ART1

Summary

ART1 (ADP-ribosyltransferase 1, HGNC:723) is a protein-coding gene on chromosome 11p15.4, encoding GPI-linked NAD(P)(+)–arginine ADP-ribosyltransferase 1 (P52961). Has ADP-ribosyltransferase activity toward GLP1R.

ADP-ribosyltransferase catalyzes the ADP-ribosylation of arginine residues in proteins. Mono-ADP-ribosylation is a posttranslational modification of proteins that is interfered with by a variety of bacterial toxins including cholera, pertussis, and heat-labile enterotoxins of E. coli. The amino acid sequence consists of predominantly hydrophobic N- and C-terminal regions, which is characteristic of glycosylphosphatidylinositol (GPI)-anchored proteins. This gene was previously designated ART2.

Source: NCBI Gene 417 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 85 total
• GTEx eGene: eQTL in 4 tissues, sQTL in 1 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.48 (unconstrained)
• MANE Select transcript: NM_004314
• Notable: 85 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:723
Approved symbol	ART1
Name	ADP-ribosyltransferase 1
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	ART2, CD296, ARTC1
Ensembl gene	ENSG00000129744
Ensembl biotype	protein_coding
OMIM	601625
Entrez	417

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000250693

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 5: 1

ENST00000250693, ENST00000529556, ENST00000948756, ENST00000948757, ENST00001143391

RefSeq mRNA: 1 — MANE Select: NM_004314 NM_004314

CCDS: CCDS7744

Canonical transcript exons

ENST00000250693 — 5 exons

Exon	Start	End
ENSE00000693077	3661372	3661413
ENSE00000693081	3659583	3660363
ENSE00001121212	3664092	3664416
ENSE00002164737	3645128	3645179
ENSE00003463386	3659162	3659276

Expression profiles

Bgee: expression breadth ubiquitous, 111 present calls, max score 89.87.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2030 / max 75.1895, expressed in 35 samples.

Highest expression (Bgee): hindlimb stylopod muscle, gastrocnemius, muscle of leg, skeletal muscle organ, muscle organ.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ART1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 4 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

5 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	sqtl	5.5e-70	-0.92	11:3655594:T:C
Nerve Tibial	eqtl	1.0e-66	+1.13	11:3650816:C:T
Heart Left Ventricle	eqtl	3.6e-16	-0.50	11:3654945:C:G
Muscle Skeletal	eqtl	1.1e-10	-0.17	11:3654905:T:C
Lung	eqtl	1.8e-05	-0.23	11:3651081:G:A

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
112731	0.2030	35

Top tissues by expression

showing 100 of 265 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	89.87	gold quality
gastrocnemius	UBERON:0001388	88.90	gold quality
muscle of leg	UBERON:0001383	87.91	gold quality
skeletal muscle organ	UBERON:0014892	81.02	gold quality
muscle organ	UBERON:0001630	81.00	gold quality
tibialis anterior	UBERON:0001385	74.57	silver quality
pancreatic ductal cell	CL:0002079	68.20	silver quality
skeletal muscle tissue	UBERON:0001134	67.90	gold quality
diaphragm	UBERON:0001103	67.78	gold quality
parotid gland	UBERON:0001831	65.43	gold quality
muscle tissue	UBERON:0002385	64.59	gold quality
tendon of biceps brachii	UBERON:0008188	64.04	gold quality
deltoid	UBERON:0001476	62.03	silver quality
cranial nerve II	UBERON:0000941	60.97	gold quality
buccal mucosa cell	CL:0002336	60.73	gold quality
olfactory bulb	UBERON:0002264	60.63	gold quality
ileal mucosa	UBERON:0000331	60.43	silver quality
type B pancreatic cell	CL:0000169	60.38	gold quality
quadriceps femoris	UBERON:0001377	59.71	gold quality
skin of hip	UBERON:0001554	58.64	gold quality
vastus lateralis	UBERON:0001379	58.49	gold quality
triceps brachii	UBERON:0001509	57.80	gold quality
biceps brachii	UBERON:0001507	57.63	gold quality
medial globus pallidus	UBERON:0002477	57.14	gold quality
gluteal muscle	UBERON:0002000	56.84	gold quality
decidua	UBERON:0002450	56.55	gold quality
myocardium	UBERON:0002349	55.71	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	55.53	gold quality
sural nerve	UBERON:0015488	55.44	silver quality
heart right ventricle	UBERON:0002080	55.04	gold quality
endometrium epithelium	UBERON:0004811	55.02	gold quality
globus pallidus	UBERON:0001875	54.31	gold quality
upper leg skin	UBERON:0004262	54.18	silver quality
nasal cavity epithelium	UBERON:0005384	52.89	gold quality
hair follicle	UBERON:0002073	52.43	gold quality
granulocyte	CL:0000094	52.22	gold quality
Brodmann (1909) area 46	UBERON:0006483	51.58	gold quality
thymus	UBERON:0002370	51.16	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
corpus epididymis	UBERON:0004359	49.83	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	49.77	silver quality
oocyte	CL:0000023	49.52	gold quality
caput epididymis	UBERON:0004358	49.37	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
oviduct epithelium	UBERON:0004804	49.06	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
cervix epithelium	UBERON:0004801	48.45	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
metanephric glomerulus	UBERON:0004736	48.01	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
renal glomerulus	UBERON:0000074	47.82	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
bone marrow cell	CL:0002092	47.71	gold quality
kidney epithelium	UBERON:0004819	47.43	gold quality
periodontal ligament	UBERON:0008266	47.14	gold quality
nephron tubule	UBERON:0001231	46.88	gold quality
amniotic fluid	UBERON:0000173	46.81	gold quality
visceral pleura	UBERON:0002401	46.16	gold quality
cauda epididymis	UBERON:0004360	46.14	gold quality
cardiac ventricle	UBERON:0002082	46.13	gold quality
heart left ventricle	UBERON:0002084	46.01	gold quality
substantia nigra pars reticulata	UBERON:0001966	45.91	gold quality
layer of synovial tissue	UBERON:0007616	45.76	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	45.35	gold quality
inferior olivary complex	UBERON:0002127	45.14	gold quality
lateral globus pallidus	UBERON:0002476	44.78	gold quality
tendon	UBERON:0000043	44.32	silver quality
palpebral conjunctiva	UBERON:0001812	44.31	gold quality
nasal cavity mucosa	UBERON:0001826	43.99	gold quality
epithelium of bronchus	UBERON:0002031	43.81	gold quality
bronchus	UBERON:0002185	43.66	gold quality
squamous epithelium	UBERON:0006914	43.42	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
prefrontal cortex	UBERON:0000451	43.29	gold quality
nipple	UBERON:0002030	43.25	gold quality
pleura	UBERON:0000977	43.15	gold quality
embryo	UBERON:0000922	43.10	gold quality
adult organism	UBERON:0007023	42.97	gold quality
epithelium of esophagus	UBERON:0001976	42.87	gold quality
substantia nigra	UBERON:0002038	42.80	silver quality
lower lobe of lung	UBERON:0008949	42.79	silver quality
adult mammalian kidney	UBERON:0000082	42.78	gold quality
kidney	UBERON:0002113	42.72	silver quality
midbrain	UBERON:0001891	42.66	silver quality
medulla oblongata	UBERON:0001896	42.61	gold quality
lung	UBERON:0002048	42.58	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
mucosa of paranasal sinus	UBERON:0005030	42.43	gold quality
trabecular bone tissue	UBERON:0002483	42.06	gold quality
cartilage tissue	UBERON:0002418	42.04	gold quality
substantia nigra pars compacta	UBERON:0001965	41.99	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.79

