Proteins / SOS1
SOS1
Son of sevenless homolog 1
GEF
UniProt Q07889
HSP90 client (literature): unknown
3D structure ↓
21 interaction partners · volcano ↗
Protein abundance under basal conditions (untreated, or vehicle where a drug arm exists). Scores are WT-relative: 1 = wild type.
8,512 variantsmissense decreased 18% · increased 7%
Other cells fade; highlighted cells are outlined.
Annotation tracks
Structure
Function
Chaperone
Variant effect
Track legend & definitions
Secondary structure
alpha helix3-10 helixpi helixbeta strandbeta bridgeturnbendno_ss
DSSP assignment on the reference structure.
Relative SASA
0.000.250.500.751.00
Side-chain solvent accessibility (0 = buried, 1 = fully exposed). The pipeline calls a residue surface-exposed above 0.25.
pLDDT
50.062.575.087.5100.0
AlphaFold per-residue confidence. The analysis drops residues below 60.
Curated feature
Protein-protein interfaceCatalytic / active siteLigand / substrate pocketRegulatory elementOther annotation
UniProt / literature annotation, coloured by class. Red marks a curated protein-protein interface — the independent comparison for our predicted interfaces.
Annotated interface
yesno
Curated protein-interface residue, independent of any structure prediction in this study.
Active site
yesno
Curated catalytic / active-site residue.
Inter-domain contact
yesno
Residue contacting another domain of the same protein (all-atom), so a variant effect there may be intramolecular rather than at a PPI.
HSP90 contact
TrueFalseUnknown
Contacts HSP90 in the chaperone-client cryo-EM structures ('Unknown' where the protein was not mapped).
CDC37 contact
TrueFalseUnknown
Contacts CDC37. These positions report kinase foldability rather than a canonical binding surface.
Fraction decreased
0%25%50%75%100%
Fraction of variants at this position classified decreased in this assay (2.5th-percentile rule).
Fraction increased
0%25%50%75%100%
Fraction of variants at this position classified increased in this assay.
Click a position for its interactions and annotations
— ■ the Interface strip marks
positions in ≥1 supported interface (darker = more partners)
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One row per interface: complexes of the same pair and source whose interfaces overlap (IoU ≥ 0.3) are merged, as in the Fig. 6c,d volcano plots (median Cohen's d; q from the geometric-mean p). Supported: at least one complex with q < 0.05 and |d| ≥ 0.2 in either basal assay.
| Partner | Source | Activity d | q | Abundance d | q | Interface positions | Supported | |
|---|---|---|---|---|---|---|---|---|
| HRAS | AF-M | -1.70 | 8.1e-97 | +0.80 | 1.1e-36 | 15 | supported | Structure ↗ |
| NRAS RasGEF | AF-M | -1.71 | 8.1e-96 | +0.77 | 2.2e-35 | 14 | supported | Structure ↗ |
| KRAS RasGEF | AF-M | -1.69 | 4.0e-95 | +0.78 | 1.2e-35 | 14 | supported | Structure ↗ |
| RAP1A | RF2-PPI | -1.60 | 1.9e-92 | +0.72 | 1.4e-31 | 14 | supported | Structure ↗ |
| HRAS RasGEF | PDB | -1.49 | 2.2e-89 | +0.72 | 5.4e-31 | 14 | supported | Structure ↗ |
| KRAS | PDB | -1.50 | 1.7e-86 | +0.69 | 3.6e-29 | 14 | supported | Structure ↗ |
| RIT2 RasGEF | AF-M | -1.67 | 8.5e-84 | +0.67 | 8.7e-26 | 13 | supported | Structure ↗ |
| RIT1 RasGEF | AF-M | -1.64 | 2.8e-83 | +0.69 | 4.6e-27 | 13 | supported | Structure ↗ |
| RASL11A | RF2-PPI | -1.71 | 2.5e-70 | +0.87 | 1.5e-28 | 9 | supported | Structure ↗ |
| ITSN1 RasGEF #2 | RF2-PPI | -1.55 | 1.4e-63 | +0.75 | 2.5e-23 | 9 | supported | Structure ↗ |
| RAC1 RasGEF | AF-M | -1.65 | 3.7e-60 | +0.92 | 7.4e-29 | 9 | supported | Structure ↗ |
| RASL11B | RF2-PPI | -1.45 | 1.2e-54 | +0.73 | 1.3e-20 | 9 | supported | Structure ↗ |
| RERGL | RF2-PPI | -1.93 | 3.2e-51 | +1.30 | 8.6e-29 | 5 | supported | Structure ↗ |
| FOXO1 | RF2-PPI | -1.59 | 6.0e-50 | +0.69 | 1.2e-16 | 7 | supported | Structure ↗ |
| NCK2 | RF2-PPI | -1.53 | 3.1e-49 | +0.57 | 5.8e-13 | 7 | supported | Structure ↗ |
| RERG | RF2-PPI | -1.38 | 9.5e-47 | +0.88 | 1.4e-24 | 8 | supported | Structure ↗ |
| C3orf18 | RF2-PPI | -1.47 | 7.7e-46 | +0.71 | 2.4e-16 | 7 | supported | Structure ↗ |
| ATRX | RF2-PPI | -1.22 | 9.4e-35 | +0.76 | 8.2e-17 | 8 | supported | Structure ↗ |
| ARHGAP39 | RF2-PPI | -1.97 | 2.2e-31 | +1.29 | 1.9e-18 | 3 | supported | Structure ↗ |
| BLNK | RF2-PPI | -0.95 | 4.5e-24 | +0.33 | 2.5e-07 | 9 | supported | Structure ↗ |
| RAC1 RasGEF #2 | AF-M | -1.42 | 1.4e-18 | +0.80 | 1.7e-07 | 3 | supported | Structure ↗ |
| KRAS RasGEF+RasGEFN | AF-M | -0.65 | 2.8e-18 | +0.59 | 4.6e-14 | 9 | supported | Structure ↗ |
| NRAS RasGEF+RasGEFN | AF-M | -0.33 | 1.4e-14 | +0.56 | 2.1e-13 | 11 | supported | Structure ↗ |
| RIT2 RasGEFN | AF-M | -0.20 | 4.9e-08 | +0.41 | 4.1e-10 | 13 | supported | Structure ↗ |
| RIT1 RasGEFN | AF-M | -0.33 | 2.4e-07 | +0.44 | 1.5e-09 | 10 | supported | Structure ↗ |
| HRAS RasGEFN | PDB | +0.02 | 7.0e-05 | +0.39 | 4.7e-09 | 16 | supported | Structure ↗ |
| EGFR | RF2-PPI | -0.58 | 1.8e-07 | +0.28 | 0.045 | 8 | supported | Structure ↗ |
| SHP2 | AF-M | +1.24 | 2.6e-06 | -0.25 | 0.020 | 4 | supported | Structure ↗ |
| PTPN6 | AF-M | +1.23 | 2.6e-06 | -0.25 | 0.020 | 4 | supported | Structure ↗ |
| SOS2 | RF2-PPI | -0.12 | 0.905 | +0.14 | 0.051 | 5 | not supported | Structure ↗ |
| ITSN1 RasGEF | RF2-PPI | +0.02 | 0.100 | +0.07 | 0.802 | 6 | not supported | Structure ↗ |