AMPD2

Summary

AMPD2 (adenosine monophosphate deaminase 2, HGNC:469) is a protein-coding gene on chromosome 1p13.3, encoding AMP deaminase 2 (Q01433). AMP deaminase plays a critical role in energy metabolism.

The protein encoded by this gene is important in purine metabolism by converting AMP to IMP. The encoded protein, which acts as a homotetramer, is one of three AMP deaminases found in mammals. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 271 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pontocerebellar hypoplasia type 9 (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 561 total — 22 pathogenic, 20 likely-pathogenic
• Phenotypes (HPO): 47
• Druggable target: yes
• MANE Select transcript: NM_001368809

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:469
Approved symbol	AMPD2
Name	adenosine monophosphate deaminase 2
Location	1p13.3
Locus type	gene with protein product
Status	Approved
Aliases	SPG63
Ensembl gene	ENSG00000116337
Ensembl biotype	protein_coding
OMIM	102771
Entrez	271

Gene structure

Transcript identifiers

Ensembl transcripts: 57 — 24 nonsense_mediated_decay, 16 retained_intron, 11 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000256578, ENST00000342115, ENST00000358729, ENST00000369840, ENST00000459643, ENST00000467071, ENST00000469039, ENST00000474459, ENST00000476688, ENST00000479919, ENST00000486282, ENST00000524975, ENST00000525415, ENST00000526301, ENST00000527846, ENST00000528270, ENST00000528454, ENST00000528667, ENST00000528958, ENST00000529299, ENST00000531203, ENST00000531734, ENST00000532851, ENST00000533132, ENST00000534144, ENST00000652975, ENST00000654851, ENST00000655992, ENST00000659122, ENST00000663749, ENST00000667949, ENST00000668421, ENST00000673915, ENST00000679379, ENST00000679593, ENST00000679880, ENST00000679892, ENST00000679981, ENST00000680132, ENST00000680148, ENST00000680170, ENST00000680192, ENST00000680519, ENST00000680531, ENST00000680820, ENST00000680832, ENST00000680929, ENST00000681108, ENST00000681121, ENST00000681132, ENST00000681181, ENST00000681218, ENST00000681246, ENST00000681496, ENST00000681834, ENST00000681862, ENST00000906732

RefSeq mRNA: 5 — MANE Select: NM_001368809 NM_001257361, NM_001308170, NM_001368809, NM_004037, NM_139156

CCDS: CCDS58016, CCDS804, CCDS805

Canonical transcript exons

ENST00000528667 — 19 exons

Exon	Start	End
ENSE00000913099	109629796	109629916
ENSE00001881763	109630943	109632051
ENSE00001900591	109619837	109620278
ENSE00001946054	109620914	109621266
ENSE00003459529	109627429	109627518
ENSE00003470581	109630233	109630406
ENSE00003514555	109628364	109628495
ENSE00003532630	109628643	109628806
ENSE00003552314	109626726	109626912
ENSE00003560412	109626160	109626228
ENSE00003569676	109629109	109629235
ENSE00003569771	109626319	109626427
ENSE00003572883	109627175	109627316
ENSE00003573762	109630683	109630793
ENSE00003579746	109629327	109629490
ENSE00003606938	109625662	109625792
ENSE00003632436	109625303	109625433
ENSE00003649890	109628083	109628277
ENSE00003650525	109627774	109627903

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 98.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.2783 / max 3051.3364, expressed in 1811 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4428	18.9748	1802
4433	7.0337	1345
4429	0.9344	372
4430	0.8954	510
4435	0.4764	167
4432	0.3520	112
4426	0.1580	17
4425	0.1417	28
4431	0.1230	54
4434	0.1189	66

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adenohypophysis	UBERON:0002196	98.72	gold quality
pituitary gland	UBERON:0000007	98.55	gold quality
granulocyte	CL:0000094	97.96	gold quality
nucleus accumbens	UBERON:0001882	97.30	gold quality
pancreatic ductal cell	CL:0002079	96.86	gold quality
stromal cell of endometrium	CL:0002255	96.52	gold quality
right frontal lobe	UBERON:0002810	96.51	gold quality
monocyte	CL:0000576	96.34	gold quality
putamen	UBERON:0001874	96.31	gold quality
caudate nucleus	UBERON:0001873	96.27	gold quality
mononuclear cell	CL:0000842	96.17	gold quality
leukocyte	CL:0000738	96.15	gold quality
blood	UBERON:0000178	96.08	gold quality
spleen	UBERON:0002106	96.06	gold quality
metanephros cortex	UBERON:0010533	95.90	gold quality
prefrontal cortex	UBERON:0000451	95.61	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.48	gold quality
endothelial cell	CL:0000115	95.42	gold quality
cingulate cortex	UBERON:0003027	95.36	gold quality
right ovary	UBERON:0002118	95.31	gold quality
anterior cingulate cortex	UBERON:0009835	95.31	gold quality
left uterine tube	UBERON:0001303	95.28	gold quality
right lung	UBERON:0002167	95.24	gold quality
right lobe of liver	UBERON:0001114	95.18	gold quality
gall bladder	UBERON:0002110	95.00	gold quality
right adrenal gland	UBERON:0001233	94.98	gold quality
right adrenal gland cortex	UBERON:0035827	94.88	gold quality
left adrenal gland cortex	UBERON:0035825	94.87	gold quality
left ovary	UBERON:0002119	94.84	gold quality
amygdala	UBERON:0001876	94.78	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

