GeneBe

ARAF

protein-coding

A-Raf proto-oncogene, serine/threonine kinase, the group of Mitogen-activated protein kinase kinase kinases|RAF family

Gene summary

Enables protein serine/threonine kinase activity. Involved in negative regulation of apoptotic process; regulation of TOR signaling; and regulation of protein metabolic process. Located in plasma membrane. Biomarker of high grade glioma. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:
  • ARAF1

MANE transcript

NM_001654.5

Inheritance

AD

ClinVar variants

U:84B:6

Top phenotype

ARAF-related disorder

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chrX:47,561,205-47,571,908

External References & Databases

Ensembl (ENSG00000078061)NCBI Gene (369)OMIM (311010)HGNC:646GenCCUniProt (P10398)AlphaFoldClinVar (ARAF)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~10.7 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

diffuse lymphatic malformationLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0015408

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ARAF variants in ClinVar

4 Conditions Cataloged
not specifiedTotal: 40
not providedTotal: 8
ARAF-related disorderTotal: 1
Lymphatic anomalyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001654.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
6
clinvar
2
clinvar
2
clinvar
 10
missense
61
clinvar
1
clinvar
1
clinvar
 63
nonsense
2
clinvar
 2
start loss
1
clinvar
 1
frameshift
0
splice donor/acceptor (+/-2bp)
14
clinvar
 14
Total00843390
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 64 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001654.5RefSeqNP_001645.115MANE Select
ENST00000377045.9EnsemblENSP00000366244.415MANE Select
NM_001256196.2RefSeqNP_001243125.115Standard
NM_001256197.2RefSeqNP_001243126.15Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
arafDanio rerio

Structure: whole organism

Quality: wholly dorsalized

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Non-small cell lung cancer - Homo sapiens (human)
  • Chronic myeloid leukemia - Homo sapiens (human)
  • Gastric cancer - Homo sapiens (human)
  • Renal cell carcinoma - Homo sapiens (human)
  • Long-term potentiation - Homo sapiens (human)

Biological Process

  • MAPK cascade
  • cellular protein modification process
  • regulation of TOR signaling
  • regulation of proteasomal ubiquitin-dependent protein catabolic process
  • positive regulation of peptidyl-serine phosphorylation

Molecular Function

  • protein kinase activity
  • protein serine/threonine kinase activity
  • protein binding
  • ATP binding
  • metal ion binding

Cellular Component

  • cellular_component
  • mitochondrion
  • cytosol

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000377045
Coding exons
15
Length
10792
Individuals with no LoFs
125643
Homozygous LoFs
3
Heterozygous LoFs
4
Defined
125650
p
0.0000279
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.451602740.5840.00002423934
Missense (PolyPhen)43122.670.350521668
Synonymous-0.4331201141.050.00001031234
Loss of Function3.92323.50.1280.00000190345

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian0.000150.00011rare
Finnish00.0absent
European (Non-Finnish)0.0000540.000035rare
South Asian0.0000530.000033rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May also regulate the TOR signaling cascade. {ECO:0000269|PubMed:22609986}.;

Recessive Scores

pRec
0.353

Intolerance Scores

LoFtool
0.172
RVIS EVS
-0.49
RVIS percentile EVS
22.36

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.985

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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