SOS2

Summary

SOS2 (SOS Ras/Rho guanine nucleotide exchange factor 2, HGNC:11188) is a protein-coding gene on chromosome 14q21.3, encoding Son of sevenless homolog 2 (Q07890). Acts as guanine nucleotide exchange factor (GEF) for RAS proteins.

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.

Source: NCBI Gene 6655 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Noonan syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 14
• Clinical variants (ClinVar): 2,067 total — 5 pathogenic, 6 likely-pathogenic (top 1% of genes corpus-wide)
• Regional missense constraint (gnomAD): 1 of 4 regions constrained (≈2% of expected missense variation)
• GTEx eGene: eQTL in 37 tissues, sQTL in 4 (q < 0.05)
• Phenotypes (HPO): 81
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.41 (moderately constrained)
• MANE Select transcript: NM_006939

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11188
Approved symbol	SOS2
Name	SOS Ras/Rho guanine nucleotide exchange factor 2
Location	14q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000100485
Ensembl biotype	protein_coding
OMIM	601247
Entrez	6655

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 14 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

MANE Select: ENST00000216373

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 3: 2, TSL 4: 1

ENST00000216373, ENST00000543680, ENST00000555666, ENST00000555794, ENST00000556452, ENST00000556469, ENST00000934708, ENST00000934709, ENST00000953731, ENST00000953732, ENST00000953733, ENST00000953734, ENST00000953735, ENST00001112312, ENST00001112313, ENST00001112314, ENST00001137310

RefSeq mRNA: 2 — MANE Select: NM_006939 NM_001411020, NM_006939

CCDS: CCDS91874, CCDS9697

Canonical transcript exons

ENST00000216373 — 23 exons

Exon	Start	End
ENSE00000656810	50120275	50120384
ENSE00000656814	50134123	50134239
ENSE00000656815	50138612	50138784
ENSE00000656816	50139942	50140059
ENSE00000656817	50145170	50145332
ENSE00000656818	50145477	50145596
ENSE00000656819	50150008	50150230
ENSE00000656821	50153070	50153173
ENSE00000656822	50156999	50157121
ENSE00000656827	50180572	50180682
ENSE00000656829	50182463	50182606
ENSE00000656830	50188497	50188700
ENSE00000854636	50129961	50130002
ENSE00000854637	50130501	50130762
ENSE00001174956	50117130	50118853
ENSE00002525812	50231197	50231578
ENSE00003482357	50199691	50199855
ENSE00003493295	50204284	50204409
ENSE00003591887	50200953	50201084
ENSE00003741626	50158565	50158646
ENSE00003743313	50159431	50160086
ENSE00003744640	50174454	50174552
ENSE00003751699	50161482	50161609

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 97.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.5551 / max 1368.4825, expressed in 1794 samples.

Highest expression (Bgee): vastus lateralis, biceps brachii, buccal mucosa cell, quadriceps femoris, skeletal muscle tissue of biceps brachii.

Genetic regulation across tissues (GTEx eQTL / sQTL)

SOS2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 37 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 41 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	eqtl	7.9e-19	+0.31	14:50178018:G:A
Brain Cerebellar Hemisphere	eqtl	9.0e-18	+0.54	14:50110317:C:T
Lung	eqtl	3.9e-14	+0.35	14:50097431:A:G
Brain Cerebellum	eqtl	5.6e-13	+0.54	14:50097431:A:G
Thyroid	eqtl	2.0e-12	+0.28	14:50234921:T:G
Spleen	eqtl	2.3e-12	+0.37	14:50234921:T:G
Testis	eqtl	2.3e-11	+0.26	14:50110317:C:T
Skin Not Sun Exposed Suprapubic	eqtl	2.0e-10	+0.29	14:50097431:A:G
Adipose Subcutaneous	eqtl	1.1e-09	+0.22	14:50110317:C:T
Cells EBV-transformed lymphocytes	eqtl	1.8e-09	+0.30	14:50234921:T:G
Artery Aorta	eqtl	4.9e-09	+0.24	14:50110317:C:T
Colon Sigmoid	eqtl	7.1e-09	+0.28	14:50178018:G:A
Prostate	eqtl	4.5e-08	+0.34	14:50234921:T:G
Whole Blood	eqtl	1.8e-07	-0.06	14:50102525:CA:C
Breast Mammary Tissue	eqtl	5.8e-07	+0.23	14:50097431:A:G
Skin Sun Exposed Lower leg	eqtl	7.7e-07	+0.22	14:50110317:C:T
Esophagus Mucosa	eqtl	8.9e-07	+0.12	14:50172505:C:T
Adipose Visceral Omentum	eqtl	1.3e-06	+0.25	14:50097431:A:G
Pituitary	eqtl	1.5e-06	+0.32	14:50110317:C:T
Brain Cortex	eqtl	2.2e-06	+0.26	14:50234921:T:G

FANTOM5 promoters

showing 10 of 12 alternative TSS:

Promoter ID	TPM avg	Samples expressed
143137	9.1988	1715
143142	2.6390	1031
143138	1.4751	808
143141	0.7738	315
143144	0.7268	409
143140	0.6739	349
143139	0.5240	272
143143	0.2493	96
207211	0.2071	76
143134	0.0561	15

