ARF3

Summary

ARF3 (ARF GTPase 3, HGNC:654) is a protein-coding gene on chromosome 12q13.12, encoding ADP-ribosylation factor 3 (P61204). GTP-binding protein that functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase.

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.

Source: NCBI Gene 377 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 42 total — 5 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 5
• MANE Select transcript: NM_001659

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:654
Approved symbol	ARF3
Name	ARF GTPase 3
Location	12q13.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000134287
Ensembl biotype	protein_coding
OMIM	103190
Entrez	377

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 22 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000256682, ENST00000447318, ENST00000472621, ENST00000485410, ENST00000536283, ENST00000539611, ENST00000541236, ENST00000541959, ENST00000541967, ENST00000545855, ENST00000882659, ENST00000882660, ENST00000882661, ENST00000882662, ENST00000882663, ENST00000882664, ENST00000882665, ENST00000882666, ENST00000882667, ENST00000882668, ENST00000882669, ENST00000927142, ENST00000927143, ENST00000927144, ENST00000948831, ENST00000948832

RefSeq mRNA: 11 — MANE Select: NM_001659 NM_001412914, NM_001412915, NM_001412916, NM_001412918, NM_001412920, NM_001412926, NM_001412928, NM_001412930, NM_001412931, NM_001412932, NM_001659

CCDS: CCDS8774

Canonical transcript exons

ENST00000256682 — 5 exons

Exon	Start	End
ENSE00001060052	48935723	48939108
ENSE00001848536	48957310	48957487
ENSE00003704073	48940948	48941188
ENSE00003705523	48939655	48939779
ENSE00003706828	48939997	48940107

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 99.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 103.1518 / max 1019.1066, expressed in 1827 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130757	91.2821	1827
130756	5.8945	1693
130759	2.4885	1289
130758	2.0710	1146
130754	1.1339	721
130755	0.2817	108

Top tissues by expression

302 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
prefrontal cortex	UBERON:0000451	99.28	gold quality
entorhinal cortex	UBERON:0002728	99.19	gold quality
postcentral gyrus	UBERON:0002581	99.12	gold quality
superior frontal gyrus	UBERON:0002661	99.09	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.09	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.09	gold quality
CA1 field of hippocampus	UBERON:0003881	99.05	gold quality
parietal lobe	UBERON:0001872	99.03	gold quality
frontal pole	UBERON:0002795	99.01	gold quality
frontal cortex	UBERON:0001870	98.97	gold quality
frontal lobe	UBERON:0016525	98.97	gold quality
nucleus accumbens	UBERON:0001882	98.83	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.83	gold quality
neocortex	UBERON:0001950	98.82	gold quality
cingulate cortex	UBERON:0003027	98.81	gold quality
anterior cingulate cortex	UBERON:0009835	98.80	gold quality
middle frontal gyrus	UBERON:0002702	98.79	gold quality
temporal lobe	UBERON:0001871	98.76	gold quality
orbitofrontal cortex	UBERON:0004167	98.76	gold quality
cerebral cortex	UBERON:0000956	98.68	gold quality
cervix squamous epithelium	UBERON:0006922	98.60	gold quality
caudate nucleus	UBERON:0001873	98.57	gold quality
amygdala	UBERON:0001876	98.56	gold quality
middle temporal gyrus	UBERON:0002771	98.56	gold quality
telencephalon	UBERON:0001893	98.55	gold quality
endothelial cell	CL:0000115	98.53	gold quality
islet of Langerhans	UBERON:0000006	98.53	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.49	gold quality
right frontal lobe	UBERON:0002810	98.45	gold quality
putamen	UBERON:0001874	98.44	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

174 targeting ARF3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-27A-3P	99.98	72.13	2955

Literature-anchored findings (GeneRIF, showing 9)

