← Lymphatic Malformation Variant Atlas

NRAS Q61K

c.181C>A NM_002524.4 RAS-MAPK transversion, gain of function

Cancer hotspot Recurrent missense variant. COSMIC COSV54736310, COSV54743343, COSV54752117

Population · gnomAD 6.8e-7 gnomAD v4

ClinVar Conflicting classifications of pathogenicity VCV000073058

Protein region switch II Residue 61 of NRAS. UniProt P01111

AlphaMissense likely pathogenic Pathogenicity score 0.99. Computational prediction, not clinical evidence.

Position in NRAS 2 catalogued

Reported in KLA

ISSVA subset	Allele fraction	Sources
KLA	lesional	PMID35202617

Pathway and targeted therapy

Driver of the RAS-MAPK pathway. Repurposed drugs already used in the clinic for this pathway: trametinib and other MEK inhibitors.

Open and recent trials (8 in vascular / lymphatic anomalies for trametinib)

Trametinib Treatment for Complicated Vascular Anomalies ACTIVE NOT RECRUITING NCT07072403 · PHASE1, PHASE2
24VA021; VATCH Trametinib for Ras/MAPK Pathway VAs ACTIVE NOT RECRUITING NCT07549646 · PHASE2
Pilot Study on Trametinib for Surgical Unruptured AVMs WITHDRAWN NCT06098872 · PHASE2
A Phase I/II Study of Trametinib and Azacitidine for Patients With Newly Diagnosed Juvenile Myelomonocytic Leukemia RECRUITING NCT05849662 · PHASE1, PHASE2
TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer RECRUITING NCT02693535 · PHASE2
Pediatric Long-Term Follow-up and Rollover Study ACTIVE NOT RECRUITING NCT03975829 · PHASE4

Primary sources (1)

Cellular variant of kaposiform lymphangiomatosis: a report of three cases, expanding the morphologic and molecular genetic spectrum of this rare entity.
Allen-Rhoades W, Al-Ibraheemi A, Kohorst M, Tollefson M, Hull N, Polites S, Folpe AL. · Hum Pathol · 2022

Mentioned in 1,448 publications indexed by Europe PMC.

Cross-references

COSMIC COSV54736310 COSMIC COSV54743343 COSMIC COSV54752117 rs121913254 gnomAD · NRAS ClinVar · Q61K OncoKB cBioPortal · NRAS VarSome UniProt · NRAS AlphaFold · NRAS