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Saturation mutagenesis identifies activating and resistance-inducing FGFR kinase domain mutations.

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Nat Genet2025PMID 41361008stubpubmedProvenance
Source
PubMed
Retrieved
Sep 8, 2026
Layer
normalized (units and labels harmonized; values unchanged)
Run
ING-CIVIC-20260908-000001
Published

Abstract

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Linked entities

Linked entities (4)

How each link was made (MeSH, dictionary, registry reference, curation…) and whether it has been validated. Candidate links are not counted in entity statistics.

Validated 4

Curated evidence

Evidence citing this paper (26)

civicProvenance
Source
CIViC — Clinical Interpretation of Variants in Cancer
Dataset
CIViC evidence items
Version
civic-2026-09-08
Retrieved
Sep 8, 2026
Layer
normalized (units and labels harmonized; values unchanged)
Evidence
expert curation
License
CC0 1.0
PMID
41361008
Run
ING-CIVIC-20260908-000001
Open at source
CuratedShowing 1–26 of 26 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.
TherapyCancerTypeLevelDirection · significanceRating (1–5)StatusEvidenceSource
FGFR2 C491S1
FutibatinibLung Non-Small Cell CarcinomaCURATED_BROADERPredictiveDSupports Resistance4submitted
EID13173

FGFR2 C491S was identified as selectively conferring futibatinib resistance in FGFR-dependent NCI-H1581 cells and was independently validated by drug-treated cell-viability and FGFR phosphorylation ex… (full text at CIViC)

PMID 41361008 · Tangermann et al., 2025 · Open in CIViC

civic
FGFR2 V564G1
PemigatinibLung Non-Small Cell CarcinomaCURATED_BROADERPredictiveDSupports Resistance4submitted
EID13172

In FGFR-dependent NCI-H1581 lung cancer cells, FGFR2 V564G was identified by saturation mutational scanning as a pemigatinib-resistance mutation and was independently validated by cell-viability and p… (full text at CIViC)

PMID 41361008 · Tangermann et al., 2025 · Open in CIViC

civic
FGFR3 A500T1
(oncogenic)Malignant NeoplasmALIASOncogenicDDoes Not Support Oncogenicity2accepted
EID13092

In a saturation mutagenesis study, all possible single nucleotide substitutions in the FGFR1-4 kinase domain (amino acids 472-807 for FGFR3) were tested. Lentiviral plasmids were infected at MOI < 0.3… (full text at CIViC)

PMID 41361008 · Tangermann et al., 2025 · Open in CIViC

civic
FGFR3 D786N1
(oncogenic)Malignant NeoplasmALIASOncogenicDSupports Oncogenicity1submitted
EID12894

In a saturation mutagenesis study, all possible point mutations in the FGFR 1-4 kinase domain (amino acids 472-807 for FGFR3) were tested. Lentiviral plasmids were infected at MOI < 0.3 into the growt… (full text at CIViC)

PMID 41361008 · Tangermann et al., 2025 · Open in CIViC

civic
FGFR3 D786Y1
(oncogenic)Malignant NeoplasmALIASOncogenicDSupports Oncogenicity1submitted
EID12895

In a saturation mutagenesis study, all possible point mutations in the FGFR 1-4 kinase domain (amino acids 472-807 for FGFR3) were tested. Lentiviral plasmids were infected at MOI < 0.3 into the growt… (full text at CIViC)

PMID 41361008 · Tangermann et al., 2025 · Open in CIViC

civic
FGFR3 I538V1
(oncogenic)Malignant NeoplasmALIASOncogenicDSupports Oncogenicity1submitted
EID12879

In a saturation mutagenesis study, all possible point mutations in the FGFR 1-4 kinase domain (amino acids 472-807 for FGFR3) were tested. Lentiviral plasmids were infected at MOI < 0.3 into the growt… (full text at CIViC)

PMID 41361008 · Tangermann et al., 2025 · Open in CIViC

civic
FGFR3 K649R1
(oncogenic)Malignant NeoplasmALIASOncogenicDSupports Oncogenicity1submitted
EID12887

In a saturation mutagenesis study, all possible point mutations in the FGFR 1-4 kinase domain (amino acids 472-807 for FGFR3) were tested. Lentiviral plasmids were infected at MOI < 0.3 into the growt… (full text at CIViC)

