| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Lymphoedema_nonsyndromic v0.46 | ARAF | Zornitza Stark Marked gene: ARAF as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lymphoedema_nonsyndromic v0.46 | ARAF | Zornitza Stark Gene: araf has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lymphoedema_nonsyndromic v0.46 | ARAF | Zornitza Stark Classified gene: ARAF as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lymphoedema_nonsyndromic v0.46 | ARAF | Zornitza Stark Gene: araf has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lymphoedema_nonsyndromic v0.45 | ARAF |
Zornitza Stark gene: ARAF was added gene: ARAF was added to Lymphoedema_nonsyndromic. Sources: Literature Mode of inheritance for gene: ARAF was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: ARAF were set to 31263281 Phenotypes for gene: ARAF were set to Lymphatic malformation, MONDO:0019313, ARAF-related Mode of pathogenicity for gene: ARAF was set to Other Review for gene: ARAF was set to AMBER Added comment: ARAF encodes a RAF family serine/threonine kinase that regulates MAPK/ERK signaling; the conserved Ser214 site mediates 14‑3‑3 binding. The paper reports two unrelated patients (a 12‑year‑old male with central conducting lymphatic anomaly and an adult female with lymphangiomatosis) each harboring the same de novo, ?somatic gain‑of‑function missense variant c.640T>C (p.S214P). Detailed clinical phenotyping, segregation analysis, and extensive functional validation (enhanced ERK1/2 activity in HEK293T/HeLa/HDLEC cells rescued by trametinib and a zebrafish lymphatic phenotype rescued by cobimetinib) support pathogenicity and guided successful MEK‑inhibitor therapy. Sources: Literature |
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