ARF3

protein-coding

ADP ribosylation factor 3, the group of ARF GTPase family

Gene summary

ADP-ribosylation factor 3 (ARF3) is a member of the human ARF gene family. These 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 gene products include 6 ARF proteins and 11 ARF-like proteins and constitute one family of the RAS superfamily. The ARF proteins are categorized as class I (ARF1, ARF2,and ARF3), class II (ARF4 and ARF5) and class III (ARF6) and members of each class share a common gene organization. [provided by RefSeq, Oct 2022]

MANE transcript

NM_001659.3

Inheritance

ClinVar variants

P:11U:22

Top phenotype

complex neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr12:48,935,723-48,957,487

External References & Databases

Ensembl (ENSG00000134287)

Transcript & Mutation Effects

hg38 • Region Span ~21.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: G2P

complex neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ARF3 variants in ClinVar

27 Conditions Cataloged

not providedTotal: 14

Inborn genetic diseasesTotal: 8

Intellectual disabilityTotal: 6

Atrophy/Degeneration affecting the central nervous systemTotal: 6

ARF3-related disorderTotal: 5

MicrocephalyTotal: 4

ScoliosisTotal: 3

HypotoniaTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001659.3. 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	4 clinvar	7 clinvar	17 clinvar			28
nonsense						0
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	4	7	22	0	0	33

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 55 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001659.3	RefSeq	NP_001650.1	4	MANE Select
ENST00000256682.9	Ensembl	ENSP00000256682.4	4	MANE Select
NM_001412914.1	RefSeq	NP_001399843.1	4	Standard
NM_001412915.1	RefSeq	NP_001399844.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endocytosis - Homo sapiens (human)
Vesicle-mediated transport
Membrane Trafficking
Metabolism of lipids
Post-translational protein modification

Biological Process

phosphatidylinositol biosynthetic process
intracellular protein transport
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum
Golgi to plasma membrane transport
vesicle-mediated transport

Molecular Function

GTPase activity
GTP binding

Cellular Component

Golgi membrane
cytoplasm
Golgi apparatus
plasma membrane
perinuclear region of cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000256682
Coding exons: 4
Length: 21829
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125740
p: 0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.82	28	112	0.250	0.00000664	1193
Missense (PolyPhen)		3	30.769	0.097499		381
Synonymous	1.19	34	44.1	0.771	0.00000269	351
Loss of Function	2.12	2	8.79	0.227	5.25e-7	87

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)	0.000018	0.000018	rare
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.;

Intolerance Scores

LoFtool: 0.297
RVIS EVS: -0.03
RVIS percentile EVS: 51.04

Essentials

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