MIRT1379988	hsa-miR-1245b-5p	CLIP-seq
MIRT1379989	hsa-miR-1252	CLIP-seq
MIRT1379990	hsa-miR-1271	CLIP-seq
MIRT1379991	hsa-miR-1276	CLIP-seq
MIRT1379992	hsa-miR-130a	CLIP-seq
MIRT1379993	hsa-miR-130b	CLIP-seq
MIRT1379994	hsa-miR-148a	CLIP-seq
MIRT1379995	hsa-miR-148b	CLIP-seq
MIRT1379996	hsa-miR-152	CLIP-seq
MIRT1379997	hsa-miR-15a	CLIP-seq
MIRT1379998	hsa-miR-15b	CLIP-seq
MIRT1379999	hsa-miR-16	CLIP-seq
MIRT1380000	hsa-miR-182	CLIP-seq
MIRT1380001	hsa-miR-195	CLIP-seq
MIRT1380002	hsa-miR-199a-3p	CLIP-seq
MIRT1380003	hsa-miR-199b-3p	CLIP-seq
MIRT1380004	hsa-miR-19a	CLIP-seq
MIRT1380005	hsa-miR-19b	CLIP-seq
MIRT1380006	hsa-miR-204	CLIP-seq
MIRT1380007	hsa-miR-208a	CLIP-seq
MIRT1380008	hsa-miR-208b	CLIP-seq
MIRT1380009	hsa-miR-21	CLIP-seq
MIRT1380010	hsa-miR-211	CLIP-seq
MIRT1380011	hsa-miR-214	CLIP-seq
MIRT1380012	hsa-miR-224	CLIP-seq
MIRT1380013	hsa-miR-2467-3p	CLIP-seq
MIRT1380014	hsa-miR-301a	CLIP-seq
MIRT1380015	hsa-miR-301b	CLIP-seq
MIRT1380016	hsa-miR-3119	CLIP-seq
MIRT1380017	hsa-miR-3129-5p	CLIP-seq
MIRT1380018	hsa-miR-3140-3p	CLIP-seq
MIRT1380019	hsa-miR-3142	CLIP-seq
MIRT1380020	hsa-miR-3176	CLIP-seq
MIRT1380021	hsa-miR-330-3p	CLIP-seq
MIRT1380022	hsa-miR-3591-3p	CLIP-seq
MIRT1380023	hsa-miR-3605-5p	CLIP-seq
MIRT1380024	hsa-miR-3617	CLIP-seq
MIRT1380025	hsa-miR-3619-5p	CLIP-seq
MIRT1380026	hsa-miR-3622a-3p	CLIP-seq
MIRT1380027	hsa-miR-3622b-3p	CLIP-seq
MIRT1380028	hsa-miR-3653	CLIP-seq
MIRT1380029	hsa-miR-3658	CLIP-seq
MIRT1380030	hsa-miR-3666	CLIP-seq
MIRT1380031	hsa-miR-3678-3p	CLIP-seq
MIRT1380032	hsa-miR-3679-5p	CLIP-seq
MIRT1380033	hsa-miR-383	CLIP-seq
MIRT1380034	hsa-miR-3922-3p	CLIP-seq
MIRT1380035	hsa-miR-424	CLIP-seq
MIRT1380036	hsa-miR-4291	CLIP-seq
MIRT1380037	hsa-miR-4295	CLIP-seq
MIRT1380038	hsa-miR-4311	CLIP-seq
MIRT1380039	hsa-miR-450b-5p	CLIP-seq
MIRT1380040	hsa-miR-4511	CLIP-seq
MIRT1380041	hsa-miR-452	CLIP-seq
MIRT1380042	hsa-miR-454	CLIP-seq
MIRT1380043	hsa-miR-4661-3p	CLIP-seq
MIRT1380044	hsa-miR-4676-3p	CLIP-seq
MIRT1380045	hsa-miR-4680-5p	CLIP-seq
MIRT1380046	hsa-miR-4714-5p	CLIP-seq
MIRT1380047	hsa-miR-4753-5p	CLIP-seq
MIRT1380048	hsa-miR-4772-5p	CLIP-seq
MIRT1380049	hsa-miR-4773	CLIP-seq
MIRT1380050	hsa-miR-4793-5p	CLIP-seq
MIRT1380051	hsa-miR-497	CLIP-seq
MIRT1380052	hsa-miR-499-5p	CLIP-seq
MIRT1380053	hsa-miR-507	CLIP-seq
MIRT1380054	hsa-miR-508-3p	CLIP-seq
MIRT1380055	hsa-miR-511	CLIP-seq
MIRT1380056	hsa-miR-520d-5p	CLIP-seq
MIRT1380057	hsa-miR-524-5p	CLIP-seq
MIRT1380058	hsa-miR-544b	CLIP-seq
MIRT1380059	hsa-miR-545	CLIP-seq
MIRT1380060	hsa-miR-548a-5p	CLIP-seq
MIRT1380061	hsa-miR-548ab	CLIP-seq
MIRT1380062	hsa-miR-548ak	CLIP-seq
MIRT1380063	hsa-miR-548b-3p	CLIP-seq
MIRT1380064	hsa-miR-548b-5p	CLIP-seq
MIRT1380065	hsa-miR-548c-3p	CLIP-seq
MIRT1380066	hsa-miR-548c-5p	CLIP-seq
MIRT1380067	hsa-miR-548d-5p	CLIP-seq
MIRT1380068	hsa-miR-548h	CLIP-seq
MIRT1380069	hsa-miR-548i	CLIP-seq
MIRT1380070	hsa-miR-548j	CLIP-seq
MIRT1380071	hsa-miR-548k	CLIP-seq
MIRT1380072	hsa-miR-548l	CLIP-seq
MIRT1380073	hsa-miR-548w	CLIP-seq
