ARAF

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

Basic information

Region (hg38): X:47561204-47571908

Previous symbols: [ "ARAF1" ]

Links

ENSG00000078061 ∙ NCBI:369 ∙ OMIM:311010 ∙ HGNC:646 ∙ Uniprot:P10398 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• diffuse lymphatic malformation (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ARAF gene.

• Inborn genetic diseases (13 variants)
• not provided (6 variants)
• ARAF-Related Disorders (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARAF gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	2	4
missense			14		1	15
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding						0
Total	0	0	14	2	3

Variants in ARAF

This is a list of pathogenic ClinVar variants found in the ARAF region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-47563004-G-A		not specified	Uncertain significance (Sep 29, 2023)
X-47563219-C-T			Uncertain significance (Oct 12, 2023)
X-47563255-C-T			Likely benign (Jan 01, 2023)
X-47565010-C-T		not specified	Uncertain significance (Jan 22, 2024)
X-47565130-A-G		not specified	Uncertain significance (Jul 06, 2022)
X-47565132-C-T		not specified	Uncertain significance (Jan 24, 2024)
X-47565277-T-C		not specified	Uncertain significance (Nov 09, 2021)
X-47565291-A-T		not specified	Uncertain significance (Mar 20, 2023)
X-47565308-C-T		not specified	Uncertain significance (Feb 10, 2022)
X-47565335-C-A		not specified	Uncertain significance (Nov 12, 2021)
X-47566652-C-T		not specified	Uncertain significance (Apr 06, 2023)
X-47566680-C-G		not specified	Uncertain significance (Jul 15, 2021)
X-47566721-T-G		Papillary renal cell carcinoma, sporadic • Lung adenocarcinoma • Malignant melanoma of skin	Likely pathogenic (May 31, 2016)
X-47566722-C-G		Non-small cell lung carcinoma • Malignant melanoma of skin • Papillary renal cell carcinoma, sporadic • Lung adenocarcinoma	Likely pathogenic (May 31, 2016)
X-47566722-C-T		Papillary renal cell carcinoma, sporadic • Lung adenocarcinoma • Malignant melanoma of skin	Likely pathogenic (May 31, 2016)
X-47566731-A-G		not specified	Uncertain significance (Mar 14, 2023)
X-47566777-C-G		not specified	Uncertain significance (Mar 01, 2023)
X-47567043-G-T		not specified	Uncertain significance (Oct 12, 2021)
X-47567066-C-G		not specified	Uncertain significance (Sep 16, 2021)
X-47567113-C-T			Likely benign (Apr 01, 2023)
X-47567290-C-G		ARAF-related disorder	Uncertain significance (Aug 05, 2023)
X-47567354-T-C		not specified	Uncertain significance (Dec 19, 2023)
X-47567358-C-T			Benign (Feb 07, 2018)
X-47568747-T-G		not specified	Uncertain significance (Jan 03, 2024)
X-47568824-C-T		not specified	Uncertain significance (Mar 21, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARAF	protein_coding	protein_coding	ENST00000377045	15	10792

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.963	0.0368	125643	3	4	125650	0.0000279

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.45	160	274	0.584	0.0000242	3934
Missense in Polyphen		43	122.67	0.35052		1668
Synonymous	-0.433	120	114	1.05	0.0000103	1234
Loss of Function	3.92	3	23.5	0.128	0.00000190	345

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000151	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000538	0.0000352
Middle Eastern	0.000151	0.000109
South Asian	0.0000531	0.0000327
Other	0.00	0.00

dbNSFP

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}.
• Pathway: 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);Serotonergic synapse - Homo sapiens (human);Melanoma - Homo sapiens (human);Bladder cancer - Homo sapiens (human);Long-term depression - Homo sapiens (human);Acute myeloid leukemia - Homo sapiens (human);Breast cancer - Homo sapiens (human);ErbB signaling pathway - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Glioma - Homo sapiens (human);Prostate cancer - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);Endometrial cancer - Homo sapiens (human);Colorectal cancer - Homo sapiens (human);Alcoholism - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Progesterone-mediated oocyte maturation - Homo sapiens (human);Vemurafenib Pathway, Pharmacodynamics;update your name in edit mode;Integrin-mediated Cell Adhesion;Signaling Pathways in Glioblastoma;Common Pathways Underlying Drug Addiction;ESC Pluripotency Pathways;Endometrial cancer;MET in type 1 papillary renal cell carcinoma;Chromosomal and microsatellite instability in colorectal cancer;MAPK Cascade;ErbB Signaling Pathway;MAP2K and MAPK activation;RAF activation;Disease;Signal Transduction;mapkinase signaling pathway;B cell receptor signaling;GPCR GroupI metabotropic glutamate receptor;GPCR signaling-G alpha q;CD4 T cell receptor signaling-ERK cascade;IGF signaling;FGF;IL-7 signaling;EGFR1;Negative regulation of MAPK pathway;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;JAK STAT pathway and regulation;NGF;EPO signaling;Signaling by RAS mutants;VEGF;Signaling by high-kinase activity BRAF mutants;Signaling by moderate kinase activity BRAF mutants;Paradoxical activation of RAF signaling by kinase inactive BRAF;Signaling by BRAF and RAF fusions;Oncogenic MAPK signaling;Diseases of signal transduction;CD4 T cell receptor signaling (Consensus)

Recessive Scores

• pRec: 0.353

Intolerance Scores

• loftool: 0.172
• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.36

Haploinsufficiency Scores

• pHI: 0.964
• hipred: Y
• hipred_score: 0.831
• ghis: 0.556

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.985

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Araf
• Phenotype: growth/size/body region phenotype; endocrine/exocrine gland phenotype; digestive/alimentary phenotype; muscle phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype

Zebrafish Information Network

• Gene name: araf
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: wholly dorsalized

Gene ontology

• 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;negative regulation of apoptotic process
• Cellular component: cellular_component;mitochondrion;cytosol
• Molecular function: protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding;metal ion binding