28 targeting AMPD2, 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-5692A	100.00	74.40	6850
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-198	98.70	67.32	920
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-210-5P	98.57	64.37	832
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-3138	98.41	67.53	744
HSA-MIR-484	98.16	66.92	1074
HSA-MIR-3155A	98.16	66.09	965
HSA-MIR-3155B	98.16	66.09	965
HSA-MIR-4640-5P	97.42	66.33	1543
HSA-MIR-4726-5P	97.24	65.67	1299
HSA-MIR-541-3P	96.07	66.11	1271
HSA-MIR-654-5P	96.07	66.18	1280
HSA-MIR-25-5P	87.02	64.95	84

Literature-anchored findings (GeneRIF, showing 11)

• N-terminal extensions of the AMPD2 polypeptide influence ATP regulation of isoform L. (PMID:12745092)
• Study concluded that AMPD2 as necessary for guanine nucleotide biosynthesis and protein translation and provide evidence that AMP deaminase activity is critical during neurogenesis. Patients with mutations in AMPD2 have characteristic brain imaging features of pontocerebellar hypoplasia due to loss of brainstem and cerebellar parenchyma. (PMID:23911318)
• In human HepG2 cells, AMPD2 activation counterregulates AMPK and increases intracellular glucose production, in association with up-regulation of PEPCK and G6Pc. (PMID:24755741)
• tofacitinib increases the cellular levels of adenosine, which is known to have anti-inflammatory activity, through the downregulation of AMPD2. This would be a novel functional aspect of tofacitinib. (PMID:25496463)
• Here we report the clinical and genetic analysis of an individual with PCH9 secondary to a novel missense variant with strong evidence of pathogenicity, located outside the catalytic domain of AMPD2 (PMID:28168832)
• The existence of various AMPD2 isoforms with different functions possibly explains the variability in phenotypes associated with AMPD2 variants: variants leaving some of the isoforms intact may cause spastic paraplegia type 63 , while those affecting all isoforms may result in the severe and early-onset Pontocerebellar hypoplasia type 9. (PMID:29463858)
• Data suggest that adenosine monophosphate deaminase 2 (AMPD2) may serve as a biomarker for outcome prediction in undifferentiated pleomorphic sarcoma (UPS). (PMID:30267407)
• These data demonstrate a novel mechanism in Systemic lupus erythematosus development that involves the targeting of AMPD2 expression by NovelmiRNA-25. (PMID:30577810)
• Homozygous variants in AMPD2 and COL11A1 lead to a complex phenotype of pontocerebellar hypoplasia type 9 and Stickler syndrome type 2. (PMID:31833174)
• Delineating the phenotype and genetic basis of AMPD2-related pontocerebellar hypoplasia. (PMID:36445597)
• IMPDH2 filaments protect from neurodegeneration in AMPD2 deficiency. (PMID:39075237)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ampd2b	ENSDARG00000029952
danio_rerio	ampd2a	ENSDARG00000104491
mus_musculus	Ampd2	ENSMUSG00000027889
rattus_norvegicus	Ampd2	ENSRNOG00000019240
drosophila_melanogaster	AMPdeam	FBGN0052626
caenorhabditis_elegans		WBGENE00016415

Paralogs (2): AMPD1 (ENSG00000116748), AMPD3 (ENSG00000133805)

Protein

Protein identifiers

AMP deaminase 2 — Q01433 (reviewed: Q01433)

Alternative names: AMP deaminase isoform L

All UniProt accessions (15): A0A590UJD1, A0A590UJX5, A0A590UJY6, A0A590UK85, A0A7P0T999, A0A7P0TB79, A0A7P0Z4H6, A0A804CCZ3, A0A804H2H4, E9PIJ1, E9PJF6, Q01433, H0Y360, H0YE32, H0YF16

UniProt curated annotations — full annotation on UniProt →

Function. AMP deaminase plays a critical role in energy metabolism. Catalyzes the deamination of AMP to IMP and plays an important role in the purine nucleotide cycle.

Subunit / interactions. Homotetramer.

Tissue specificity. Highly expressed in cerebellum.

