ART4

Summary

ART4 (ADP-ribosyltransferase 4 (inactive) (Dombrock blood group), HGNC:726) is a protein-coding gene on chromosome 12p12.3, encoding Ecto-ADP-ribosyltransferase 4 (Q93070).

This gene encodes a protein that contains a mono-ADP-ribosylation (ART) motif. It is a member of the ADP-ribosyltransferase gene family but enzymatic activity has not been demonstrated experimentally. Antigens of the Dombrock blood group system are located on the gene product, which is glycosylphosphatidylinosotol-anchored to the erythrocyte membrane. Allelic variants, some of which lead to adverse transfusion reactions, are known.

Source: NCBI Gene 420 — RefSeq curated summary.

At a glance

• Gene–disease (curated): age related macular degeneration 8 (Moderate, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_021071

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:726
Approved symbol	ART4
Name	ADP-ribosyltransferase 4 (inactive) (Dombrock blood group)
Location	12p12.3
Locus type	gene with protein product
Status	Approved
Aliases	DOK1, CD297, ARTC4
Ensembl gene	ENSG00000111339
Ensembl biotype	protein_coding
OMIM	110600
Entrez	420

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000228936, ENST00000420600, ENST00000430129, ENST00000544616

RefSeq mRNA: 2 — MANE Select: NM_021071 NM_001354646, NM_021071

CCDS: CCDS8668

Canonical transcript exons

ENST00000228936 — 3 exons

Exon	Start	End
ENSE00000723031	14840445	14841153
ENSE00000915534	14842970	14843526
ENSE00001603649	14825569	14829462

Expression profiles

Bgee: expression breadth ubiquitous, 161 present calls, max score 84.96.

FANTOM5 (CAGE): breadth broad, TPM avg 1.8424 / max 192.7353, expressed in 332 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129856	1.1344	305
129857	0.6288	214
129858	0.0792	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
liver	UBERON:0002107	84.96	gold quality
right lobe of liver	UBERON:0001114	84.38	gold quality
right coronary artery	UBERON:0001625	82.75	gold quality
right atrium auricular region	UBERON:0006631	80.73	gold quality
thoracic aorta	UBERON:0001515	80.49	gold quality
ascending aorta	UBERON:0001496	80.28	gold quality
gall bladder	UBERON:0002110	80.23	gold quality
cardiac atrium	UBERON:0002081	79.95	gold quality
descending thoracic aorta	UBERON:0002345	79.18	gold quality
left coronary artery	UBERON:0001626	78.78	gold quality
trabecular bone tissue	UBERON:0002483	78.69	gold quality
spleen	UBERON:0002106	78.10	gold quality
lymph node	UBERON:0000029	78.00	gold quality
coronary artery	UBERON:0001621	77.83	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.08	gold quality
aorta	UBERON:0000947	76.35	gold quality
diaphragm	UBERON:0001103	75.39	gold quality
cardiac muscle of right atrium	UBERON:0003379	73.90	silver quality
popliteal artery	UBERON:0002250	73.53	gold quality
tibial artery	UBERON:0007610	73.53	gold quality
saphenous vein	UBERON:0007318	72.38	gold quality
heart	UBERON:0000948	72.18	gold quality
bone marrow	UBERON:0002371	71.87	gold quality
right lobe of thyroid gland	UBERON:0001119	70.68	gold quality
left ventricle myocardium	UBERON:0006566	70.39	gold quality
left lobe of thyroid gland	UBERON:0001120	70.10	gold quality
thyroid gland	UBERON:0002046	69.87	gold quality
right adrenal gland cortex	UBERON:0035827	68.86	gold quality
apex of heart	UBERON:0002098	68.65	gold quality
omental fat pad	UBERON:0010414	68.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.07

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 7)

• Expression of ART4 was analyzed in mononuclear leukocytes. (PMID:16140404)
• Dombrock genotyping in a native Congolese cohort reveals two novel alleles. (PMID:19413734)
• The Dombrock blood group system (PMID:20932078)
• The production, serologic evaluation, and epitope mapping of ten murine monoclonal Dombrock antibodies. (PMID:23421541)
• Characterization of two novel DO*B alleles highlights the value of testing selected ethnic groups in understanding DO allele diversity. (PMID:25988428)
• A novel variant DO*A allele with a c.370delT mutation leading to a DO-null phenotype in a Syrian family. (PMID:33206405)
• Development of DO*A and DO*B Allele Detections to Predict Transfusion-Induced Alloimmunization Risks in Thai Populations. (PMID:34655192)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-145b13.6	ENSDARG00000069998
mus_musculus	Art4	ENSMUSG00000030217
rattus_norvegicus	Art4	ENSRNOG00000005670