HPA expression

RNA tissue specificity: Group enriched

26 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Skeletal muscle	tissue	44.4
Tongue	tissue	34.3
Esophagus	tissue	0.7
Hippocampus	tissue	0.6
Locus coeruleus	tissue	0.4
Postcentral gyrus	tissue	0.4
Nucleus accumbens	tissue	0.3
Choroid plexus	tissue	0.3
Lung	tissue	0.3
Prostate	tissue	0.2
Heart muscle	tissue	0.1
Cerebral cortex	tissue	0.1
Basal ganglia	tissue	0.1
Putamen	tissue	0.1
Midbrain	tissue	0.1
Medulla oblongata	tissue	0.1
Substantia nigra	tissue	0.1
Thyroid gland	tissue	0.1
Kidney	tissue	0.1
Spinal cord	tissue	0.1
Corpus callosum	tissue	0.1
Ventral forebrain	tissue	0.1
Retrosplenial and cingulate cortex	tissue	0.1
Olfactory bulb	tissue	0.1
Septum	tissue	0.1
Insular cortex	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 184; highest nTPM — Area parastriata, superior (1.1), Parietal operculum (0.9), Area striata (0.8), Flocculonodular lobe (0.8), Inferior colliculus (0.8).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MEF2A, MYOG, RUNX1

miRNA regulators (miRDB)

Targeting ART1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

1 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6856-3P	96.47	66.27	781

Functional genomics

gnomAD constraint: pLI 1.29e-11, LOEUF 1.48, missense Z -0.785 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000250693 — one region, missense o/e 1.13.

Literature-anchored findings (GeneRIF, showing 10)

• ADP-ribosylation of HNP-1 appears to be primarily an activity of ART1 and occurs in inflammatory conditions and disease (PMID:16627471)
• ADPRT Ala762Val polymorphism may play a role in the etiology of squamous cell carcinoma of the head and neck or in linkage disequilibrium with other untyped protective alleles. (PMID:17614107)
• This study provides evidence that ARTC1 is activated during the endoplasmic-reticulum stress response, which results in acute ADP-ribosylation of GRP78/BiP paralleling translational inhibition. (PMID:25292337)
• The altered function and expression of P2X7 and ART1 in the human CD39+ Treg or CD39- Treg cells could participate in the resistance against cell death induced by ATP or NAD. (PMID:26307000)
• Arginine ADP-ribosyltransferase 1 promotes angiogenesis in colorectal cancer via the PI3K/Akt pathway (PMID:26847718)
• Our data suggest that ART1 could regulate EMT by regulating the RhoA/ROCK1/AKT/beta-catenin pathway and its downstream factors (snail1, vimentin, N-cadherin and E-cadherin) and that it therefore plays an important role in the progression of colon carcinoma. (PMID:27277835)
• up-regulation of ART1 expression is associated with the aggressiveness of glioma. (PMID:27466078)
• Expression of the mono-ADP-ribosyltransferase ART1 by tumor cells mediates immune resistance in non-small cell lung cancer. (PMID:35294260)
• ARTC1-mediated VAPB ADP-ribosylation regulates calcium homeostasis. (PMID:37381178)
• ART1 knockdown decreases the IL-6-induced proliferation of colorectal cancer cells. (PMID:38504172)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-145b13.6	ENSDARG00000069998
mus_musculus	Art1	ENSMUSG00000030996
rattus_norvegicus	Art1	ENSRNOG00000020251

Paralogs (3): ART4 (ENSG00000111339), ART3 (ENSG00000156219), ART5 (ENSG00000167311)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:107511) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 10 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased circulating calcium level	1
enlarged lymph nodes	1
decreased exploration in new environment	1
abnormal skin morphology	1
increased basophil cell number	1
increased thigmotaxis	1
increased circulating alanine transaminase level	1
abnormal behavior	1
decreased circulating sodium level	1
decreased grip strength	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pan troglodytes	Q95NE0	99.4%	Diamond
Oryctolagus cuniculus	Q03515	81.3%	Diamond
Gallus gallus	P55806	81.1%	Diamond
Bos taurus	Q0VC22	67.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CHRNA10	protein-coding	57053
NUP98	protein-coding	4928
ART5	protein-coding	116969
PGAP2	protein-coding	27315
RHOG	protein-coding	391

