ART3

Summary

ART3 (ADP-ribosyltransferase 3 (inactive), HGNC:725) is a protein-coding gene on chromosome 4q21.1, encoding Ecto-ADP-ribosyltransferase 3 (Q13508).

This gene encodes an arginine-specific ADP-ribosyltransferase. The encoded protein catalyzes a reversible reaction which modifies proteins by the addition or removal of ADP-ribose to an arginine residue to regulate the function of the modified protein. An ADP-ribosyltransferase pseudogene is located on chromosome 11. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 419 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 133 total — 1 pathogenic
• MANE Select transcript: NM_001130016

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:725
Approved symbol	ART3
Name	ADP-ribosyltransferase 3 (inactive)
Location	4q21.1
Locus type	gene with protein product
Status	Approved
Aliases	ARTC3
Ensembl gene	ENSG00000156219
Ensembl biotype	protein_coding
OMIM	603086
Entrez	419

Gene structure

Transcript identifiers

Ensembl transcripts: 47 — 40 protein_coding, 6 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000341029, ENST00000349321, ENST00000355810, ENST00000395688, ENST00000504112, ENST00000504914, ENST00000506313, ENST00000506667, ENST00000510423, ENST00000510669, ENST00000510863, ENST00000511188, ENST00000513122, ENST00000513353, ENST00000513494, ENST00000700440, ENST00000700441, ENST00000883925, ENST00000883926, ENST00000883927, ENST00000883928, ENST00000883929, ENST00000883930, ENST00000883931, ENST00000883932, ENST00000930906, ENST00000960237, ENST00000960238, ENST00000960239, ENST00000960240, ENST00000960241, ENST00000960242, ENST00000960243, ENST00000960244, ENST00000960245, ENST00000960246, ENST00000960247, ENST00000960248, ENST00000960249, ENST00000960250, ENST00000960251, ENST00000960252, ENST00000960253, ENST00000960254, ENST00000960255, ENST00000960256, ENST00000960257

RefSeq mRNA: 16 — MANE Select: NM_001130016 NM_001130016, NM_001130017, NM_001179, NM_001377173, NM_001377174, NM_001377175, NM_001377176, NM_001377177, NM_001377178, NM_001377179, NM_001377180, NM_001377181, NM_001377182, NM_001377183, NM_001377184, NM_001377185

CCDS: CCDS3575, CCDS47079, CCDS47080, CCDS93546

Canonical transcript exons

ENST00000355810 — 12 exons

Exon	Start	End
ENSE00003459278	76100795	76100824
ENSE00003471687	76097644	76097676
ENSE00003500894	76107761	76107793
ENSE00003541826	76100291	76100320
ENSE00003564182	76104597	76104629
ENSE00003574788	76100990	76101019
ENSE00003627369	76081824	76082535
ENSE00003632224	76103937	76103969
ENSE00003641892	76098955	76098987
ENSE00003661772	76075881	76075958
ENSE00003899244	76112386	76112786
ENSE00003904111	76074709	76074819

Expression profiles

Bgee: expression breadth ubiquitous, 199 present calls, max score 98.60.

FANTOM5 (CAGE): breadth broad, TPM avg 3.0637 / max 349.4972, expressed in 190 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
48320	2.5570	177
48311	0.2296	6
48319	0.1793	71
48312	0.0977	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	98.60	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.54	gold quality
biceps brachii	UBERON:0001507	98.28	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.14	gold quality
vastus lateralis	UBERON:0001379	98.10	gold quality
quadriceps femoris	UBERON:0001377	98.00	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.60	gold quality
right testis	UBERON:0004534	97.59	gold quality
muscle organ	UBERON:0001630	97.51	gold quality
muscle of leg	UBERON:0001383	97.40	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.40	gold quality
skeletal muscle tissue	UBERON:0001134	97.39	gold quality
left testis	UBERON:0004533	97.34	gold quality
diaphragm	UBERON:0001103	97.28	gold quality
apex of heart	UBERON:0002098	96.80	gold quality
myocardium	UBERON:0002349	96.65	gold quality
left ventricle myocardium	UBERON:0006566	96.62	gold quality
heart left ventricle	UBERON:0002084	96.46	gold quality
tibialis anterior	UBERON:0001385	96.41	gold quality
deltoid	UBERON:0001476	96.30	silver quality
cardiac ventricle	UBERON:0002082	96.29	gold quality
heart right ventricle	UBERON:0002080	96.10	gold quality
right atrium auricular region	UBERON:0006631	95.84	gold quality
cardiac atrium	UBERON:0002081	95.58	gold quality
muscle tissue	UBERON:0002385	94.58	gold quality
testis	UBERON:0000473	94.56	gold quality
triceps brachii	UBERON:0001509	93.99	gold quality
gluteal muscle	UBERON:0002000	93.02	gold quality
heart	UBERON:0000948	92.69	gold quality
tibial nerve	UBERON:0001323	92.59	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.48