Top tissues by expression

showing 100 of 299 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
vastus lateralis	UBERON:0001379	97.15	gold quality
biceps brachii	UBERON:0001507	96.94	gold quality
buccal mucosa cell	CL:0002336	96.69	gold quality
quadriceps femoris	UBERON:0001377	96.68	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.59	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.13	gold quality
jejunal mucosa	UBERON:0000399	95.75	gold quality
jejunum	UBERON:0002115	95.49	gold quality
skeletal muscle tissue	UBERON:0001134	95.36	gold quality
diaphragm	UBERON:0001103	95.25	gold quality
germinal epithelium of ovary	UBERON:0001304	95.03	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	94.99	gold quality
body of tongue	UBERON:0011876	94.30	gold quality
corpus callosum	UBERON:0002336	94.25	gold quality
subthalamic nucleus	UBERON:0001906	93.85	gold quality
muscle tissue	UBERON:0002385	93.82	gold quality
inferior vagus X ganglion	UBERON:0005363	93.66	gold quality
deltoid	UBERON:0001476	93.63	gold quality
corpus epididymis	UBERON:0004359	93.52	gold quality
inferior olivary complex	UBERON:0002127	93.45	gold quality
mammary duct	UBERON:0001765	93.44	gold quality
parietal pleura	UBERON:0002400	93.36	gold quality
epithelium of mammary gland	UBERON:0003244	93.22	gold quality
heart right ventricle	UBERON:0002080	93.03	gold quality
skeletal muscle organ	UBERON:0014892	92.93	gold quality
muscle organ	UBERON:0001630	92.92	gold quality
pleura	UBERON:0000977	92.89	gold quality
superficial temporal artery	UBERON:0001614	92.82	gold quality
medulla oblongata	UBERON:0001896	92.81	gold quality
bone marrow	UBERON:0002371	92.76	gold quality
calcaneal tendon	UBERON:0003701	92.74	gold quality
tongue	UBERON:0001723	92.73	gold quality
lateral globus pallidus	UBERON:0002476	92.68	gold quality
renal glomerulus	UBERON:0000074	92.61	gold quality
cranial nerve II	UBERON:0000941	92.59	gold quality
visceral pleura	UBERON:0002401	92.39	gold quality
nephron tubule	UBERON:0001231	92.35	gold quality
bone element	UBERON:0001474	92.33	gold quality
metanephric glomerulus	UBERON:0004736	92.32	gold quality
urethra	UBERON:0000057	92.27	gold quality
palpebral conjunctiva	UBERON:0001812	92.17	gold quality
colonic mucosa	UBERON:0000317	92.14	gold quality
skin of hip	UBERON:0001554	92.14	gold quality
kidney epithelium	UBERON:0004819	92.11	gold quality
tibia	UBERON:0000979	92.06	gold quality
seminal vesicle	UBERON:0000998	92.03	gold quality
synovial joint	UBERON:0002217	91.98	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.98	gold quality
tibialis anterior	UBERON:0001385	91.92	gold quality
cauda epididymis	UBERON:0004360	91.88	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.83	gold quality
mucosa of paranasal sinus	UBERON:0005030	91.80	gold quality
bone marrow cell	CL:0002092	91.76	gold quality
CA1 field of hippocampus	UBERON:0003881	91.67	gold quality
muscle of leg	UBERON:0001383	91.66	gold quality
amniotic fluid	UBERON:0000173	91.62	gold quality
renal medulla	UBERON:0000362	91.59	gold quality
adrenal tissue	UBERON:0018303	91.54	gold quality
superior surface of tongue	UBERON:0007371	91.40	gold quality
sperm	CL:0000019	91.35	gold quality
gastrocnemius	UBERON:0001388	91.34	gold quality
placenta	UBERON:0001987	91.31	gold quality
duodenum	UBERON:0002114	91.30	gold quality
esophagus squamous epithelium	UBERON:0006920	91.29	gold quality
superior vestibular nucleus	UBERON:0007227	91.28	gold quality
saphenous vein	UBERON:0007318	91.23	gold quality
dorsal plus ventral thalamus	UBERON:0001897	91.20	gold quality
upper leg skin	UBERON:0004262	91.12	gold quality
trabecular bone tissue	UBERON:0002483	91.04	gold quality
substantia nigra pars reticulata	UBERON:0001966	91.03	gold quality
lower lobe of lung	UBERON:0008949	91.00	gold quality
epithelium of nasopharynx	UBERON:0001951	90.90	gold quality
ventral tegmental area	UBERON:0002691	90.80	gold quality
male germ cell	CL:0000015	90.79	gold quality
mammary gland	UBERON:0001911	90.70	gold quality
mononuclear cell	CL:0000842	90.69	gold quality
thoracic mammary gland	UBERON:0005200	90.69	gold quality
monocyte	CL:0000576	90.68	gold quality
gingival epithelium	UBERON:0001949	90.65	gold quality
leukocyte	CL:0000738	90.56	gold quality
trigeminal ganglion	UBERON:0001675	90.51	gold quality
epithelial cell of pancreas	CL:0000083	90.34	gold quality
blood	UBERON:0000178	90.30	gold quality
myocardium	UBERON:0002349	90.29	gold quality
substantia nigra pars compacta	UBERON:0001965	90.28	gold quality
secondary oocyte	CL:0000655	90.27	gold quality
caput epididymis	UBERON:0004358	90.25	gold quality
dorsal root ganglion	UBERON:0000044	90.18	gold quality
squamous epithelium	UBERON:0006914	90.15	gold quality
gingiva	UBERON:0001828	90.14	gold quality
globus pallidus	UBERON:0001875	90.04	gold quality
pharyngeal mucosa	UBERON:0000355	89.99	gold quality
periodontal ligament	UBERON:0008266	89.88	gold quality
triceps brachii	UBERON:0001509	89.76	gold quality
epithelium of esophagus	UBERON:0001976	89.72	gold quality
gluteal muscle	UBERON:0002000	89.63	gold quality
cardia of stomach	UBERON:0001162	89.62	gold quality
ganglionic eminence	UBERON:0004023	89.50	gold quality
choroid plexus epithelium	UBERON:0003911	89.37	gold quality
oral cavity	UBERON:0000167	89.33	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.19