Disease relevance. Pontocerebellar hypoplasia 9 (PCH9) [MIM:615809] A form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum, evident upon brain imaging. PCH9 features include severely delayed psychomotor development, progressive microcephaly, spasticity, seizures, and brain abnormalities, including brain atrophy, thin corpus callosum, and delayed myelination. The disease is caused by variants affecting the gene represented in this entry. Spastic paraplegia 63, autosomal recessive (SPG63) [MIM:615686] A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. 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 (4)

UniProt ID	Names	Canonical?
Q01433-1	Ex1B-2-3	yes
Q01433-2	Ex1A-2-3
Q01433-4	Ex1B-3
Q01433-5	5

RefSeq proteins (5): NP_001244290, NP_001295099, NP_001355738, NP_004028, NP_631895 (=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 (90 total): helix 35, strand 17, modified residue 11, binding site 8, turn 5, splice variant 4, sequence variant 4, sequence conflict 2, chain 1, region of interest 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
4NO3	X-RAY DIFFRACTION	1.7
4NO5	X-RAY DIFFRACTION	2.1
8HU6	X-RAY DIFFRACTION	2.33
8HUB	X-RAY DIFFRACTION	3.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01433-F1	81.28	0.59

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): 655 (proton acceptor)

Ligand- & substrate-binding residues (8): 710; 711–714; 364; 366; 366; 435–440; 633; 636

Post-translational modifications (11): 22, 45, 46, 64, 80, 91, 97, 114, 134, 136, 138

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-74217	Purine salvage
R-HSA-1430728	Metabolism
R-HSA-15869	Metabolism of nucleotides
R-HSA-8956321	Nucleotide salvage

MSigDB gene sets: 320 (showing top): RNGTGGGC_UNKNOWN, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_STEROL_HOMEOSTASIS, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CYCLIC_NUCLEOTIDE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, RIZKI_TUMOR_INVASIVENESS_3D_DN, GOBP_KIDNEY_EPITHELIUM_DEVELOPMENT, USF_C, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PURINE_CONTAINING_COMPOUND_SALVAGE

GO Biological Process (13): IMP biosynthetic process (GO:0006188), GMP salvage (GO:0032263), IMP salvage (GO:0032264), cholesterol homeostasis (GO:0042632), AMP metabolic process (GO:0046033), ATP metabolic process (GO:0046034), GTP metabolic process (GO:0046039), cyclic purine nucleotide metabolic process (GO:0052652), podocyte development (GO:0072015), energy homeostasis (GO:0097009), nucleoside phosphate metabolic process (GO:0006753), nucleotide metabolic process (GO:0009117), purine ribonucleoside monophosphate biosynthetic process (GO:0009168)

GO Molecular Function (6): AMP deaminase activity (GO:0003876), identical protein binding (GO:0042802), metal ion binding (GO:0046872), protein binding (GO:0005515), hydrolase activity (GO:0016787), deaminase activity (GO:0019239)

GO Cellular Component (1): cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Nucleotide salvage	1
Metabolism	1
Metabolism of nucleotides	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
purine ribonucleotide metabolic process	3
purine ribonucleotide salvage	2
purine ribonucleoside monophosphate metabolic process	2
purine ribonucleoside triphosphate metabolic process	2
purine ribonucleotide biosynthetic process	1
purine ribonucleoside monophosphate biosynthetic process	1
IMP metabolic process	1
GMP biosynthetic process	1
IMP biosynthetic process	1
sterol homeostasis	1
purine nucleotide metabolic process	1
cyclic nucleotide metabolic process	1
podocyte differentiation	1
glomerular epithelial cell development	1
multicellular organismal-level homeostasis	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
protein binding	1
cation binding	1
binding	1
catalytic activity	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1800 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AMPD2	ADSS2	P30520	921
AMPD2	ADA	P00813	901
AMPD2	PNP	P00491	739
AMPD2	ADSL	P30566	729
AMPD2	ADK	P55263	728
AMPD2	GNAI3	P08754	726
AMPD2	ALDOB	P05062	724
AMPD2	APRT	P07741	699
AMPD2	GMPS	P49915	669
AMPD2	KHK	P50053	623
AMPD2	IMPDH2	P12268	582
AMPD2	IMPDH1	P20839	582
AMPD2	GDA	Q9Y2T3	579
AMPD2	NT5C2	P49902	569
AMPD2	ASS1	P00966	543

IntAct

91 interactions, top by confidence:

A	B	Type	Score
CTBP1	ZEB2	psi-mi:“MI:0914”(association)	0.800
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
NME7	TUBG1	psi-mi:“MI:0914”(association)	0.730
HIRIP3	CSNK2B	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
HIRIP3	AMPD2	psi-mi:“MI:0915”(physical association)	0.710
CCNDBP1	AMPD2	psi-mi:“MI:0915”(physical association)	0.670
AMPD2	CCNDBP1	psi-mi:“MI:0915”(physical association)	0.670
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
GPR156	PLD2	psi-mi:“MI:0914”(association)	0.640
SDC2	PDPK1	psi-mi:“MI:0914”(association)	0.640
AMPD2	SDC2	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAZ	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
GPBP1L1	CNOT1	psi-mi:“MI:0914”(association)	0.530
DCAF8	TCP1	psi-mi:“MI:0914”(association)	0.530
DCAF8	DCAF8L1	psi-mi:“MI:0914”(association)	0.530
RNPS1	CASC3	psi-mi:“MI:0914”(association)	0.530
PHF8	AMPD2	psi-mi:“MI:0914”(association)	0.530
CD44	PDPK1	psi-mi:“MI:0914”(association)	0.530
HDGFL2	CDC7	psi-mi:“MI:0914”(association)	0.530
TERF1	AMPD2	psi-mi:“MI:0915”(physical association)	0.510