PMID 41361008 · Tangermann et al., 2025 · Open in CIViC

civic
FGFR3 K650E1
(oncogenic)Malignant NeoplasmALIASOncogenicDSupports Oncogenicity2submitted
EID12889

In a saturation mutagenesis study, all possible point mutations in the FGFR 1-4 kinase domain (amino acids 472-807 for FGFR3) were tested. Lentiviral plasmids were infected at MOI < 0.3 into the growt… (full text at CIViC)

PMID 41361008 · Tangermann et al., 2025 · Open in CIViC

civic
FGFR3 K650M1
(oncogenic)Malignant NeoplasmALIASOncogenicDSupports Oncogenicity1submitted
EID12890

In a saturation mutagenesis study, all possible point mutations in the FGFR 1-4 kinase domain (amino acids 472-807 for FGFR3) were tested. Lentiviral plasmids were infected at MOI < 0.3 into the growt… (full text at CIViC)

PMID 41361008 · Tangermann et al., 2025 · Open in CIViC

civic
FGFR3 K650Q1
(oncogenic)Malignant NeoplasmALIASOncogenicDSupports Oncogenicity1submitted
EID12888

In a saturation mutagenesis study, all possible point mutations in the FGFR 1-4 kinase domain (amino acids 472-807 for FGFR3) were tested. Lentiviral plasmids were infected at MOI < 0.3 into the growt… (full text at CIViC)

PMID 41361008 · Tangermann et al., 2025 · Open in CIViC

civic
FGFR3 K650T1
(oncogenic)Malignant NeoplasmALIASOncogenicDSupports Oncogenicity1submitted
EID12891

In a saturation mutagenesis study, all possible point mutations in the FGFR 1-4 kinase domain (amino acids 472-807 for FGFR3) were tested. Lentiviral plasmids were infected at MOI < 0.3 into the growt… (full text at CIViC)

PMID 41361008 · Tangermann et al., 2025 · Open in CIViC

civic
FGFR3 L645H1
(oncogenic)Malignant NeoplasmALIASOncogenicDSupports Oncogenicity1submitted
EID12884

In a saturation mutagenesis study, all possible point mutations in the FGFR 1-4 kinase domain (amino acids 472-807 for FGFR3) were tested. Lentiviral plasmids were infected at MOI < 0.3 into the growt… (full text at CIViC)

PMID 41361008 · Tangermann et al., 2025 · Open in CIViC

civic
FGFR3 L645R1
(oncogenic)Malignant NeoplasmALIASOncogenicDSupports Oncogenicity1submitted
EID12886

In a saturation mutagenesis study, all possible point mutations in the FGFR 1-4 kinase domain (amino acids 472-807 for FGFR3) were tested. Lentiviral plasmids were infected at MOI < 0.3 into the growt… (full text at CIViC)

PMID 41361008 · Tangermann et al., 2025 · Open in CIViC

civic
FGFR3 M528I1
(oncogenic)Malignant NeoplasmALIASOncogenicDSupports Oncogenicity2submitted
EID12878

In a saturation mutagenesis study, all possible point mutations in the FGFR 1-4 kinase domain (amino acids 472-807 for FGFR3) were tested. Lentiviral plasmids were infected at MOI < 0.3 into the growt… (full text at CIViC)

PMID 41361008 · Tangermann et al., 2025 · Open in CIViC

civic
FGFR3 N540K1
(oncogenic)Malignant NeoplasmALIASOncogenicDSupports Oncogenicity2accepted
EID12881

In a saturation mutagenesis study, all possible point mutations in the FGFR 1-4 kinase domain (amino acids 472-807 for FGFR3) were tested. Lentiviral plasmids were infected at MOI < 0.3 into the growt… (full text at CIViC)

PMID 41361008 · Tangermann et al., 2025 · Open in CIViC

civic
FGFR3 N540S1
(oncogenic)Malignant NeoplasmALIASOncogenicDSupports Oncogenicity1submitted
EID12880

In a saturation mutagenesis study, all possible point mutations in the FGFR 1-4 kinase domain (amino acids 472-807 for FGFR3) were tested. Lentiviral plasmids were infected at MOI < 0.3 into the growt… (full text at CIViC)

PMID 41361008 · Tangermann et al., 2025 · Open in CIViC

civic
FGFR3 R669G1
(oncogenic)Malignant NeoplasmALIASOncogenicDSupports Oncogenicity2submitted
EID12892

