AMPD3

Summary

AMPD3 (adenosine monophosphate deaminase 3, HGNC:470) is a protein-coding gene on chromosome 11p15.4, encoding AMP deaminase 3 (Q01432). AMP deaminase plays a critical role in energy metabolism.

This gene encodes a member of the AMP deaminase gene family. The encoded protein is a highly regulated enzyme that catalyzes the hydrolytic deamination of adenosine monophosphate to inosine monophosphate, a branch point in the adenylate catabolic pathway. This gene encodes the erythrocyte (E) isoforms, whereas other family members encode isoforms that predominate in muscle (M) and liver (L) cells. Mutations in this gene lead to the clinically asymptomatic, autosomal recessive condition erythrocyte AMP deaminase deficiency. Alternatively spliced transcript variants encoding different isoforms of this gene have been described.

Source: NCBI Gene 272 — RefSeq curated summary.

At a glance

• Gene–disease (curated): adenosine monophosphate deaminase deficiency (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 31
• Clinical variants (ClinVar): 234 total — 1 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 8
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001025389

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:470
Approved symbol	AMPD3
Name	adenosine monophosphate deaminase 3
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000133805
Ensembl biotype	protein_coding
OMIM	102772
Entrez	272

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 18 protein_coding, 6 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay, 1 retained_intron

ENST00000295663, ENST00000396553, ENST00000396554, ENST00000444303, ENST00000524866, ENST00000527261, ENST00000527369, ENST00000528723, ENST00000529507, ENST00000529744, ENST00000529834, ENST00000529835, ENST00000530864, ENST00000531227, ENST00000532250, ENST00000532966, ENST00000533116, ENST00000534047, ENST00000902501, ENST00000902502, ENST00000902503, ENST00000902504, ENST00000902505, ENST00000902506, ENST00000902507, ENST00000902508, ENST00000930062, ENST00000930063, ENST00000968291

RefSeq mRNA: 5 — MANE Select: NM_001025389 NM_000480, NM_001025389, NM_001025390, NM_001172430, NM_001172431

CCDS: CCDS41617, CCDS44537, CCDS53601, CCDS7802

Canonical transcript exons

ENST00000396553 — 15 exons

Exon	Start	End
ENSE00000911006	10496812	10496938
ENSE00001038150	10484820	10485039
ENSE00001100333	10478526	10478730
ENSE00001525443	10455264	10455448
ENSE00001721787	10505708	10507579
ENSE00003498021	10482063	10482225
ENSE00003519008	10494899	10495030
ENSE00003539426	10495570	10495733
ENSE00003562614	10502721	10502894
ENSE00003586801	10501470	10501590
ENSE00003609311	10504549	10504659
ENSE00003642478	10493349	10493543
ENSE00003653578	10500086	10500249
ENSE00003659163	10487235	10487364
ENSE00003693996	10461515	10461740

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 98.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.6962 / max 586.8744, expressed in 1647 samples.

FANTOM5 promoters (21 alternative TSS)

Promoter ID	TPM avg	Samples expressed
113049	7.3620	615
113054	4.9551	629
113052	2.2243	720
113057	1.3468	410
113047	1.3217	696
113050	1.2703	242
113043	1.1128	500
113055	0.9658	300
113058	0.8875	284
113042	0.5662	314

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gluteal muscle	UBERON:0002000	98.54	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	95.89	gold quality
tibialis anterior	UBERON:0001385	95.70	gold quality
cartilage tissue	UBERON:0002418	95.31	gold quality
inferior olivary complex	UBERON:0002127	95.11	gold quality
secondary oocyte	CL:0000655	94.80	gold quality
trabecular bone tissue	UBERON:0002483	94.77	gold quality
right uterine tube	UBERON:0001302	94.21	gold quality
oocyte	CL:0000023	94.11	gold quality
bone marrow	UBERON:0002371	93.37	gold quality
bone marrow cell	CL:0002092	93.32	gold quality
inferior vagus X ganglion	UBERON:0005363	93.32	gold quality
gastrocnemius	UBERON:0001388	93.19	gold quality
bronchial epithelial cell	CL:0002328	92.80	gold quality
epithelium of bronchus	UBERON:0002031	91.94	gold quality
deltoid	UBERON:0001476	91.54	gold quality
bronchus	UBERON:0002185	91.54	gold quality
subthalamic nucleus	UBERON:0001906	91.05	gold quality
muscle of leg	UBERON:0001383	91.01	gold quality
medulla oblongata	UBERON:0001896	90.62	gold quality
nasal cavity epithelium	UBERON:0005384	90.61	gold quality
left adrenal gland	UBERON:0001234	90.03	gold quality
right adrenal gland	UBERON:0001233	90.01	gold quality
corpus callosum	UBERON:0002336	89.92	gold quality
cervix squamous epithelium	UBERON:0006922	89.92	gold quality
lateral globus pallidus	UBERON:0002476	89.87	gold quality
right adrenal gland cortex	UBERON:0035827	89.77	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.64	gold quality
ventral tegmental area	UBERON:0002691	89.60	gold quality
adrenal cortex	UBERON:0001235	89.58	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.50