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR3C1

miRNA regulators (miRDB)

42 targeting ART3, 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-3646	100.00	73.56	5283
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548AW	99.99	72.57	3559
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-422A	99.18	65.83	550
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-548S	98.50	67.17	1213
HSA-MIR-378A-3P	98.43	66.10	548

Literature-anchored findings (GeneRIF, showing 4)

• ART3 protein is expressed in testes in particular on spermatocytes, indicating that ART3 exerts a specific function only required at a particular stage of spermatogenesis. (PMID:16625277)
• ART3 expression appears to be governed by a combination of differential splicing and tissue-preferential use of two alternative promoters. (PMID:16934346)
• genome-wide gene expression analyses were used to identify genes involved in the pathogenesis of non-obstructive azoospermia, and ART3 was subsequently identified as a susceptibility gene (PMID:18266473)
• knockdown of ART3 in breast cancer cells inhibited cell proliferation and invasion. (PMID:27374177)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-145b13.6	ENSDARG00000069998
mus_musculus	Art3	ENSMUSG00000034842
rattus_norvegicus	Art3	ENSRNOG00000002256

Paralogs (3): ART4 (ENSG00000111339), ART1 (ENSG00000129744), ART5 (ENSG00000167311)

Protein

Protein identifiers

Ecto-ADP-ribosyltransferase 3 — Q13508 (reviewed: Q13508)

Alternative names: ADP-ribosyltransferase C2 and C3 toxin-like 3, Mono(ADP-ribosyl)transferase 3, NAD(P)(+)–arginine ADP-ribosyltransferase 3

All UniProt accessions (8): Q13508, A0A8V8TPP7, A0A8V8TQ78, E7ER42, E7ESB3, E7EX61, E9PGR5, H0Y8V6

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cell membrane.

Tissue specificity. Testis specific.

Post-translational modifications. O-glycosylated with core 1 or possibly core 8 glycans.

Similarity. Belongs to the Arg-specific ADP-ribosyltransferase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q13508-1	3	yes
Q13508-2	1
Q13508-3	2

RefSeq proteins (16): NP_001123488, NP_001123489, NP_001170, NP_001364102, NP_001364103, NP_001364104, NP_001364105, NP_001364106, NP_001364107, NP_001364108, NP_001364109, NP_001364110, NP_001364111, NP_001364112, NP_001364113, NP_001364114 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000768	ART	Family
IPR050999	ADP-ribosyltransferase_ARG	Family

Pfam: PF01129

Catalyzed reactions (Rhea), 1 shown:

• L-arginyl-[protein] + NAD(+) = N(omega)-(ADP-D-ribosyl)-L-arginyl-[protein] + nicotinamide + H(+) (RHEA:19149)

UniProt features (21 total): repeat 3, binding site 2, glycosylation site 2, splice variant 2, sequence variant 2, region of interest 2, signal peptide 1, chain 1, lipid moiety-binding region 1, disulfide bond 1, propeptide 1, sequence conflict 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13508-F1	74.56	0.50

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 (2): 101; 163

Post-translational modifications (1): 362

Disulfide bonds (1): 43–256

Glycosylation sites (2): 248, 346

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-163125	Post-translational modification: synthesis of GPI-anchored proteins
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 149 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, MODULE_255, MODULE_64, MODULE_317, MARTINEZ_RB1_TARGETS_UP, MORF_ZNF10, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, MCBRYAN_PUBERTAL_BREAST_5_6WK_UP, TSENG_IRS1_TARGETS_DN, MORF_EPHA7, MORF_RAB3A, MORF_BMPR2, SMID_BREAST_CANCER_RELAPSE_IN_BRAIN_UP, MORF_WNT1, CUI_TCF21_TARGETS_2_DN

GO Biological Process (0):