Protein

Protein identifiers

GPI-linked NAD(P)(+)–arginine ADP-ribosyltransferase 1 — P52961 (reviewed: P52961)

Alternative names: ADP-ribosyltransferase C2 and C3 toxin-like 1, Mono(ADP-ribosyl)transferase 1

All UniProt accessions (1): P52961

UniProt curated annotations — full annotation on UniProt →

Function. Has ADP-ribosyltransferase activity toward GLP1R.

Subcellular location. Sarcoplasmic reticulum membrane.

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

RefSeq proteins (1): NP_004305* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000768	ART	Family
IPR050999	ADP-ribosyltransferase_ARG	Family

Pfam: PF01129

Enzyme classification (BRENDA)

• EC 2.4.2.31 — NAD+-protein-arginine ADP-ribosyltransferase (BRENDA: 29 organisms, 161 substrates, 61 inhibitors, 61 Km, 19 kcat entries)

Substrate kinetics (BRENDA)

12 substrates with measured Km, best-characterized 12. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NAD+	0.0007–8.67	44
AGMATINE	1–9.4	3
ARGININE METHYL ESTER	1.3–3	3
1-(4-AMINOBUTYL)GUANIDINE	0.26–15	2
ALPHA-ACTIN-L-ARGININE	0.0025	1
BETA/GAMMA-ACTIN-L-ARGININE	0.015	1
GAMMA-ACTIN-L-ARGININE	0.01	1
NOMEGA-(ADP-D-RIBOSYL)-AGMATINE-L-ARGININE	0.272	1
PROTEIN L-ARGININE	4.1	1
PROTEIN L-ARGININE METHYL ESTER	1.3	1
PROTEIN NALPHA-ACETYL-L-ARGININE	6.3	1
PROTEIN NALPHA-ACETYL-L-ARGININE METHYL ESTER	0.9	1

Catalyzed reactions (Rhea)

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

UniProt features (18 total): sequence variant 3, active site 3, binding site 3, glycosylation site 2, disulfide bond 2, signal peptide 1, chain 1, lipid moiety-binding region 1, propeptide 1, domain 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P52961-F1	85.03	0.66

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, CD markers, Predicted membrane proteins, UniProt - Evidence at transcript level

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH uncertain

Functional residue map

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

Catalytic / active sites (3)

Position	Role
179
202
240

Ligand- & substrate-binding residues (3)

Position	Role
121	NAD(+)
179	NAD(+)
233	NAD(+)

Post-translational modifications (1)

Type	Positions
Gpi-anchor amidated serine	295

Disulfide bonds (2)

Type	Positions
Disulfide bond	53–277, 174–224

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	65, 253

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-1462054	Alpha-defensins	curated
R-HSA-6803157	Antimicrobial peptides	—
R-HSA-1461973	Defensins	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—

MSigDB gene sets: 78 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GAANYNYGACNY_UNKNOWN, MODULE_64, GOCC_CELL_SURFACE, CAGCTG_AP4_Q5, MARTINEZ_RB1_TARGETS_UP, HOSHIDA_LIVER_CANCER_LATE_RECURRENCE_DN, WINTER_HYPOXIA_METAGENE, MARTINEZ_RB1_AND_TP53_TARGETS_UP, GOCC_SARCOPLASMIC_RETICULUM_MEMBRANE, GOCC_SIDE_OF_MEMBRANE, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_SARCOPLASM, GOCC_ORGANELLE_SUBCOMPARTMENT

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): plasma membrane (GO:0005886), cell surface (GO:0009986), sarcoplasmic reticulum membrane (GO:0033017), side of membrane (GO:0098552), membrane (GO:0016020)