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, MYC

miRNA regulators (miRDB)

86 targeting AMPD3, 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-513A-5P	100.00	69.77	2465
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524

Literature-anchored findings (GeneRIF, showing 7)

• N-terminal sequence and distal histidine residues are responsible for pH-regulated cytoplasmic membrane binding (PMID:12213808)
• mtDNA deletion coordinately induces AMP deaminase to contribute to the loss of atrial adenine nucleotides through degrading AMP excessively. (PMID:12604357)
• The primary underlying mechanism for increased catabolic flow through the AMP deaminase reaction in circulating erythrocytes of individuals with familial phosphofructokinase deficiency is Ca2+-calmodulin activation of AMP deaminase isoform E. (PMID:16670071)
• may control the systemic metabolic status by changing AMPK activity through the AMP level. (PMID:18409530)
• Down-regulation of AMPD3 Is Associated With Poor Survival in Head and Neck Squamous Cell Carcinoma. (PMID:35241525)
• Adenosine monophosphate deaminase in the endoplasmic reticulum-mitochondria interface promotes mitochondrial Ca[2+] overload in type 2 diabetes rat hearts. (PMID:36815317)
• Erythrocyte ENT1-AMPD3 Axis is an Essential Purinergic Hypoxia Sensor and Energy Regulator Combating CKD in a Mouse Model. (PMID:37725437)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ampd3a	ENSDARG00000005800
danio_rerio	ampd3b	ENSDARG00000032469
mus_musculus	Ampd3	ENSMUSG00000005686
rattus_norvegicus	Ampd3	ENSRNOG00000018262

Paralogs (2): AMPD2 (ENSG00000116337), AMPD1 (ENSG00000116748)

Protein

Protein identifiers

AMP deaminase 3 — Q01432 (reviewed: Q01432)

Alternative names: AMP deaminase isoform E, Erythrocyte AMP deaminase

All UniProt accessions (7): Q01432, E9PIR5, E9PKC5, E9PLK6, E9PPG2, H0YDC3, H0YDY8

UniProt curated annotations — full annotation on UniProt →

Function. AMP deaminase plays a critical role in energy metabolism.

Subunit / interactions. Homotetramer.

Disease relevance. Adenosine monophosphate deaminase deficiency erythrocyte type (AMPDDE) [MIM:612874] A metabolic disorder due to lack of activity of the erythrocyte isoform of AMP deaminase. It is a clinically asymptomatic condition characterized by a 50% increase in steady-state levels of ATP in affected cells. Individuals with complete deficiency of erythrocyte AMP deaminase are healthy and have no hematologic disorders. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 zinc ion per subunit.

Pathway. Purine metabolism; IMP biosynthesis via salvage pathway; IMP from AMP: step 1/1.

Similarity. Belongs to the metallo-dependent hydrolases superfamily. Adenosine and AMP deaminases family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q01432-1	1B	yes
Q01432-2	1A
Q01432-3	1C
Q01432-4	2
Q01432-5	3
Q01432-6	4

RefSeq proteins (5): NP_000471, NP_001020560, NP_001020561, NP_001165901, NP_001165902 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006329	AMPD	Family
IPR006650	A/AMP_deam_AS	Active_site
IPR032466	Metal_Hydrolase	Homologous_superfamily

Pfam: PF19326

Enzyme classification (BRENDA):

• EC 3.5.4.6 — AMP deaminase (BRENDA: 31 organisms, 17 substrates, 106 inhibitors, 29 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
AMP	0.025–13	20

Catalyzed reactions (Rhea), 1 shown:

• AMP + H2O + H(+) = IMP + NH4(+) (RHEA:14777)

UniProt features (31 total): sequence variant 12, binding site 8, splice variant 5, region of interest 2, modified residue 2, chain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01432-F1	85.74	0.68

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 (1): 608 (proton acceptor)

Ligand- & substrate-binding residues (8): 663; 664–667; 317; 319; 319; 388–393; 586; 589

Post-translational modifications (2): 85, 107

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-74217	Purine salvage
R-HSA-1430728	Metabolism
R-HSA-15869	Metabolism of nucleotides
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-8956321	Nucleotide salvage

MSigDB gene sets: 309 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TGACCTY_ERR1_Q2, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_1, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PURINE_CONTAINING_COMPOUND_SALVAGE, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, RICKMAN_METASTASIS_DN

GO Biological Process (7): IMP biosynthetic process (GO:0006188), AMP catabolic process (GO:0006196), IMP salvage (GO:0032264), AMP metabolic process (GO:0046033), nucleoside phosphate metabolic process (GO:0006753), nucleotide metabolic process (GO:0009117), purine ribonucleoside monophosphate biosynthetic process (GO:0009168)

GO Molecular Function (5): AMP deaminase activity (GO:0003876), metal ion binding (GO:0046872), protein binding (GO:0005515), hydrolase activity (GO:0016787), deaminase activity (GO:0019239)

GO Cellular Component (4): extracellular region (GO:0005576), cytosol (GO:0005829), secretory granule lumen (GO:0034774), ficolin-1-rich granule lumen (GO:1904813)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Innate Immune System	1
Nucleotide salvage	1
Metabolism	1
Immune System	1
Metabolism of nucleotides	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
purine ribonucleoside monophosphate metabolic process	2
cellular anatomical structure	2
purine ribonucleotide biosynthetic process	1
purine ribonucleoside monophosphate biosynthetic process	1
IMP metabolic process	1
purine ribonucleotide catabolic process	1
purine ribonucleoside monophosphate catabolic process	1
AMP metabolic process	1
IMP biosynthetic process	1
purine ribonucleotide salvage	1
purine ribonucleotide metabolic process	1
organophosphate metabolic process	1
nucleobase-containing small molecule metabolic process	1
nucleoside phosphate metabolic process	1
purine nucleoside monophosphate biosynthetic process	1
ribonucleoside monophosphate biosynthetic process	1
adenosine-phosphate deaminase activity	1
cation binding	1
binding	1
catalytic activity	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds	1
cytoplasm	1
secretory granule	1
cytoplasmic vesicle lumen	1
intracellular organelle lumen	1
ficolin-1-rich granule	1

Protein interactions and networks

STRING

1712 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AMPD3	ADSS2	P30520	927
AMPD3	ADA	P00813	910
AMPD3	PNP	P00491	747
AMPD3	ADSL	P30566	742
AMPD3	ADK	P55263	729
AMPD3	ALDOB	P05062	718
AMPD3	APRT	P07741	706
AMPD3	GMPS	P49915	665
AMPD3	GDA	Q9Y2T3	588
AMPD3	KHK	P50053	583
AMPD3	IMPDH2	P12268	582
AMPD3	IMPDH1	P20839	569
AMPD3	ADSS1	Q8N142	558
AMPD3	ASS1	P00966	536
AMPD3	MPI	P34949	532

IntAct

12 interactions, top by confidence:

A	B	Type	Score
AMPD3	HSP90AB1	psi-mi:“MI:0914”(association)	0.500
HSP90AB1	AMPD3	psi-mi:“MI:0915”(physical association)	0.500
AMPD3	H3-4	psi-mi:“MI:0915”(physical association)	0.400
AMPD3	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
AMPD3	AMPD2	psi-mi:“MI:0915”(physical association)	0.400
ALB	SH3BP5	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
ITGB2	CD151	psi-mi:“MI:0914”(association)	0.350
TTC14	AMPD3	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
AMPD3	katG	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): AMPD3 (Synthetic Lethality), AMPD3 (Two-hybrid), KCNIP1 (Two-hybrid), HIST3H3 (Proximity Label-MS), HIST1H2BH (Proximity Label-MS), AMPD3 (Affinity Capture-MS), AMPD3 (Affinity Capture-MS), AMPD2 (Affinity Capture-MS), AMPD3 (Affinity Capture-MS), AMPD3 (Affinity Capture-MS), AMPD3 (Cross-Linking-MS (XL-MS)), LRBA (Co-fractionation), TMEM259 (Co-fractionation), AMPD3 (Affinity Capture-Western), AMPD3 (Affinity Capture-MS)

ESM2 similar proteins: A1A5G6, A7Z064, G5EEK9, G5EGP4, O13742, O97681, P00347, P00365, P04035, P09610, P10759, P13807, P15920, P16393, P17625, P20715, P23109, P25286, P30628, P32563, P37296, P38329, P54840, P57103, P70549, Q00955, Q01237, Q01290, Q01432, Q09573, Q1W675, Q29466, Q29512, Q54E04, Q5R422, Q5R6N3, Q5R9H0, Q8AVM5, Q8MJ26, Q8RWZ7

Diamond homologs: A0A0K1SC59, A0A1Y3DYH2, A0A509ALD0, A0L2R5, A0LRH8, A1RDZ6, A1S1P1, A3CYL9, A3QJD9, A4TEW1, A4YCD7, A5KE01, A6UET5, A6UXT7, A6VWL7, A6WUH7, A9KWZ3, B1ZYW1, B2U7U6, B3PXN1, B3R3T1, B5ZXI3, B7V265, B8EDT7, B9J6V8, C5BDE0, K6UCV4, O08739, O09178, P15287, P58780, P58781, Q01432, Q02UT0, Q06K61, Q08A11, Q0HD92, Q0HPH4, Q0KCW5, Q11C48

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
AMPD3	“down-regulates quantity”	AMP	“chemical modification”
AMPD3	“down-regulates quantity”	water	“chemical modification”
AMPD3	“up-regulates quantity”	IMP	“chemical modification”
AMPD3	“up-regulates quantity”	ammonium	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	3
Uncertain significance	176
Likely benign	12
Benign	16

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
18270	NM_001025389.2(AMPD3):c.1717C>T (p.Arg573Cys)	Pathogenic
3065721	NM_001025389.2(AMPD3):c.1815_1816del (p.Ile606fs)	Likely pathogenic
4367070	NM_001025389.2(AMPD3):c.809+1G>C	Likely pathogenic
4526607	NM_001025389.2(AMPD3):c.648dup (p.Asn217fs)	Likely pathogenic

SpliceAI

2636 predictions. Top by Δscore:

Variant	Effect	Δscore
11:10455436:GCA:G	donor_gain	1.0000
11:10455439:G:GG	donor_gain	1.0000
11:10455445:GGCT:G	donor_gain	1.0000
11:10455446:GCT:G	donor_gain	1.0000
11:10455446:GCTG:G	donor_gain	1.0000
11:10455449:G:GG	donor_gain	1.0000
11:10461509:T:TA	acceptor_gain	1.0000
11:10461511:CTAG:C	acceptor_loss	1.0000
11:10461512:TA:T	acceptor_loss	1.0000
11:10461513:A:AC	acceptor_loss	1.0000
11:10461513:A:AG	acceptor_gain	1.0000
11:10461513:AGCT:A	acceptor_gain	1.0000
11:10461514:G:GT	acceptor_gain	1.0000
11:10461514:GC:G	acceptor_gain	1.0000
11:10461514:GCT:G	acceptor_gain	1.0000
11:10461514:GCTG:G	acceptor_gain	1.0000
11:10461514:GCTGA:G	acceptor_gain	1.0000
11:10461676:G:GT	donor_gain	1.0000
11:10461738:AAGG:A	donor_loss	1.0000
11:10461740:GGT:G	donor_loss	1.0000
11:10461742:T:A	donor_loss	1.0000
11:10482062:GATC:G	acceptor_gain	1.0000
11:10482223:CAG:C	donor_loss	1.0000
11:10482224:AGG:A	donor_loss	1.0000
11:10485038:AC:A	donor_gain	1.0000
11:10485040:G:GG	donor_gain	1.0000
11:10485041:T:TC	donor_loss	1.0000
11:10485712:GCCT:G	donor_gain	1.0000
11:10487360:GAAAG:G	donor_gain	1.0000
11:10487361:AAAG:A	donor_loss	1.0000