MIRT1380074	hsa-miR-548y	CLIP-seq
MIRT1380075	hsa-miR-557	CLIP-seq
MIRT1380076	hsa-miR-559	CLIP-seq
MIRT1380077	hsa-miR-562	CLIP-seq
MIRT1380078	hsa-miR-579	CLIP-seq
MIRT1380079	hsa-miR-582-5p	CLIP-seq
MIRT1380080	hsa-miR-583	CLIP-seq
MIRT1380081	hsa-miR-587	CLIP-seq
MIRT1380082	hsa-miR-590-5p	CLIP-seq
MIRT1380083	hsa-miR-641	CLIP-seq
MIRT1380084	hsa-miR-668	CLIP-seq
MIRT1380085	hsa-miR-761	CLIP-seq
MIRT1380086	hsa-miR-802	CLIP-seq
MIRT1380087	hsa-miR-885-3p	CLIP-seq
MIRT1380088	hsa-miR-922	CLIP-seq
MIRT1380089	hsa-miR-936	CLIP-seq
MIRT1380090	hsa-miR-96	CLIP-seq
MIRT1379987	hsa-miR-1185	CLIP-seq
MIRT1379990	hsa-miR-1271	CLIP-seq
MIRT1380000	hsa-miR-182	CLIP-seq
MIRT1553943	hsa-miR-193a-3p	CLIP-seq
MIRT1553944	hsa-miR-193b	CLIP-seq
MIRT1380020	hsa-miR-3176	CLIP-seq
MIRT1380023	hsa-miR-3605-5p	CLIP-seq
MIRT1380032	hsa-miR-3679-5p	CLIP-seq
MIRT1380034	hsa-miR-3922-3p	CLIP-seq
MIRT1380043	hsa-miR-4661-3p	CLIP-seq
MIRT1380087	hsa-miR-885-3p	CLIP-seq
MIRT1553945	hsa-miR-892b	CLIP-seq
MIRT1380090	hsa-miR-96	CLIP-seq
MIRT1379987	hsa-miR-1185	CLIP-seq
MIRT1379989	hsa-miR-1252	CLIP-seq
MIRT2113630	hsa-miR-135a	CLIP-seq
MIRT2113631	hsa-miR-135b	CLIP-seq
MIRT2113632	hsa-miR-154	CLIP-seq
MIRT1379997	hsa-miR-15a	CLIP-seq
MIRT1379998	hsa-miR-15b	CLIP-seq
MIRT1379999	hsa-miR-16	CLIP-seq
MIRT1380001	hsa-miR-195	CLIP-seq
MIRT1380007	hsa-miR-208a	CLIP-seq
MIRT1380008	hsa-miR-208b	CLIP-seq
MIRT1380011	hsa-miR-214	CLIP-seq
MIRT2113633	hsa-miR-3123	CLIP-seq
MIRT2113634	hsa-miR-3149	CLIP-seq
MIRT1380022	hsa-miR-3591-3p	CLIP-seq
MIRT1380023	hsa-miR-3605-5p	CLIP-seq
MIRT1380024	hsa-miR-3617	CLIP-seq
MIRT1380025	hsa-miR-3619-5p	CLIP-seq
MIRT1380026	hsa-miR-3622a-3p	CLIP-seq
MIRT1380027	hsa-miR-3622b-3p	CLIP-seq
MIRT1380029	hsa-miR-3658	CLIP-seq
MIRT1380032	hsa-miR-3679-5p	CLIP-seq
MIRT2113635	hsa-miR-3925-5p	CLIP-seq
MIRT1380035	hsa-miR-424	CLIP-seq
MIRT2113636	hsa-miR-4274	CLIP-seq
MIRT1380036	hsa-miR-4291	CLIP-seq
MIRT2113637	hsa-miR-4493	CLIP-seq
MIRT2113638	hsa-miR-4519	CLIP-seq
MIRT1380041	hsa-miR-452	CLIP-seq
MIRT2113639	hsa-miR-4524	CLIP-seq
MIRT2113640	hsa-miR-4635	CLIP-seq
MIRT1380044	hsa-miR-4676-3p	CLIP-seq
MIRT1380051	hsa-miR-497	CLIP-seq
MIRT1380052	hsa-miR-499-5p	CLIP-seq
MIRT1380055	hsa-miR-511	CLIP-seq
MIRT2113641	hsa-miR-513b	CLIP-seq
MIRT1380056	hsa-miR-520d-5p	CLIP-seq
MIRT1380057	hsa-miR-524-5p	CLIP-seq
MIRT1380058	hsa-miR-544b	CLIP-seq
MIRT1380059	hsa-miR-545	CLIP-seq
MIRT1380065	hsa-miR-548c-3p	CLIP-seq
MIRT1380071	hsa-miR-548k	CLIP-seq
MIRT1380081	hsa-miR-587	CLIP-seq
MIRT1380083	hsa-miR-641	CLIP-seq
MIRT1380085	hsa-miR-761	CLIP-seq
MIRT1380086	hsa-miR-802	CLIP-seq
MIRT1380088	hsa-miR-922	CLIP-seq
MIRT1379987	hsa-miR-1185	CLIP-seq
MIRT1379989	hsa-miR-1252	CLIP-seq
MIRT1379990	hsa-miR-1271	CLIP-seq
MIRT2336553	hsa-miR-129-5p	CLIP-seq
MIRT1379992	hsa-miR-130a	CLIP-seq
MIRT1379993	hsa-miR-130b	CLIP-seq
MIRT1379994	hsa-miR-148a	CLIP-seq
MIRT1379995	hsa-miR-148b	CLIP-seq
MIRT1379996	hsa-miR-152	CLIP-seq
MIRT1379997	hsa-miR-15a	CLIP-seq
MIRT1379998	hsa-miR-15b	CLIP-seq