GO Molecular Function (5): NAD+ poly-ADP-ribosyltransferase activity (GO:0003950), nucleotidyltransferase activity (GO:0016779), NAD+-protein-arginine ADP-ribosyltransferase activity (GO:0106274), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (5): extracellular region (GO:0005576), plasma membrane (GO:0005886), extracellular exosome (GO:0070062), side of membrane (GO:0098552), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
membrane	2
pentosyltransferase activity	1
transferase activity, transferring phosphorus-containing groups	1
NAD+-protein mono-ADP-ribosyltransferase activity	1
catalytic activity	1
transferase activity	1
cell periphery	1
extracellular vesicle	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

1445 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ART3	SEPTIN4	O43236	863
ART3	PARG	Q86W56	796
ART3	MEAK7	Q6P9B6	447
ART3	CXCL11	O14625	443
ART3	CXCL10	P02778	425
ART3	GALNT18	Q6P9A2	390
ART3	DNALI1	O14645	387
ART3	MAP3K7CL	P57077	386
ART3	ART4	Q93070	381
ART3	GOLGA7B	Q2TAP0	372
ART3	CCDC182	A6NF36	370
ART3	DYNC2LI1	Q8TCX1	362
ART3	ACTN3	Q08043	360
ART3	IFT172	Q9UG01	353
ART3	BBS5	Q8N3I7	353
ART3	IFT122	Q9HBG6	353
ART3	POLR2G	P52433	353

IntAct

6 interactions, top by confidence:

A	B	Type	Score
ART3	ALCAM	psi-mi:“MI:0915”(physical association)	0.370
TEX101	PSMD12	psi-mi:“MI:0914”(association)	0.350
TEX101	NDUFA4	psi-mi:“MI:0914”(association)	0.350
TEX101	ITGB1	psi-mi:“MI:0914”(association)	0.350
ART3	NCF1	psi-mi:“MI:0914”(association)	0.350

BioGRID (43): MDN1 (Affinity Capture-MS), ATP12A (Affinity Capture-MS), PIGO (Affinity Capture-MS), RAB39B (Affinity Capture-MS), DDX19B (Affinity Capture-MS), CHD1L (Affinity Capture-MS), DYNC2LI1 (Affinity Capture-MS), PAM (Affinity Capture-MS), NAGLU (Affinity Capture-MS), ARSK (Affinity Capture-MS), HSPA12A (Affinity Capture-MS), GPD1L (Affinity Capture-MS), ITGA7 (Affinity Capture-MS), MGAT5 (Affinity Capture-MS), CBWD3 (Affinity Capture-MS)

ESM2 similar proteins: D0G895, O15466, O35227, O35696, O35975, O43173, O73746, O73798, P16368, P17981, P17982, P20974, P23613, P35625, P38566, P38567, P38568, P39876, P48032, P48794, P61269, P61643, P61644, P61646, P61647, P61648, P70126, P79121, Q07977, Q0VC22, Q13508, Q3TT99, Q5PXZ9, Q62803, Q63180, Q64663, Q64689, Q64692, Q6W3E5, Q6ZXC8

Diamond homologs: O35975, P17981, P17982, P20974, P52961, P55806, P55807, P70352, Q03515, Q0VC22, Q13508, Q5XHY4, Q60935, Q8R2G4, Q92080, Q93070, Q95NE0, Q96L15, Q9CRA0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	99
Likely benign	7
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1456083	NC_000004.11:g.(?76481293)(77700330_?)del	Pathogenic

SpliceAI

2063 predictions. Top by Δscore:

Variant	Effect	Δscore
4:76022361:CCTA:C	donor_loss	1.0000
4:76022365:C:CG	donor_loss	1.0000
4:76022369:T:A	donor_gain	1.0000
4:76022451:TAGCA:T	acceptor_gain	1.0000
4:76022452:AGCA:A	acceptor_gain	1.0000
4:76022453:GCA:G	acceptor_gain	1.0000
4:76022453:GCAC:G	acceptor_loss	1.0000
4:76022454:CA:C	acceptor_gain	1.0000
4:76022454:CAC:C	acceptor_gain	1.0000
4:76022456:C:CC	acceptor_gain	1.0000
4:76022456:C:CG	acceptor_loss	1.0000
4:76022457:T:C	acceptor_loss	1.0000
4:76022458:G:C	acceptor_gain	1.0000
4:76022458:G:GC	acceptor_gain	1.0000
4:76022464:A:AC	acceptor_gain	1.0000
4:76022464:A:C	acceptor_gain	1.0000
4:76022685:ACTC:A	donor_loss	1.0000
4:76022687:TCA:T	donor_loss	1.0000
4:76022688:CA:C	donor_loss	1.0000
4:76022689:A:AC	donor_gain	1.0000
4:76022689:ACA:A	donor_loss	1.0000
4:76022690:C:CC	donor_gain	1.0000
4:76022813:TACTC:T	acceptor_gain	1.0000
4:76022815:CTC:C	acceptor_gain	1.0000
4:76022816:TC:T	acceptor_gain	1.0000
4:76022816:TCCTG:T	acceptor_loss	1.0000
4:76022817:CC:C	acceptor_gain	1.0000
4:76022817:CCTGT:C	acceptor_loss	1.0000
4:76022818:C:CA	acceptor_loss	1.0000
4:76022818:C:CC	acceptor_gain	1.0000