• expression and subcellular redistribution by heregulin (PMID:12135740)
• These results suggest that Arf3 plays a unique function at the trans-Golgi network that likely involves recruitment by a specific receptor. (PMID:20357002)
• ARF1 and ARF3 are redundantly required for the integrity of recycling endosomes (PMID:22971977)
• ARF1+ARF3 are required for integrity of recycling endosomes but are involved in distinct transport pathways: they are required for the transferrin recycling pathway from endosomes to the plasma membrane. (PMID:23783033)
• activated ARF3 is associated with Unc93B1 and TLR9, suggesting that ARF3 conducts TLR9 trafficking by forming the TLR9-Unc93B1-ARF3 complex. (PMID:26067373)
• observations indicate that Arf1 and Arf3 as well as Arf6 play important roles in cytokinesis. (PMID:26330566)
• Upregulation of ARF3 is associated with ovarian cancer. (PMID:28098897)
• Dominant ARF3 variants disrupt Golgi integrity and cause a neurodevelopmental disorder recapitulated in zebrafish. (PMID:36369169)
• The small GTPase ARF3 controls invasion modality and metastasis by regulating N-cadherin levels. (PMID:36880595)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	arf3b	ENSDARG00000036998
danio_rerio	arf3a	ENSDARG00000070539
mus_musculus	Arf3	ENSMUSG00000051853
rattus_norvegicus	Arf3	ENSRNOG00000054775
drosophila_melanogaster	Arf1	FBGN0010348
caenorhabditis_elegans		WBGENE00000182

Paralogs (30): ARF5 (ENSG00000004059), SAR1A (ENSG00000079332), ARFRP1 (ENSG00000101246), TRIM23 (ENSG00000113595), ARL6 (ENSG00000113966), ARL1 (ENSG00000120805), ARL4A (ENSG00000122644), ARL8B (ENSG00000134108), ARL3 (ENSG00000138175), ARL5C (ENSG00000141748), ARF1 (ENSG00000143761), ARL8A (ENSG00000143862), ARL11 (ENSG00000152213), SAR1B (ENSG00000152700), ARL5A (ENSG00000162980), ARF6 (ENSG00000165527), ARL5B (ENSG00000165997), ARF4 (ENSG00000168374), ARL13B (ENSG00000169379), ARL13A (ENSG00000174225), ARL10 (ENSG00000175414), ARL4D (ENSG00000175906), ARL14 (ENSG00000179674), ARL15 (ENSG00000185305), ARL17A (ENSG00000185829), ARL4C (ENSG00000188042), ARL9 (ENSG00000196503), ARL2 (ENSG00000213465), ARL16 (ENSG00000214087), ARL17B (ENSG00000228696)

Protein

Protein identifiers

ADP-ribosylation factor 3 — P61204 (reviewed: P61204)

All UniProt accessions (4): P61204, F5H0C7, F5H1V1, F5H6T5

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Interacts with PRKCABP. Interacts with PI4KB and NCS1/FREQ at the Golgi complex.

Subcellular location. Golgi apparatus. Cytoplasm. Perinuclear region.

Similarity. Belongs to the small GTPase superfamily. Arf family.

Isoforms (2)

UniProt ID	Names	Canonical?
P61204-1	1	yes
P61204-2	2

RefSeq proteins (11): NP_001399843, NP_001399844, NP_001399845, NP_001399847, NP_001399849, NP_001399855, NP_001399857, NP_001399859, NP_001399860, NP_001399861, NP_001650* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005225	Small_GTP-bd	Domain
IPR006689	Small_GTPase_ARF/SAR	Family
IPR024156	Small_GTPase_ARF	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR045872	Arf1-5-like	Family

Pfam: PF00025

UniProt features (21 total): helix 7, strand 6, binding site 3, initiator methionine 1, chain 1, turn 1, lipid moiety-binding region 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6II6	X-RAY DIFFRACTION	2.1
8P50	ELECTRON MICROSCOPY	4.04

