Gene

RAF1

Raf-1 proto-oncogene, serine/threonine kinase

Explore in graph →CI-GENE-00022885HGNC:9829 ENSG00000132155 NCBI 5894 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (15)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 1–15 of 15 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
RAF1 Fusion1
Trametinib	Melanoma	Predictive	C	Supports Sensitivity Response	4	accepted	EID9021 In a case report of a patient with metastatic melanoma harhouring an in-frame ANO10-RAF1 fusion, a MEK inhibitor (trametinib) treatment resulted in brief, but significant, tumor regression and symptom…

Cohorts

Alteration frequency by cohort (33)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

cbioportalObserved33 cohort rows · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Colorectal Cancer (MSK, Cancer Discovery 2022) coadread_mskresistance_2022	Colorectal Adenocarcinoma	Ssm	8

Literature

Linked publications (9)

25 per page, newest first.

pubmedPublishedShowing 1–9 of 9 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Oncogenic and sorafenib-sensitive ARAF mutations in lung adenocarcinoma.
· J Clin Invest · 2014 · PMID 24569458 · validated civic_curation pubmed
Copy Number Changes Are Associated with Response to Treatment with Carboplatin, Paclitaxel, and Sorafenib in Melanoma.
· Clin Cancer Res · 2016 · PMID 26307133 · validated civic_curation pubmed
Profound MEK inhibitor response in a cutaneous melanoma harboring a GOLGA4-RAF1 fusion.
· J Clin Invest · 2019 · PMID 30835257 · validated civic_curation pubmed
Significant Clinical Response to a MEK Inhibitor Therapy in a Patient With Metastatic Melanoma Harboring an RAF1 Fusion.
· JCO Precis Oncol · 2018 · PMID 35135096 · validated civic_curation

RAF1 Fusion1
Binimetinib	Melanoma	Predictive	C	Supports Sensitivity Response	3	accepted	EID13147 A patient with metastatic melanoma harboring a GCC2-RAF1 fusion involving RAF1 intron 7 (which retains the kinase domain) received binimetinib 45 mg twice daily after progression on multiple prior sys… (full text at CIViC) PMID 39504576 · Khaddour et al., 2025 · Open in CIViC	civic

RAF1 Fusion1

Binimetinib

Melanoma

Predictive

Supports Sensitivity Response

accepted

EID13147

A patient with metastatic melanoma harboring a GCC2-RAF1 fusion involving RAF1 intron 7 (which retains the kinase domain) received binimetinib 45 mg twice daily after progression on multiple prior sys… (full text at CIViC)

PMID 39504576 · Khaddour et al., 2025 · Open in CIViC

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RAF1 Fusion2
Binimetinib	Acral Lentiginous Melanoma	Predictive	C	Supports Sensitivity Response	3	accepted	EID13148 An 88-year-old patient with metastatic acral melanoma harboring a GOLGA4-RAF1 fusion received binimetinib 45 mg twice daily after progression on multiple immunotherapy regimens and clinical deteriorat… (full text at CIViC) PMID 39504576 · Khaddour et al., 2025 · Open in CIViC	civic
Cobimetinib + TrametinibSubstitutes	Melanoma	Predictive	C	Supports Sensitivity Response	5	accepted	EID8374 In a case study of a metastatic melanoma with a GOLGA4-RAF1 fusion, the patient was administered MEK inhibitor therapy in the absence of other actionable variants. This resulted in a profound and clin… (full text at CIViC) PMID 30835257 · McEvoy et al., 2019 · Open in CIViC	civic

RAF1 Fusion2

Binimetinib

Acral Lentiginous Melanoma

Predictive

Supports Sensitivity Response

accepted

EID13148

An 88-year-old patient with metastatic acral melanoma harboring a GOLGA4-RAF1 fusion received binimetinib 45 mg twice daily after progression on multiple immunotherapy regimens and clinical deteriorat… (full text at CIViC)

PMID 39504576 · Khaddour et al., 2025 · Open in CIViC

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Cobimetinib + TrametinibSubstitutes

Melanoma

Predictive

Supports Sensitivity Response

accepted

EID8374

In a case study of a metastatic melanoma with a GOLGA4-RAF1 fusion, the patient was administered MEK inhibitor therapy in the absence of other actionable variants. This resulted in a profound and clin… (full text at CIViC)

PMID 30835257 · McEvoy et al., 2019 · Open in CIViC

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RAF1 Fusion1
Belvarafenib	Cutaneous MelanomaALIAS	Predictive	C	Supports Sensitivity Response	3	accepted	EID13152 A patient with recurrent melanoma harboring a MIPOL1-RAF1 fusion with an intact RAF1 kinase domain received belvarafenib after progression following pembrolizumab with radiotherapy. Belvarafenib was i… (full text at CIViC) PMID 38470950 · Kim et al., 2024 · Open in CIViC	civic