Paralogs (3): ART1 (ENSG00000129744), ART3 (ENSG00000156219), ART5 (ENSG00000167311)

Protein

Protein identifiers

Ecto-ADP-ribosyltransferase 4 — Q93070 (reviewed: Q93070)

Alternative names: ADP-ribosyltransferase C2 and C3 toxin-like 4, Dombrock blood group carrier molecule, Mono(ADP-ribosyl)transferase 4, NAD(P)(+)–arginine ADP-ribosyltransferase 4

All UniProt accessions (4): Q93070, H7C2G2, Q3KZ29, Q3KZ30

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cell membrane.

Tissue specificity. Expressed in spleen and T-cells.

Polymorphism. Variations in the ART4 gene are the basis of the Dombrock blood group system (Do). ART4 carries two antithetical antigens (Do(a) and Do(b)) and 3 high-incidence antigens, Gregory (Gy(a)), Holley (Hy), and Joseph (Jo(a)). Do(a) and Do(b) differ by a single variation at position 265, with Asn-265 corresponding to Do(a) and Asp-265 (shown in this entry) to Do(b).

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

RefSeq proteins (2): NP_001341575, NP_066549* (*=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 (23 total): sequence variant 6, glycosylation site 5, binding site 3, disulfide bond 2, sequence conflict 2, signal peptide 1, chain 1, propeptide 1, domain 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q93070-F1	81.00	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): 126; 206; 240

Post-translational modifications (1): 285

Disulfide bonds (2): 69–280, 182–231

Glycosylation sites (5): 222, 257, 274, 114, 178

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: 329 (showing top): PID_BCR_5PATHWAY, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, MORF_RAGE, GGGACCA_MIR133A_MIR133B, DAVIES_MULTIPLE_MYELOMA_VS_MGUS_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_RESPONSE_TO_PEPTIDE, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, MODULE_45, MORF_ATRX, RIZKI_TUMOR_INVASIVENESS_3D_DN, MORF_ESR1, MODULE_16, BROWNE_HCMV_INFECTION_48HR_DN, MODULE_120

GO Biological Process (1): arginine metabolic process (GO:0006525)

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 (4): extracellular region (GO:0005576), plasma membrane (GO:0005886), 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
amino acid metabolic process	1
carboxylic acid metabolic process	1
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
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

280 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ART4	PCYOX1	Q9UHG3	443
ART4	PDCD1	Q15116	389
ART4	ART3	Q13508	381
ART4	PARP15	Q460N3	342
ART4	PARP12	Q9H0J9	330
ART4	PARP8	Q8N3A8	313
ART4	HPF1	Q9NWY4	305
ART4	QPRT	Q15274	304
ART4	CELSR2	Q9HCU4	296
ART4	PARP14	Q460N5	295
ART4	PNPT1	Q8TCS8	294
ART4	ZC3HAV1	Q7Z2W4	263
ART4	BCAM	P50895	248
ART4	BOLA2	Q9H3K6	245
ART4	ART1	P52961	237

IntAct

4 interactions, top by confidence:

A	B	Type	Score
TNFAIP3	KIF5C	psi-mi:“MI:0914”(association)	0.350
ART4	GPAA1	psi-mi:“MI:0914”(association)	0.350
TMEM231	FHL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (17): ART4 (Affinity Capture-MS), GPAA1 (Affinity Capture-MS), GPM6A (Affinity Capture-MS), CANX (Affinity Capture-MS), PKD2 (Affinity Capture-MS), PIGS (Affinity Capture-MS), PIGU (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), TMX1 (Affinity Capture-MS), ART4 (Proximity Label-MS), ART4 (Affinity Capture-MS), ART4 (Protein-RNA), ART4 (Affinity Capture-MS), ART4 (Affinity Capture-MS), ART4 (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

246 predictions. Top by Δscore:

Variant	Effect	Δscore
12:14840567:T:TA	donor_gain	1.0000
12:14841154:C:CC	acceptor_gain	0.9900
12:14841154:CT:C	acceptor_loss	0.9900
12:14841155:T:A	acceptor_loss	0.9900
12:14842964:CCCTA:C	donor_loss	0.9900
12:14842965:CCTA:C	donor_loss	0.9900
12:14842966:CTAC:C	donor_loss	0.9900
12:14842967:TAC:T	donor_loss	0.9900
12:14842971:TCAGA:T	donor_gain	0.9900
12:14841150:CAAC:C	acceptor_gain	0.9800
12:14842973:AGAAC:A	donor_gain	0.9800
12:14829376:CT:C	donor_gain	0.9700
12:14841149:GCAAC:G	acceptor_gain	0.9700
12:14841150:CAACC:C	acceptor_gain	0.9700
12:14829376:CTCTG:C	donor_gain	0.9600
12:14841152:AC:A	acceptor_gain	0.9600
12:14841153:CC:C	acceptor_gain	0.9600
12:14840568:C:A	donor_gain	0.9500
12:14841151:AAC:A	acceptor_gain	0.9500
12:14841075:CCATA:C	donor_gain	0.9400
12:14841156:G:GC	acceptor_gain	0.9400
12:14839291:A:T	donor_gain	0.9300
12:14841012:T:TA	donor_gain	0.9300
12:14843086:T:TA	donor_gain	0.9100
12:14840588:TG:T	donor_gain	0.9000
12:14841078:TA:T	donor_gain	0.9000
12:14841079:AA:A	donor_gain	0.9000
12:14842969:CCTCA:C	donor_gain	0.9000
12:14843050:T:C	donor_gain	0.8900
12:14842972:CAGA:C	donor_gain	0.8700

AlphaMissense

2070 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:14840677:G:C	F207L	0.964
12:14840677:G:T	F207L	0.964
12:14840679:A:G	F207L	0.964
12:14840802:C:G	A166P	0.958
12:14840836:G:C	F154L	0.955
12:14840836:G:T	F154L	0.955
12:14840838:A:G	F154L	0.955
12:14840539:A:C	F253L	0.946
12:14840539:A:T	F253L	0.946
12:14840541:A:G	F253L	0.946
12:14841112:A:C	F62L	0.940
12:14841112:A:T	F62L	0.940
12:14841114:A:G	F62L	0.940
12:14840678:A:G	F207S	0.939
12:14840810:A:G	L163P	0.936
12:14840545:C:A	E251D	0.927
12:14840545:C:G	E251D	0.927
12:14840540:A:C	F253C	0.926
12:14840540:A:G	F253S	0.926
12:14840470:G:C	S276R	0.925
12:14840470:G:T	S276R	0.925
12:14840472:T:G	S276R	0.925
12:14840678:A:C	F207C	0.923
12:14840817:A:C	Y161D	0.919
12:14840492:A:G	L269S	0.918
12:14840801:G:T	A166E	0.918
12:14841101:T:G	Y66S	0.916
12:14841007:C:A	W97C	0.915
12:14841007:C:G	W97C	0.915
12:14840459:C:G	C280S	0.914

dbSNP variants (sampled 300 via entrez): RS1000034030 (12:14843788 T>C), RS1000106851 (12:14835102 G>A,C), RS1000138037 (12:14835306 G>T), RS1000335056 (12:14842033 C>T), RS1000585943 (12:14841502 T>G), RS1000680542 (12:14828111 A>G), RS1001096 (12:14835521 G>A), RS1001316786 (12:14826835 A>T), RS1001384649 (12:14828490 TA>T,TAA), RS1001477412 (12:14833532 T>C), RS1001781064 (12:14833707 T>C), RS1001812133 (12:14833953 C>T), RS1001907824 (12:14838644 T>G), RS1001922303 (12:14839105 A>G), RS1001953610 (12:14839388 A>G)

Disease associations

OMIM: gene MIM:110600 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
age related macular degeneration 8	Moderate	Autosomal recessive

Mondo (1): age related macular degeneration 8 (MONDO:0013416)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005830_95	Hand grip strength	1.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006941	grip strength measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	3
Acetaminophen	decreases expression	2
Benzo(a)pyrene	decreases expression	2
Estradiol	decreases expression	2
Valproic Acid	affects cotreatment, increases expression, decreases expression	2
dicrotophos	decreases expression	1
propionaldehyde	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	affects expression	1
perfluorooctanoic acid	decreases expression	1
ferrous chloride	increases expression	1
epigallocatechin gallate	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
bisphenol S	decreases expression	1
Acetylcysteine	decreases expression	1
Arsenic	affects methylation	1
Cytarabine	decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Urethane	decreases expression	1
Aflatoxin B1	affects expression	1
Sodium Selenite	decreases expression	1
Okadaic Acid	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E8VR	Jurkat-hART4	Cancer cell line	Male

Clinical trials (associated diseases)

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