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P61204-F1	86.23	0.57

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3): 24–31; 67–71; 126–129

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-1660514	Synthesis of PIPs at the Golgi membrane
R-HSA-6807878	COPI-mediated anterograde transport
R-HSA-6811434	COPI-dependent Golgi-to-ER retrograde traffic
R-HSA-1430728	Metabolism
R-HSA-1483255	PI Metabolism
R-HSA-1483257	Phospholipid metabolism
R-HSA-199977	ER to Golgi Anterograde Transport
R-HSA-199991	Membrane Trafficking
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-556833	Metabolism of lipids
R-HSA-5653656	Vesicle-mediated transport
R-HSA-597592	Post-translational protein modification
R-HSA-6811442	Intra-Golgi and retrograde Golgi-to-ER traffic
R-HSA-8856688	Golgi-to-ER retrograde transport
R-HSA-948021	Transport to the Golgi and subsequent modification

MSigDB gene sets: 280 (showing top): MORF_MTA1, FXR_IR1_Q6, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, TSENG_IRS1_TARGETS_UP, MORF_RAB5A, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, MORF_HDAC1, HSIAO_HOUSEKEEPING_GENES, TGACCTY_ERR1_Q2, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GGGTGGRR_PAX4_03, PATIL_LIVER_CANCER, WANG_ESOPHAGUS_CANCER_VS_NORMAL_DN, MORF_SKP1A

GO Biological Process (4): intracellular protein transport (GO:0006886), retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum (GO:0006890), vesicle-mediated transport (GO:0016192), protein transport (GO:0015031)

GO Molecular Function (4): GTPase activity (GO:0003924), GTP binding (GO:0005525), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (6): Golgi membrane (GO:0000139), cytoplasm (GO:0005737), plasma membrane (GO:0005886), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), Golgi apparatus (GO:0005794)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Membrane Trafficking	2
PI Metabolism	1
ER to Golgi Anterograde Transport	1
Golgi-to-ER retrograde transport	1
Phospholipid metabolism	1
Metabolism of lipids	1
Transport to the Golgi and subsequent modification	1
Vesicle-mediated transport	1
Post-translational protein modification	1
Metabolism	1
Metabolism of proteins	1
Intra-Golgi and retrograde Golgi-to-ER traffic	1
Asparagine N-linked glycosylation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular protein localization	2
transport	2
cellular anatomical structure	2
cytoplasm	2
protein transport	1
intracellular transport	1
Golgi vesicle transport	1
cellular process	1
establishment of protein localization	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
extracellular vesicle	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

55 interactions, top by confidence:

A	B	Type	Score
ARF1	ARFIP2	psi-mi:“MI:0914”(association)	0.620
ARF3	LNX1	psi-mi:“MI:0915”(physical association)	0.560
APP	ARF3	psi-mi:“MI:0915”(physical association)	0.560
ARF5	ARF4	psi-mi:“MI:0914”(association)	0.530
ARF5	ARF3	psi-mi:“MI:0914”(association)	0.530
ARFIP1	ARF3	psi-mi:“MI:0915”(physical association)	0.400
Kif1c	KIF1C	psi-mi:“MI:0915”(physical association)	0.400
Bach1	BACH1	psi-mi:“MI:0915”(physical association)	0.400
Bles03		psi-mi:“MI:0915”(physical association)	0.400
Proser1	ARF3	psi-mi:“MI:0915”(physical association)	0.400
MAF1b1	ARF3	psi-mi:“MI:0915”(physical association)	0.370
ARF3	ARFIP2	psi-mi:“MI:0915”(physical association)	0.370
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
MAPK13	DDX3X	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
FAF2	ERLIN2	psi-mi:“MI:0914”(association)	0.350
TAGLN	LOC392647	psi-mi:“MI:0914”(association)	0.350
CNR2	ILVBL	psi-mi:“MI:0914”(association)	0.350
LOXL2	TUBB	psi-mi:“MI:0914”(association)	0.350
KLF16		psi-mi:“MI:0914”(association)	0.350
	AGPS	psi-mi:“MI:0914”(association)	0.350
ARF3	ARF3	psi-mi:“MI:0914”(association)	0.350
ARF3	ARF4	psi-mi:“MI:0914”(association)	0.350

