Gene

ARAF

A-Raf proto-oncogene, serine/threonine kinase

Explore in graph →CI-GENE-00011135HGNC:646 ENSG00000078061 NCBI 369 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (10)

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

civicCuratedShowing 1–10 of 10 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
ARAF Mutation1
Cobimetinib	Langerhans Cell Histiocytosis	Predictive	B	Supports Sensitivity Response	4	submitted	EID11297

Cohorts

Alteration frequency by cohort (85)

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

cbioportalObserved85 cohort rows (showing 50, sorted by frequency) · 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

Literature

Linked publications (3)

25 per page, newest first.

pubmedPublishedShowing 1–3 of 3 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
Phase IB Study of Vemurafenib in Combination with Irinotecan and Cetuximab in Patients with Metastatic Colorectal Cancer with BRAFV600E Mutation.
· Cancer Discov · 2016 · PMID 27729313 · validated civic_curation pubmed
High-throughput Phenotyping of Lung Cancer Somatic Mutations.
· Cancer Cell · 2016 · PMID 27478040 · validated civic_curation pubmed

ARAF Mutation + ARAF P216A + ARAF S225V1
Cobimetinib	Erdheim-Chester Disease	Predictive	B	Supports Sensitivity Response	4	submitted	EID11296 In an open-label, phase II trial, 18 patients with histiocytosis, including 12 patients with Erdheim-Chester disease, one patient with ARAF S225V, and one patient with ARAF P216A, of any mutational st… (full text at CIViC) PMID 30867592 · Diamond et al., 2019 · Open in CIViC	civic

ARAF Mutation + ARAF P216A + ARAF S225V1

Cobimetinib

Erdheim-Chester Disease

Predictive

Supports Sensitivity Response

submitted

EID11296

In an open-label, phase II trial, 18 patients with histiocytosis, including 12 patients with Erdheim-Chester disease, one patient with ARAF S225V, and one patient with ARAF P216A, of any mutational st… (full text at CIViC)

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

civic

ARAF S214C4
(oncogenic)	Malignant Lung Neoplasm	Oncogenic	D	Supports Oncogenicity	3	accepted	EID11147 194 somatic mutations seen in primary lung cancers were functionally evaluated using three approaches: (1) differences in pattern or extent of changes in gene expression in A549 cells induced by trans… (full text at CIViC) PMID 27478040 · Berger et al., 2016 · Open in CIViC	civic
Sorafenib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	C	Supports Sensitivity Response	2	accepted	EID17 In one patient with S214C mutation, the use of sorafenib has led to more than 5 years of survival and near remission. PMID 24569458 · Imielinski et al., 2014 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	accepted	EID40 Sorafenib can inhibit ARF-mediated MEK phosphorylation and soft agar colony formation of AALE cells expressing ARAF S214C in vitro. PMID 24569458 · Imielinski et al., 2014 · Open in CIViC	civic
Trametinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	accepted	EID41 Trametinib can inhibit ARF-mediated ERK phosphorylation and soft agar colony formation of AALE cells expressing ARAF S214C in vitro. PMID 24569458 · Imielinski et al., 2014 · Open in CIViC	civic

ARAF S214C4

(oncogenic)

Malignant Lung Neoplasm

Oncogenic

Supports Oncogenicity

accepted

EID11147

194 somatic mutations seen in primary lung cancers were functionally evaluated using three approaches: (1) differences in pattern or extent of changes in gene expression in A549 cells induced by trans… (full text at CIViC)

PMID 27478040 · Berger et al., 2016 · Open in CIViC

civic

Sorafenib

Lung Non-Small Cell CarcinomaCURATED_BROADER

Predictive

Supports Sensitivity Response

accepted

EID17

In one patient with S214C mutation, the use of sorafenib has led to more than 5 years of survival and near remission.

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

civic

〃

Lung Non-Small Cell CarcinomaCURATED_BROADER

Predictive

Supports Sensitivity Response

accepted

EID40

Sorafenib can inhibit ARF-mediated MEK phosphorylation and soft agar colony formation of AALE cells expressing ARAF S214C in vitro.

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

civic

Trametinib

Lung Non-Small Cell CarcinomaCURATED_BROADER

Predictive

Supports Sensitivity Response

accepted

EID41

Trametinib can inhibit ARF-mediated ERK phosphorylation and soft agar colony formation of AALE cells expressing ARAF S214C in vitro.

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

civic

ARAF S214F2
(functional)	—UNRESOLVED	Functional	B	Supports Gain Of Function	5	accepted	EID12972 Imielinski et al displays functional evidence (Figure 3A) showing the S214F variant causes increased colony formation and increased pMEK/MEK ratio. PMID 24569458 · Imielinski et al., 2014 · Open in CIViC	civic
(oncogenic)	Malignant Lung Neoplasm	Oncogenic	D	Supports Oncogenicity	3	accepted	EID11146 194 somatic mutations seen in primary lung cancers were functionally evaluated using three approaches: (1) differences in pattern or extent of changes in gene expression in A549 cells induced by trans… (full text at CIViC) PMID 27478040 · Berger et al., 2016 · Open in CIViC	civic

ARAF S214F2

(functional)

—UNRESOLVED

Functional

Supports Gain Of Function

accepted

EID12972

Imielinski et al displays functional evidence (Figure 3A) showing the S214F variant causes increased colony formation and increased pMEK/MEK ratio.

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

civic

(oncogenic)

Malignant Lung Neoplasm

Oncogenic

Supports Oncogenicity

accepted

EID11146

PMID 27478040 · Berger et al., 2016 · Open in CIViC

civic

ARAF V145L1
(oncogenic)	Malignant Lung Neoplasm	Oncogenic	D	Does Not Support Oncogenicity	3	accepted	EID11148 194 somatic mutations seen in primary lung cancers were functionally evaluated using three approaches: (1) differences in pattern or extent of changes in gene expression in A549 cells induced by trans… (full text at CIViC) PMID 27478040 · Berger et al., 2016 · Open in CIViC	civic

ARAF V145L1

(oncogenic)

Malignant Lung Neoplasm

Oncogenic

Does Not Support Oncogenicity

accepted

EID11148

PMID 27478040 · Berger et al., 2016 · Open in CIViC

civic

ARAF S490T + BRAF V600EBRAF ARAF1
Cetuximab + Irinotecan + VemurafenibCombination	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	1	accepted	EID1905 Phase 1b study of vemurafenib, cetuximab and irinotecan in 19 BRAF V600E mutant colorectal cancer patients. cfDNA panel sequencing was performed in 10 patients after disease progression. One patient h… (full text at CIViC) PMID 27729313 · Hong et al., 2016 · Open in CIViC	civic

ARAF S490T + BRAF V600EBRAF ARAF1

Cetuximab + Irinotecan + VemurafenibCombination

Malignant Colorectal NeoplasmCURATED_BROADER

Predictive

Supports Resistance

accepted

EID1905

Phase 1b study of vemurafenib, cetuximab and irinotecan in 19 BRAF V600E mutant colorectal cancer patients. cfDNA panel sequencing was performed in 10 patients after disease progression. One patient h… (full text at CIViC)

PMID 27729313 · Hong et al., 2016 · Open in CIViC

civic