Juvenile myelomonocytic leukemia: genes and variants
Explore variant evidence for Juvenile myelomonocytic leukemia across 5 analyzed proteins (PTPN11, NF1, CBL, NRAS, KRAS). Linked ClinVar records include 9 pathogenic or likely pathogenic variants, 115 variants of uncertain significance and 15 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. Counts refer to the selected disease label.
Data updated 2026-10-10. Automated aggregation, not a clinical review date.
Download variant evidence (CSV)
Genes linked to Juvenile myelomonocytic leukemia
PTPN11: Tyrosine-protein phosphatase non-receptor type 11
Its SHP2 phosphatase activity promotes RAS-MAPK signaling downstream of many receptor tyrosine kinases and cytokine receptors. Germline dysregulating variants cause Noonan-spectrum disorders, while somatic activating variants drive juvenile myelomonocytic leukemia and other cancers.
5 ClinVar pathogenic / likely pathogenic and 27 uncertain variants in PTPN11 have source records linked to Juvenile myelomonocytic leukemia. Association strength is not clinical gene validity.
NF1: Neurofibromin
It accelerates conversion of active RAS-GTP to inactive RAS-GDP and therefore restrains RAS-MAPK signaling. Loss-of-function variants cause neurofibromatosis type 1 with neurofibromas, pigmentary features, learning difficulties, and increased tumor risk.
2 ClinVar pathogenic / likely pathogenic and 70 uncertain variants in NF1 have source records linked to Juvenile myelomonocytic leukemia. Association strength is not clinical gene validity.
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.
2 ClinVar pathogenic / likely pathogenic and 32 uncertain variants in CBL have source records linked to Juvenile myelomonocytic leukemia. Association strength is not clinical gene validity.
NRAS: GTPase NRas
Its active GTP-bound state drives RAF-MEK-ERK and PI3K signaling downstream of growth-factor receptors. Somatic activating variants are common drivers of melanoma, leukemia, and other cancers, while germline activating variants can cause Noonan syndrome.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in NRAS have source records linked to Juvenile myelomonocytic leukemia. Association strength is not clinical gene validity.
KRAS: GTPase KRas
A small GTPase that acts as a molecular switch in the RAS-MAPK signaling pathway. By cycling between GDP- and GTP-bound states, it relays growth and survival signals, and activating KRAS variants are common drivers of cancer.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in KRAS have source records linked to Juvenile myelomonocytic leukemia. Association strength is not clinical gene validity.
Weakly linked (only a few uncertain records): ASXL1.
Where Juvenile myelomonocytic leukemia variants cluster
- PTPN11 Tyrosine-protein phosphatase (positions 247–517): 4 of 5 ClinVar pathogenic / likely pathogenic variants, 1.8× more than its size predicts.
ClinVar pathogenic and likely pathogenic variants linked to Juvenile myelomonocytic leukemia
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| CBL Y371S | 371 | Linker | Pathogenic / likely pathogenic (★★) |
| CBL Y371H | 371 | Linker | Pathogenic / likely pathogenic (★★) |
| PTPN11 D61G | 61 | SH2 1 | Pathogenic / likely pathogenic (★★) |
| PTPN11 G268S | 268 | Tyrosine-protein phosphatase | Pathogenic / likely pathogenic (★★) |
| PTPN11 G503E | 503 | Tyrosine-protein phosphatase | Pathogenic / likely pathogenic (★★) |
| PTPN11 S502T | 502 | Tyrosine-protein phosphatase | Pathogenic / likely pathogenic (★★) |
| NF1 M1I | 1 | Pathogenic / likely pathogenic (★★) | |
| NF1 V917D | 917 | Pathogenic / likely pathogenic (★★) | |
| PTPN11 P491A | 491 | Tyrosine-protein phosphatase | Pathogenic / likely pathogenic (★★) |
Which prediction tools work for Juvenile myelomonocytic leukemia
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- CATVariant: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 79 out of 100
- PolyPhen-2: 76 out of 100 (learned from overlapping clinical labels, so this is optimistic)
Same protein, different disease
- RASopathy also has ClinVar records linked to PTPN11 variants; they fall mostly in different places as the Juvenile myelomonocytic leukemia variants (51 pathogenic / likely pathogenic).
- Noonan syndrome also has ClinVar records linked to PTPN11 variants; they fall mostly in different places as the Juvenile myelomonocytic leukemia variants (44 pathogenic / likely pathogenic).
- Noonan syndrome and Noonan-related syndrome also has ClinVar records linked to PTPN11 variants; they fall mostly in different places as the Juvenile myelomonocytic leukemia variants (29 pathogenic / likely pathogenic).
- LEOPARD syndrome 1 also has ClinVar records linked to PTPN11 variants; they fall mostly in different places as the Juvenile myelomonocytic leukemia variants (16 pathogenic / likely pathogenic).
- Metachondromatosis also has ClinVar records linked to PTPN11 variants; they fall mostly in different places as the Juvenile myelomonocytic leukemia variants (11 pathogenic / likely pathogenic).
- Neurofibromatosis also has ClinVar records linked to NF1 variants; they fall mostly in different places as the Juvenile myelomonocytic leukemia variants (51 pathogenic / likely pathogenic).
- RASopathy also has ClinVar records linked to CBL variants; they fall mostly in different places as the Juvenile myelomonocytic leukemia variants (8 pathogenic / likely pathogenic).
Diseases related to Juvenile myelomonocytic leukemia
- RASopathy, also linked to CBL, KRAS, NRAS and PTPN11
- Noonan syndrome, also linked to CBL, KRAS, NRAS and PTPN11
- Noonan syndrome and Noonan-related syndrome, also linked to CBL, KRAS, NRAS and PTPN11
- Acute myeloid leukemia, also linked to KRAS, NRAS and PTPN11
- Cardiofaciocutaneous syndrome, also linked to KRAS and NRAS
- Autoimmune lymphoproliferative syndrome, also linked to KRAS and NRAS
- Colorectal cancer, also linked to KRAS and NRAS
- Urinary bladder cancer, also linked to KRAS and NF1
- Vascular malformation, also linked to KRAS and NRAS
- Multiple myeloma, also linked to KRAS and NRAS
- Linear nevus sebaceus syndrome, also linked to KRAS and NRAS
- Melanoma, also linked to NF1 and NRAS
Frequently asked questions
Which genes have records linked to Juvenile myelomonocytic leukemia?
This view contains 5 analyzed proteins: PTPN11, NF1, CBL, NRAS, KRAS. 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, 115 variants of uncertain significance and 15 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 159 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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