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Tongue	tissue	59.5
Skeletal muscle	tissue	53.8	low
Corpus callosum	tissue	38.4
Bone marrow	tissue	37.2	high
Parathyroid gland	tissue	36.9	medium
Nucleus accumbens	tissue	36.1
Choroid plexus	tissue	31.8
Cerebellum	tissue	31.4	medium
Hippocampus	tissue	31.2	high
Locus coeruleus	tissue	29.7
Midbrain	tissue	29.2
Spinal cord	tissue	29.0
Postcentral gyrus	tissue	29.0
Medulla oblongata	tissue	28.0
Substantia nigra	tissue	27.4
Testis	tissue	26.0	high
Periaqueductal gray	tissue	25.9
Thalamus	tissue	25.7
Putamen	tissue	25.6
Pons	tissue	25.0
Superior colliculi	tissue	24.3
Ventral forebrain	tissue	23.8
Hypothalamus	tissue	23.7
Thyroid gland	tissue	23.5	high
Septum	tissue	23.1
Small intestine	tissue	23.0	medium
Kidney	tissue	22.8	medium
Adipose tissue	tissue	22.2	not detected
Hippocampal formation	tissue	22.1
Amygdala	tissue	21.3
Epididymis	tissue	21.1	medium
Olfactory bulb	tissue	21.0
Cerebral cortex	tissue	20.8	high
Motor cortex	tissue	20.8
Basal ganglia	tissue	20.7	medium
Occipital cortex	tissue	20.6
Retrosplenial cortex	tissue	20.5
Prefrontal cortex	tissue	20.3
Duodenum	tissue	20.2	high
Heart muscle	tissue	20.1	medium
Insular cortex	tissue	19.7
Entorhinal cortex	tissue	19.6
Retrosplenial and cingulate cortex	tissue	19.6
Somatosensory cortex	tissue	19.6
Temporal cortex	tissue	19.1
Seminal vesicle	tissue	17.5	high
Smooth muscle	tissue	16.8	medium
Breast	tissue	16.7	medium
Spleen	tissue	16.7	low
Skin 1	tissue	16.6	medium
Colon	tissue	16.3	medium
Rectum	tissue	16.2	high
Placenta	tissue	16.0	high
Caudate putamen	tissue	15.5
Esophagus	tissue	15.4	low
Thymus	tissue	15.2
Pancreas	tissue	14.9	high
Lung	tissue	14.8	high
Appendix	tissue	14.4
Prostate	tissue	14.3	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Cerebellar white matter (51.8), Parieto-temporal junction (white matter) (48.8), Corpus callosum, genu (white matter) (48.7), Temporal white matter (48.7), Globus pallidus, internus (47.3).

Regulation

Is transcription factor: no

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.415, missense Z 1.67 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000216373 splits into 4 regions with different missense tolerance; 1 is missense-constrained (≈2% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
14:50,118,347–50,130,689	354 / 347.7	1.02	no
14:50,130,690–50,159,435	408 / 506.6	0.81	no
14:50,159,436–50,159,496	5 / 24.7	0.20	yes (p 7.3e-05)
14:50,159,497–50,231,283	574 / 711.1	0.81	no
ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 10)

• Significant association of single nucleotide polymorphism within three genes–PPARgamma, SOS2, and PCK1–with Alzheimer’s disease, was confirmed. (PMID:17440948)
• Loss of MADD expression resulted in reduced Grb2 and Sos1/2 recruitment to the TNFR1 complex and decreased Ras and MEKK1/2 activation (PMID:19289468)
• intracellular Francisella tularensis novicida triggers temporal and early activation of Ras through the SOS2/GrB2/PKCalpha/PKCbetaI quaternary complex; Ras signalling by intracellular F. tularensis is essential for intracellular proliferation in the cytosol (PMID:20618341)
• multicenter pharmacogenetic study in children (ages 6-11): Data suggest that SNP in SOS2 (rs13379306) in children with growth hormone deficiency is associated with drug resistance to hormone replacement therapy with recombinant human growth hormone. (PMID:23761422)
• We identified two novel genes, SOS2 and LZTR1, associated with Noonan syndrome, thereby expanding the molecular spectrum of RASopathies. (PMID:25795793)
• Activating Mutations Affecting the Dbl Homology Domain of SOS2 Cause Noonan Syndrome (PMID:26173643)
• miR-148a-3p inhibits NSCLC cells proliferation and epithelial-mesenchymal transition by reducing the expression of SOS2 (PMID:30536836)
• Variants of SOS2 are a rare cause of Noonan syndrome with particular predisposition for lymphatic complications. (PMID:32788663)
• First prenatal case of Noonan syndrome with SOS2 mutation: Implications of early diagnosis for genetic counseling. (PMID:33750022)
• Genetic variants of SOS2, MAP2K1 and RASGRF2 in the RAS pathway genes predict survival of HBV-related hepatocellular carcinoma patients. (PMID:37029817)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sos2	ENSDARG00000060506
mus_musculus	Sos2	ENSMUSG00000034801
rattus_norvegicus	Sos2	ENSRNOG00000004826