BioGRID (133): AMPD2 (Two-hybrid), CCNDBP1 (Two-hybrid), AMPD2 (Affinity Capture-MS), AMPD2 (Affinity Capture-MS), TBC1D9B (Co-fractionation), AMPD2 (Affinity Capture-MS), AMPD2 (Affinity Capture-MS), AMPD2 (Affinity Capture-MS), AMPD2 (Affinity Capture-MS), AMPD2 (Affinity Capture-MS), AMPD2 (Affinity Capture-MS), AMPD2 (Affinity Capture-MS), AMPD2 (Affinity Capture-MS), AMPD2 (Affinity Capture-MS), AMPD2 (Affinity Capture-MS)

ESM2 similar proteins: A0JMH0, A2ARP1, A5PK74, A7Z050, A9JTG5, B5DE73, B5DFG1, D3YY23, D3ZU57, O00562, O35954, O43304, P0C644, P0CB42, P16386, Q01433, Q02356, Q09200, Q10468, Q32P28, Q3SZL5, Q3U308, Q3V1T4, Q4KLM6, Q5HZW3, Q5RDF1, Q5RF50, Q5U2N3, Q5ZMM1, Q68J42, Q6ICH7, Q6JHU7, Q6PD26, Q6PFW1, Q6YRM6, Q80VP9, Q86TL0, Q8BGV9, Q8BGW1, Q8CG71

Diamond homologs: A1RDZ6, A3CYL9, A6T9W8, A6WUH7, A9KWZ3, B1ZYW1, B5XWQ7, O08739, O09178, O80452, P10759, P15274, P23109, P50998, Q01432, Q01433, Q02356, Q0HD92, Q20YN2, Q3B2Q0, Q3V1D3, Q54DD0, Q553U5, Q84NP7, Q9DBT5, Q9P6I7, P38150, P40361, A0L2R5, A4YCD7, A5I0I2, A7FSN7, A7GC28, B1IHX4, B1KY93, B8EDT7, C1FVJ1, P81072, P81073, Q0HPH4

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
AMPD2	“down-regulates quantity”	AMP	“chemical modification”
AMPD2	“down-regulates quantity”	water	“chemical modification”
AMPD2	“up-regulates quantity”	IMP	“chemical modification”
AMPD2	“up-regulates quantity”	ammonium	“chemical modification”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 99 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	8	73.6×	8e-12
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	8	73.6×	8e-12
Activation of BAD and translocation to mitochondria	7	73.0×	3e-10
Activation of BH3-only proteins	7	47.6×	6e-09
RHO GTPases activate PKNs	8	34.8×	5e-09
Intrinsic Pathway for Apoptosis	7	28.1×	2e-07
FOXO-mediated transcription	5	23.0×	6e-05
Apoptosis	8	18.4×	5e-07

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	21.1×	2e-03
intracellular protein localization	8	9.6×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	22
Likely pathogenic	20
Uncertain significance	216
Likely benign	216
Benign	42

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
101075	NM_001368809.2(AMPD2):c.157del (p.Cys53fs)	Pathogenic
1027468	NM_001368809.2(AMPD2):c.808del (p.Arg270fs)	Pathogenic
1098293	NM_001368809.2(AMPD2):c.247G>T (p.Glu83Ter)	Pathogenic
1180624	NM_001368809.2(AMPD2):c.532-1G>T	Pathogenic
132810	NM_001368809.2(AMPD2):c.2172G>C (p.Glu724Asp)	Pathogenic
132811	NM_001368809.2(AMPD2):c.885C>A (p.Tyr295Ter)	Pathogenic
132812	NM_001368809.2(AMPD2):c.2215G>T (p.Asp739Tyr)	Pathogenic
1339563	NM_001368809.2(AMPD2):c.895C>T (p.Gln299Ter)	Pathogenic
1991577	NM_001368809.2(AMPD2):c.-43_-24dup	Pathogenic
2004862	NM_001368809.2(AMPD2):c.319C>T (p.Gln107Ter)	Pathogenic
225763	NM_001368809.2(AMPD2):c.2094C>G (p.Tyr698Ter)	Pathogenic
2500190	NM_001368809.2(AMPD2):c.265_277del (p.Ala89fs)	Pathogenic
3758013	NM_001368809.2(AMPD2):c.42del (p.Lys14fs)	Pathogenic
429743	NM_001368809.2(AMPD2):c.531+2T>G	Pathogenic
4785536	NM_001368809.2(AMPD2):c.2007C>A (p.Tyr669Ter)	Pathogenic
4787223	NM_001368809.2(AMPD2):c.886_887del (p.Tyr295_Pro296insTer)	Pathogenic
4789804	NM_001368809.2(AMPD2):c.-90_-69dup	Pathogenic
4790266	NM_001368809.2(AMPD2):c.-42dup	Pathogenic
488467	NM_001368809.2(AMPD2):c.2165T>G (p.Leu722Arg)	Pathogenic
810627	NM_001368809.2(AMPD2):c.333del (p.Gln112fs)	Pathogenic
871869	NM_001368809.2(AMPD2):c.134_138del (p.Arg45fs)	Pathogenic
975089	NM_001368809.2(AMPD2):c.1198C>T (p.Gln400Ter)	Pathogenic
1098294	NM_001368809.2(AMPD2):c.1859G>T (p.Arg620Leu)	Likely pathogenic
1325790	NM_001368809.2(AMPD2):c.2366G>A (p.Arg789His)	Likely pathogenic
1334982	NM_001368809.2(AMPD2):c.271dup (p.Tyr91fs)	Likely pathogenic
2031731	NM_001368809.2(AMPD2):c.1408-3_1418del	Likely pathogenic
224991	NM_001368809.2(AMPD2):c.971G>C (p.Arg324Pro)	Likely pathogenic
225018	NM_001368809.2(AMPD2):c.1070A>G (p.Asn357Ser)	Likely pathogenic
2503047	NM_001368809.2(AMPD2):c.1858C>A (p.Arg620Ser)	Likely pathogenic
3338426	GRCh37/hg19 1p13.3(chr1:110163633-110173775)x0	Likely pathogenic