In a saturation mutagenesis study, all possible point mutations in the FGFR 1-4 kinase domain (amino acids 472-807 for FGFR3) were tested. Lentiviral plasmids were infected at MOI < 0.3 into the growt… (full text at CIViC)

PMID 41361008 · Tangermann et al., 2025 · Open in CIViC

civic
FGFR3 S782P1
(oncogenic)Malignant NeoplasmALIASOncogenicDSupports Oncogenicity1submitted
EID12893

In a saturation mutagenesis study, all possible point mutations in the FGFR 1-4 kinase domain (amino acids 472-807 for FGFR3) were tested. Lentiviral plasmids were infected at MOI < 0.3 into the growt… (full text at CIViC)

PMID 41361008 · Tangermann et al., 2025 · Open in CIViC

civic
FGFR3 V555L1
(oncogenic)Malignant NeoplasmALIASOncogenicDSupports Oncogenicity2submitted
EID12883

In a saturation mutagenesis study, all possible point mutations in the FGFR 1-4 kinase domain (amino acids 472-807 for FGFR3) were tested. Lentiviral plasmids were infected at MOI < 0.3 into the growt… (full text at CIViC)

PMID 41361008 · Tangermann et al., 2025 · Open in CIViC

civic
FGFR3 V555M1
(oncogenic)Malignant NeoplasmALIASOncogenicDSupports Oncogenicity1submitted
EID12882

In a saturation mutagenesis study, all possible point mutations in the FGFR 1-4 kinase domain (amino acids 472-807 for FGFR3) were tested. Lentiviral plasmids were infected at MOI < 0.3 into the growt… (full text at CIViC)

PMID 41361008 · Tangermann et al., 2025 · Open in CIViC

civic
FGFR3 Y647C1
(oncogenic)Malignant NeoplasmALIASOncogenicDDoes Not Support Oncogenicity2submitted
EID13202

In a saturation mutagenesis study, all possible point mutations in the FGFR 1-4 kinase domain (amino acids 472-807 for FGFR3) were tested. Lentiviral plasmids were infected at MOI < 0.3 into the growt… (full text at CIViC)

PMID 41361008 · Tangermann et al., 2025 · Open in CIViC

civic
FGFR2 A726D1
(functional)—UNRESOLVEDFunctionalDSupports Gain Of Function4submitted
EID13169

FGFR2 A726D was identified as an activating mutation by saturation mutational scanning and independently demonstrated increased FGFR/FRS2 phosphorylation, growth under low-serum conditions, and anchor… (full text at CIViC)

PMID 41361008 · Tangermann et al., 2025 · Open in CIViC

civic
FGFR2 E711K1
(functional)—UNRESOLVEDFunctionalDSupports Gain Of Function3submitted
EID13171

FGFR2 E711K was identified as activating in the saturation mutational screen and independently demonstrated increased FGFR and FRS2 phosphorylation compared with wild-type FGFR2 in MCF10A cells, suppo… (full text at CIViC)

PMID 41361008 · Tangermann et al., 2025 · Open in CIViC

civic
FGFR2 I654K1
(functional)—UNRESOLVEDFunctionalDSupports Gain Of Function4submitted
EID13167

FGFR2 I654K was identified as an activating mutation by saturation mutational scanning and was independently validated in MCF10A and NIH-3T3 models. FGFR2 I654K increased FGFR/FRS2 phosphorylation rel… (full text at CIViC)

PMID 41361008 · Tangermann et al., 2025 · Open in CIViC

civic
FGFR2 I654R1
(functional)—UNRESOLVEDFunctionalDSupports Gain Of Function4submitted
EID13168

FGFR2 I654R was identified as an activating kinase-domain mutation in the functional screen and independently evaluated in NIH-3T3 cells, where it supported proliferation under low-serum conditions re… (full text at CIViC)

PMID 41361008 · Tangermann et al., 2025 · Open in CIViC

civic
FGFR2 N727D1
(functional)—UNRESOLVEDFunctionalDSupports Gain Of Function4submitted
EID13170

FGFR2 N727D was classified as activating by saturation mutational scanning and independently validated by increased FGFR/FRS2 phosphorylation, proliferation under low-serum conditions, and anchorage-i… (full text at CIViC)

PMID 41361008 · Tangermann et al., 2025 · Open in CIViC

civic