Noonan syndrome-like disorder with juvenile myelomonocytic leukemia: genes and variants
Explore variant evidence for Noonan syndrome-like disorder with juvenile myelomonocytic leukemia across 2 analyzed proteins (CBL, CDC42). Linked ClinVar records include 9 pathogenic or likely pathogenic variants, 78 variants of uncertain significance and 25 with conflicting classifications.
Coverage includes proteins already analyzed in CATVariant, not every gene involved in this condition. Database links are associations, not an assessment of clinical gene–disease validity. Computable evidence prioritizes variants for expert review and does not reclassify them. Source labels are pooled across this disease family.
Data updated 2026-10-21. Automated aggregation, not a clinical review date.
Download variant evidence (CSV)
Genes linked to Noonan syndrome-like disorder with juvenile myelomonocytic leukemia
CBL: E3 ubiquitin-protein ligase CBL
It limits receptor-tyrosine-kinase signaling by ubiquitinating activated receptors and promoting their internalization and degradation. Germline or somatic pathogenic variants can prolong RAS-MAPK signaling and cause Noonan-like developmental disease or myeloid malignancy.
8 ClinVar pathogenic / likely pathogenic and 103 uncertain variants in CBL have source records linked to Noonan syndrome-like disorder with juvenile myelomonocytic leukemia. Association strength is not clinical gene validity.
CDC42: Cell division control protein 42 homolog
It acts as a molecular switch controlling actin organization, cell polarity, migration, vesicle trafficking, and multiple developmental signaling pathways. Germline dysregulating variants can cause Takenouchi-Kosaki syndrome and related neurodevelopmental disorders with hematologic and immune abnormalities.
1 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in CDC42 have source records linked to Noonan syndrome-like disorder with juvenile myelomonocytic leukemia. Association strength is not clinical gene validity.
Where Noonan syndrome-like disorder with juvenile myelomonocytic leukemia variants cluster
- CBL Linker (positions 352–380): 5 of 8 ClinVar pathogenic / likely pathogenic variants, 19.5× more than its size predicts.
- CBL RING-type (positions 381–420): 3 of 8 ClinVar pathogenic / likely pathogenic variants, 8.5× more than its size predicts.
ClinVar pathogenic and likely pathogenic variants linked to Noonan syndrome-like disorder with juvenile myelomonocytic leukemia
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| CBL Y371S | 371 | Linker | Pathogenic / likely pathogenic (★★) |
| CBL Y371D | 371 | Linker | Pathogenic / likely pathogenic (★★) |
| CBL Y371H | 371 | Linker | Pathogenic / likely pathogenic (★★) |
| CBL Y371N | 371 | Linker | Pathogenic / likely pathogenic (★★) |
| CBL R420L | 420 | RING-type | Pathogenic / likely pathogenic (★★) |
| CBL R420Q | 420 | RING-type | Pathogenic / likely pathogenic (★★) |
| CBL Q367P | 367 | Linker | Pathogenic / likely pathogenic (★★) |
| CDC42 E171K | 171 | Pathogenic / likely pathogenic (★★) | |
| CBL D390Y | 390 | RING-type | Pathogenic / likely pathogenic |
Which prediction tools work for Noonan syndrome-like disorder with juvenile myelomonocytic leukemia
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- AlphaMissense: 100 out of 100
- ESM1b (LLR): 100 out of 100
- CATVariant: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- PolyPhen-2: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 88 out of 100
Same protein, different disease
- RASopathy also has ClinVar records linked to CBL variants; they fall partly in the same places as the Noonan syndrome-like disorder with juvenile myelomonocytic leukemia variants (8 pathogenic / likely pathogenic).
- Macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome also has ClinVar records linked to CDC42 variants; they fall mostly in different places as the Noonan syndrome-like disorder with juvenile myelomonocytic leukemia variants (6 pathogenic / likely pathogenic).
Diseases related to Noonan syndrome-like disorder with juvenile myelomonocytic leukemia
- RASopathy, also linked to CBL
- Noonan syndrome, also linked to CBL
- Noonan syndrome and Noonan-related syndrome, also linked to CBL
- Fetal anomalies with a likely genetic cause, also linked to CDC42
- Myelomonocytic leukemia, also linked to CBL
- Familial hemophagocytic lymphohistiocytosis, also linked to CDC42
- Macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome, also linked to CDC42
Frequently asked questions
Which genes have records linked to Noonan syndrome-like disorder with juvenile myelomonocytic leukemia?
This view contains 2 analyzed proteins: CBL, CDC42. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.
What do the clinical classifications mean?
Linked records include 9 pathogenic or likely pathogenic variants, 78 variants of uncertain significance and 25 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.
Does the evidence score change a VUS classification?
No. 0 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.
Can I download the variant evidence?
Download the CSV for all 130 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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