Reactome top-level categories

4 top-level categories:

Category	Pathways
Defensins	1
Antimicrobial peptides	1
Immune System	1
Innate Immune System	1

GO top-level categories

12 GO namespaces:

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
endoplasmic reticulum membrane	1
sarcoplasmic reticulum	1
bounding membrane of organelle	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

showing 15 of 344 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ART1	PARG	Q86W56	743
ART1	SEPTIN4	O43236	741
ART1	ODF1	Q14990	703
ART1	DEFA1	P11479	554
ART1	DEFA4	P12838	553
ART1	DEFA1	P11479	506
ART1	DEFB1	P60022	495
ART1	DEFA6	Q01524	490
ART1	DEFA5	Q01523	486
ART1	DEFB4A	O15263	440
ART1	HBB	P02023	403
ART1	ITIH4	Q14624	400
ART1	ADPRH	P54922	393
ART1	PROP1	O75360	387
ART1	P2RX7	Q99572	385

IntAct

Human interaction partners of ART1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
IMPDH1	association	0.350	1
OR52N5	association	0.350	1

BioGRID (7 interactions; top human partners by supporting records): ANLN (Affinity Capture-MS), ATR (Affinity Capture-MS), ERMP1 (Affinity Capture-MS), GHITM (Affinity Capture-MS), IMPDH1 (Affinity Capture-MS), OR52N5 (Affinity Capture-MS), SIRT2 (Affinity Capture-MS)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
NPR1	“down-regulates activity”	ART1	phosphorylation

Disease & clinical

Genetic variants

Variant evidence for ART1: 85 ClinVar records (0 pathogenic / likely pathogenic); 3 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	77
Likely benign	4
Benign	2

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 24 predictions of 585):

Position(s)	Effect	Δscore	Sites
11:3645180–3645181	donor_loss	0.9900	5
11:3659581–3659582	acceptor_loss	0.9900	6
11:3659625	acceptor_gain	0.9900
11:3659625	acceptor_gain	0.9800
11:3660350	donor_gain	0.9800
11:3660364–3660365	donor_loss	0.9800	6
11:3661369	acceptor_gain	0.9700
11:3648579	acceptor_gain	0.9600
11:3660363	donor_loss	0.9500
11:3660363	donor_loss	0.9300

AlphaMissense

481 missense substitutions predicted likely pathogenic (of 2,132 scored), across 121 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F249	8	0.942	0.991
F200	8	0.937	0.992
D48	8	0.926	0.958
D47	8	0.903	0.952
F219	8	0.891	0.957
F149	7	0.947	0.985
F151	7	0.944	0.980
F156	7	0.944	0.985
C277	7	0.928	0.968
E247	7	0.917	0.980
C53	7	0.914	0.958
W79	7	0.907	0.979
F213	7	0.905	0.984
F186	7	0.875	0.940
F46	7	0.862	0.976
E240	7	0.850	0.908
R196	7	0.849	0.946
F178	7	0.838	0.960
C224	7	0.837	0.883
F131	7	0.823	0.968

HPA cancer prognostics

RNA cancer specificity: Not detected

Disease associations

OMIM: gene MIM:601625 | disease phenotypes:

GWAS associations

3 associations:

Study	Trait	p-value
GCST010725_95	Malaria	4e-69
GCST010725_8	Malaria	2e-67
GCST010725_26	Malaria	1e-55

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2158 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
sodium arsenite	decreases expression	1
pinosylvin	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Azacitidine	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	decreases expression, increases abundance	1
Cadmium Chloride	decreases expression, increases abundance	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL636752	Binding	Inhibition of ADP-ribosyltransferase 1 that catalyze ADP-ribosyltransferase was measured at 0 uM concentration	Specific inhibition of poly(ADP-ribose) glycohydrolase by adenosine diphosphate (hydroxymethyl)pyrrolidinediol. — *J Med Chem*

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7KI	Ubigene A-549 ART1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.