Vascular malformation: genes and variants

Genes linked to Vascular malformation

• 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.

  4 disease-causing and 2 uncertain variants in KRAS are linked to Vascular malformation.

• 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.

  2 disease-causing and 1 uncertain variants in BRAF are linked to Vascular malformation.

• 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.

  1 disease-causing and 0 uncertain variants in MAP2K1 are linked to Vascular malformation.

• GNA11: Guanine nucleotide-binding protein subunit alpha-11

  It transmits signals from Gq-coupled receptors to phospholipase C and downstream calcium and protein-kinase-C pathways. Germline activating variants can cause autosomal dominant hypocalcemia, while somatic activating variants drive uveal melanoma and some vascular lesions.

  1 disease-causing and 0 uncertain variants in GNA11 are linked to Vascular malformation.

• 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.

  1 disease-causing and 0 uncertain variants in NRAS are linked to Vascular malformation.

• PIK3R1: Phosphatidylinositol 3-kinase regulatory subunit alpha

  Its p85-family products stabilize and regulate class IA PI3K catalytic subunits and couple receptors to PI3K activation. Pathogenic variants can cause activated PI3K-delta syndrome type 2 or SHORT syndrome depending on how they alter pathway output.

  1 disease-causing and 0 uncertain variants in PIK3R1 are linked to Vascular malformation.

• IDH2: Isocitrate dehydrogenase [NADP], mitochondrial

  It normally generates alpha-ketoglutarate and NADPH inside mitochondria. Recurrent R140 and R172 cancer-associated variants instead produce D-2-hydroxyglutarate, an oncometabolite that drives epigenetic dysregulation in acute myeloid leukemia and other tumors.

  1 disease-causing and 0 uncertain variants in IDH2 are linked to Vascular malformation.

Weakly linked (only a few uncertain records): RASA1.

Known disease-causing variants in Vascular malformation

Which prediction tools work for Vascular malformation

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• MetaLR: 92 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 90 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 89 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 88 out of 100

Same protein, different disease

• RASopathy is also caused by KRAS variants; they fall partly in the same places as the Vascular malformation variants (23 disease-causing).
• Noonan syndrome is also caused by KRAS variants; they fall mostly in different places as the Vascular malformation variants (16 disease-causing).
• Cardiofaciocutaneous syndrome is also caused by KRAS variants; they fall partly in the same places as the Vascular malformation variants (9 disease-causing).
• Autoimmune lymphoproliferative syndrome is also caused by KRAS variants; they fall partly in the same places as the Vascular malformation variants (5 disease-causing).
• Non-small cell lung carcinoma is also caused by KRAS variants; they fall partly in the same places as the Vascular malformation variants (5 disease-causing).
• RASopathy is also caused by BRAF variants; they fall mostly in different places as the Vascular malformation variants (36 disease-causing).
• Cardio-facio-cutaneous syndrome is also caused by BRAF variants; they fall mostly in different places as the Vascular malformation variants (26 disease-causing).
• Cardiofaciocutaneous syndrome is also caused by BRAF variants; they fall mostly in different places as the Vascular malformation variants (17 disease-causing).
• Noonan syndrome is also caused by BRAF variants; they fall mostly in different places as the Vascular malformation variants (11 disease-causing).
• Noonan syndrome and Noonan-related syndrome is also caused by BRAF variants; they fall mostly in different places as the Vascular malformation variants (10 disease-causing).
• RASopathy is also caused by MAP2K1 variants; they fall mostly in different places as the Vascular malformation variants (14 disease-causing).
• Cardiofaciocutaneous syndrome is also caused by MAP2K1 variants; they fall mostly in different places as the Vascular malformation variants (14 disease-causing).
• Cardio-facio-cutaneous syndrome is also caused by MAP2K1 variants; they fall mostly in different places as the Vascular malformation variants (6 disease-causing).
• Autosomal dominant hypocalcemia is also caused by GNA11 variants; they fall mostly in different places as the Vascular malformation variants (6 disease-causing).
• Familial hypocalciuric hypercalcemia is also caused by GNA11 variants; they fall mostly in different places as the Vascular malformation variants (4 disease-causing).
• Noonan syndrome is also caused by NRAS variants; they fall mostly in different places as the Vascular malformation variants (9 disease-causing).
• RASopathy is also caused by NRAS variants; they fall mostly in different places as the Vascular malformation variants (6 disease-causing).

Diseases related to Vascular malformation

• RASopathy, also linked to BRAF, KRAS, MAP2K1 and NRAS
• Noonan syndrome, also linked to BRAF, KRAS, MAP2K1 and NRAS
• Noonan syndrome and Noonan-related syndrome, also linked to BRAF, KRAS, MAP2K1 and NRAS
• Cardiofaciocutaneous syndrome, also linked to BRAF, KRAS, MAP2K1 and NRAS
• Hypertrophic cardiomyopathy, also linked to BRAF, MAP2K1 and NRAS
• Cardio-facio-cutaneous syndrome, also linked to BRAF, KRAS and MAP2K1
• Acute myeloid leukemia, also linked to IDH2, KRAS and NRAS
• Colorectal cancer, also linked to BRAF, KRAS and NRAS
• Non-small cell lung carcinoma, also linked to BRAF, KRAS and MAP2K1
• Costello syndrome, also linked to BRAF, MAP2K1 and NRAS
• Melanoma, also linked to BRAF, MAP2K1 and NRAS
• Autoimmune lymphoproliferative syndrome, also linked to KRAS and NRAS

Frequently asked questions

Which genes are linked to Vascular malformation?

In CATVariant, Vascular malformation is linked to 7 analyzed proteins: KRAS (GTPase KRas), BRAF (Serine/threonine-protein kinase B-raf), MAP2K1 (Dual specificity mitogen-activated protein kinase kinase 1), GNA11 (Guanine nucleotide-binding protein subunit alpha-11), NRAS (GTPase NRas), PIK3R1 (Phosphatidylinositol 3-kinase regulatory subunit alpha) and 1 more.

How many genetic variants are linked to Vascular malformation?

18 variants: 11 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 3 are of uncertain significance or have conflicting reports.

Which uncertain variants in Vascular malformation look disease-causing?

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

Which variant effect predictor works best for Vascular malformation?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.88, based on 9 disease-causing and 47 harmless variants).

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.

Download every variant as CSV · Browse all diseases · Methods · About the Center