SpliceAI

2779 predictions. Top by Δscore:

Variant	Effect	Δscore
1:109625657:CCCA:C	acceptor_loss	1.0000
1:109625658:CCA:C	acceptor_loss	1.0000
1:109625659:CAG:C	acceptor_loss	1.0000
1:109625660:A:AG	acceptor_gain	1.0000
1:109625660:AG:A	acceptor_gain	1.0000
1:109625661:G:A	acceptor_gain	1.0000
1:109625661:G:GA	acceptor_gain	1.0000
1:109625661:GGA:G	acceptor_gain	1.0000
1:109625661:GGAGC:G	acceptor_gain	1.0000
1:109625785:G:GT	donor_gain	1.0000
1:109625788:GTCAA:G	donor_gain	1.0000
1:109625792:AGTG:A	donor_loss	1.0000
1:109625793:G:GG	donor_gain	1.0000
1:109625793:GTGA:G	donor_loss	1.0000
1:109625794:T:A	donor_loss	1.0000
1:109625803:C:T	donor_gain	1.0000
1:109625806:G:GT	donor_gain	1.0000
1:109625807:C:T	donor_gain	1.0000
1:109626158:AGGCT:A	acceptor_gain	1.0000
1:109626159:GGCTG:G	acceptor_gain	1.0000
1:109626221:GACC:G	donor_gain	1.0000
1:109626229:G:GG	donor_gain	1.0000
1:109626234:G:GT	donor_gain	1.0000
1:109626423:GTGGG:G	donor_gain	1.0000
1:109626424:TGGG:T	donor_gain	1.0000
1:109626425:GGG:G	donor_gain	1.0000
1:109626425:GGGG:G	donor_gain	1.0000
1:109626426:GG:G	donor_gain	1.0000
1:109626426:GGG:G	donor_gain	1.0000
1:109626427:GG:G	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000236889 (1:109629731 CAG>C), RS1000348546 (1:109625129 G>A), RS1000535749 (1:109624711 G>A), RS1000571179 (1:109631816 C>T), RS1000836670 (1:109628005 G>C), RS1000850803 (1:109617907 C>T), RS1001055655 (1:109623239 G>A), RS1001458611 (1:109619662 G>A,C), RS1001503093 (1:109631291 C>A,T), RS1001539693 (1:109625956 C>G,T), RS1001987719 (1:109624391 C>T), RS1002460372 (1:109621770 A>C), RS1002536078 (1:109627576 C>G,T), RS1002653744 (1:109627340 G>A), RS1002860542 (1:109621388 C>T)

Disease associations

OMIM: gene MIM:102771 | disease phenotypes: MIM:615686, MIM:615809, MIM:108600, MIM:607596, MIM:303350

GenCC curated gene-disease

Disease	Classification	Inheritance
pontocerebellar hypoplasia type 9	Definitive	Autosomal recessive
hereditary spastic paraplegia 63	Supportive	Autosomal recessive

Mondo (8): hereditary spastic paraplegia 63 (MONDO:0014305), pontocerebellar hypoplasia type 9 (MONDO:0014351), spastic ataxia (MONDO:0017845), congenital nervous system disorder (MONDO:0002320), pontocerebellar hypoplasia (MONDO:0020135), intellectual disability (MONDO:0001071), hereditary spastic paraplegia (MONDO:0019064), microcephaly (MONDO:0001149)

Orphanet (7): Autosomal recessive spastic paraplegia type 63 (Orphanet:401805), Pontocerebellar hypoplasia type 9 (Orphanet:369920), Spastic ataxia (Orphanet:316226), Non-syndromic pontocerebellar hypoplasia (Orphanet:98523), Non-syndromic cerebral malformation (Orphanet:199633), Hereditary spastic paraplegia (Orphanet:685), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

47 total (30 of 47 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000158	Macroglossia
HP:0000188	Short upper lip
HP:0000297	Facial hypotonia
HP:0000341	Narrow forehead
HP:0000377	Abnormal pinna morphology
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000648	Optic atrophy
HP:0000737	Irritability
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001257	Spasticity
HP:0001258	Spastic paraplegia
HP:0001263	Global developmental delay
HP:0001276	Hypertonia
HP:0001288	Gait disturbance
HP:0001321	Cerebellar hypoplasia
HP:0001332	Dystonia
HP:0001344	Absent speech
HP:0001347	Hyperreflexia
HP:0002015	Dysphagia
HP:0002079	Hypoplasia of the corpus callosum
HP:0002119	Ventriculomegaly
HP:0002120	Cerebral cortical atrophy
HP:0002151	Increased circulating lactate concentration
HP:0002169	Clonus
HP:0002194	Delayed gross motor development
HP:0002518	Abnormal periventricular white matter morphology
HP:0003202	Skeletal muscle atrophy

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000578_3	Major depressive disorder	1.000000e-06
GCST007102_4	Seasonality and depression	3.000000e-06
GCST010243_74	Apolipoprotein B levels	5.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006876	seasonality measurement
EFO:0004615	apolipoprotein B measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D015419	Spastic Paraplegia, Hereditary	C10.500.300.820; C10.574.500.495.820; C10.668.829.800.300.820; C16.131.666.300.820; C16.320.400.375.820
C580383	Pontocerebellar Hypoplasia (supp.)
C564815	Spastic Ataxia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2997 (SINGLE PROTEIN)

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

62 potent at pChembl≥5 of 77 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.52	IC50	30	nM	CHEMBL5269095
7.22	IC50	60	nM	CHEMBL5271711
7.00	IC50	100	nM	CHEMBL5272816
6.96	IC50	110	nM	CHEMBL5270167
6.89	IC50	130	nM	CHEMBL5287644
6.85	IC50	140	nM	CHEMBL5287535
6.77	IC50	170	nM	CHEMBL5276735
6.77	IC50	170	nM	CHEMBL5281489
6.75	IC50	180	nM	CHEMBL5284620
6.72	IC50	190	nM	CHEMBL5289502
6.70	IC50	200	nM	CHEMBL5271550
6.70	IC50	200	nM	CHEMBL5281034
6.62	IC50	240	nM	CHEMBL5266374
6.58	IC50	260	nM	CHEMBL5283087
6.57	IC50	270	nM	CHEMBL5280447
6.57	IC50	270	nM	CHEMBL5284666
6.52	Ki	300	nM	CHEMBL36045
6.52	IC50	300	nM	CHEMBL5277889
6.39	Ki	410	nM	CHEMBL35929
6.39	IC50	410	nM	CHEMBL5280490
6.30	IC50	500	nM	CHEMBL5284646
6.30	IC50	500	nM	CHEMBL5282638
6.19	Ki	640	nM	CHEMBL290887
6.13	IC50	740	nM	CHEMBL5290923
6.10	Ki	800	nM	CHEMBL290887
6.10	Ki	790	nM	CHEMBL38113
6.07	Ki	860	nM	CHEMBL417506
6.04	Ki	920	nM	CHEMBL284799
6.01	Ki	970	nM	CHEMBL37713
5.96	Ki	1100	nM	CHEMBL289052
5.96	IC50	1100	nM	CHEMBL5269095
5.96	IC50	1100	nM	CHEMBL5284837
5.89	IC50	1300	nM	CHEMBL5287535
5.85	Ki	1400	nM	CHEMBL433444
5.85	IC50	1400	nM	CHEMBL5276735
5.77	Ki	1700	nM	CHEMBL37142
5.77	IC50	1700	nM	CHEMBL5284620
5.77	IC50	1700	nM	CHEMBL5289502
5.75	IC50	1800	nM	CHEMBL5271711
5.75	IC50	1800	nM	CHEMBL5271550
5.72	IC50	1900	nM	CHEMBL5266374
5.68	Ki	2100	nM	CHEMBL288348
5.66	IC50	2200	nM	CHEMBL5282210
5.64	IC50	2300	nM	CHEMBL5277889
5.62	Ki	2400	nM	CHEMBL38002
5.58	IC50	2600	nM	CHEMBL5270167
5.52	Ki	3000	nM	CHEMBL37641
5.52	IC50	3000	nM	CHEMBL5280447
5.51	IC50	3100	nM	CHEMBL5290923
5.42	Ki	3800	nM	CHEMBL289823