RAF1 Fusion1

Belvarafenib

Cutaneous MelanomaALIAS

Predictive

Supports Sensitivity Response

accepted

EID13152

A patient with recurrent melanoma harboring a MIPOL1-RAF1 fusion with an intact RAF1 kinase domain received belvarafenib after progression following pembrolizumab with radiotherapy. Belvarafenib was i… (full text at CIViC)

PMID 38470950 · Kim et al., 2024 · Open in CIViC

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KRAS Mutation + MAP2K1 Mutation + MAP2K2 Mutation + NRAS Mutation + RAF1 MutationRAF1 MAP2K1 MAP2K2 KRAS NRAS2
Cobimetinib	Erdheim-Chester Disease	Predictive	B	Supports Sensitivity Response	4	submitted	EID11328 In an open-label, phase II trial, 18 patients with histiocytosis of any mutational status were enrolled. The overall response rate was 89% (90% CI: 73 - 100). Responses were durable, with no acquired … (full text at CIViC) PMID 30867592 · Diamond et al., 2019 · Open in CIViC	civic
〃	Langerhans Cell Histiocytosis	Predictive	B	Supports Sensitivity Response	4	submitted	EID11329 In an open-label, phase II trial, 18 patients with histiocytosis of any mutational status were enrolled. Patients received cobimetinib at a starting dose of 60 mg daily for 21 days of each 28-day cycl… (full text at CIViC) PMID 30867592 · Diamond et al., 2019 · Open in CIViC	civic

KRAS Mutation + MAP2K1 Mutation + MAP2K2 Mutation + NRAS Mutation + RAF1 MutationRAF1 MAP2K1 MAP2K2 KRAS NRAS2

Cobimetinib

Erdheim-Chester Disease

Predictive

Supports Sensitivity Response

submitted

EID11328

In an open-label, phase II trial, 18 patients with histiocytosis of any mutational status were enrolled. The overall response rate was 89% (90% CI: 73 - 100). Responses were durable, with no acquired … (full text at CIViC)

PMID 30867592 · Diamond et al., 2019 · Open in CIViC

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〃

Langerhans Cell Histiocytosis

Predictive

Supports Sensitivity Response

submitted

EID11329

In an open-label, phase II trial, 18 patients with histiocytosis of any mutational status were enrolled. Patients received cobimetinib at a starting dose of 60 mg daily for 21 days of each 28-day cycl… (full text at CIViC)

PMID 30867592 · Diamond et al., 2019 · Open in CIViC

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RAF1 Fusion1
Trametinib	Spindle Cell Sarcoma	Predictive	C	Supports Sensitivity Response	3	accepted	EID10326 Case report of a 27-year old female patient with spindle cell sarcoma. Initial treatment consisted of eight cycles of alternating vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide plus… (full text at CIViC) PMID 35050712 · Panet et al., 2022 · Open in CIViC	civic

RAF1 Fusion1

Trametinib

Spindle Cell Sarcoma

Predictive

Supports Sensitivity Response

accepted

EID10326

Case report of a 27-year old female patient with spindle cell sarcoma. Initial treatment consisted of eight cycles of alternating vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide plus… (full text at CIViC)

PMID 35050712 · Panet et al., 2022 · Open in CIViC

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RAF1 Amplification3
Carboplatin + Paclitaxel + SorafenibCombination	Cutaneous MelanomaALIAS	Predictive	B	Supports Sensitivity Response	2	accepted	EID1496 Retrospective analysis of somatic mutations and copy number changes in 119 patients treated with carboplatin, paclitaxel, ± sorafenib (CPS) in the E2603 trial. CPS therapy was associated with improved… (full text at CIViC) PMID 26307133 · Wilson et al., 2016 · Open in CIViC	civic
Sorafenib	Hepatocellular Carcinoma	Predictive	D	Supports Sensitivity Response	2	submitted	EID9113 Through the histological examination of 25 patient tumor samples with hepatocellular carcinoma, the efficacy of postoperative sorafenib treatment may be correlated with higher levels of c-Raf-1 expres… (full text at CIViC) PMID 26981887 · Lei et al., 2016 · Open in CIViC	civic
B-Raf/VEGFR-2 Inhibitor RAF265 + TrametinibCombination	Bladder Carcinoma	Predictive	D	Supports Sensitivity Response	3	submitted	EID11767 In this pre-clinical study, RAF inhibition and RAF inhibition in combination with MEK inhibition was tested in vivo in RAF1-amplified tumors (in both mice and PDX tumor models). The models were treate… (full text at CIViC) PMID 34554931 · Bekele et al., 2021 · Open in CIViC	civic

RAF1 Amplification3

Carboplatin + Paclitaxel + SorafenibCombination

Cutaneous MelanomaALIAS

Predictive

Supports Sensitivity Response

accepted

EID1496

Retrospective analysis of somatic mutations and copy number changes in 119 patients treated with carboplatin, paclitaxel, ± sorafenib (CPS) in the E2603 trial. CPS therapy was associated with improved… (full text at CIViC)

PMID 26307133 · Wilson et al., 2016 · Open in CIViC

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Sorafenib

Hepatocellular Carcinoma

Predictive

Supports Sensitivity Response

submitted

EID9113

Through the histological examination of 25 patient tumor samples with hepatocellular carcinoma, the efficacy of postoperative sorafenib treatment may be correlated with higher levels of c-Raf-1 expres… (full text at CIViC)

PMID 26981887 · Lei et al., 2016 · Open in CIViC

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B-Raf/VEGFR-2 Inhibitor RAF265 + TrametinibCombination

Bladder Carcinoma

Predictive

Supports Sensitivity Response

submitted

EID11767

In this pre-clinical study, RAF inhibition and RAF inhibition in combination with MEK inhibition was tested in vivo in RAF1-amplified tumors (in both mice and PDX tumor models). The models were treate… (full text at CIViC)

PMID 34554931 · Bekele et al., 2021 · Open in CIViC

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RAF1 R391W2
(functional)	—UNRESOLVED	Functional	D	Supports Gain Of Function	3	accepted	EID11044 RAF1 (CRAF) R391W was observed in a melanoma patient from which cell line M375 was derived (wild-type for BRAF and NRAS). RAF1 R391W expressed in 293T cells showed increased phosphorylation of MEK and… (full text at CIViC) PMID 27273450 · Atefi et al., 2016 · Open in CIViC	civic
Vemurafenib	Melanoma	Predictive	D	Supports Resistance	—	submitted	EID4824 In an in vitro study, M375 and M238 cell lines expressing RAF1 (CRAF) R391W demonstrated resistant to vemurafenib treatment compared to M397 cells expressing BRAF V600E (a known vemurafenib sensitizin… (full text at CIViC) PMID 27273450 · Atefi et al., 2016 · Open in CIViC	civic

RAF1 R391W2

(functional)

—UNRESOLVED

Functional

Supports Gain Of Function

accepted

EID11044

RAF1 (CRAF) R391W was observed in a melanoma patient from which cell line M375 was derived (wild-type for BRAF and NRAS). RAF1 R391W expressed in 293T cells showed increased phosphorylation of MEK and… (full text at CIViC)

PMID 27273450 · Atefi et al., 2016 · Open in CIViC

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Vemurafenib

Melanoma

Predictive

Supports Resistance

—

submitted

EID4824

In an in vitro study, M375 and M238 cell lines expressing RAF1 (CRAF) R391W demonstrated resistant to vemurafenib treatment compared to M397 cells expressing BRAF V600E (a known vemurafenib sensitizin… (full text at CIViC)

PMID 27273450 · Atefi et al., 2016 · Open in CIViC

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RAF1 S257L1
(oncogenic)	Malignant NeoplasmALIAS	Oncogenic	D	Supports Oncogenicity	4	accepted	EID12991 RAF1 p.S257L (and p.S259A) induced anchorage-independent growth and increased MEK/ERK phosphorylation in AALE and NIH-3T3 cells in a sorafenib- and trametinib-sensitive manner. Supporting data is foun… (full text at CIViC) PMID 24569458 · Imielinski et al., 2014 · Open in CIViC	civic

RAF1 S257L1

(oncogenic)

Malignant NeoplasmALIAS

Oncogenic

Supports Oncogenicity

accepted

EID12991

RAF1 p.S257L (and p.S259A) induced anchorage-independent growth and increased MEK/ERK phosphorylation in AALE and NIH-3T3 cells in a sorafenib- and trametinib-sensitive manner. Supporting data is foun… (full text at CIViC)

PMID 24569458 · Imielinski et al., 2014 · Open in CIViC

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RAF1 Fusion1
Binimetinib	Cutaneous MelanomaALIAS	Predictive	C	Supports Sensitivity Response	2	accepted	EID13149 A 51 year old male patient with metastatic cutaneous melanoma harboring a RUFY1::RAF1 fusion received the MEK inhibitor binimetinib after prior pembrolizumab and ipilimumab/nivolumab. During four mont… (full text at CIViC) PMID 35871080 · Moran et al., 2022 · Open in CIViC	civic

RAF1 Fusion1

Binimetinib

Cutaneous MelanomaALIAS

Predictive

Supports Sensitivity Response

accepted

EID13149

A 51 year old male patient with metastatic cutaneous melanoma harboring a RUFY1::RAF1 fusion received the MEK inhibitor binimetinib after prior pembrolizumab and ipilimumab/nivolumab. During four mont… (full text at CIViC)

PMID 35871080 · Moran et al., 2022 · Open in CIViC

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