ADPRH

Summary

ADPRH (ADP-ribosylarginine hydrolase, HGNC:269) is a protein-coding gene on chromosome 3q13.33, encoding ADP-ribosylhydrolase ARH1 (P54922). Specifically acts as an arginine mono-ADP-ribosylhydrolase by mediating the removal of mono-ADP-ribose attached to arginine residues on proteins.

The enzyme encoded by this gene catalyzes removal of mono-ADP-ribose from arginine residues of proteins in the ADP-ribosylation cycle. Unlike the rat and mouse enzymes that require DTT for maximal activity, the human enzyme is DTT-independent. Alternatively spliced transcript variants that encode different protein isoforms have been described.

Source: NCBI Gene 141 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 66 total — 2 pathogenic
• MANE Select transcript: NM_001125

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:269
Approved symbol	ADPRH
Name	ADP-ribosylarginine hydrolase
Location	3q13.33
Locus type	gene with protein product
Status	Approved
Aliases	ARH1
Ensembl gene	ENSG00000144843
Ensembl biotype	protein_coding
OMIM	603081
Entrez	141

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000357003, ENST00000465513, ENST00000471850, ENST00000478399, ENST00000478927, ENST00000481816, ENST00000485496, ENST00000867088, ENST00000947918, ENST00000947919, ENST00000947920, ENST00000947921, ENST00000947922

RefSeq mRNA: 5 — MANE Select: NM_001125 NM_001125, NM_001291949, NM_001291950, NM_001371092, NM_001391992

CCDS: CCDS2990

Canonical transcript exons

ENST00000357003 — 5 exons

Exon	Start	End
ENSE00000967456	119582134	119582467
ENSE00001419912	119579492	119579851
ENSE00001516409	119580551	119580636
ENSE00001881583	119587464	119589945
ENSE00003529351	119586285	119586645

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 86.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.1675 / max 155.1108, expressed in 1162 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38127	2.0506	715
38124	1.3024	675
38126	0.4047	193
38125	0.2316	102
38128	0.1553	76
38129	0.0230	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	86.67	gold quality
mononuclear cell	CL:0000842	86.33	gold quality
tendon of biceps brachii	UBERON:0008188	86.31	silver quality
leukocyte	CL:0000738	86.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.70	gold quality
right lung	UBERON:0002167	82.81	gold quality
gastrocnemius	UBERON:0001388	81.30	gold quality
hindlimb stylopod muscle	UBERON:0004252	80.87	gold quality
muscle of leg	UBERON:0001383	80.49	gold quality
descending thoracic aorta	UBERON:0002345	79.58	gold quality
thoracic aorta	UBERON:0001515	79.44	gold quality
ascending aorta	UBERON:0001496	79.30	gold quality
right coronary artery	UBERON:0001625	79.29	gold quality
granulocyte	CL:0000094	79.12	gold quality
upper lobe of left lung	UBERON:0008952	78.94	gold quality
upper lobe of lung	UBERON:0008948	78.74	gold quality
left coronary artery	UBERON:0001626	78.32	gold quality
omental fat pad	UBERON:0010414	78.31	gold quality
heart left ventricle	UBERON:0002084	78.26	gold quality
peritoneum	UBERON:0002358	78.25	gold quality
gall bladder	UBERON:0002110	78.10	gold quality
lymph node	UBERON:0000029	78.02	gold quality
aorta	UBERON:0000947	77.90	gold quality
spleen	UBERON:0002106	77.86	gold quality
cardiac ventricle	UBERON:0002082	77.84	gold quality
adipose tissue of abdominal region	UBERON:0007808	77.82	gold quality
vermiform appendix	UBERON:0001154	77.76	gold quality
subcutaneous adipose tissue	UBERON:0002190	77.45	gold quality
lower lobe of lung	UBERON:0008949	77.43	gold quality
islet of Langerhans	UBERON:0000006	77.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.69

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

99 targeting ADPRH, 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-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4267	99.96	66.53	2368
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514

Literature-anchored findings (GeneRIF, showing 2)

• Silencing of the putative maternally imprinted tumor suppressor gene ARHI serves as a key early event in follicular thyroid carcinogenesis. (PMID:15546898)
• prerequisite for obtaining well diffracting crystals was the performance of X-ray fluorescence analysis on poorly diffracting apo hARH1 crystals, which revealed the presence of trace amounts of K(+) in the crystal (PMID:19407395)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	adprh	ENSDARG00000040712
mus_musculus	Adprh	ENSMUSG00000002844
rattus_norvegicus	Adprh	ENSRNOG00000027260

Paralogs (1): ADPRHL1 (ENSG00000153531)

Protein

Protein identifiers

ADP-ribosylhydrolase ARH1 — P54922 (reviewed: P54922)

Alternative names: ADP-ribose-L-arginine cleaving enzyme, [Protein ADP-ribosylarginine] hydrolase

All UniProt accessions (2): P54922, C9JZW7

UniProt curated annotations — full annotation on UniProt →

Function. Specifically acts as an arginine mono-ADP-ribosylhydrolase by mediating the removal of mono-ADP-ribose attached to arginine residues on proteins.

Subunit / interactions. Monomer.

Cofactor. Binds 2 magnesium ions per subunit.

Similarity. Belongs to the ADP-ribosylglycohydrolase family.

RefSeq proteins (5): NP_001116, NP_001278878, NP_001278879, NP_001358021, NP_001378921 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005502	Ribosyl_crysJ1	Family
IPR012108	ADP-ribosylarg_hydro	Family
IPR036705	Ribosyl_crysJ1_sf	Homologous_superfamily
IPR050792	ADP-ribosylglycohydrolase	Family

Pfam: PF03747

Enzyme classification (BRENDA):

• EC 3.2.2.19 — [protein ADP-ribosylarginine] hydrolase (BRENDA: 13 organisms, 42 substrates, 20 inhibitors, 6 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ADP-RIBOSYLARGININE	0.0262–0.065	2
2’-PHOSPHO-ADP-RIBOSYLARGININE	0.0472	1
ADP-RIBOSE DABSYL-L-ARGININE METHYL ESTER	0.0053	1
ADP-RIBOSYLARGININE METHYL ESTER	0.005	1
ADP-RIBOSYLGUANIDINE	0.0271	1

Catalyzed reactions (Rhea), 2 shown:

• N(omega)-(ADP-D-ribosyl)-L-arginyl-[protein] + H2O = ADP-D-ribose + L-arginyl-[protein] (RHEA:14885)
• alpha-NAD(+) + H2O = ADP-D-ribose + nicotinamide + H(+) (RHEA:68792)

UniProt features (51 total): helix 23, binding site 14, mutagenesis site 5, turn 5, strand 3, chain 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6IUX	X-RAY DIFFRACTION	1.2
6G28	X-RAY DIFFRACTION	1.23
6G2A	X-RAY DIFFRACTION	1.8
3HFW	X-RAY DIFFRACTION	1.92

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P54922-F1	98.46	0.99

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 (14): 54; 269–270; 302; 304; 304; 305; 55; 56; 85; 101–103; 124; 130 …

Mutagenesis-validated functional residues (5):

Position	Phenotype
54	complete loss of activity.
55	complete loss of activity.
56	complete loss of activity.
302	complete loss of activity.
305	complete loss of activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 114 (showing top): BARRIER_CANCER_RELAPSE_TUMOR_SAMPLE_DN, XU_GH1_EXOGENOUS_TARGETS_DN, GOMF_MAGNESIUM_ION_BINDING, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_GLYCOSYL_BONDS, GOMF_ALKALI_METAL_ION_BINDING, GOMF_POTASSIUM_ION_BINDING, CHEN_METABOLIC_SYNDROM_NETWORK, GOBP_PROTEIN_DE_ADP_RIBOSYLATION, GSE14415_TCONV_VS_FOXP3_KO_INDUCED_TREG_UP, KAECH_NAIVE_VS_DAY8_EFF_CD8_TCELL_DN, KAECH_DAY8_EFF_VS_DAY15_EFF_CD8_TCELL_UP, KAECH_DAY8_EFF_VS_MEMORY_CD8_TCELL_UP, ZNF618_TARGET_GENES, ZNF92_TARGET_GENES, MIR8485

GO Biological Process (2): protein modification process (GO:0036211), protein de-ADP-ribosylation (GO:0051725)

GO Molecular Function (7): magnesium ion binding (GO:0000287), ADP-ribosylarginine-[protein] hydrolase activity (GO:0003875), potassium ion binding (GO:0030955), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, hydrolyzing N-glycosyl compounds (GO:0016799), metal ion binding (GO:0046872)