Paralogs (24): RASGRF1 (ENSG00000058335), RASGRP2 (ENSG00000068831), RAPGEF3 (ENSG00000079337), RAPGEF4 (ENSG00000091428), RAPGEF1 (ENSG00000107263), RAPGEFL1 (ENSG00000108352), RAPGEF2 (ENSG00000109756), RASGRF2 (ENSG00000113319), SOS1 (ENSG00000115904), RALGPS2 (ENSG00000116191), RAPGEF5 (ENSG00000136237), RALGPS1 (ENSG00000136828), RASGEF1B (ENSG00000138670), RGL1 (ENSG00000143344), RASGEF1C (ENSG00000146090), RASGRP3 (ENSG00000152689), RAPGEF6 (ENSG00000158987), RGL4 (ENSG00000159496), RALGDS (ENSG00000160271), RASGRP4 (ENSG00000171777), RASGRP1 (ENSG00000172575), RASGEF1A (ENSG00000198915), RGL3 (ENSG00000205517), RGL2 (ENSG00000237441)

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Drosophila melanogaster	P26675	50.7%	Diamond
Dictyostelium discoideum	Q54TK8	43.9%	Diamond
Caenorhabditis elegans	Q9N5D3	37.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MAP4K5	protein-coding	11183
LINC01599	ncRNA	196913
DMAC2L	protein-coding	27109
VCPKMT	protein-coding	79609
L2HGDH	protein-coding	79944
CDKL1	protein-coding	8814
MIR4504	ncRNA	100616261
MIR6076	ncRNA	102464828
LINC01588	ncRNA	283551

Protein

Protein identifiers

Son of sevenless homolog 2 — Q07890 (reviewed: Q07890)

All UniProt accessions (3): A0A087X277, Q07890, G3V5W3

UniProt curated annotations — full annotation on UniProt →

Function. Acts as guanine nucleotide exchange factor (GEF) for RAS proteins. Catalyzes the GDP-to-GTP exchange, resulting in an increase of the active GTP-bound form of HRAS. Acts as a key modulator of PI3K-AKT signaling.

Subunit / interactions. Interacts with TTC1. Interacts with GNA15.

Disease relevance. Noonan syndrome 9 (NS9) [MIM:616559] A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q07890-1	1	yes
Q07890-2	2

RefSeq proteins (2): NP_001397949, NP_008870* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000219	DH_dom	Domain
IPR000651	Ras-like_Gua-exchang_fac_N	Domain
IPR001849	PH_domain	Domain
IPR001895	RASGEF_cat_dom	Domain
IPR008937	Ras-like_GEF	Family
IPR009072	Histone-fold	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR019804	Ras_G-nucl-exch_fac_CS	Conserved_site
IPR023578	Ras_GEF_dom_sf	Homologous_superfamily
IPR035899	DBL_dom_sf	Homologous_superfamily
IPR036964	RASGEF_cat_dom_sf	Homologous_superfamily
IPR055251	SOS1_NGEF_PH	Domain

Pfam: PF00617, PF00618, PF00621, PF22697

UniProt features (94 total): helix 37, sequence conflict 17, sequence variant 10, strand 10, compositionally biased region 5, turn 5, domain 4, region of interest 3, chain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

11 structures by resolution:

PDB	Title	Method	Resolution (Å)
8UF2	Apo SOS2 crystal structure in P1 space group	X-RAY DIFFRACTION	1.6
9BVI	Identification of multiple ligand hotspots on SOS2, compound 2	X-RAY DIFFRACTION	1.79
8T5M	SOS2 crystal structure with fragment bound (compound 14)	X-RAY DIFFRACTION	1.79
9BVF	Identification of multiple ligand hotspots on SOS2, compound 6	X-RAY DIFFRACTION	1.82
8T5G	SOS2 co-crystal structure with fragment bound (compound 12)	X-RAY DIFFRACTION	1.92
9GIN	SOS2 in complex with compound 11	X-RAY DIFFRACTION	2.06
8T5R	SOS2 crystal structure with fragment bound (compound 13)	X-RAY DIFFRACTION	2.12
9BVE	Identification of multiple ligand hotspots on SOS2, compound 9	X-RAY DIFFRACTION	2.4
8UC9	SOS2 co-crystal structure with fragment bound (compound 9)	X-RAY DIFFRACTION	2.44
6EIE	Ras guanine nucleotide exchange factor SOS2 (Rem-cdc25), with surface mutations	X-RAY DIFFRACTION	2.72
8UH0	SOS2 co-crystal structure with fragment bound (compound 10)	X-RAY DIFFRACTION	2.73

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q07890-F1	74.67	0.37

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, RAS pathway related proteins, Disease related genes, Human disease related genes, Congenital malformations, Other congenital malformations

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; vesicles

Antibody reliability (HPA): IH approved · IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1)

Type	Positions
Asymmetric dimethylarginine	1321

Function

Pathways and Gene Ontology

Reactome pathways

4 curated (TAS) of 22; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

22 pathways:

ID	Pathway	Evidence
R-HSA-416482	G alpha (12/13) signalling events	curated
R-HSA-8983432	Interleukin-15 signaling	curated
R-HSA-193648	NRAGE signals death through JNK	curated
R-HSA-9013149	RAC1 GTPase cycle	curated
R-HSA-428540	Activation of RAC1	electronic
R-HSA-422475	Axon guidance	—
R-HSA-204998	Cell death signalling via NRAGE, NRIF and NADE	—
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-73887	Death Receptor Signaling	—
R-HSA-1266738	Developmental Biology	—
R-HSA-388396	GPCR downstream signalling	—
R-HSA-168256	Immune System	—
R-HSA-451927	Interleukin-2 family signaling	—
R-HSA-9675108	Nervous system development	—
R-HSA-9012999	RHO GTPase cycle	—
R-HSA-162582	Signal Transduction	—
R-HSA-372790	Signaling by GPCR	—
R-HSA-449147	Signaling by Interleukins	—
R-HSA-376176	Signaling by ROBO receptors	—
R-HSA-194315	Signaling by Rho GTPases	—
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3	—
R-HSA-193704	p75 NTR receptor-mediated signalling	—