AlphaMissense

2592 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:76082520:T:A	C256S	0.994
4:76082521:G:C	C256S	0.994
4:76081881:T:A	C43S	0.993
4:76081882:G:C	C43S	0.993
4:76082151:T:C	F133L	0.992
4:76082153:C:A	F133L	0.992
4:76082153:C:G	F133L	0.992
4:76082520:T:C	C256R	0.991
4:76081881:T:C	C43R	0.990
4:76082162:A:C	K136N	0.988
4:76082162:A:T	K136N	0.988
4:76081860:T:C	F36L	0.987
4:76081862:T:A	F36L	0.987
4:76081862:T:G	F36L	0.987
4:76081964:G:C	W70C	0.987
4:76081964:G:T	W70C	0.987
4:76082172:T:C	F140L	0.987
4:76082174:T:A	F140L	0.987
4:76082174:T:G	F140L	0.987
4:76082179:T:C	L142P	0.986
4:76082446:T:G	F231C	0.986
4:76082445:T:C	F231L	0.985
4:76082447:T:A	F231L	0.985
4:76082447:T:G	F231L	0.985
4:76082044:C:A	A97D	0.984
4:76082047:T:C	L98P	0.984
4:76082522:T:G	C256W	0.984
4:76081872:T:C	Y40H	0.983
4:76082052:G:C	A100P	0.983
4:76081985:G:C	W77C	0.982

dbSNP variants (sampled 300 via entrez): RS1000003317 (4:76074667 T>A), RS10000130 (4:76018182 T>C), RS1000024629 (4:76107988 A>G), RS1000042782 (4:76028868 T>G), RS10000436 (4:76018491 T>A,C), RS1000044955 (4:76068541 T>C), RS1000059348 (4:76068808 A>C), RS1000103946 (4:76029328 G>A,T), RS1000137559 (4:76036210 T>C), RS1000175389 (4:76012708 A>G), RS10001988 (4:76046788 G>A,T), RS1000202610 (4:76082623 G>A,T), RS1000209865 (4:76090530 G>A,T), RS10002099 (4:76046876 G>A,C,T), RS10002214 (4:76047012 G>A,C,T)

Disease associations

OMIM: gene MIM:603086 | disease phenotypes: MIM:254800

GenCC curated gene-disease

Mondo (1): progressive myoclonus epilepsy (MONDO:0020074)

Orphanet (2): Progressive myoclonic epilepsy type 1 (Orphanet:308), Progressive myoclonic epilepsy (Orphanet:98261)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST006585_1311	Blood protein levels	3.000000e-18
GCST006585_588	Blood protein levels	5.000000e-21
GCST007009_3	Hippocampal volume	7.000000e-07
GCST007009_4	Hippocampal volume	3.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005035	hippocampal volume

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D020191	Myoclonic Epilepsies, Progressive	C10.228.140.490.375.130.650; C10.228.140.490.493.063.650

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs56061981	ART3, CXCL10	3	2.75	1	peginterferon alfa-2a;peginterferon alfa-2b

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, increases expression	2
Progesterone	affects cotreatment, increases expression	2
Valproic Acid	affects expression, decreases methylation	2
methyleugenol	decreases expression	1
sodium arsenite	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
(+)-JQ1 compound	decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Doxorubicin	decreases expression	1
Sodium Dodecyl Sulfate	increases expression	1
Tretinoin	decreases expression	1
Triclosan	decreases expression	1
Cyclosporine	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06593951	Not specified	RECRUITING	Registry and Natural History Study for Progressive Myoclonus Epilepsy Type 1 (EPM1)
NCT06923241	Not specified	COMPLETED	Nutri-score Labelling in a UK Restaurant Setting: a Randomised Control Trial