GO Cellular Component (1): obsolete extracellular space (GO:0005615)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
macromolecule modification	1
protein modification process	1
metal ion binding	1
hydrolase activity, hydrolyzing N-glycosyl compounds	1
catalytic activity, acting on a protein	1
alkali metal ion binding	1
binding	1
catalytic activity	1
hydrolase activity, acting on glycosyl bonds	1
cation binding	1

Protein interactions and networks

STRING

368 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADPRH	ADPRS	Q9NX46	668
ADPRH	ART5	Q96L15	616
ADPRH	MACROD2	A1Z1Q3	534
ADPRH	TRIM72	Q6ZMU5	492
ADPRH	ITGA7	Q13683	476
ADPRH	MACROD1	Q9BQ69	458
ADPRH	NECAP2	Q9NVZ3	435
ADPRH	OARD1	Q9Y530	431
ADPRH	ART1	P52961	429
ADPRH	HPF1	Q9NWY4	395
ADPRH	PARG	Q86W56	391
ADPRH	PELO	Q9BRX2	378
ADPRH	GPALPP1	Q8IXQ4	373
ADPRH	CARNMT1	Q8N4J0	365
ADPRH	GLG1	Q92896	363

IntAct

15 interactions, top by confidence:

A	B	Type	Score
ADPRH	TFCP2	psi-mi:“MI:0915”(physical association)	0.560
TFCP2	ADPRH	psi-mi:“MI:0915”(physical association)	0.560
ADPRH	SPSB1	psi-mi:“MI:0915”(physical association)	0.560
ZNF286A	HERC2	psi-mi:“MI:0914”(association)	0.530
SRPK2	ADPRH	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
ADPRH	SRPK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
H1-1	ADPRH	psi-mi:“MI:0194”(cleavage reaction)	0.440
ACD	ADPRH	psi-mi:“MI:0915”(physical association)	0.370
ADPRH	OBSL1	psi-mi:“MI:0914”(association)	0.350
COQ8A	GAPDHS	psi-mi:“MI:0914”(association)	0.350
ADPRH	SPSB1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): TFCP2 (Two-hybrid), XRN1 (Affinity Capture-MS), OBSL1 (Affinity Capture-MS), BCAT1 (Affinity Capture-MS), SPSB1 (Two-hybrid), ADPRH (Affinity Capture-MS), XRN1 (Affinity Capture-MS), OBSL1 (Affinity Capture-MS), ADPRH (Affinity Capture-MS), ADPRH (Two-hybrid), ADPRH (Biochemical Activity), ADPRH (Biochemical Activity)

ESM2 similar proteins: B1PK17, B4G0F3, B8BKI7, C6JS30, H3BCW1, O00116, P31254, P31754, P52624, P54922, P54923, P97275, Q01415, Q02589, Q0ZHH6, Q16798, Q16831, Q28FQ6, Q32KR8, Q3SYV9, Q3ZBM1, Q5R6J8, Q5RCJ0, Q5XIB3, Q5XIG6, Q5XJB9, Q5ZI51, Q66HT8, Q68FH4, Q6AZR2, Q6DD88, Q84VX0, Q8BGK2, Q8BGT5, Q8BMF3, Q8C0I1, Q8CG72, Q8NDY3, Q8TD30, Q91WS4

Diamond homologs: P54922, P54923, Q02589, Q32KR8, Q3ZBM1, Q54H71, Q5RCJ0, Q5XIB3, Q5XJB9, Q6AZR2, Q8BGK2, Q8NDY3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	53
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
146711	GRCh38/hg38 3q13.31-21.1(chr3:115019074-122513398)x1	Pathogenic
154658	GRCh38/hg38 3q13.2-13.33(chr3:112520553-120031022)x1	Pathogenic

SpliceAI

689 predictions. Top by Δscore:

Variant	Effect	Δscore
3:119582131:A:G	acceptor_gain	1.0000
3:119586280:CCCA:C	acceptor_loss	1.0000
3:119586281:CCAG:C	acceptor_loss	1.0000
3:119586282:CAGGT:C	acceptor_loss	1.0000
3:119586283:A:AC	acceptor_loss	1.0000
3:119586283:AGGT:A	acceptor_gain	1.0000
3:119586284:GGTG:G	acceptor_gain	1.0000
3:119580608:G:GT	donor_gain	0.9900
3:119582119:A:AG	acceptor_gain	0.9900
3:119582128:A:AG	acceptor_gain	0.9900
3:119582130:A:AG	acceptor_gain	0.9900
3:119582131:AAGA:A	acceptor_loss	0.9900
3:119582133:GACA:G	acceptor_gain	0.9900
3:119582463:ACCAG:A	donor_loss	0.9900
3:119582464:CCAG:C	donor_loss	0.9900
3:119582465:CAG:C	donor_loss	0.9900
3:119582466:AG:A	donor_loss	0.9900
3:119582467:GG:G	donor_loss	0.9900
3:119582468:GTGAG:G	donor_loss	0.9900
3:119582469:T:A	donor_loss	0.9900
3:119586283:A:AG	acceptor_gain	0.9900
3:119586284:G:GG	acceptor_gain	0.9900
3:119586284:GGT:G	acceptor_gain	0.9900
3:119586446:G:GG	donor_gain	0.9900
3:119586650:GTCT:G	donor_gain	0.9900
3:119582129:C:G	acceptor_gain	0.9800
3:119582132:A:G	acceptor_gain	0.9800
3:119582133:GAC:G	acceptor_gain	0.9800
3:119582133:GACAC:G	acceptor_gain	0.9800
3:119586283:AG:A	acceptor_gain	0.9800

AlphaMissense

2341 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:119586449:A:C	S155R	0.993
3:119586451:C:A	S155R	0.993
3:119586451:C:G	S155R	0.993
3:119586465:G:C	R160P	0.992
3:119586458:A:C	S158R	0.991
3:119586460:T:A	S158R	0.991
3:119586460:T:G	S158R	0.991
3:119586557:T:A	W191R	0.991
3:119586557:T:C	W191R	0.991
3:119582329:A:C	S54R	0.990
3:119582331:T:A	S54R	0.990
3:119582331:T:G	S54R	0.990
3:119587483:T:A	W227R	0.990
3:119587483:T:C	W227R	0.990
3:119582359:G:C	A64P	0.987
3:119586497:G:T	G171W	0.986
3:119587645:G:C	A281P	0.986
3:119587669:T:A	W289R	0.985
3:119587669:T:C	W289R	0.985
3:119587637:C:A	A278D	0.984
3:119587741:T:A	W313R	0.984
3:119587741:T:C	W313R	0.984
3:119582245:T:C	F26L	0.983
3:119582247:C:A	F26L	0.983
3:119582247:C:G	F26L	0.983
3:119587718:C:T	S305F	0.983
3:119582200:A:C	S11R	0.981
3:119582202:T:A	S11R	0.981
3:119582202:T:G	S11R	0.981
3:119582330:G:T	S54I	0.980

dbSNP variants (sampled 300 via entrez): RS1000316758 (3:119588977 C>G), RS1000798660 (3:119578864 T>C), RS1001140618 (3:119585120 G>A,C), RS1001464032 (3:119581960 A>C), RS1001581272 (3:119583770 A>G), RS1001833575 (3:119589362 G>A), RS1002227662 (3:119580689 G>C), RS1002503605 (3:119577684 A>G), RS1002903757 (3:119583555 A>C), RS1003023700 (3:119589010 T>C,G), RS1003167820 (3:119580498 C>G), RS1003611273 (3:119587413 A>T), RS1004290077 (3:119590353 G>A), RS1004549117 (3:119578283 C>A,G), RS1004577348 (3:119584680 T>C)

Disease associations

OMIM: gene MIM:603081 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004785_13	Vitiligo	5.000000e-15

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	2
Valproic Acid	affects expression, decreases expression	2
GSK-J4	decreases expression	1
decabromobiphenyl ether	increases expression	1
beta-lapachone	decreases expression	1
tetrabromobisphenol A	increases expression	1
hydroquinone	increases expression	1
ADP-ribosylarginine	increases hydrolysis	1
CGP 52608	increases reaction, affects binding	1
2-palmitoylglycerol	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	decreases methylation	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Adenosine Diphosphate Ribose	increases hydrolysis	1
Air Pollutants	increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Antirheumatic Agents	decreases expression	1
O-Acetyl-ADP-Ribose	increases hydrolysis	1
Particulate Matter	increases expression, increases abundance	1

Clinical trials (associated diseases)

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