ADPRM

Summary

ADPRM (ADP-ribose/CDP-alcohol diphosphatase, manganese dependent, HGNC:30925) is a protein-coding gene on chromosome 17p13.1, encoding Manganese-dependent ADP-ribose/CDP-alcohol diphosphatase (Q3LIE5). Hydrolyzes ADP-ribose, IDP-ribose, CDP-glycerol, CDP-choline and CDP-ethanolamine, but not other non-reducing ADP-sugars or CDP-glucose.

Predicted to enable 2’,3’-cyclic-nucleotide 2’-phosphodiesterase activity; manganese ion binding activity; and pyrophosphatase activity. Predicted to be located in cytosol.

Source: NCBI Gene 56985 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 46 total — 1 pathogenic
• MANE Select transcript: NM_020233

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30925
Approved symbol	ADPRM
Name	ADP-ribose/CDP-alcohol diphosphatase, manganese dependent
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	MDS006
Ensembl gene	ENSG00000170222
Ensembl biotype	protein_coding
OMIM	621211
Entrez	56985

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000379774, ENST00000468843, ENST00000527582, ENST00000609540, ENST00000895386, ENST00000923982

RefSeq mRNA: 1 — MANE Select: NM_020233 NM_020233

CCDS: CCDS11159

Canonical transcript exons

ENST00000379774 — 4 exons

Exon	Start	End
ENSE00001482437	10704910	10705527
ENSE00002714041	10697594	10697667
ENSE00003665152	10710834	10711558
ENSE00003675266	10706438	10706554

Expression profiles

Bgee: expression breadth ubiquitous, 238 present calls, max score 87.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.2715 / max 186.5104, expressed in 1755 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159593	8.2715	1755

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.30	gold quality
calcaneal tendon	UBERON:0003701	86.94	gold quality
cartilage tissue	UBERON:0002418	85.75	gold quality
lymph node	UBERON:0000029	85.66	gold quality
oocyte	CL:0000023	85.31	gold quality
left ovary	UBERON:0002119	84.89	gold quality
popliteal artery	UBERON:0002250	84.87	gold quality
tibial artery	UBERON:0007610	84.87	gold quality
endocervix	UBERON:0000458	84.79	gold quality
cortical plate	UBERON:0005343	84.48	gold quality
body of uterus	UBERON:0009853	84.41	gold quality
gastrocnemius	UBERON:0001388	84.18	gold quality
ganglionic eminence	UBERON:0004023	83.90	gold quality
muscle of leg	UBERON:0001383	83.78	gold quality
ectocervix	UBERON:0012249	83.73	gold quality
aorta	UBERON:0000947	83.69	gold quality
right ovary	UBERON:0002118	83.67	gold quality
prostate gland	UBERON:0002367	83.64	gold quality
body of stomach	UBERON:0001161	82.98	gold quality
body of pancreas	UBERON:0001150	82.81	gold quality
granulocyte	CL:0000094	82.78	gold quality
descending thoracic aorta	UBERON:0002345	82.77	gold quality
right lobe of liver	UBERON:0001114	82.72	gold quality
left lobe of thyroid gland	UBERON:0001120	82.72	gold quality
ovary	UBERON:0000992	82.61	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.34	gold quality
ascending aorta	UBERON:0001496	82.28	gold quality
thoracic aorta	UBERON:0001515	82.27	gold quality
thyroid gland	UBERON:0002046	82.18	gold quality
muscle layer of sigmoid colon	UBERON:0035805	82.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.06

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting ADPRM, 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-12136	99.98	72.81	5713
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-4728-3P	99.47	68.94	981
HSA-MIR-4751	98.80	64.95	525
HSA-MIR-496	98.66	69.80	931
HSA-MIR-640	98.44	66.93	644
HSA-MIR-6884-3P	98.05	65.32	750
HSA-MIR-4468	98.01	66.85	1187
HSA-MIR-4670-3P	97.37	68.35	1378
HSA-MIR-27B-5P	97.34	66.55	549
HSA-MIR-6895-5P	97.05	64.96	522
HSA-MIR-1296-5P	93.94	67.71	305