MSigDB gene sets: 552 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, REACTOME_INTERLEUKIN_2_FAMILY_SIGNALING, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_B_CELL_HOMEOSTASIS, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, KEGG_MAPK_SIGNALING_PATHWAY, GOLDRATH_IMMUNE_MEMORY, GOBP_LYMPHOCYTE_HOMEOSTASIS, KEGG_DORSO_VENTRAL_AXIS_FORMATION, REACTOME_NRAGE_SIGNALS_DEATH_THROUGH_JNK, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, BEIER_GLIOMA_STEM_CELL_DN

GO Biological Process (3): Ras protein signal transduction (GO:0007265), insulin receptor signaling pathway (GO:0008286), small GTPase-mediated signal transduction (GO:0007264)

GO Molecular Function (3): guanyl-nucleotide exchange factor activity (GO:0005085), protein heterodimerization activity (GO:0046982), protein binding (GO:0005515)

GO Cellular Component (2): cytosol (GO:0005829), plasma membrane (GO:0005886)

Reactome top-level categories

16 top-level categories:

Category	Pathways
Signal Transduction	2
Cell death signalling via NRAGE, NRIF and NADE	1
GPCR downstream signalling	1
Signaling by ROBO receptors	1
Interleukin-2 family signaling	1
RHO GTPase cycle	1
Immune System	1
Death Receptor Signaling	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
p75 NTR receptor-mediated signalling	1
Axon guidance	1
Signaling by GPCR	1
Nervous system development	1
Cytokine Signaling in Immune system	1
Signaling by Interleukins	1
Signaling by Rho GTPases	1

GO top-level categories

13 GO namespaces:

Category	Terms
small GTPase-mediated signal transduction	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
intracellular signaling cassette	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
protein dimerization activity	1
binding	1
cytoplasm	1
cellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

showing 15 of 1,436 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SOS2	GRB2	P29354	915
SOS2	RABIF	P47224	795
SOS2	GRAP2	O75791	757
SOS2	SHC1	P29353	741
SOS2	GRAP	Q13588	706
SOS2	ARL4A	P40617	677
SOS2	PRLH	P81277	633
SOS2	SHOC2	Q9UQ13	630
SOS2	PTPN11	Q06124	627
SOS2	LCP2	Q13094	625
SOS2	LZTR1	Q8N653	610
SOS2	RAF1	P04049	607
SOS2	RASA2	Q15283	605
SOS2	NRAS	P01111	597
SOS2	MAP2K1	Q02750	596

IntAct

Human interaction partners of SOS2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

21 partners by confidence:

Partner	Interaction type	MIscore	Records
GRB2	physical association	0.940	7
NCK1	physical association	0.670	3
CRK	physical association	0.670	1
PLCG1	physical association	0.600	4
EGFR	physical association	0.550	2
PACSIN3	physical association	0.520	2
SNX9	physical association	0.520	2
ABL1	physical association	0.400	2
CD2AP	physical association	0.400	1
FYN	physical association	0.400	1
PIK3R1	physical association	0.400	1
SNX18	physical association	0.400	1
SRC	physical association	0.400	1
LOX	physical association	0.370	1
GRB7	proximity	0.270	1
KRAS	proximity	0.270	1
CLU	physical association	0.000	1
DSCAM	physical association	0.000	1
ITSN1	physical association	0.000	1
RXRB	physical association	0.000	1
UBASH3A	physical association	0.000	1

BioGRID (68 interactions; top human partners by supporting records): GRB2 (Affinity Capture-MS; 11 records), EGFR (Two-hybrid; 8 records), CRK (Affinity Capture-MS; 2 records), PLCG1 (Two-hybrid; 2 records), SHC1 (Affinity Capture-Western; 2 records), ALDH18A1 (Affinity Capture-MS), BIN1 (Reconstituted Complex), CKB (Affinity Capture-MS), CREBBP (Two-hybrid), CRKL (Affinity Capture-MS), CWC15 (Affinity Capture-MS), DSCAM (Two-hybrid), DUT (Affinity Capture-MS), DYRK1A (Affinity Capture-MS), EIF6 (Affinity Capture-MS)

SIGNOR signaling

3 signaling interactions:

A	Effect	B	Mechanism
GRB2	up-regulates	SOS2	binding
SOS2	up-regulates	HRAS	“guanine nucleotide exchange factor”
SOS2	up-regulates	KRAS	“guanine nucleotide exchange factor”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 21 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Constitutive Signaling by EGFRvIII	5	178.4×	7e-09
Signaling by ERBB2 ECD mutants	5	167.9×	7e-09
Downstream signal transduction	8	152.3×	4e-14
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	5	142.8×	1e-08
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	5	129.8×	1e-08
Signaling by ERBB2 KD Mutants	5	105.7×	3e-08
DAP12 signaling	5	92.1×	6e-08
Signaling by CSF1 (M-CSF) in myeloid cells	5	86.5×	8e-08

GO biological processes:

GO term	Partners	Fold	FDR
ephrin receptor signaling pathway	5	81.9×	9e-07
epidermal growth factor receptor signaling pathway	6	70.8×	1e-07

