ARF6

protein-coding

ADP ribosylation factor 6, the group of ARF GTPase family

Gene summary

This gene encodes a member of the human ARF gene family, which is part of the RAS superfamily. The ARF genes encode small guanine nucleotide-binding proteins that stimulate the ADP-ribosyltransferase activity of cholera toxin and play a role in vesicular trafficking and as activators of phospholipase D. The product of this gene is localized to the plasma membrane, and regulates vesicular trafficking, remodelling of membrane lipids, and signaling pathways that lead to actin remodeling. A pseudogene of this gene is located on chromosome 7. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001663.4

Inheritance

—

ClinVar variants

U:6B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr14:49,893,079-49,897,054

External References & Databases

Ensembl (ENSG00000165527)

Transcript & Mutation Effects

hg38 • Region Span ~4.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ARF6 variants in ClinVar

2 Conditions Cataloged

not providedTotal: 4

not specifiedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001663.4. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous					2 clinvar	2
missense			6 clinvar			6
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	6	0	2	8

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001663.4	RefSeq	NP_001654.1	1	MANE Select
ENST00000298316.7	Ensembl	ENSP00000298316.5	1	MANE Select
ENST00000692608.1	Ensembl	ENSP00000510807.1	1	Standard
ENST00000692608.2	Ensembl	ENSP00000510807.1	1	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
arf6b	Danio rerio	Structure: intrahepatic bile duct Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

arf6b

Danio rerio

Structure: intrahepatic bile duct

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Fc gamma R-mediated phagocytosis - Homo sapiens (human)
Endocytosis - Homo sapiens (human)
Ras signaling pathway - Homo sapiens (human)
Phospholipase D signaling pathway - Homo sapiens (human)
Integrated Lung Cancer Pathway

Biological Process

liver development
intracellular protein transport
cell cycle
cell adhesion
vesicle-mediated transport

Molecular Function

GTPase activity
protein binding
GTP binding
thioesterase binding
protein N-terminus binding

Cellular Component

ruffle
cytoplasm
endosome
early endosome
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000298316
Coding exons: 1
Length: 1681
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.78	23	102	0.226	0.00000462	1142
Missense (PolyPhen)		7	47.258	0.14812		534
Synonymous	-2.05	60	42.9	1.40	0.00000201	355
Loss of Function	1.89	0	4.14	0.00	1.79e-7	50

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: GTP-binding protein involved in protein trafficking that regulates endocytic recycling and cytoskeleton remodeling (PubMed:11266366, PubMed:21170023, PubMed:16737952, PubMed:7589240, PubMed:18400762). Required for normal completion of mitotic cytokinesis (By similarity). Plays a role in the reorganization of the actin cytoskeleton and the formation of stress fibers (By similarity). Involved in the regulation of dendritic spine development, contributing to the regulation of dendritic branching and filopodia extension (PubMed:14978216). Plays an important role in membrane trafficking, during junctional remodeling and epithelial polarization. Regulates surface levels of adherens junction proteins such as CDH1 (By similarity). {ECO:0000250|UniProtKB:P62331, ECO:0000269|PubMed:11266366, ECO:0000269|PubMed:14978216, ECO:0000269|PubMed:16099990, ECO:0000269|PubMed:16737952, ECO:0000269|PubMed:18400762, ECO:0000269|PubMed:21170023, ECO:0000269|PubMed:7589240}.;

Recessive Scores

pRec: 0.413

Intolerance Scores

RVIS EVS: -0.14
RVIS percentile EVS: 42.88

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.782