ARF4

protein-coding

ADP ribosylation factor 4, the group of ARF GTPase family

Gene summary

This gene is a member of the human ARF gene family whose members 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 gene products include 5 ARF proteins and 11 ARF-like proteins and constitute one family of the RAS superfamily. The ARF proteins are categorized as class I, class II and class III; this gene is a class II member. The members of each class share a common gene organization. The ARF4 gene spans approximately 12kb and contains six exons and five introns. This gene is the most divergent member of the human ARFs. Conflicting map positions at 3p14 or 3p21 have been reported for this gene. [provided by RefSeq, Jul 2008]

Previous symbols:

ARF2

MANE transcript

NM_001660.4

Inheritance

—

ClinVar variants

U:9

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr3:57,571,363-57,598,220

External References & Databases

Ensembl (ENSG00000168374)

Transcript & Mutation Effects

hg38 • Region Span ~26.9 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 ARF4 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001660.4. 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						0
missense			9 clinvar			9
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	9	0	0	9

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001660.4	RefSeq	NP_001651.1	6	MANE Select
ENST00000303436.11	Ensembl	ENSP00000306010.6	6	MANE Select
ENST00000463880.1	Ensembl	ENSP00000420254.1	5	Standard
ENST00000486310.5	Ensembl	ENSP00000420655.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

miR-targeted genes in epithelium - TarBase
miR-targeted genes in leukocytes - TarBase
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in muscle cell - TarBase
miR-targeted genes in squamous cell - TarBase

Biological Process

protein ADP-ribosylation
intracellular protein transport
endoplasmic reticulum to Golgi vesicle-mediated transport
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum
Golgi to plasma membrane transport

Molecular Function

GTPase activity
ARF guanyl-nucleotide exchange factor activity
epidermal growth factor receptor binding
protein binding
GTP binding

Cellular Component

cytoplasm
Golgi apparatus
cytosol
plasma membrane
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000303436
Coding exons: 6
Length: 26858
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	2.11	38	96.1	0.395	0.00000462	1175
Missense (PolyPhen)		5	34.67	0.14422		470
Synonymous	0.276	31	33.0	0.939	0.00000151	345
Loss of Function	2.94	0	10.0	0.00	4.29e-7	119

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 that functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP- ribosyltransferase. Involved in protein trafficking; may modulate vesicle budding and uncoating within the Golgi apparatus.;

Recessive Scores

pRec: 0.363

Intolerance Scores

RVIS EVS: 0.06
RVIS percentile EVS: 58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.955