Disease & clinical

Genetic variants

Variant evidence for SOS2: 2,067 ClinVar records (11 pathogenic / likely pathogenic); 7 ClinGen expert-panel interpretations; 14 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

2,067 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	6
Uncertain significance	966
Likely benign	759
Benign	118

Top pathogenic / likely-pathogenic (11)

Showing all 11 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
209092	NM_006939.4(SOS2):c.800T>A (p.Met267Lys)	Likely pathogenic	reviewed by expert panel	8
209091	NM_006939.4(SOS2):c.1127C>G (p.Thr376Ser)	Pathogenic	criteria provided, multiple submitters, no conflicts	10
373114	NM_006939.4(SOS2):c.800T>C (p.Met267Thr)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
974590	NM_006939.4(SOS2):c.791C>G (p.Thr264Arg)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
684625	NM_006939.4(SOS2):c.1126A>T (p.Thr376Ser)	Pathogenic	criteria provided, single submitter	2
2039738	NM_006939.4(SOS2):c.1291G>A (p.Glu431Lys)	Pathogenic	criteria provided, single submitter	1
974591	NM_006939.4(SOS2):c.798_800delinsCAA (p.Glu266_Met267delinsAspLys)	Likely pathogenic	criteria provided, single submitter	1
2821826	NM_006939.4(SOS2):c.1127C>T (p.Thr376Ile)	Likely pathogenic	criteria provided, single submitter	1
4796475	NM_006939.4(SOS2):c.530A>T (p.Asp177Val)	Likely pathogenic	criteria provided, single submitter	1
4864952	NM_006939.4(SOS2):c.1649G>T (p.Arg550Leu)	Likely pathogenic	criteria provided, single submitter	1
4921701	NM_006939.4(SOS2):c.799A>G (p.Met267Val)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore SOS2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

ClinGen expert-panel interpretations (7)

Expert ACMG interpretations from RASopathy VCEP for RASopathy — a higher-authority tier than individual ClinVar submissions.

Assertion	Variants
Likely Pathogenic	1
Uncertain Significance	4
Likely Benign	1
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 40 predictions of 2,257):

Position(s)	Effect	Δscore	Sites
14:50134121–50134122	donor_loss	1.0000	5
14:50134240–50134241	acceptor_loss	1.0000	6
14:50134246	acceptor_gain	1.0000
14:50134252	acceptor_gain	1.0000
14:50145168–50145169	donor_loss	1.0000	4
14:50145475–50145476	donor_loss	1.0000	5
14:50150006–50150007	donor_loss	1.0000	5
14:50150231–50150232	acceptor_loss	1.0000	6
14:50157002	donor_gain	1.0000
14:50157122–50157123	acceptor_loss	1.0000	6

AlphaMissense

3,702 missense substitutions predicted likely pathogenic (of 8,819 scored), across 837 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M267	9	0.935	0.997
M173	9	0.909	0.995
M166	9	0.874	0.997
M420	9	0.871	0.977
M724	9	0.855	0.985
D140	8	0.999	1.000
D169	8	0.999	1.000
D701	8	0.998	0.999
D161	8	0.995	0.999
H698	8	0.995	0.999
F78	8	0.993	0.999
F176	8	0.993	0.999
F625	8	0.992	0.999
F632	8	0.992	1.000
F956	8	0.992	1.000
D263	8	0.989	0.999
D618	8	0.989	0.998
N689	8	0.988	1.000
H614	8	0.987	0.998
N865	8	0.986	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	4.01e-08
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000205

Disease associations

OMIM: gene MIM:601247 | disease phenotypes: MIM:616559, MIM:163950

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
Noonan syndrome 9	Definitive	Autosomal dominant	5
Noonan syndrome	Definitive	Autosomal dominant	2

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
Noonan syndrome	Definitive	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (15 panels, 13 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

15 panels:

Panel	Rating
DDG2P	green
Fetal anomalies	green
Fetal hydrops	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Monogenic short stature	green
Paediatric disorders	green
Paediatric or syndromic cardiomyopathy	green
Pigmentary skin disorders	green
Primary lymphoedema	green
RASopathies	green
Unexplained death in infancy and sudden unexplained death in childhood	green
Adult solid tumours cancer susceptibility	amber
Childhood solid tumours	amber

Mondo (4): Noonan syndrome 9 (MONDO:0014691), Noonan syndrome 1 (MONDO:0008104), Noonan syndrome (MONDO:0018997), RASopathy (MONDO:0021060)

Orphanet (2): Noonan syndrome (Orphanet:648), RASopathy (Orphanet:536391)

HPO phenotypes

showing 60 of 81 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000072	Hydroureter
HP:0000078	Abnormality of the genital system
HP:0000179	Thick lower lip vermilion
HP:0000218	High palate
HP:0000316	Hypertelorism
HP:0000325	Triangular face
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000391	Thickened helices
HP:0000407	Sensorineural hearing impairment
HP:0000465	Webbed neck
HP:0000470	Short neck
HP:0000474	Thickened nuchal skin fold
HP:0000476	Cystic hygroma
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000508	Ptosis
HP:0000520	Proptosis
HP:0000635	Blue irides
HP:0000639	Nystagmus
HP:0000767	Pectus excavatum
HP:0000768	Pectus carinatum
HP:0000938	Osteopenia
HP:0000978	Bruising susceptibility
HP:0000995	Melanocytic nevus
HP:0001004	Lymphedema
HP:0001156	Brachydactyly
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001324	Muscle weakness
HP:0001328	Specific learning disability
HP:0001382	Joint hypermobility
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001639	Hypertrophic cardiomyopathy
HP:0001641	Abnormal pulmonary valve morphology
HP:0001642	Pulmonic stenosis
HP:0001643	Patent ductus arteriosus
HP:0001680	Coarctation of aorta
HP:0001743	Abnormality of the spleen
HP:0001892	Abnormal bleeding
HP:0001928	Abnormality of coagulation
HP:0002162	Low posterior hairline
HP:0002167	Abnormal speech pattern
HP:0002208	Coarse hair
HP:0002212	Curly hair
HP:0002240	Hepatomegaly
HP:0002650	Scoliosis
HP:0002750	Delayed skeletal maturation
HP:0002974	Radioulnar synostosis
HP:0003115	Abnormal EKG
HP:0004209	Clinodactyly of the 5th finger
HP:0004322	Short stature
HP:0004415	Pulmonary artery stenosis

GWAS associations

14 associations:

Study	Trait	p-value
GCST007930_140	Medication use (agents acting on the renin-angiotensin system)	2e-14
GCST006412_111	Intraocular pressure	4e-11
GCST005580_18	Intraocular pressure	6e-11
GCST007269_34	Pulse pressure	1e-10
GCST007928_93	Medication use (diuretics)	1e-10
GCST006394_45	Intraocular pressure	2e-10
GCST009725_95	Intraocular pressure	2e-10
GCST008362_134	Birth weight	6e-10
GCST90002384_188	Hemoglobin	8e-10
GCST90002403_497	Red blood cell count	6e-9
GCST007876_33	Estimated glomerular filtration rate	3e-8
GCST007929_16	Medication use (calcium channel blockers)	3e-8
GCST002380_4	Erythema nodosum in inflammatory bowel disease	7e-6
GCST002312_10	Periodontal disease-related phenotype (Socransky)	8e-6

EFO canonical traits (from GWAS)

8 canonical traits:

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0005763	pulse pressure measurement
EFO:0009928	Diuretic use measurement
EFO:0009930	Calcium channel blocker use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0004344	birth weight
EFO:0004509	hemoglobin measurement
EFO:0004305	erythrocyte count

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D009634	Noonan Syndrome	C05.660.207.690; C14.240.400.787; C14.280.400.787; C16.131.240.400.784; C16.131.621.207.690; C17.300.690

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4524041 (SINGLE PROTEIN), CHEMBL5169071 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 35,550 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL95	TACRINE	4	35,550

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

5 measured of 11 human assays (23 total across all organisms); most potent 5 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
6,7-dimethoxy-N-[(1R)-1-(1-naphthyl)ethyl]quinazolin-4-amine	IC50	553 nM	US-20240083857: 2-Methyl-Quinazolines
CHEMBL6161927	KD	159000 nM
CHEMBL5428862	KD	490000 nM
CHEMBL2321985	KD	730000 nM
CHEMBL5413281	KD	960000 nM

ChEMBL bioactivities

6 potent at pChembl≥5 of 16 total, top 6 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.89	Kd	1300	nM	CHEMBL6159919
5.85	Kd	1400	nM	CHEMBL6163045
5.80	Kd	1600	nM	CHEMBL6167330
5.47	Kd	3400	nM	CHEMBL6164095
5.34	Kd	4600	nM	CHEMBL1198612
5.28	Kd	5300	nM	CHEMBL6134434

PubChem BioAssay actives

6 with measured affinity, of 36 total; 6 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-[[4-(1,4-diazepan-1-yl)quinazolin-2-yl]amino]phenol	2232101: Binding affinity to N-terminal GST tagged SOS2 (562 to 1047 residues) (unknown origin) extracted from Escherichia coli strain BL21 (DE3) assessed as dissociation constant by SPR analysis	kd	1.3000	uM
4-[[4-[(3S)-3-methyl-1,4-diazepan-1-yl]quinazolin-2-yl]amino]phenol	2232101: Binding affinity to N-terminal GST tagged SOS2 (562 to 1047 residues) (unknown origin) extracted from Escherichia coli strain BL21 (DE3) assessed as dissociation constant by SPR analysis	kd	1.4000	uM
6-[[4-[(3S)-3-methylpiperazin-1-yl]quinazolin-2-yl]amino]-3,4-dihydro-1H-quinolin-2-one	2232101: Binding affinity to N-terminal GST tagged SOS2 (562 to 1047 residues) (unknown origin) extracted from Escherichia coli strain BL21 (DE3) assessed as dissociation constant by SPR analysis	kd	1.6000	uM
N-(3H-benzimidazol-5-yl)-4-(4-methylpiperazin-1-yl)quinazolin-2-amine	2232101: Binding affinity to N-terminal GST tagged SOS2 (562 to 1047 residues) (unknown origin) extracted from Escherichia coli strain BL21 (DE3) assessed as dissociation constant by SPR analysis	kd	3.4000	uM
4-[[4-(4-methylpiperazin-1-yl)quinazolin-2-yl]amino]phenol	2232101: Binding affinity to N-terminal GST tagged SOS2 (562 to 1047 residues) (unknown origin) extracted from Escherichia coli strain BL21 (DE3) assessed as dissociation constant by SPR analysis	kd	4.6000	uM
4-[[4-(4-propan-2-ylpiperazin-1-yl)-5,6,7,8-tetrahydroquinazolin-2-yl]amino]phenol	2232101: Binding affinity to N-terminal GST tagged SOS2 (562 to 1047 residues) (unknown origin) extracted from Escherichia coli strain BL21 (DE3) assessed as dissociation constant by SPR analysis	kd	5.3000	uM

CTD chemical–gene interactions

51 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, increases abundance	4
Valproic Acid	affects expression, decreases expression, decreases methylation	4
potassium chromate(VI)	affects cotreatment, decreases expression	2
perfluorooctane sulfonic acid	affects expression, affects cotreatment, decreases expression	2
Air Pollutants	increases abundance, increases expression	2
Arsenic	increases methylation, increases abundance, increases expression	2
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
moringin	affects cotreatment, decreases expression	1
geldanamycin	increases expression	1
testosterone enanthate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
trichostatin A	decreases expression	1
arsenite	decreases reaction, affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	affects cotreatment, affects expression	1
ochratoxin A	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression	1
entinostat	decreases expression	1
ON 01910	increases expression	1
perfluorobutanesulfonic acid	decreases expression, affects cotreatment, affects expression	1
asparanin A	decreases expression	1
jinfukang	decreases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	decreases expression	1
Leflunomide	decreases expression	1

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4881445	Binding	KRAS(G12C)–SOS2(cat) activation assay	Data for DCP probe BAY-293

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D8BA	Ubigene A-549 SOS2 KO	Cancer cell line	Male
CVCL_D8W1	Ubigene HCT 116 SOS2 KO	Cancer cell line	Male
CVCL_D9SR	Ubigene HEK293 SOS2 KO	Transformed cell line	Female
CVCL_E0PQ	Ubigene HeLa SOS2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 327 trials:

NCT	Phase	Status	Title
NCT00668824	Phase 4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	Phase 4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	Phase 4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	Phase 4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	Phase 4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	Phase 4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	Phase 4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	Phase 4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	Phase 4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	Phase 4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	Phase 4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	Phase 4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00452725	Phase 3	COMPLETED	Effect of MAXOMAT ® on the Growth of Small Children to NOONAN’s Syndrome
NCT01529840	Phase 3	COMPLETED	Somatropin Effect on Linear Growth and Final Height in Subjects With Noonan Syndrome
NCT01529944	Phase 3	COMPLETED	Genetic Testing of Noonan Subjects Previously Treated With Norditropin®. An Extension to Trial GHNOO-1658
NCT01927861	Phase 3	COMPLETED	Investigating the Long-term Efficacy and Safety of Two Doses of NN-220 (Somatropin) in Short Stature Due to Noonan Syndrome
NCT02713945	Phase 3	COMPLETED	Treatment With HMG-COA Reductase Inhibitor of Growth and Bone Abnormalities in Children With Noonan Syndrome
NCT05723835	Phase 3	ACTIVE_NOT_RECRUITING	A Research Study Looking at How Safe Somapacitan is and How Well it Works in Children Who Need Help to Grow - REAL 9
NCT00000470	Phase 3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	Phase 3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	Phase 3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	Phase 3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	Phase 3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	Phase 3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	Phase 3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	Phase 3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	Phase 3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	Phase 3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	Phase 3	UNKNOWN	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	Phase 3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	Phase 3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	Phase 3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	Phase 3	RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00351221	Phase 2	TERMINATED	Research Study Using Recombinant Human Insulin-Like Growth Factor-1/Recombinant Human Insulin-Like Growth Factor Binding Protein-3 for Children With Noonan Syndrome
NCT06555237	Phase 2	RECRUITING	MEK Inhibitors for the Treatment of Hypertrophic Cardiomyopathy in Patients With RASopathies
NCT06668805	Phase 2	RECRUITING	A Study of Vosoritide in Children With Noonan Syndrome With Inadequate Growth During or After Human Growth Hormone Treatment
NCT00115375	Phase 2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	Phase 2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	Phase 2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	Phase 2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	Phase 2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	Phase 2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	Phase 2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	Phase 2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	Phase 2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	Phase 2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	Phase 2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	Phase 2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	Phase 2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE
NCT01841177	Phase 2	COMPLETED	Evaluating Precision of Therapy - Milrinone
NCT02046135	Phase 2	TERMINATED	Sodium Bicarbonate to Prevent Acute Kidney Injury in Children Undergoing Cardiac Surgery
NCT02133573	Phase 2	COMPLETED	Randomized Trial of Maternal Progesterone Therapy
NCT02232399	Phase 2	COMPLETED	Is Levosimendan Superior to Milrinone Regarding Acute Kidney Injury After Cardiac Surgery for Congenital Heart Disease?
NCT02492269	Phase 2	COMPLETED	Stress Response and Neurodevelopmental Outcome After Cardiac Surgery Utilizing CPB in Children: A Prospective, Double Blinded and Randomized Study
NCT02564796	Phase 2	TERMINATED	Erythropoietin to Prevent Unnecessary Transfusions In Patients With Cyanotic CHD - A Prospective Control Trial
NCT02618824	Phase 2	UNKNOWN	Role of Terminal Warm Blood Cardioplegia as Myocardial Protection in the Use of Histidine-Tryptophan-Ketoglutarate Cardioplegia in Complex Congenital Heart Surgery
NCT02769624	Phase 2	TERMINATED	Acute Effects of Inhaled Treprostinil in Fontan Patients
NCT02877238	Phase 2	COMPLETED	Remote Preconditioning and Myocardial Protection
NCT03082716	Phase 2	COMPLETED	Custodiol Versus Blood Cardioplegaia in Paediatric Cardiac Surgery
NCT03425734	Phase 2	UNKNOWN	The Effect of Dexmedetomidine on Kidney Perfusion in Paediatric Patients

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for SOS2 across ~30M SureChEMBL compounds — explore on Sugi Predict.