BioGRID (177): ARF3 (Reconstituted Complex), ARF3 (Affinity Capture-MS), ARF3 (Affinity Capture-MS), GGA1 (Two-hybrid), GGA3 (Two-hybrid), ARF3 (Affinity Capture-MS), ARF3 (Affinity Capture-MS), ARF3 (Affinity Capture-RNA), ARF3 (Affinity Capture-MS), ARF3 (Affinity Capture-MS), ARF3 (Affinity Capture-MS), ARF3 (Affinity Capture-MS), ARF3 (Affinity Capture-MS), ARF3 (Affinity Capture-MS), APBA2 (Two-hybrid)

ESM2 similar proteins: O00909, O23778, O48649, O48920, P0CM16, P0CM17, P0DH91, P11076, P18085, P19146, P22274, P36397, P36579, P49076, P49702, P51643, P51644, P51821, P51822, P51823, P61204, P61205, P61206, P61207, P61750, P61751, P84077, P84078, P84079, P84080, P84081, P84082, P84083, P84084, P84085, P91924, Q06396, Q10943, Q25761, Q3SZF2

Diamond homologs: A1CRG9, A1D4D1, A3LTA2, A5DR82, A5E5G3, A8ISN6, O04266, O04267, O04834, O45379, O48649, O48920, P0C583, P0C950, P0C951, P0CM16, P0CM17, P0CR30, P0CR31, P0CT16, P0CT17, P0DH91, P11076, P18085, P19146, P20606, P22274, P34727, P36397, P36536, P36579, P38116, P40940, P40945, P40994, P49702, P51643, P51821, P51823, P51824

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ARFGEF1	“up-regulates activity”	ARF3	“guanine nucleotide exchange factor”
ARF3	up-regulates	Vesicle_transport

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 66 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
ER to Golgi Anterograde Transport	5	15.8×	1e-03
Golgi-to-ER retrograde transport	5	15.8×	1e-03
Intra-Golgi and retrograde Golgi-to-ER traffic	6	15.0×	4e-04
COPI-dependent Golgi-to-ER retrograde traffic	5	13.2×	2e-03
COPI-mediated anterograde transport	5	13.1×	2e-03
Transport to the Golgi and subsequent modification	5	12.2×	3e-03
Membrane Trafficking	10	8.8×	5e-05
Asparagine N-linked glycosylation	6	8.6×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

42 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	5
Uncertain significance	17
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
1697209	NM_001659.3(ARF3):c.95C>A (p.Thr32Asn)	Pathogenic
1697211	NM_001659.3(ARF3):c.200A>T (p.Asp67Val)	Pathogenic
1697213	NM_001659.3(ARF3):c.379A>G (p.Lys127Glu)	Pathogenic
3244386	NC_000012.11:g.(?49308167)(49375423_?)del	Pathogenic
3378073	NM_001659.3(ARF3):c.55C>T (p.Arg19Cys)	Pathogenic
1697208	NM_001659.3(ARF3):c.34C>G (p.Leu12Val)	Likely pathogenic
3911669	NM_001659.3(ARF3):c.296G>T (p.Arg99Leu)	Likely pathogenic
4277377	NM_001659.3(ARF3):c.179A>T (p.Asn60Ile)	Likely pathogenic
4277378	NM_001659.3(ARF3):c.200A>C (p.Asp67Ala)	Likely pathogenic
4277379	NM_001659.3(ARF3):c.376A>G (p.Asn126Asp)	Likely pathogenic

SpliceAI

994 predictions. Top by Δscore:

Variant	Effect	Δscore
12:48938950:CTT:C	donor_gain	1.0000
12:48938952:T:TA	donor_gain	1.0000
12:48939107:TCC:T	acceptor_loss	1.0000
12:48939110:T:C	acceptor_loss	1.0000
12:48939115:C:CT	acceptor_gain	1.0000
12:48939117:CG:C	acceptor_gain	1.0000
12:48939118:G:C	acceptor_gain	1.0000
12:48939118:G:GC	acceptor_gain	1.0000
12:48939649:TCTCA:T	donor_loss	1.0000
12:48939650:CTCAC:C	donor_loss	1.0000
12:48939651:TCACC:T	donor_loss	1.0000
12:48939652:CAC:C	donor_loss	1.0000
12:48939654:CCT:C	donor_gain	1.0000
12:48939654:CCTG:C	donor_gain	1.0000
12:48939654:CCTGT:C	donor_gain	1.0000
12:48939775:CAACC:C	acceptor_gain	1.0000
12:48939776:AACC:A	acceptor_gain	1.0000
12:48939778:CC:C	acceptor_gain	1.0000
12:48939779:CC:C	acceptor_gain	1.0000
12:48939780:C:CC	acceptor_gain	1.0000
12:48939992:CATA:C	donor_loss	1.0000
12:48939995:A:C	donor_loss	1.0000
12:48939995:ACC:A	donor_loss	1.0000
12:48939996:C:CA	donor_loss	1.0000
12:48940106:CC:C	acceptor_gain	1.0000
12:48940106:CCCTT:C	acceptor_gain	1.0000
12:48940107:CCTT:C	acceptor_gain	1.0000
12:48940108:C:A	acceptor_loss	1.0000
12:48940108:C:CA	acceptor_loss	1.0000
12:48940108:C:CC	acceptor_gain	1.0000

AlphaMissense

1195 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:48938988:C:G	G169R	1.000
12:48939000:C:A	G165W	1.000
12:48939014:G:T	A160D	1.000
12:48939036:A:G	W153R	1.000
12:48939036:A:T	W153R	1.000
12:48939658:T:A	K127N	1.000
12:48939658:T:G	K127N	1.000
12:48939659:T:A	K127I	1.000
12:48939660:T:C	K127E	1.000
12:48939661:G:C	N126K	1.000
12:48939661:G:T	N126K	1.000
12:48939674:A:G	L122P	1.000
12:48939743:C:G	R99P	1.000
12:48939761:T:A	D93V	1.000
12:48939762:C:G	D93H	1.000
12:48939764:A:T	V92D	1.000
12:48939767:A:T	V91E	1.000
12:48939773:A:T	I89K	1.000
12:48939779:C:T	G87E	1.000
12:48939997:C:A	G87W	1.000
12:48940024:A:G	W78R	1.000
12:48940024:A:T	W78R	1.000
12:48940026:A:G	L77P	1.000
12:48940026:A:T	L77H	1.000
12:48940047:C:A	G70V	1.000
12:48940047:C:T	G70D	1.000
12:48940048:C:A	G70C	1.000
12:48940048:C:G	G70R	1.000
12:48940050:C:A	G69V	1.000
12:48940050:C:T	G69D	1.000

dbSNP variants (sampled 300 via entrez): RS1000314829 (12:48940062 A>G), RS1000455117 (12:48953427 A>G), RS1000536951 (12:48945667 G>A), RS1000818505 (12:48945454 G>A), RS1000904211 (12:48958479 G>A), RS1001047939 (12:48938245 T>C), RS1001117665 (12:48951657 G>A), RS1001479031 (12:48938742 C>G,T), RS1001538917 (12:48947376 G>A,C), RS1001648755 (12:48946972 C>G,T), RS1001652270 (12:48939917 G>A,C,T), RS1001669798 (12:48952942 C>A), RS1001729039 (12:48953196 C>T), RS1001766239 (12:48952577 G>A), RS1001818662 (12:48952936 T>A)

Disease associations

OMIM: gene MIM:103190 | disease phenotypes: MIM:209850, MIM:169300, MIM:192100, MIM:147920

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Strong	Autosomal dominant
neurodevelopmental disorder	Strong	Autosomal dominant

Mondo (10): intellectual disability (MONDO:0001071), microcephaly (MONDO:0001149), dystonic disorder (MONDO:0003441), scoliosis (MONDO:0005392), autism (MONDO:0005260), pectus excavatum (MONDO:0008213), bifid uvula (MONDO:0008637), Kabuki syndrome (MONDO:0016512), complex neurodevelopmental disorder (MONDO:0100038), neurodevelopmental disorder (MONDO:0700092)

Orphanet (3): Bifid uvula (Orphanet:99771), Kabuki syndrome (Orphanet:2322), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000252	Microcephaly
HP:0001332	Dystonia
HP:0002650	Scoliosis
HP:0000717	Autism
HP:0000767	Pectus excavatum

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006979_897	Heel bone mineral density	2.000000e-14
GCST008103_109	Bipolar disorder	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D020821	Dystonic Disorders	C10.228.662.300
D005660	Funnel Chest	C05.116.099.386; C05.660.386; C16.131.621.386
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625
D012600	Scoliosis	C05.116.900.800.875
C537705	Kabuki syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression	2
Acetaminophen	increases expression, decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Valproic Acid	affects expression, increases expression	2
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
salinomycin	decreases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
ochratoxin A	affects binding	1
cupric oxide	decreases expression	1
ochratoxin B	affects binding	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Sunitinib	decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Dexamethasone	increases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Ethinyl Estradiol	decreases expression	1
Fluorouracil	affects response to substance	1
Indomethacin	affects cotreatment, increases expression	1
Lead	decreases expression	1
Nickel	increases expression	1
Quercetin	increases expression	1
Thiram	decreases expression	1

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2RY	Abcam HEK293T ARF3 KO	Transformed cell line	Female
CVCL_SD27	HAP1 ARF3 (-) 1	Cancer cell line	Male
CVCL_SD28	HAP1 ARF3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

492 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00142259	PHASE4	UNKNOWN	Efficacy and Safety of DBS of the GPi in Patients With Primary Generalized and Segmental Dystonia
NCT00950196	PHASE4	COMPLETED	Amantadine for Improving Neurologic Symptoms in Ataxia-Telangiectasia
NCT00998660	PHASE4	COMPLETED	RECHARGE Sub-Study to the Implantable Systems Performance Registry (ISPR)
NCT02263417	PHASE4	COMPLETED	A Randomized Controlled Trail Comparing Subthalamic and Pallidal Deep Brain Stimulation for Dystonia
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00169403	PHASE3	UNKNOWN	Pallidal Stimulation in Patients With Idiopathic Generalised Dystonia
NCT03232320	PHASE3	COMPLETED	Meditoxin® Treatment in Patients With Cervical Dystonia
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00001784	PHASE2	COMPLETED	Mexiletine for the Treatment of Focal Dystonia
NCT00105430	PHASE2	COMPLETED	Deep Brain Stimulation for Cervical Dystonia
NCT00106782	PHASE2	COMPLETED	Transcranial Electrical Polarization to Treat Focal Hand Dystonia
NCT00122044	PHASE2	COMPLETED	Childhood Hypertonia of Central Origin: A Trial of Anticholinergic Treatment Effects
NCT00169338	PHASE2	COMPLETED	Pallidal Stimulation in Patients With Post-anoxic and Idiopathic Dystonia
NCT00331669	PHASE2	UNKNOWN	Efficacy and Safety of Deep Brain Stimulation (DBS) of the Pallidal (GPi) in Patients With Tardive Dystonia
NCT02107261	PHASE2	COMPLETED	Incobotulinum Toxin A (Xeomin®) As A Treatment For Focal Task-Specific Dystonia Of The Musician’s Hand
NCT02470325	PHASE2	UNKNOWN	The Effects of Cannabis on Dystonia and Spasticity on Pediatric Patients
NCT05027997	PHASE2	COMPLETED	Exploratory Study of Dipraglurant (ADX48621) for the Treatment of Patients With Blepharospasm
NCT06412653	PHASE2	COMPLETED	Prospective Pilot Trial to Address Feasibility and Safety of Oral Zinc in GNAO1 Associated Disorders
NCT07304089	PHASE2	RECRUITING	A Study to Evaluate the Efficacy, Safety, and Tolerability of VIM0423 in Individuals With Isolated Dystonia
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities