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 (top 4% of genes corpus-wide)
• Clinical variants (ClinVar): 248 total — 1 pathogenic, 3 likely-pathogenic
• GTEx eGene: eQTL in 44 tissues, sQTL in 11 (q < 0.05)
• Phenotypes (HPO): 8
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.82 (unconstrained)
• MANE Select transcript: NM_001025389
• Notable: 248 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 34 — 20 protein_coding, 7 nonsense_mediated_decay, 6 protein_coding_CDS_not_defined, 1 retained_intron

MANE Select: ENST00000396553

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 8, TSL 2: 4, TSL 3: 2, TSL 4: 2, TSL 5: 2

ENST00000396553, ENST00000295663, 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, ENST00000990826, ENST00000990827, ENST00001013344, ENST00001110235, ENST00001144183

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.

Highest expression (Bgee): gluteal muscle, dorsal motor nucleus of vagus nerve, tibialis anterior, cartilage tissue, inferior olivary complex.

Genetic regulation across tissues (GTEx eQTL / sQTL)

AMPD3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 44 tissues and its splicing (sQTL) in 11 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 55 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	7.0e-42	+0.47	11:10450191:A:G
Esophagus Muscularis	eqtl	8.5e-40	+0.64	11:10453920:G:A
Brain Putamen basal ganglia	eqtl	3.1e-29	+0.51	11:10452463:G:A
Brain Caudate basal ganglia	eqtl	1.2e-28	+0.46	11:10452342:C:T
Esophagus Gastroesophageal Junction	eqtl	2.0e-28	+0.61	11:10453920:G:A
Esophagus Mucosa	eqtl	2.5e-27	+0.39	11:10468868:T:C
Muscle Skeletal	eqtl	3.3e-25	+0.22	11:10455142:A:G
Brain Spinal cord cervical c-1	eqtl	1.3e-23	+0.70	11:10452342:C:T
Adipose Subcutaneous	eqtl	5.1e-23	+0.32	11:10455142:A:G
Nerve Tibial	eqtl	1.1e-22	+0.31	11:10453823:G:A
Brain Hippocampus	eqtl	3.1e-21	+0.43	11:10452463:G:A
Brain Nucleus accumbens basal ganglia	eqtl	2.3e-20	+0.35	11:10452342:C:T
Brain Substantia nigra	eqtl	2.1e-19	+0.59	11:10452342:C:T
Brain Hypothalamus	eqtl	3.5e-15	+0.41	11:10452463:G:A
Pancreas	eqtl	1.4e-14	+0.42	11:10450191:A:G
Stomach	eqtl	4.3e-14	+0.38	11:10455142:A:G
Brain Amygdala	eqtl	5.2e-14	+0.55	11:10452342:C:T
Cells Cultured fibroblasts	eqtl	2.2e-13	-0.23	11:10376646:A:G
Colon Sigmoid	eqtl	2.5e-12	+0.34	11:10455142:A:G
Artery Tibial	eqtl	2.0e-11	+0.22	11:10483093:A:C

FANTOM5 promoters

showing 10 of 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

showing 100 of 294 tissues 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
globus pallidus	UBERON:0001875	89.58	gold quality
blood	UBERON:0000178	89.57	gold quality
left adrenal gland cortex	UBERON:0035825	89.56	gold quality
amniotic fluid	UBERON:0000173	89.55	gold quality
substantia nigra pars reticulata	UBERON:0001966	89.25	gold quality
medial globus pallidus	UBERON:0002477	89.23	gold quality
spinal cord	UBERON:0002240	89.12	gold quality
adrenal gland	UBERON:0002369	88.99	gold quality
muscle organ	UBERON:0001630	88.89	gold quality
pituitary gland	UBERON:0000007	88.70	gold quality
midbrain	UBERON:0001891	88.62	gold quality
superior vestibular nucleus	UBERON:0007227	88.57	gold quality
substantia nigra	UBERON:0002038	88.56	gold quality
dorsal plus ventral thalamus	UBERON:0001897	88.20	gold quality
epithelium of nasopharynx	UBERON:0001951	88.05	gold quality
tongue squamous epithelium	UBERON:0006919	88.01	silver quality
esophagus squamous epithelium	UBERON:0006920	87.86	gold quality
vermiform appendix	UBERON:0001154	87.63	gold quality
substantia nigra pars compacta	UBERON:0001965	87.58	gold quality
squamous epithelium	UBERON:0006914	87.58	gold quality
palpebral conjunctiva	UBERON:0001812	87.51	gold quality
lymph node	UBERON:0000029	87.45	gold quality
parotid gland	UBERON:0001831	87.39	silver quality
adenohypophysis	UBERON:0002196	87.22	gold quality
monocyte	CL:0000576	86.91	gold quality
epithelium of esophagus	UBERON:0001976	86.90	gold quality
mononuclear cell	CL:0000842	86.84	gold quality
leukocyte	CL:0000738	86.79	gold quality
granulocyte	CL:0000094	86.74	gold quality
lateral nuclear group of thalamus	UBERON:0002736	86.55	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	86.43	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.38	gold quality
caecum	UBERON:0001153	86.09	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.02	gold quality
cranial nerve II	UBERON:0000941	85.63	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.30	gold quality
skeletal muscle tissue	UBERON:0001134	85.25	gold quality
skin of leg	UBERON:0001511	84.84	gold quality
stromal cell of endometrium	CL:0002255	84.59	gold quality
upper leg skin	UBERON:0004262	84.56	gold quality
biceps brachii	UBERON:0001507	84.35	gold quality
sperm	CL:0000019	84.27	gold quality
mucosa of urinary bladder	UBERON:0001259	84.20	gold quality
tonsil	UBERON:0002372	84.14	gold quality
spleen	UBERON:0002106	84.12	gold quality
triceps brachii	UBERON:0001509	84.08	gold quality
decidua	UBERON:0002450	84.08	gold quality
skin of abdomen	UBERON:0001416	84.01	gold quality
gingiva	UBERON:0001828	83.76	gold quality
oviduct epithelium	UBERON:0004804	83.72	gold quality
male germ cell	CL:0000015	83.71	gold quality
zone of skin	UBERON:0000014	83.48	gold quality
gingival epithelium	UBERON:0001949	83.35	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.29	gold quality
superior surface of tongue	UBERON:0007371	83.29	gold quality
nasal cavity mucosa	UBERON:0001826	83.23	gold quality
hypothalamus	UBERON:0001898	83.20	gold quality
cervix epithelium	UBERON:0004801	83.20	silver quality
putamen	UBERON:0001874	82.92	gold quality
middle temporal gyrus	UBERON:0002771	82.88	gold quality
muscle tissue	UBERON:0002385	82.84	gold quality
epithelial cell of pancreas	CL:0000083	82.76	silver quality
postcentral gyrus	UBERON:0002581	82.62	gold quality
buccal mucosa cell	CL:0002336	82.55	gold quality
tongue	UBERON:0001723	82.53	gold quality
Ammon’s horn	UBERON:0001954	82.51	gold quality
pharyngeal mucosa	UBERON:0000355	82.49	gold quality
parietal lobe	UBERON:0001872	82.30	gold quality
body of tongue	UBERON:0011876	82.30	gold quality
Brodmann (1909) area 46	UBERON:0006483	82.26	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	56.8	high
Locus coeruleus	tissue	25.3
Choroid plexus	tissue	24.4
Parathyroid gland	tissue	21.5	low
Nucleus accumbens	tissue	21.2
Appendix	tissue	18.8	low
Hippocampus	tissue	18.7	not detected
Tonsil	tissue	18.0	low
Caudate putamen	tissue	16.6
Lymph node	tissue	15.9	medium
Pituitary gland	tissue	15.8
Putamen	tissue	15.6
Adrenal gland	tissue	15.1	not detected
Postcentral gyrus	tissue	14.5
Skin 1	tissue	13.9	not detected
Frontal cortex	tissue	13.2
Basal ganglia	tissue	12.9	not detected
Thymus	tissue	12.5
Cerebral cortex	tissue	10.6	not detected
Hippocampal formation	tissue	10.6
Somatosensory cortex	tissue	10.6
Motor cortex	tissue	10.0
Fallopian tube	tissue	10.0	medium
Ventral forebrain	tissue	9.8
Retrosplenial cortex	tissue	9.4
Occipital cortex	tissue	9.3
Prefrontal cortex	tissue	9.2
Retrosplenial and cingulate cortex	tissue	9.2
Spleen	tissue	8.6	high
Superior colliculi	tissue	8.5
Urinary bladder	tissue	8.4	medium
Thalamus	tissue	8.4
Tongue	tissue	8.1
Skeletal muscle	tissue	8.0	low
Insular cortex	tissue	8.0
Midbrain	tissue	7.8
Pons	tissue	7.7
Entorhinal cortex	tissue	7.6
Vagina	tissue	7.1	not detected
Substantia nigra	tissue	6.8
Hypothalamus	tissue	6.6
Retina	tissue	6.5
Medulla oblongata	tissue	6.5
Temporal cortex	tissue	6.5
Prostate	tissue	6.4	not detected
Septum	tissue	6.4
Stomach 1	tissue	5.9	low
Rectum	tissue	5.9	low
Duodenum	tissue	5.9	medium
Gallbladder	tissue	5.8	low
Periaqueductal gray	tissue	5.6
Esophagus	tissue	5.0	low
Amygdala	tissue	5.0
Lung	tissue	4.8	not detected
Spinal cord	tissue	4.8
Olfactory bulb	tissue	4.8
Small intestine	tissue	4.7	medium
Salivary gland	tissue	4.4	low
Colon	tissue	4.4	medium
Kidney	tissue	4.3	medium

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Parieto-temporal junction (white matter) (60.2), Cerebellar white matter (53.2), Temporal white matter (50.5), Corpus callosum, splenium (white matter) (49.1), Corpus callosum, genu (white matter) (48.5).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, MYC

miRNA regulators (miRDB)

Targeting AMPD3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 86 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 1.53e-12, LOEUF 0.817, missense Z 2.08 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000396553 — one region, missense o/e 0.87.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1096344) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 9 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased leukocyte cell number	1
lung inflammation	1
increased mean corpuscular volume	1
abnormal erythrocyte physiology	1
abnormal nucleotide metabolism	1
abnormal behavior	1
abnormal oxygen consumption	1
abnormal enzyme/coenzyme activity	1
increased erythrocyte osmotic fragility	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
Oryctolagus cuniculus	P81072	96.2%	Diamond
Arabidopsis thaliana	O80452	70.2%	Diamond
Oryza sativa Japonica Group	Q84NP7	70.1%	Diamond
Hahella chejuensis KCTC 2396	Q2SLW3	69.6%	Diamond
Saccharomyces cerevisiae S288C	P15274	64.2%	Diamond
Schizosaccharomyces pombe 972h-	P50998	64.2%	Diamond
Dictyostelium discoideum	Q54DD0	61.3%	Diamond
Vibrio parahaemolyticus RIMD 2210633	Q87GM3	61.0%	Diamond
Pelodictyon luteolum DSM 273	Q3B2Q0	60.7%	Diamond
Opitutus terrae PB90-1	B1ZYW1	42.6%	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
MIR4485	ncRNA	100616263
ADM	protein-coding	133
SBF2	protein-coding	81846
IRAG1-AS1	ncRNA	100129827
CAND1.11	ncRNA	100130460
LYVE1	protein-coding	10894
RNF141	protein-coding	50862
IRAG1	protein-coding	10335

Protein

Protein identifiers

AMP deaminase 3 — Q01432 (reviewed: Q01432)

Alternative names: AMP deaminase isoform E, Erythrocyte AMP deaminase

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

• 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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of nucleotide metabolism

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nuclear membrane; nucleoli

Antibody reliability (HPA): IH uncertain · IF approved

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)

Position	Role
608	proton acceptor

Ligand- & substrate-binding residues (8)

Position	Role
663	Zn(2+)
664–667	substrate
317	Zn(2+)
319	substrate
319	Zn(2+)
388–393	substrate
586	Zn(2+)
589	substrate

Post-translational modifications (2)

Type	Positions
Phosphoserine	85, 107

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-6798695	Neutrophil degranulation	curated
R-HSA-74217	Purine salvage	curated
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-1430728	Metabolism	—
R-HSA-15869	Metabolism of nucleotides	—
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 (12): 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), erythrocyte homeostasis (GO:0034101), ADP metabolic process (GO:0046031), ADP catabolic process (GO:0046032), ATP metabolic process (GO:0046034), GTP metabolic process (GO:0046039)

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

5 top-level categories:

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

GO top-level categories

32 GO namespaces:

Category	Terms
purine ribonucleotide metabolic process	4
purine ribonucleotide catabolic process	2
purine ribonucleoside monophosphate metabolic process	2
nucleoside triphosphate metabolic process	2
purine ribonucleoside triphosphate metabolic process	2
cellular anatomical structure	2
purine ribonucleotide biosynthetic process	1
purine ribonucleoside monophosphate biosynthetic process	1
IMP metabolic process	1
purine ribonucleoside monophosphate catabolic process	1
AMP metabolic process	1
IMP biosynthetic process	1
purine ribonucleotide salvage	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
myeloid cell homeostasis	1
purine ribonucleoside diphosphate metabolic process	1
purine ribonucleoside diphosphate catabolic process	1
ADP metabolic 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

showing 15 of 1,038 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AMPD3	ADSS2	P30520	916
AMPD3	ADA	P00813	888
AMPD3	ALDOB	P05062	746
AMPD3	PNP	P00491	720
AMPD3	ADK	P55263	694
AMPD3	ADSL	P30566	688
AMPD3	APRT	P07741	685
AMPD3	KHK	P50053	603
AMPD3	GMPS	P49915	593
AMPD3	IMPDH2	P12268	581
AMPD3	MPI	P34949	533
AMPD3	GUSB	P08236	528
AMPD3	IMPDH1	P20839	525
AMPD3	ASS1	P00966	524
AMPD3	GDA	Q9Y2T3	510

IntAct

Human interaction partners of AMPD3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

5 partners by confidence:

Partner	Interaction type	MIscore	Records
HSP90AB1	association	0.500	2
AMPD2	physical association	0.400	1
H2BC9	physical association	0.400	1
H3-4	physical association	0.400	1
TTC14	association	0.350	1

BioGRID (16 interactions; top human partners by supporting records): ALB (Affinity Capture-MS), AMPD1 (Two-hybrid), AMPD2 (Affinity Capture-MS), CCR1 (Affinity Capture-MS), CIT (Affinity Capture-MS), CSK (Synthetic Lethality), HIST1H2BH (Cross-Linking-MS (XL-MS)), HIST3H3 (Cross-Linking-MS (XL-MS)), ITGB2 (Affinity Capture-MS), KCNIP1 (Two-hybrid), LRBA (Co-fractionation), PARP9 (Proximity Label-MS), RAD21 (Affinity Capture-Western), TMEM259 (Co-fractionation), TTC14 (Affinity Capture-MS)

SIGNOR signaling

4 signaling 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

Genetic variants

Variant evidence for AMPD3: 248 ClinVar records (4 pathogenic / likely pathogenic); 31 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	3
Uncertain significance	174
Likely benign	26
Benign	16

Top pathogenic / likely-pathogenic (4)

Showing all 4 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
18270	NM_001025389.2(AMPD3):c.1717C>T (p.Arg573Cys)	Pathogenic	criteria provided, single submitter	3
4367070	NM_001025389.2(AMPD3):c.809+1G>C	Likely pathogenic	criteria provided, single submitter	2
3065721	NM_001025389.2(AMPD3):c.1815_1816del (p.Ile606fs)	Likely pathogenic	criteria provided, single submitter	1
4526607	NM_001025389.2(AMPD3):c.648dup (p.Asn217fs)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore AMPD3’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 48 predictions of 1,410):

Position(s)	Effect	Δscore	Sites
11:10461513–10461514	acceptor_loss	1.0000	6
11:10461741–10461742	donor_loss	1.0000	5
11:10482226–10482227	donor_loss	1.0000	4
11:10485040–10485041	donor_loss	1.0000	5
11:10487365–10487366	donor_loss	1.0000	5
11:10493544–10493545	donor_loss	1.0000	5
11:10494897–10494898	acceptor_loss	1.0000	5
11:10495031–10495032	donor_loss	1.0000	4
11:10495568–10495569	acceptor_loss	1.0000	6
11:10500250–10500251	donor_loss	1.0000	3

AlphaMissense

2,347 missense substitutions predicted likely pathogenic (of 5,084 scored), across 520 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
M324	9	0.876	0.981
H608	8	0.999	1.000
D663	8	0.999	1.000
D307	8	0.998	0.999
D315	8	0.998	0.999
H317	8	0.998	0.999
H319	8	0.997	1.000
D387	8	0.997	0.999
D524	8	0.997	0.999
H586	8	0.996	0.999
F640	8	0.996	1.000
D527	8	0.995	0.999
D664	8	0.995	0.999
F386	8	0.994	1.000
H669	8	0.994	0.999
F389	8	0.992	1.000
F668	8	0.992	1.000
D528	8	0.989	0.999
H595	8	0.988	0.997
S635	8	0.988	1.000

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Kidney Chromophobe)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Chromophobe (TCGA)	unfavorable	0.000798

Disease associations

OMIM: gene MIM:102772 | disease phenotypes:

GenCC curated gene-disease

2 curated gene-disease records:

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

Mondo (2): adenosine monophosphate deaminase deficiency (MONDO:0013028), (MONDO:0020734)

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

HPO phenotypes

8 phenotypes (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

showing 30 of 31 associations:

Study	Trait	p-value
GCST007099_148	Systolic blood pressure	1e-20
GCST90002405_547	Reticulocyte count	2e-19
GCST90002385_505	High light scatter reticulocyte count	1e-18
GCST010241_67	Apolipoprotein A1 levels	6e-18
GCST90002386_194	High light scatter reticulocyte percentage of red cells	2e-15
GCST90002406_343	Reticulocyte fraction of red cells	2e-15
GCST010083_44	Hemoglobin levels	8e-15
GCST90000025_608	Appendicular lean mass	2e-14
GCST90014033_20	Haemorrhoidal disease	1e-13
GCST007094_169	Diastolic blood pressure	2e-13
GCST007096_213	Pulse pressure	6e-13
GCST010242_348	HDL cholesterol levels	1e-12
GCST90002384_310	Hemoglobin	1e-12
GCST90002383_128	Hematocrit	1e-10
GCST90020026_741	Hip index	1e-10
GCST90020028_1095	Hip circumference adjusted for BMI	3e-10
GCST90002383_127	Hematocrit	1e-9
GCST90002384_309	Hemoglobin	1e-9
GCST90002399_110	Neutrophil percentage of white cells	1e-9
GCST90020028_1093	Hip circumference adjusted for BMI	1e-9
GCST90002407_392	White blood cell count	4e-9
GCST010302_45	Cutaneous melanoma or hair colour	4e-8
GCST000755_10	HDL cholesterol	5e-8
GCST002223_29	HDL cholesterol	5e-8
GCST010241_205	Apolipoprotein A1 levels	5e-8
GCST012228_326	Waist-hip index	5e-8
GCST007250_10	Nonunion in individuals with fractures	2e-7
GCST007095_55	Systolic blood pressure	5e-7
GCST007203_12	Total cholesterol levels	1e-6
GCST004232_59	HDL cholesterol levels	3e-6

EFO canonical traits (from GWAS)

15 canonical traits:

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

1 disease descriptors:

Descriptor	Name	Tree numbers
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

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 617 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL284483	COFORMYCIN	2	617

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

48 measured of 49 human assays (49 total across all organisms); most potent 48 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
1-Benzyloxy-4-[2-(8-hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-ethyl]-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid	KI	9 nM
4-[2-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-ethyl]-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid	KI	15 nM
4-[2-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-ethyl]-naphthalene-2-carboxylic acid	KI	20 nM
2-[4-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-butyl]-2-(3-trifluoromethyl-benzyl)-malonic acid 1(C2H5)3N.1.5H2O	KI	29 nM
4-[2-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-ethyl]-1-methoxy-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid	KI	30 nM
6-[4-({[(1S)-1-(isoquinolin-8-yl)ethyl]amino}methyl)phenyl]pyridine-3-carboxylic acid (Compound 3)	IC50	38 nM
2-[4-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-butyl]-2-(4-trifluoromethyl-benzyl)-malonic acid (2H2O)	KI	40 nM
4-[2-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-ethyl]-3-methoxy-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid	KI	40 nM
2-[4-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-butyl]-2-(2-trifluoromethyl-benzyl)-malonic acid (3H2O)	KI	41 nM
1,3-Dichloro-4-[2-(8-hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-ethyl]-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid	KI	50 nM
4-[2-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-ethyl]-1-isopropoxy-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid	KI	90 nM
2-Benzyl-2-[4-(8-hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-butyl]-malonic acid 0.5H2O.0.5(C2H5)2O	KI	170 nM
4-[2-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-ethyl]-8-trifluoromethyl-naphthalene-2-carboxylic acid	KI	220 nM
2-[4-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-butyl]-2-(2-trifluoromethyl-benzyl)-malonic acid dibenzyl ester	KI	250 nM
1,3-Dichloro-4-[2-(8-hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-ethyl]-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid benzyl ester	KI	300 nM
1-Benzyloxy-4-[2-(8-hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-ethyl]-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid ethyl ester	KI	300 nM
2-[4-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-butyl]-malonic acid monobenzyl ester (1H2O)	KI	360 nM
2-[4-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-butyl]-2-(2-trifluoromethyl-benzyl)-malonic acid diethyl ester	KI	360 nM
2-Benzyl-6-(8-hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-hexanoic acid	KI	410 nM
3-[2-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-ethyl]-benzoic acid	KI	500 nM
1,3-Dichloro-4-[2-(8-hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-ethyl]-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid ethyl ester	KI	500 nM
1-Bromo-4-[2-(8-hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-ethyl]-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid	IC50	500 nM
2-[4-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-butyl]-2-methyl-malonic acid monobenzyl ester (1.33H2O)	KI	900 nM
CHEMBL2042530	IC50	900 nM
6-Bromo-4-[2-(8-hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-ethyl]-naphthalene-2-carboxylic acid	KI	960 nM
1-Bromo-4-[2-(8-hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-ethyl]-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid ethyl ester	KI	1000 nM
6-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-2-methyl-2-(3-trifluoromethyl-benzyl)-hexanoic acid 1H2O.0.5CH3CO2H	KI	1200 nM
2-(4-Chloro-benzylcarbamoyl)-6-(8-hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-hexanoic acid 1H2O.025CH3CO2H	KI	1300 nM
4-[2-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-ethyl]-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid ethyl ester	KI	1300 nM
4-[2-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-ethyl]-naphthalene-2-carboxylic acid methyl ester	KI	1800 nM
6-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-2-methyl-2-phenethylcarbamoyl-hexanoic acid 0.75H2O.0.3CH3CO2H	KI	2100 nM
4-[2-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-ethyl]-1-methoxy-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid ethyl ester	KI	2300 nM
2-Benzylcarbamoyl-6-(8-hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-hexanoic acid 1.5H2O.0.15CH3CO2H	KI	2400 nM
4-[2-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-ethyl]-3-methoxy-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid ethyl ester	KI	2400 nM
2-Benzyl-2-[4-(8-hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-butyl]-malonic acid diethyl ester (0.5H2O)	KI	2600 nM
2-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-5-hydroxymethyl-tetrahydro-furan-3,4-diol (Coformycin)	KI	3000 nM
4-[2-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-ethyl]-1-isopropoxy-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid ethyl ester	KI	3800 nM
6-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-hexanoic acid	KI	4200 nM
4-[2-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-ethyl]-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid benzyl ester	KI	5000 nM
2-[4-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-butyl]-malonic acid (1.33H2O)	KI	5100 nM
2-[4-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-butyl]-2-methyl-malonic acid dibenzyl ester	KI	5200 nM
2-Cyclohexylcarbamoyl-6-(8-hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-2-methyl-hexanoic acid 2H2O.0.5CH3CO2H	KI	5200 nM
2-[4-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-butyl]-2-methyl-malonic acid (1H2O.1(C6H11)2NH)	KI	6000 nM
2-Carbamoyl-6-(8-hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-2-methyl-hexanoic acid 0.75H2O.0.025CH3CO2H	KI	7800 nM
6-Bromo-4-[2-(8-hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-ethyl]-naphthalene-2-carboxylic acid ethyl ester	KI	14000 nM
4-[2-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-ethyl]-8-trifluoromethyl-naphthalene-2-carboxylic acid ethyl ester	KI	35000 nM
2-[4-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-butyl]-2-methyl-malonic acid diethyl ester	KI	44800 nM
CHEMBL2042529	IC50	370000 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	increases expression, affects cotreatment	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	affects cotreatment, increases expression	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)

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

5 trials:

NCT	Phase	Status	Title
NCT03600649	Phase 1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT05266196	Phase 1/2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	Phase 1/2	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	Phase 1/2	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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for AMPD3 across ~30M SureChEMBL compounds — explore on Sugi Predict.