Noonan syndrome with multiple lentigines: genes and variants

Genes linked to Noonan syndrome with multiple lentigines

• 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.

  4 disease-causing and 0 uncertain variants in PTPN11 are linked to Noonan syndrome with multiple lentigines.

• BRAF: Serine/threonine-protein kinase B-raf

  It relays activated RAS signals through MEK and ERK to control proliferation, differentiation, and survival. Activating variants, especially V600E, drive melanoma and several other cancers and create sensitivity to pathway-directed therapies.

  0 disease-causing and 0 uncertain variants in BRAF are linked to Noonan syndrome with multiple lentigines.

• MAP2K1: Dual specificity mitogen-activated protein kinase kinase 1

  It phosphorylates ERK1 and ERK2 downstream of RAF and thereby propagates RAS-MAPK growth and developmental signals. Activating somatic variants occur in several cancers, while germline activating variants can cause cardio-facio-cutaneous syndrome and related RASopathies.

  0 disease-causing and 0 uncertain variants in MAP2K1 are linked to Noonan syndrome with multiple lentigines.

Weakly linked (only a few uncertain records): RAF1.

Known disease-causing variants in Noonan syndrome with multiple lentigines

Same protein, different disease

• RASopathy is also caused by PTPN11 variants; they fall mostly in different places as the Noonan syndrome with multiple lentigines variants (51 disease-causing).
• Noonan syndrome is also caused by PTPN11 variants; they fall mostly in different places as the Noonan syndrome with multiple lentigines variants (44 disease-causing).
• Noonan syndrome and Noonan-related syndrome is also caused by PTPN11 variants; they fall mostly in different places as the Noonan syndrome with multiple lentigines variants (29 disease-causing).
• LEOPARD syndrome 1 is also caused by PTPN11 variants; they fall mostly in different places as the Noonan syndrome with multiple lentigines variants (16 disease-causing).
• Metachondromatosis is also caused by PTPN11 variants; they fall mostly in different places as the Noonan syndrome with multiple lentigines variants (11 disease-causing).

Diseases related to Noonan syndrome with multiple lentigines

• RASopathy, also linked to BRAF, MAP2K1 and PTPN11
• Noonan syndrome, also linked to BRAF, MAP2K1 and PTPN11
• Noonan syndrome and Noonan-related syndrome, also linked to BRAF, MAP2K1 and PTPN11
• Hypertrophic cardiomyopathy, also linked to BRAF and MAP2K1
• Cardiofaciocutaneous syndrome, also linked to BRAF and MAP2K1
• Cardio-facio-cutaneous syndrome, also linked to BRAF and MAP2K1
• LEOPARD syndrome 1, also linked to BRAF and PTPN11
• Non-small cell lung carcinoma, also linked to BRAF and MAP2K1
• Costello syndrome, also linked to BRAF and MAP2K1
• Vascular malformation, also linked to BRAF and MAP2K1
• Male infertility with azoospermia or oligozoospermia due to single gene mutation, also linked to MAP2K1 and PTPN11
• Melanoma, also linked to BRAF and MAP2K1

Frequently asked questions

Which genes are linked to Noonan syndrome with multiple lentigines?

In CATVariant, Noonan syndrome with multiple lentigines is linked to 3 analyzed proteins: PTPN11 (Tyrosine-protein phosphatase non-receptor type 11), BRAF (Serine/threonine-protein kinase B-raf) and MAP2K1 (Dual specificity mitogen-activated protein kinase kinase 1).

How many genetic variants are linked to Noonan syndrome with multiple lentigines?

14 variants: 4 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 0 are of uncertain significance or have conflicting reports.

Which uncertain variants in Noonan syndrome with multiple lentigines look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis 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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