PubChem BioAssay actives

63 with measured affinity, of 112 total; 44 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
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	0.0160	uM
4-benzyl-5-fluoro-3,3-dimethyl-2H-quinoxaline-1-carboxamide	1937188: Inhibition of recombinant human AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis	ic50	0.0300	uM
4-benzyl-5,6-difluoro-3,3-dimethyl-2H-quinoxaline-1-carboxamide	1937188: Inhibition of recombinant human AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis	ic50	0.0600	uM
5,6-difluoro-4-[[4-[[4-(hydroxymethyl)phenoxy]methyl]phenyl]methyl]-3,3-dimethyl-2H-quinoxaline-1-carboxamide	1937188: Inhibition of recombinant human AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis	ic50	0.1000	uM
3,3-dimethyl-4-[[4-(phenoxymethyl)phenyl]methyl]-2H-quinoxaline-1-carboxamide	1937188: Inhibition of recombinant human AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis	ic50	0.1100	uM
5,6-difluoro-3,3-dimethyl-4-[[4-(phenoxymethyl)phenyl]methyl]-2H-quinoxaline-1-carboxamide	1937188: Inhibition of recombinant human AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis	ic50	0.1300	uM
3,3-dimethyl-4-[[3-(trifluoromethoxy)phenyl]methyl]-2H-quinoxaline-1-carboxamide	1937188: Inhibition of recombinant human AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis	ic50	0.1400	uM
4-[[4-[(4-acetamidophenoxy)methyl]phenyl]methyl]-5,6-difluoro-3,3-dimethyl-2H-quinoxaline-1-carboxamide	1937188: Inhibition of recombinant human AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis	ic50	0.1700	uM
3,3-dimethyl-4-[(4-methylphenyl)methyl]-2H-quinoxaline-1-carboxamide	1937188: Inhibition of recombinant human AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis	ic50	0.1700	uM
4-benzyl-5-chloro-3,3-dimethyl-2H-quinoxaline-1-carboxamide	1937188: Inhibition of recombinant human AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis	ic50	0.1800	uM
4-[(4-chlorophenyl)methyl]-3,3-dimethyl-2H-quinoxaline-1-carboxamide	1937188: Inhibition of recombinant human AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis	ic50	0.1900	uM
4-[(3-chlorophenyl)methyl]-3,3-dimethyl-2H-quinoxaline-1-carboxamide	1937188: Inhibition of recombinant human AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis	ic50	0.2000	uM
4-[[4-[(4-carbamoylphenoxy)methyl]phenyl]methyl]-5,6-difluoro-3,3-dimethyl-2H-quinoxaline-1-carboxamide	1937188: Inhibition of recombinant human AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis	ic50	0.2000	uM
4-benzyl-7-fluoro-3,3-dimethyl-2H-quinoxaline-1-carboxamide	1937188: Inhibition of recombinant human AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis	ic50	0.2400	uM
4-benzyl-5,7-difluoro-3,3-dimethyl-2H-quinoxaline-1-carboxamide	1937188: Inhibition of recombinant human AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis	ic50	0.2600	uM
4-benzyl-3,3-dimethyl-2H-quinoxaline-1-carboxamide	1937188: Inhibition of recombinant human AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis	ic50	0.2700	uM
3,3-dimethyl-4-[[4-(trifluoromethoxy)phenyl]methyl]-2H-quinoxaline-1-carboxamide	1937188: Inhibition of recombinant human AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis	ic50	0.2700	uM
2-[(2-bromophenyl)methyl]-6-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)hexanoic acid	31739: Evaluated for the inhibition of porcine heart or human L-type Adenosine 5’-monophosphate deaminase (AMPDA)	ki	0.3000	uM
3,3-dimethyl-4-[(3-methylphenyl)methyl]-2H-quinoxaline-1-carboxamide	1937188: Inhibition of recombinant human AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis	ic50	0.3000	uM
3,3-dimethyl-4-[[4-(2-phenylethyl)phenyl]methyl]-2H-quinoxaline-1-carboxamide	1937188: Inhibition of recombinant human AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis	ic50	0.4100	uM
2-benzyl-6-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)hexanoic acid	31739: Evaluated for the inhibition of porcine heart or human L-type Adenosine 5’-monophosphate deaminase (AMPDA)	ki	0.4100	uM
4-benzyl-8-fluoro-3,3-dimethyl-2H-quinoxaline-1-carboxamide	1937188: Inhibition of recombinant human AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis	ic50	0.5000	uM
3,3-dimethyl-4-[[3-(2-phenylethyl)phenyl]methyl]-2H-quinoxaline-1-carboxamide	1937188: Inhibition of recombinant human AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis	ic50	0.5000	uM
2-[(3-bromophenyl)methyl]-6-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)-2-methylhexanoic acid	31739: Evaluated for the inhibition of porcine heart or human L-type Adenosine 5’-monophosphate deaminase (AMPDA)	ki	0.6400	uM
3,3-dimethyl-4-[(4-phenylmethoxyphenyl)methyl]-2H-quinoxaline-1-carboxamide	1937188: Inhibition of recombinant human AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis	ic50	0.7400	uM
2-[(3-bromophenyl)methyl]-6-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)hexanoic acid	31739: Evaluated for the inhibition of porcine heart or human L-type Adenosine 5’-monophosphate deaminase (AMPDA)	ki	0.7900	uM
6-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)-2,2-bis(2-methylpropyl)hexanoic acid	31739: Evaluated for the inhibition of porcine heart or human L-type Adenosine 5’-monophosphate deaminase (AMPDA)	ki	0.8600	uM
6-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)-2,2-diphenylhexanoic acid	31739: Evaluated for the inhibition of porcine heart or human L-type Adenosine 5’-monophosphate deaminase (AMPDA)	ki	0.9200	uM
2-[4-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)butyl]-1,3-dihydroindene-2-carboxylic acid	31739: Evaluated for the inhibition of porcine heart or human L-type Adenosine 5’-monophosphate deaminase (AMPDA)	ki	0.9700	uM
2-[(4-bromophenyl)methyl]-6-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)hexanoic acid	31739: Evaluated for the inhibition of porcine heart or human L-type Adenosine 5’-monophosphate deaminase (AMPDA)	ki	1.1000	uM
4-benzyl-6-fluoro-3,3-dimethyl-2H-quinoxaline-1-carboxamide	1937188: Inhibition of recombinant human AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis	ic50	1.1000	uM
2-[(3-chlorophenyl)methyl]-6-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)hexanoic acid	31739: Evaluated for the inhibition of porcine heart or human L-type Adenosine 5’-monophosphate deaminase (AMPDA)	ki	1.4000	uM
2-[(4-chlorophenyl)methyl]-6-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)hexanoic acid	31739: Evaluated for the inhibition of porcine heart or human L-type Adenosine 5’-monophosphate deaminase (AMPDA)	ki	1.7000	uM
6-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)-2-phenylhexanoic acid	31739: Evaluated for the inhibition of porcine heart or human L-type Adenosine 5’-monophosphate deaminase (AMPDA)	ki	2.1000	uM
4-benzyl-3,3,5-trimethyl-2H-quinoxaline-1-carboxamide	1937188: Inhibition of recombinant human AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis	ic50	2.2000	uM
2-(3-bromophenyl)-6-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)hexanoic acid	31739: Evaluated for the inhibition of porcine heart or human L-type Adenosine 5’-monophosphate deaminase (AMPDA)	ki	2.4000	uM
ethyl 2-[(3-bromophenyl)methyl]-6-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)-2-methylhexanoate	31739: Evaluated for the inhibition of porcine heart or human L-type Adenosine 5’-monophosphate deaminase (AMPDA)	ki	3.0000	uM
ethyl 2-[(3-bromophenyl)methyl]-6-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)hexanoate	31739: Evaluated for the inhibition of porcine heart or human L-type Adenosine 5’-monophosphate deaminase (AMPDA)	ki	3.8000	uM
sodium 6-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)hexanoate	31739: Evaluated for the inhibition of porcine heart or human L-type Adenosine 5’-monophosphate deaminase (AMPDA)	ki	4.2000	uM
3-[5-(2H-tetrazol-5-yl)pentyl]-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-8-ol	31739: Evaluated for the inhibition of porcine heart or human L-type Adenosine 5’-monophosphate deaminase (AMPDA)	ki	6.0000	uM
6-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)-2,2-dimethylhexanoic acid	31739: Evaluated for the inhibition of porcine heart or human L-type Adenosine 5’-monophosphate deaminase (AMPDA)	ki	8.2000	uM
ethyl 6-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)-2-phenylhexanoate	31739: Evaluated for the inhibition of porcine heart or human L-type Adenosine 5’-monophosphate deaminase (AMPDA)	ki	9.6000	uM
ethyl 2-(3-bromophenyl)-6-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)hexanoate	31739: Evaluated for the inhibition of porcine heart or human L-type Adenosine 5’-monophosphate deaminase (AMPDA)	ki	9.7000	uM
7-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)heptanoic acid	31739: Evaluated for the inhibition of porcine heart or human L-type Adenosine 5’-monophosphate deaminase (AMPDA)	ki	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol F	increases expression, affects cotreatment, decreases expression	2
Acetaminophen	decreases expression	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance, affects expression	2
Estradiol	increases expression	2
Ozone	affects cotreatment, decreases expression, increases abundance, affects expression	2
aristolochic acid I	increases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
bisphenol A	increases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
coumarin	increases phosphorylation	1
methacrylaldehyde	decreases expression, increases abundance, affects cotreatment	1
M-VAC protocol	decreases response to substance	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
2-palmitoylglycerol	increases expression	1
tofacitinib	affects abundance, decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
Sunitinib	decreases expression	1
Acrolein	decreases expression, increases abundance, affects cotreatment	1
Adenosine	affects abundance, decreases expression	1
Benzene	increases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases phosphorylation	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
CHEMBL5240592	Binding	Inhibition of recombinant human AMPD2 using AMP as substrate incubated for 30 mins by spectrophotometric analysis	The discovery of 3,3-dimethyl-1,2,3,4-tetrahydroquinoxaline-1-carboxamides as AMPD2 inhibitors with a novel mechanism of action. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2RK	Abcam HEK293T AMPD2 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT07542548	PHASE4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT03961906	PHASE2	COMPLETED	Physiotherapy in Hereditary Spastic Paraplegia
NCT04768166	PHASE2	COMPLETED	Testing Miglustat Administration in Subjects With Spastic Paraplegia 11
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT06117020	PHASE1	COMPLETED	Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT04297891	Not specified	UNKNOWN	Phenotypes, Biomarkers and Pathophysiology in Spastic Ataxias
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study