MIRT1379999	hsa-miR-16	CLIP-seq
MIRT1380000	hsa-miR-182	CLIP-seq
MIRT1380001	hsa-miR-195	CLIP-seq
MIRT1380004	hsa-miR-19a	CLIP-seq
MIRT1380005	hsa-miR-19b	CLIP-seq
MIRT1380007	hsa-miR-208a	CLIP-seq
MIRT1380008	hsa-miR-208b	CLIP-seq
MIRT1380011	hsa-miR-214	CLIP-seq
MIRT1380013	hsa-miR-2467-3p	CLIP-seq
MIRT1380014	hsa-miR-301a	CLIP-seq
MIRT1380015	hsa-miR-301b	CLIP-seq
MIRT2113634	hsa-miR-3149	CLIP-seq
MIRT1380023	hsa-miR-3605-5p	CLIP-seq
MIRT1380024	hsa-miR-3617	CLIP-seq
MIRT1380025	hsa-miR-3619-5p	CLIP-seq
MIRT1380029	hsa-miR-3658	CLIP-seq
MIRT1380030	hsa-miR-3666	CLIP-seq
MIRT1380031	hsa-miR-3678-3p	CLIP-seq
MIRT1380032	hsa-miR-3679-5p	CLIP-seq
MIRT1380035	hsa-miR-424	CLIP-seq
MIRT1380036	hsa-miR-4291	CLIP-seq
MIRT1380037	hsa-miR-4295	CLIP-seq
MIRT1380039	hsa-miR-450b-5p	CLIP-seq
MIRT1380041	hsa-miR-452	CLIP-seq
MIRT1380042	hsa-miR-454	CLIP-seq
MIRT1380043	hsa-miR-4661-3p	CLIP-seq
MIRT1380044	hsa-miR-4676-3p	CLIP-seq
MIRT1380051	hsa-miR-497	CLIP-seq
MIRT1380052	hsa-miR-499-5p	CLIP-seq
MIRT1380053	hsa-miR-507	CLIP-seq
MIRT1380055	hsa-miR-511	CLIP-seq
MIRT1380059	hsa-miR-545	CLIP-seq
MIRT1380075	hsa-miR-557	CLIP-seq
MIRT1380078	hsa-miR-579	CLIP-seq
MIRT1380079	hsa-miR-582-5p	CLIP-seq
MIRT1380081	hsa-miR-587	CLIP-seq
MIRT1380083	hsa-miR-641	CLIP-seq
MIRT1380084	hsa-miR-668	CLIP-seq
MIRT1380085	hsa-miR-761	CLIP-seq
MIRT1380087	hsa-miR-885-3p	CLIP-seq
MIRT1380088	hsa-miR-922	CLIP-seq
MIRT1380090	hsa-miR-96	CLIP-seq
MIRT1380041	hsa-miR-452	CLIP-seq
MIRT1380044	hsa-miR-4676-3p	CLIP-seq
MIRT2433367	hsa-miR-4744	CLIP-seq
MIRT2433368	hsa-miR-4760-3p	CLIP-seq
MIRT2433369	hsa-miR-548u	CLIP-seq
MIRT1380081	hsa-miR-587	CLIP-seq
MIRT2433370	hsa-miR-598	CLIP-seq
MIRT2433371	hsa-miR-664	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001782	Process	B cell homeostasis	IEA
GO:0002260	Process	Lymphocyte homeostasis	IEA
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	IBA
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	IEA
GO:0005515	Function	Protein binding	IPI	7629138, 14679214, 17474147, 19380743, 20936779, 21706016, 21988832, 28514442, 31980649, 33961781
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IBA
GO:0007264	Process	Small GTPase-mediated signal transduction	IEA
GO:0007264	Process	Small GTPase-mediated signal transduction	IEA
GO:0007265	Process	Ras protein signal transduction	IBA
GO:0008286	Process	Insulin receptor signaling pathway	IEA
GO:0033081	Process	Regulation of T cell differentiation in thymus	IEA
GO:0042129	Process	Regulation of T cell proliferation	IEA
GO:0046982	Function	Protein heterodimerization activity	IEA
GO:2000973	Process	Regulation of pro-B cell differentiation	IEA

Other IDs

• MIM: 601247
• HGNC: 11188
• e!Ensembl: ENSG00000100485

Protein

• UniProt ID: Q07890
• Protein name: Son of sevenless homolog 2 (SOS-2)
• Protein function: Promotes the exchange of Ras-bound GDP by GTP.
• PDB: 6EIE, 8T5G, 8T5M, 8T5R, 8UC9, 8UF2, 8UH0, 9BVE, 9BVF, 9BVI, 9GIN
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00125	Histone	54 → 169	Core histone H2A/H2B/H3/H4	Domain
  PF00621	RhoGEF	203 → 386	RhoGEF domain	Domain
  PF00169	PH	426 → 544	PH domain	Domain
  PF00618	RasGEF_N	598 → 715	RasGEF N-terminal motif	Domain
  PF00617	RasGEF	781 → 960	RasGEF domain	Family

• Sequence:

  MQQAPQPYEFFSEENSPKWRGLLVSALRKVQEQVHPTLSANEESLYYIEELIFQLLNKLC
  MAQPRTVQDVEERVQKTFPHPIDKWAIADAQSAIEKRKRRNPLLLPVDKIHPSLKEVLGY
  KVDYHVSLYIVAVLEYISADILKLAGNYVFNIRHYEISQQDIKVSMCADKVLMDMFDQDD
  IGLVSLCEDEPSSSGELNYYDLVRTEIAEERQYLRELNMIIKVFREAFLSDRKLFKPSDI
  EKIFSNISDIHELTVKLLGLIEDTVEMTDESSPHPLAGSCFEDLAEEQAFDPYETLSQDI
  LSPEFHEHFNKLMARPAVALHFQSIADGFKEAVRYVLPRLMLVPVYHCWHYFELLKQLKA
  CSEEQEDRECLNQAITALMNLQGSMDRIYKQYSPRRRPGDPVCPFYSHQLRSKHLAIKKM
  NEIQKNIDGWEGKDIGQCCNEFIMEGPLTRIGAKHERHIFLFDGLMISCKPNHGQTRLPG
  YSSAEYRLKEKFVMRKIQICDKEDTCEHKHAFELVSKDENSIIFAAKSAEEKNNWMAALI
  SLHYRSTLDRMLDSVLLKEENEQPLRLPSPEVYRFVVKDSEENIVFEDNLQSRSGIPIIK
  GGTVVKLIERLTYHMYADPNFVRTFLTTYRSFCKPQELLSLLIERFEIPEPEPTDADKLA
  IEKGEQPISADLKRFRKEYVQPVQLRILNVFRHWVEHHFYDFERDLELLERLESFISSVR
  GKAMKKWVESIAKIIRRKKQAQANGVSHNITFESPPPPIEWHISKPGQFETFDLMTLHPI
  EIARQLTLLESDLYRKVQPSELVGSVWTKEDKEINSPNLLKMIRHTTNLTLWFEKCIVEA
  ENFEERVAVLSRIIEILQVFQDLNNFNGVLEIVSAVNSVSVYRLDHTFEALQERKRKILD
  EAVELSQDHFKKYLVKLKSINPPCVPFFGIYLTNILKTEEGNNDFLKKKGKDLINFSKRR
  KVAEITGEIQQYQNQPYCLRIEPDMRRFFENLNPMGSASEKEFTDYLFNKSLEIEPRNCK
  QPPRFPRKSTFSLKSPGIRPNTGRHGSTSGTLRGHPTPLEREPCKISFSRIAETELESTV
  SAPTSPNTPSTPPVSASSDLSVFLDVDLNSSCGSNSIFAPVLLPHSKSFFSSCGSLHKLS
  EEPLIPPPLPPRKKFDHDASNSKGNMKSDDDPPAIPPRQPPPPKVKPRVPVPTGAFDGPL
  HSPPPPPPRDPLPDTPPPVPLRPPEHFINCPFNLQPPPLGHLHRDSDWLRDISTCPNSPS
  TPPSTPSPRVPRRCYVLSSSQNNLAHPPAPPVPPRQNSSPHLPKLPPKTYKRELSHPPLY
  RLPLLENAETPQ

• Sequence length: 1332

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Male infertility due to gonadal dysgenesis or sperm disorder	Likely pathogenic	rs2503347123	RCV003991600	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Noonan syndrome	Pathogenic; Likely pathogenic	rs869320687, rs797045167, rs1594982548, rs1595001710	RCV000845122 RCV001251214 RCV000845123 RCV000845124 RCV001251213	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Noonan syndrome 1	Pathogenic	rs869320687	RCV003454490	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Noonan syndrome 9	Pathogenic; Likely pathogenic	rs869320687, rs797045167, rs2502991901, rs1594982548, rs1595001710, rs1885777585	RCV000191030 RCV000191031 RCV002900123 RCV003755523 RCV001250768 RCV000699741 RCV003223414 RCV001250766 RCV001250767 RCV001250765	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
RASopathy	Likely pathogenic; Pathogenic	rs797045167, rs1595001710	RCV004732469 RCV001264473 RCV001269182	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
SOS2-related disorder	Likely pathogenic; Pathogenic	rs797045167	RCV003411629	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
CARDIOVASCULAR DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cardiovascular phenotype	Conflicting classifications of pathogenicity; Uncertain significance; Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC KIDNEY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital heart disease	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL MALFORMATION SYNDROMES ASSOCIATED WITH SHORT STATURE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DESBUQUOIS SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Developmental disorder	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EBV-positive nodal T- and NK-cell lymphoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ESSENTIAL HYPERTENSION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GOUT	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTENSION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
KIDNEY FAILURE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MALE INFERTILITY DUE TO TESTICULAR DYSGENESIS OR SPERM DISORDER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Noonan syndrome and Noonan-related syndrome	Benign; Likely benign; Conflicting classifications of pathogenicity; Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
OPEN-ANGLE GLAUCOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Abnormal dermatoglyphic pattern	Abnormal dermatoglyphic pattern	HPO_DG			★☆☆☆☆ Found in Text Mining only
Aortic coarctation	Aortic Coarctation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Blepharoptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Brachydactyly	Brachydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Byzanthine arch palate	High palate	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cardio-facio-cutaneous syndrome	Cardiofaciocutaneous syndrome	CLINGEN_DG			★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular Diseases	GWASCAT_DG	30595370		★☆☆☆☆ Found in Text Mining only
Chronic Periodontitis	Periodontitis	Pubtator	24347629	Associate	★☆☆☆☆ Found in Text Mining only
Clinodactyly of the 5th finger	Camptodactyly of fingers	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital pectus carinatum	Congenital Pectus Carinatum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital pectus excavatum	Congenital Pectus Excavatum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Costello syndrome (disorder)	Costello syndrome	CLINGEN_DG			★☆☆☆☆ Found in Text Mining only
Cryptorchidism	Cryptorchidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dysarthria	Dysarthria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Exophthalmos	Proptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	31616474		★☆☆☆☆ Found in Text Mining only
Heart Defects Congenital	Congenital heart defect	Pubtator	32788663	Associate	★☆☆☆☆ Found in Text Mining only
Heart Diseases	Heart disease	Pubtator	32788663	Associate	★☆☆☆☆ Found in Text Mining only
Heart Septal Defects	Heart Septal Defects	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hemochromatosis	Hemochromatosis	Pubtator	23761422	Associate	★☆☆☆☆ Found in Text Mining only
Hydrops Fetalis	Hydrops fetalis	Pubtator	36959127	Associate	★☆☆☆☆ Found in Text Mining only
Hydrops Fetalis	Hydrops Fetalis	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Hyperkeratosis pilaris	Hyperkeratosis Pilaris	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypogonadotropic hypogonadism	Hypogonadotropic Hypogonadism	HPO_DG			★☆☆☆☆ Found in Text Mining only
LEOPARD Syndrome	LEOPARD Syndrome	CLINGEN_DG			★☆☆☆☆ Found in Text Mining only
Lymphangioma, Cystic	Cystic hygroma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	15138850		★☆☆☆☆ Found in Text Mining only
Melanocytic nevus	Melanocytic nevus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Micrognathism	Micrognathism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neck webbing	Neck Webbing	HPO_DG			★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	30536836		★☆☆☆☆ Found in Text Mining only
Noonan Syndrome	Noonan Syndrome	CLINGEN_DG	10938118, 23875798, 25795793, 26173643		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Noonan Syndrome	Noonan Syndrome	GENOMICS_ENGLAND_DG	10938118		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Noonan Syndrome	Noonan Syndrome	BEFREE	25795793, 26173643		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Noonan Syndrome	Noonan Syndrome	ORPHANET_DG	25795793		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Noonan syndrome	Noonan Syndrome	Orphanet			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Noonan Syndrome	Noonan syndrome	Pubtator	32788663, 34136918	Associate	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Noonan Syndrome 1	Noonan Syndrome	CLINVAR_DG	26173643		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
NOONAN SYNDROME 9	Noonan Syndrome	CLINVAR_DG	25795793, 26173643		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NOONAN SYNDROME 9	Noonan Syndrome	UNIPROT_DG	25795793		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NOONAN SYNDROME 9	Noonan Syndrome	GENOMICS_ENGLAND_DG	25795793, 26173643		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NOONAN SYNDROME 9	Noonan Syndrome	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Noonan syndrome-like disorder with loose anagen hair	Noonan-Like Syndrome With Loose Anagen Hair	CLINGEN_DG			★☆☆☆☆ Found in Text Mining only
Noonan-Like Syndrome With Loose Anagen Hair	Noonan-Like Syndrome With Loose Anagen Hair	CLINGEN_DG			★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pulmonary Stenosis	Pulmonary Stenosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Radioulnar Synostosis	Radioulnar Synostosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Scoliosis, unspecified	Scoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Skin Neoplasms	Skin Neoplasms	BEFREE	29844066		★☆☆☆☆ Found in Text Mining only
Somatotropin deficiency	Somatotropin Deficiency	BEFREE	23761422		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma	Carcinoma	BEFREE	16681758		★☆☆☆☆ Found in Text Mining only
Strabismus	Strabismus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Turner Syndrome	Turner Syndrome	BEFREE	23761422		★☆☆☆☆ Found in Text Mining only
Turner Syndrome	Turner syndrome	Pubtator	23761422	Associate	★☆☆☆☆ Found in Text Mining only