KRAS G12D

c.35G>A NM_004985.5 RAS-MAPK transition, gain of function

Cancer hotspot Recurrent missense variant. COSMIC COSV55497369, COSV55497419, COSV55497479

Population · gnomAD 1.3e-5 gnomAD v4

ClinVar Pathogenic/Likely pathogenic VCV000012582

Protein region P-loop, phosphate binding Residue 12 of KRAS. UniProt P01116

AlphaMissense likely pathogenic Pathogenicity score 1.00. Computational prediction, not clinical evidence.

Position in KRAS 6 catalogued

ISSVA subset	Allele fraction	Sources
CCLA	1.4-44%	PMC10243805 PMC11184491
KLA	0.55%	PMC11184491

Bars show the reported allele-fraction range on a 0 to 50 percent axis.

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

Lymphatic disorders caused by mosaic, activating KRAS variants respond to MEK inhibition.
Sheppard SE, March ME, Seiler C, Matsuoka LS, Kim SE, Kao C, Rubin AI, Battig MR, Khalek N, Schindewolf E, O'Connor N, Pinto E, Priestley JR, Sanders VR, Niazi R, Ganguly A, Hou C, Slater D, Frieden IJ, Huynh T, Shieh JT, Krantz ID, Guerrero JC, Surrey LF, Biko DM, Laje P, Castelo-Soccio L, Nakano TA, Snyder K, Smith CL, Li D, Dori Y, Hakonarson H. · JCI Insight · 2023
Genomic profiling informs diagnoses and treatment in vascular anomalies.
Li D, Sheppard SE, March ME, Battig MR, Surrey LF, Srinivasan AS, Matsuoka LS, Tian L, Wang F, Seiler C, Dayneka J, Borst AJ, Matos MC, Paulissen SM, Krishnamurthy G, Nriagu B, Sikder T, Casey M, Williams L, Rangu S, O'Connor N, Thomas A, Pinto E, Hou C, Nguyen K, Pellegrino da Silva R, Chehimi SN, Kao C, Biroc L, Britt AD, Queenan M, Reid JR, Napoli JA, Low DM, Vatsky S, Treat J, Smith CL, Cahill AM, Snyder KM, Adams DM, Dori Y, Hakonarson H. · Nat Med · 2023

Mentioned in 12,412 publications indexed by Europe PMC.