Literature-anchored findings (GeneRIF, showing 1)

• Results from homology modeling and simulation studies of docking and molecular dynamics revealed the structural and dynamic information on human ADPRibase-Mn with the catalytic sites. (PMID:25692488)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	adprm	ENSDARG00000026090
mus_musculus	Adprm	ENSMUSG00000020910
rattus_norvegicus	Adprm	ENSRNOG00000003397

Protein

Protein identifiers

Manganese-dependent ADP-ribose/CDP-alcohol diphosphatase — Q3LIE5 (reviewed: Q3LIE5)

Alternative names: ADPRibase-Mn, CDP-choline phosphohydrolase

All UniProt accessions (3): Q3LIE5, V9GYR6, W0NWJ0

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolyzes ADP-ribose, IDP-ribose, CDP-glycerol, CDP-choline and CDP-ethanolamine, but not other non-reducing ADP-sugars or CDP-glucose. May be involved in immune cell signaling as suggested by the second-messenger role of ADP-ribose, which activates TRPM2 as a mediator of oxidative/nitrosative stress.

Subunit / interactions. Monomer.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the ADPRibase-Mn family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q3LIE5-1	1	yes
Q3LIE5-3	2

RefSeq proteins (1): NP_064618* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004843	Calcineurin-like_PHP	Domain
IPR029052	Metallo-depent_PP-like	Homologous_superfamily
IPR041869	MPP_ADPRM	Domain

Pfam: PF00149

Enzyme classification (BRENDA):

• EC 3.6.1.13 — ADP-ribose diphosphatase (BRENDA: 21 organisms, 113 substrates, 38 inhibitors, 159 Km, 142 kcat entries)
• EC 3.6.1.53 — Mn2+-dependent ADP-ribose/CDP-alcohol diphosphatase (BRENDA: 4 organisms, 35 substrates, 3 inhibitors, 70 Km, 69 kcat entries)

Substrate kinetics (BRENDA)

24 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ADP-RIBOSE	0.0019–2.1	55
ADPRIBOSE	0.0004–0.37	23
ADP-D-RIBOSE	0.0209–0.3213	21
ADP-RIBOSE	0.015–2.1	19
CDP-CHOLINE	0.3–43	18
2’,3’-CAMP	0.76–7.6	16
CDP-CHOLINE	0.35–43	16
CYCLIC ADP-RIBOSE	0.17–0.78	5
CADP-RIBOSE	0.19–0.78	4
ADP	0.201–19	4
CDP-ETHANOLAMINE	1.422–31	4
CDP-GLYCEROL	0.304–6.3	4
8-OXO-DGDP	0.0035–0.0038	2
ADP	2.65–19	2

Catalyzed reactions (Rhea), 3 shown:

• ADP-D-ribose + H2O = D-ribose 5-phosphate + AMP + 2 H(+) (RHEA:10412)
• CDP-glycerol + H2O = sn-glycerol 3-phosphate + CMP + 2 H(+) (RHEA:21692)
• CDP-choline + H2O = phosphocholine + CMP + 2 H(+) (RHEA:32487)

UniProt features (16 total): binding site 8, splice variant 2, sequence variant 2, sequence conflict 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3LIE5-F1	94.59	0.92

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 (8): 25; 27; 74; 74; 110; 241; 278; 280

Post-translational modifications (1): 1

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-2393930	Phosphate bond hydrolysis by NUDT proteins
R-HSA-1430728	Metabolism
R-HSA-15869	Metabolism of nucleotides
R-HSA-74259	Purine catabolism
R-HSA-8956319	Nucleotide catabolism

MSigDB gene sets: 153 (showing top): CAGCAGG_MIR370, AAAGGGA_MIR204_MIR211, KEGG_PURINE_METABOLISM, HAN_SATB1_TARGETS_DN, ACEVEDO_LIVER_CANCER_UP, BRACHAT_RESPONSE_TO_CAMPTOTHECIN_DN, OSMAN_BLADDER_CANCER_DN, CTGAGCC_MIR24, CHEN_HOXA5_TARGETS_9HR_UP, SCGGAAGY_ELK1_02, GOMF_CYCLIC_NUCLEOTIDE_PHOSPHODIESTERASE_ACTIVITY, GOMF_PHOSPHORIC_DIESTER_HYDROLASE_ACTIVITY, GOMF_MANGANESE_ION_BINDING, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ACID_ANHYDRIDES

GO Biological Process (0):

GO Molecular Function (6): 2’,3’-cyclic-nucleotide 2’-phosphodiesterase activity (GO:0008663), manganese ion binding (GO:0030145), ADP-ribose diphosphatase activity (GO:0047631), CDP-glycerol diphosphatase activity (GO:0047734), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (2): cytosol (GO:0005829), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Purine catabolism	1
Metabolism	1
Nucleotide catabolism	1
Metabolism of nucleotides	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
pyrophosphatase activity	2
cellular anatomical structure	2
cyclic-nucleotide phosphodiesterase activity	1
transition metal ion binding	1
catalytic activity	1
cation binding	1
cytoplasm	1

Protein interactions and networks

STRING

444 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADPRM	TMEM220	Q6QAJ8	683
ADPRM	A0A2U3TZT1	A0A2U3TZT1	623
ADPRM	MYH13	Q9UKX3	603
ADPRM	MYH8	P13535	507
ADPRM	MYO1G	B0I1T2	463
ADPRM	CCDC154	A6NI56	447
ADPRM	BST1	Q10588	427
ADPRM	LCLAT1	Q6UWP7	401
ADPRM	C6orf136	Q5SQH8	400
ADPRM	NXPE4	Q6UWF7	399
ADPRM	CRLS1	Q9UJA2	397
ADPRM	CABLES2	Q9BTV7	381
ADPRM	PLPP1	O14494	374
ADPRM	MAP7D2	Q96T17	344
ADPRM	PHOSPHO1	Q8TCT1	340

IntAct

2 interactions, top by confidence:

A	B	Type	Score
rep	VWA8	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): FH (Positive Genetic), GTF2H4 (Negative Genetic), PHF5A (Positive Genetic), XPO1 (Negative Genetic), ADPRM (Affinity Capture-RNA)

ESM2 similar proteins: A2VCW9, A4IG42, A7YY53, O15442, O54820, O97860, P06760, P09889, P12265, P13686, P17812, P29288, P70698, Q05117, Q0IHA5, Q10RB4, Q1L8D2, Q28FE0, Q29LW1, Q3LIE5, Q3ZC91, Q58DC0, Q5M886, Q5RCR9, Q5RET5, Q5U3W0, Q641Z7, Q66H71, Q66JJ3, Q6ING7, Q6NTR1, Q6ZJJ0, Q7T0Q0, Q7T291, Q811A3, Q84LR6, Q8BFS6, Q8BXJ9, Q8H5F8, Q91ZG2

Diamond homologs: A7YY53, Q3LIE5, Q5M886, Q66JJ3, Q7T0Q0, Q7T291, Q8H5F8, Q99KS6, Q9SB68

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	32
Likely benign	5
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
150528	GRCh38/hg38 17p13.1-12(chr17:10334509-10900316)x1	Pathogenic

SpliceAI

696 predictions. Top by Δscore:

Variant	Effect	Δscore
17:10704908:A:AG	acceptor_gain	1.0000
17:10704909:G:GG	acceptor_gain	1.0000
17:10706551:GTGA:G	donor_gain	1.0000
17:10706552:TGA:T	donor_gain	1.0000
17:10706553:GA:G	donor_gain	1.0000
17:10706553:GAG:G	donor_gain	1.0000
17:10706555:G:C	donor_loss	1.0000
17:10706555:G:GG	donor_gain	1.0000
17:10706556:T:G	donor_loss	1.0000
17:10710833:GGCC:G	acceptor_gain	1.0000
17:10697667:GGTA:G	donor_loss	0.9900
17:10697668:G:GG	donor_gain	0.9900
17:10697668:GTAG:G	donor_loss	0.9900
17:10697983:G:GT	donor_gain	0.9900
17:10704908:A:AC	acceptor_loss	0.9900
17:10704909:G:GA	acceptor_loss	0.9900
17:10704909:GA:G	acceptor_gain	0.9900
17:10704909:GAA:G	acceptor_gain	0.9900
17:10705278:AGAG:A	donor_gain	0.9900
17:10706432:TTTCA:T	acceptor_loss	0.9900
17:10706433:TTCA:T	acceptor_loss	0.9900
17:10706434:TCAG:T	acceptor_loss	0.9900
17:10706435:CA:C	acceptor_loss	0.9900
17:10706436:A:AG	acceptor_gain	0.9900
17:10706436:A:T	acceptor_loss	0.9900
17:10706437:G:GA	acceptor_gain	0.9900
17:10706437:GGA:G	acceptor_gain	0.9900
17:10706437:GGAC:G	acceptor_gain	0.9900
17:10706437:GGACT:G	acceptor_gain	0.9900
17:10706543:T:TA	donor_gain	0.9900

AlphaMissense

2309 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:10705147:A:T	D74V	0.998
17:10705144:G:T	G73V	0.997
17:10705147:A:C	D74A	0.997
17:10705256:C:A	N110K	0.997
17:10705256:C:G	N110K	0.997
17:10710881:T:A	W256R	0.997
17:10710881:T:C	W256R	0.997
17:10706471:G:A	G212E	0.996
17:10706554:A:C	S240R	0.996
17:10710835:C:A	S240R	0.996
17:10710835:C:G	S240R	0.996
17:10710836:C:G	H241D	0.996
17:10705144:G:A	G73E	0.995
17:10705148:T:A	D74E	0.995
17:10705148:T:G	D74E	0.995
17:10705252:G:T	G109V	0.995
17:10706464:T:C	F210L	0.995
17:10706466:T:A	F210L	0.995
17:10706466:T:G	F210L	0.995
17:10711050:T:A	V312D	0.995
17:10705101:T:A	W59R	0.994
17:10705101:T:C	W59R	0.994
17:10705146:G:C	D74H	0.994
17:10705257:C:G	H111D	0.994
17:10705402:G:C	R159P	0.994
17:10706513:T:C	L226P	0.994
17:10710945:G:A	G277D	0.994
17:10705143:G:A	G73R	0.993
17:10705143:G:C	G73R	0.993
17:10705147:A:G	D74G	0.993

dbSNP variants (sampled 300 via entrez): RS1000040695 (17:10708990 T>G), RS1000146269 (17:10703157 C>T), RS1000168686 (17:10696140 G>A), RS1000259904 (17:10709985 A>G), RS1000375540 (17:10701331 G>A), RS1000391063 (17:10695899 T>C,G), RS1000759187 (17:10707547 T>C), RS1000906559 (17:10698501 G>A), RS1000997377 (17:10701004 G>T), RS1001696398 (17:10707408 C>T), RS1001713214 (17:10700696 C>G,T), RS1001721275 (17:10698178 G>A,C), RS1001815380 (17:10704845 T>G), RS1002128483 (17:10699826 C>G,T), RS1002181048 (17:10699651 T>A,C)

Disease associations

OMIM: gene MIM:621211 | 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
GCST002183_2	Relative hand skill in reading disability	8.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009902	handedness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, decreases expression	3
Cyclosporine	increases expression	3
sodium arsenite	decreases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
GSK-J4	increases expression	1
decabromobiphenyl ether	affects expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	increases expression	1
enzalutamide	decreases expression	1
NSC 689534	increases expression, affects binding	1
mono(carboxy-isooctyl)phthalate	affects expression	1
Temozolomide	increases expression	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Copper	affects binding, increases expression	1
Methyl Methanesulfonate	increases expression	1
Phthalic Acids	decreases methylation	1
Quercetin	increases expression	1
Dihydrotestosterone	increases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tunicamycin	increases expression	1

Clinical trials (associated diseases)

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