AlphaMissense

5084 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:10487247:T:G	C274W	1.000
11:10487258:T:C	L278P	1.000
11:10487364:G:C	K313N	1.000
11:10487364:G:T	K313N	1.000
11:10493364:C:G	H319D	1.000
11:10494920:T:C	F386L	1.000
11:10494921:T:G	F386C	1.000
11:10494922:T:A	F386L	1.000
11:10494922:T:G	F386L	1.000
11:10494929:T:C	F389L	1.000
11:10494931:C:A	F389L	1.000
11:10494931:C:G	F389L	1.000
11:10500101:A:C	S525R	1.000
11:10500103:C:A	S525R	1.000
11:10500103:C:G	S525R	1.000
11:10501509:T:G	C587W	1.000
11:10501510:G:T	G588W	1.000
11:10501511:G:A	G588E	1.000
11:10501570:C:G	H608D	1.000
11:10501572:C:A	H608Q	1.000
11:10501572:C:G	H608Q	1.000
11:10501573:G:A	G609R	1.000
11:10501573:G:C	G609R	1.000
11:10501573:G:T	G609W	1.000
11:10501574:G:A	G609E	1.000
11:10501583:T:A	L612H	1.000
11:10502781:A:C	S635R	1.000
11:10502783:C:A	S635R	1.000
11:10502783:C:G	S635R	1.000
11:10502786:C:A	N636K	1.000

dbSNP variants (sampled 300 via entrez): RS1000023634 (11:10507024 T>C), RS1000106115 (11:10465940 T>G), RS1000172404 (11:10455873 C>A,G,T), RS1000258285 (11:10483952 C>T), RS1000267343 (11:10456240 A>G), RS1000327197 (11:10489193 C>T), RS1000377290 (11:10450845 C>G), RS1000493134 (11:10471383 A>G), RS1000505364 (11:10454642 T>C), RS1000576925 (11:10504906 G>A), RS1000581713 (11:10465548 G>A), RS1000599613 (11:10454963 C>G), RS1000618173 (11:10483595 C>G,T), RS1000682466 (11:10449606 G>A), RS1000704169 (11:10477180 A>C)

Disease associations

OMIM: gene MIM:102772 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
adenosine monophosphate deaminase deficiency	Supportive	Autosomal recessive
erythrocyte AMP deaminase deficiency	Limited	Autosomal recessive

Mondo (3): myoepithelial tumor (MONDO:0002380), adenosine monophosphate deaminase deficiency (MONDO:0013028), (MONDO:0020734)

Orphanet (1): Adenosine monophosphate deaminase deficiency (Orphanet:45)

HPO phenotypes

8 total (8 of 8 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0002151	Increased circulating lactate concentration
HP:0003326	Myalgia
HP:0003394	Muscle spasm
HP:0003690	Limb muscle weakness
HP:0003738	Exercise-induced myalgia
HP:0008331	Elevated creatine kinase after exercise
HP:0009020	Exercise-induced muscle fatigue

GWAS associations

31 associations (top):

Study	Trait	p-value
GCST000755_10	HDL cholesterol	5.000000e-08
GCST002223_40	HDL cholesterol	5.000000e-08
GCST004232_84	HDL cholesterol levels	3.000000e-06
GCST007094_206	Diastolic blood pressure	2.000000e-13
GCST007095_36	Systolic blood pressure	5.000000e-07
GCST007095_37	Systolic blood pressure	6.000000e-06
GCST007096_138	Pulse pressure	6.000000e-13
GCST007099_144	Systolic blood pressure	1.000000e-20
GCST007203_6	Total cholesterol levels	1.000000e-06
GCST007250_10	Nonunion in individuals with fractures	2.000000e-07
GCST010083_180	Hemoglobin levels	8.000000e-15
GCST010241_17	Apolipoprotein A1 levels	6.000000e-18
GCST010241_257	Apolipoprotein A1 levels	5.000000e-08
GCST010242_349	HDL cholesterol levels	1.000000e-12
GCST010302_48	Cutaneous melanoma or hair colour	4.000000e-08
GCST012228_533	Waist-hip index	5.000000e-08
GCST90000025_196	Appendicular lean mass	2.000000e-14
GCST90002383_28	Hematocrit	1.000000e-09
GCST90002383_29	Hematocrit	1.000000e-10
GCST90002384_284	Hemoglobin	1.000000e-09
GCST90002384_285	Hemoglobin	1.000000e-12
GCST90002385_192	High light scatter reticulocyte count	1.000000e-18
GCST90002386_343	High light scatter reticulocyte percentage of red cells	2.000000e-15
GCST90002399_60	Neutrophil percentage of white cells	1.000000e-09
GCST90002405_274	Reticulocyte count	2.000000e-19
GCST90002406_361	Reticulocyte fraction of red cells	2.000000e-15
GCST90002407_324	White blood cell count	4.000000e-09
GCST90014033_97	Haemorrhoidal disease	1.000000e-13
GCST90020026_767	Hip index	1.000000e-10
GCST90020028_1818	Hip circumference adjusted for BMI	1.000000e-09

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0004574	total cholesterol measurement
EFO:0009707	fractures, ununited
EFO:0004509	hemoglobin measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0003924	hair color
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004980	appendicular lean mass
EFO:0004348	hematocrit
EFO:0007986	reticulocyte count
EFO:0007990	neutrophil percentage of leukocytes
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585
C538234	Adenosine monophosphate deaminase deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2912 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 615 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL284483	COFORMYCIN	2	615

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

Binding affinities (BindingDB)

1 measured of 2 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
6-[4-({[(1S)-1-(isoquinolin-8-yl)ethyl]amino}methyl)phenyl]pyridine-3-carboxylic acid (Compound 3)	IC50	38 nM

ChEMBL bioactivities

45 potent at pChembl≥5 of 48 total, top 43 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.70	Ki	2	nM	CHEMBL346040
8.05	Ki	9	nM	CHEMBL157468
7.82	Ki	15	nM	CHEMBL157949
7.70	Ki	20	nM	CHEMBL346360
7.54	Ki	29	nM	CHEMBL37273
7.52	Ki	30	nM	CHEMBL160174
7.40	Ki	40	nM	CHEMBL157743
7.40	Ki	40	nM	CHEMBL289398
7.39	Ki	41	nM	CHEMBL288742
7.30	Ki	50	nM	CHEMBL280097
7.05	Ki	90	nM	CHEMBL158023
6.77	Ki	170	nM	CHEMBL39940
6.66	Ki	220	nM	CHEMBL157426
6.60	Ki	250	nM	CHEMBL37079
6.52	Ki	300	nM	CHEMBL158136
6.52	Ki	300	nM	CHEMBL350676
6.44	Ki	360	nM	CHEMBL286566
6.44	Ki	360	nM	CHEMBL39406
6.39	Ki	410	nM	CHEMBL35929
6.30	Ki	500	nM	CHEMBL154259
6.30	Ki	500	nM	CHEMBL35524
6.05	IC50	900	nM	CHEMBL2042530
6.05	Ki	900	nM	CHEMBL37278
6.02	Ki	960	nM	CHEMBL156217
6.00	Ki	1000	nM	CHEMBL157669
5.92	Ki	1200	nM	CHEMBL291059
5.89	Ki	1300	nM	CHEMBL37650
5.89	Ki	1300	nM	CHEMBL156990
5.75	Ki	1800	nM	CHEMBL157951
5.68	Ki	2100	nM	CHEMBL287822
5.64	Ki	2300	nM	CHEMBL157800
5.62	Ki	2400	nM	CHEMBL160384
5.62	Ki	2400	nM	CHEMBL39386
5.58	Ki	2600	nM	CHEMBL286464
5.52	Ki	3000	nM	COFORMYCIN
5.42	Ki	3800	nM	CHEMBL347030
5.38	Ki	4200	nM	CHEMBL36690
5.30	Ki	5000	nM	CHEMBL157723
5.29	Ki	5100	nM	CHEMBL290684
5.28	Ki	5200	nM	CHEMBL284858
5.28	Ki	5200	nM	CHEMBL289639
5.22	Ki	6000	nM	CHEMBL284277
5.11	Ki	7800	nM	CHEMBL288461

PubChem BioAssay actives

47 with measured affinity, of 51 total; 45 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-bromo-4-[2-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)ethyl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid	34757: Inhibition of recombinant human E-type adenylate deaminase	ki	0.0020	uM
4-[2-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)ethyl]-1-phenylmethoxy-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid	34757: Inhibition of recombinant human E-type adenylate deaminase	ki	0.0090	uM
4-[2-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)ethyl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid	34757: Inhibition of recombinant human E-type adenylate deaminase	ki	0.0150	uM
4-[2-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)ethyl]naphthalene-2-carboxylic acid	34757: Inhibition of recombinant human E-type adenylate deaminase	ki	0.0200	uM
2-[4-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)butyl]-2-[[3-(trifluoromethyl)phenyl]methyl]propanedioic acid	31738: Inhibitory activity against porcine heart or recombinant human E-type AMPDA	ki	0.0290	uM
4-[2-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)ethyl]-1-methoxy-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid	34757: Inhibition of recombinant human E-type adenylate deaminase	ki	0.0300	uM
2-[4-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)butyl]-2-[[4-(trifluoromethyl)phenyl]methyl]propanedioic acid	31738: Inhibitory activity against porcine heart or recombinant human E-type AMPDA	ki	0.0400	uM
4-[2-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)ethyl]-3-methoxy-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid	34757: Inhibition of recombinant human E-type adenylate deaminase	ki	0.0400	uM
2-[4-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)butyl]-2-[[2-(trifluoromethyl)phenyl]methyl]propanedioic acid	31738: Inhibitory activity against porcine heart or recombinant human E-type AMPDA	ki	0.0410	uM
1,3-dichloro-4-[2-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)ethyl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid	34757: Inhibition of recombinant human E-type adenylate deaminase	ki	0.0500	uM
6-[4-[[[(1S)-1-isoquinolin-8-ylethyl]amino]methyl]phenyl]pyridine-3-carboxylic acid	1801154: AMPD Enzymatic Activity Assay from Article 10.1016/j.chembiol.2014.09.011: “Inhibition of AMP deaminase activity does not improve glucose control in rodent models of insulin resistance or diabetes.”	ic50	0.0750	uM
4-[2-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)ethyl]-1-propan-2-yloxy-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid	34757: Inhibition of recombinant human E-type adenylate deaminase	ki	0.0900	uM
2-benzyl-2-[4-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)butyl]propanedioic acid	31738: Inhibitory activity against porcine heart or recombinant human E-type AMPDA	ki	0.1700	uM
4-[2-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)ethyl]-8-(trifluoromethyl)naphthalene-2-carboxylic acid	34757: Inhibition of recombinant human E-type adenylate deaminase	ki	0.2200	uM
dibenzyl 2-[4-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)butyl]-2-[[2-(trifluoromethyl)phenyl]methyl]propanedioate	31738: Inhibitory activity against porcine heart or recombinant human E-type AMPDA	ki	0.2500	uM
ethyl 4-[2-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)ethyl]-1-phenylmethoxy-5,6,7,8-tetrahydronaphthalene-2-carboxylate	34757: Inhibition of recombinant human E-type adenylate deaminase	ki	0.3000	uM
benzyl 1,3-dichloro-4-[2-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)ethyl]-5,6,7,8-tetrahydronaphthalene-2-carboxylate	34757: Inhibition of recombinant human E-type adenylate deaminase	ki	0.3000	uM
6-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)-2-phenylmethoxycarbonylhexanoic acid	31738: Inhibitory activity against porcine heart or recombinant human E-type AMPDA	ki	0.3600	uM
diethyl 2-[4-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)butyl]-2-[[2-(trifluoromethyl)phenyl]methyl]propanedioate	31738: Inhibitory activity against porcine heart or recombinant human E-type AMPDA	ki	0.3600	uM
2-benzyl-6-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)hexanoic acid	34757: Inhibition of recombinant human E-type adenylate deaminase	ki	0.4100	uM
ethyl 1,3-dichloro-4-[2-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)ethyl]-5,6,7,8-tetrahydronaphthalene-2-carboxylate	34757: Inhibition of recombinant human E-type adenylate deaminase	ki	0.5000	uM
3-[2-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)ethyl]benzoic acid	34757: Inhibition of recombinant human E-type adenylate deaminase	ki	0.5000	uM
6-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)-2-methyl-2-phenylmethoxycarbonylhexanoic acid	31738: Inhibitory activity against porcine heart or recombinant human E-type AMPDA	ki	0.9000	uM
4-(2-imidazo[2,1-f][1,2,4]triazin-7-ylethyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid	668714: Inhibition of human recombinant AMPD3-1b expressed in Sf9 cells	ic50	0.9000	uM
6-bromo-4-[2-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)ethyl]naphthalene-2-carboxylic acid	34757: Inhibition of recombinant human E-type adenylate deaminase	ki	0.9600	uM
ethyl 1-bromo-4-[2-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)ethyl]-5,6,7,8-tetrahydronaphthalene-2-carboxylate	34757: Inhibition of recombinant human E-type adenylate deaminase	ki	1.0000	uM
6-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)-2-methyl-2-[[3-(trifluoromethyl)phenyl]methyl]hexanoic acid	31738: Inhibitory activity against porcine heart or recombinant human E-type AMPDA	ki	1.2000	uM
ethyl 4-[2-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)ethyl]-5,6,7,8-tetrahydronaphthalene-2-carboxylate	34757: Inhibition of recombinant human E-type adenylate deaminase	ki	1.3000	uM
2-[(4-chlorophenyl)methylcarbamoyl]-6-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)hexanoic acid	31738: Inhibitory activity against porcine heart or recombinant human E-type AMPDA	ki	1.3000	uM
methyl 4-[2-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)ethyl]naphthalene-2-carboxylate	34757: Inhibition of recombinant human E-type adenylate deaminase	ki	1.8000	uM
6-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)-2-methyl-2-(2-phenylethylcarbamoyl)hexanoic acid	31738: Inhibitory activity against porcine heart or recombinant human E-type AMPDA	ki	2.1000	uM
ethyl 4-[2-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)ethyl]-1-methoxy-5,6,7,8-tetrahydronaphthalene-2-carboxylate	34757: Inhibition of recombinant human E-type adenylate deaminase	ki	2.3000	uM
2-(benzylcarbamoyl)-6-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)hexanoic acid	31738: Inhibitory activity against porcine heart or recombinant human E-type AMPDA	ki	2.4000	uM
ethyl 4-[2-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)ethyl]-3-methoxy-5,6,7,8-tetrahydronaphthalene-2-carboxylate	34757: Inhibition of recombinant human E-type adenylate deaminase	ki	2.4000	uM
diethyl 2-benzyl-2-[4-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)butyl]propanedioate	31738: Inhibitory activity against porcine heart or recombinant human E-type AMPDA	ki	2.6000	uM
(2R,3R,4S,5R)-2-[(8R)-8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl]-5-(hydroxymethyl)oxolane-3,4-diol	34757: Inhibition of recombinant human E-type adenylate deaminase	ki	3.0000	uM
ethyl 4-[2-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)ethyl]-1-propan-2-yloxy-5,6,7,8-tetrahydronaphthalene-2-carboxylate	34757: Inhibition of recombinant human E-type adenylate deaminase	ki	3.8000	uM
6-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)hexanoic acid	31738: Inhibitory activity against porcine heart or recombinant human E-type AMPDA	ki	4.2000	uM
benzyl 4-[2-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)ethyl]-5,6,7,8-tetrahydronaphthalene-2-carboxylate	34757: Inhibition of recombinant human E-type adenylate deaminase	ki	5.0000	uM
2-[4-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)butyl]propanedioic acid	31738: Inhibitory activity against porcine heart or recombinant human E-type AMPDA	ki	5.1000	uM
2-(cyclohexylcarbamoyl)-6-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)-2-methylhexanoic acid	31738: Inhibitory activity against porcine heart or recombinant human E-type AMPDA	ki	5.2000	uM
dibenzyl 2-[4-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)butyl]-2-methylpropanedioate	31738: Inhibitory activity against porcine heart or recombinant human E-type AMPDA	ki	5.2000	uM
2-[4-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)butyl]-2-methylpropanedioic acid	31738: Inhibitory activity against porcine heart or recombinant human E-type AMPDA	ki	6.0000	uM
6-[4-[[[(1R)-1-isoquinolin-8-ylethyl]amino]methyl]phenyl]pyridine-3-carboxylic acid	1801154: AMPD Enzymatic Activity Assay from Article 10.1016/j.chembiol.2014.09.011: “Inhibition of AMP deaminase activity does not improve glucose control in rodent models of insulin resistance or diabetes.”	ic50	7.3000	uM
2-carbamoyl-6-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)-2-methylhexanoic acid	31738: Inhibitory activity against porcine heart or recombinant human E-type AMPDA	ki	7.8000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression, increases mutagenesis	6
sodium arsenite	increases abundance, increases expression	4
Cyclosporine	affects cotreatment, increases expression	3
Acetaminophen	increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Thiram	increases expression	2
Aflatoxin B1	decreases expression, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
bisphenol F	affects cotreatment, increases methylation	1
sotorasib	decreases expression, affects cotreatment	1
propionaldehyde	increases expression	1
captax	increases expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	increases expression, affects cotreatment	1
bisphenol A	decreases methylation	1
testosterone undecanoate	increases expression	1
cinnamaldehyde	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	increases expression	1
1,6-hexamethylene diisocyanate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
ammonium hexachloroplatinate	increases expression	1
zinc chromate	increases abundance, increases expression	1
cupric chloride	increases expression	1
nickel sulfate	affects expression	1
7-aminocephalosporanic acid	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
diallyl trisulfide	increases expression	1
nefazodone	affects cotreatment, increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
chloropicrin	increases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2044562	Binding	Inhibition of human recombinant AMPD3	Synthesis and Biochemical Testing of 3-(Carboxyphenylethyl)imidazo[2,1-f][1,2,4]triazines as Inhibitors of AMP Deaminase. — ACS Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis