AMPD1

Summary

AMPD1 (adenosine monophosphate deaminase 1, HGNC:468) is a protein-coding gene on chromosome 1p13.2, encoding AMP deaminase 1 (P23109). AMP deaminase plays a critical role in energy metabolism.

Adenosine monophosphate deaminase 1 catalyzes the deamination of AMP to IMP in skeletal muscle and plays an important role in the purine nucleotide cycle. Two other genes have been identified, AMPD2 and AMPD3, for the liver- and erythocyte-specific isoforms, respectively. Deficiency of the muscle-specific enzyme is apparently a common cause of exercise-induced myopathy and probably the most common cause of metabolic myopathy in the human. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene.

Source: NCBI Gene 270 — RefSeq curated summary.

At a glance

• Gene–disease (curated): myopathy due to myoadenylate deaminase deficiency (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 599 total — 3 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 16
• Druggable target: yes
• MANE Select transcript: NM_000036

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:468
Approved symbol	AMPD1
Name	adenosine monophosphate deaminase 1
Location	1p13.2
Locus type	gene with protein product
Status	Approved
Aliases	MAD, MADA
Ensembl gene	ENSG00000116748
Ensembl biotype	protein_coding
OMIM	102770
Entrez	270

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 protein_coding_CDS_not_defined, 2 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000369538, ENST00000485564, ENST00000520113, ENST00000637080, ENST00000638214, ENST00000639077, ENST00000639274

RefSeq mRNA: 2 — MANE Select: NM_000036 NM_000036, NM_001172626

CCDS: CCDS53349, CCDS876

Canonical transcript exons

ENST00000520113 — 16 exons

Exon	Start	End
ENSE00000784346	114686745	114686910
ENSE00000784348	114680259	114680478
ENSE00000784349	114679579	114679708
ENSE00000800101	114688561	114688741
ENSE00001648228	114675877	114676003
ENSE00001668368	114693436	114693447
ENSE00001696965	114673909	114674082
ENSE00001717849	114673639	114673749
ENSE00001729052	114677351	114677514
ENSE00001748663	114675530	114675693
ENSE00001750224	114677910	114678041
ENSE00001806058	114674752	114674872
ENSE00002025520	114678333	114678527
ENSE00002105326	114695450	114695546
ENSE00002174348	114673098	114673272
ENSE00003610624	114684199	114684364

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 99.70.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.8333 / max 1209.3275, expressed in 51 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13954	1.6786	45
13953	0.1376	27
13955	0.0172	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
triceps brachii	UBERON:0001509	99.70	gold quality
vastus lateralis	UBERON:0001379	99.62	gold quality
quadriceps femoris	UBERON:0001377	99.57	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.50	gold quality
biceps brachii	UBERON:0001507	99.48	gold quality
gluteal muscle	UBERON:0002000	99.45	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.45	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.07	gold quality
skeletal muscle tissue	UBERON:0001134	98.96	gold quality
diaphragm	UBERON:0001103	98.87	gold quality
deltoid	UBERON:0001476	98.68	gold quality
gastrocnemius	UBERON:0001388	98.16	gold quality
tibialis anterior	UBERON:0001385	97.86	gold quality
body of tongue	UBERON:0011876	97.43	gold quality
muscle organ	UBERON:0001630	97.05	gold quality
muscle of leg	UBERON:0001383	96.16	gold quality
muscle tissue	UBERON:0002385	91.15	gold quality
jejunum	UBERON:0002115	88.82	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.85	gold quality
tongue	UBERON:0001723	86.73	gold quality
jejunal mucosa	UBERON:0000399	82.22	gold quality
mucosa of transverse colon	UBERON:0004991	79.77	gold quality
duodenum	UBERON:0002114	79.12	gold quality
rectum	UBERON:0001052	78.49	gold quality
superior surface of tongue	UBERON:0007371	78.48	gold quality
trabecular bone tissue	UBERON:0002483	77.90	gold quality
bone marrow cell	CL:0002092	76.08	gold quality
pharyngeal mucosa	UBERON:0000355	73.79	gold quality
minor salivary gland	UBERON:0001830	71.58	gold quality
colonic epithelium	UBERON:0000397	71.10	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-11	yes	18.49
E-ANND-3	yes	7.54

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MEF2C, MXD1

Literature-anchored findings (GeneRIF, showing 38)

• A G468T AMPD1 mutant allele contributes to the high incidence of myoadenylate deaminase deficiency in the Caucasian population. (PMID:12117480)
• Significantly higher frequency of mutation among donors with healthy hearts used for transplantation. Lower frequency in dysfunctional donor hearts. Frequency of C34T mutation in chronic heart failure was not different. (Review) (PMID:15239633)
• The AMPD1 C34T polymorphism influences transplant-free cardiovascular survival in the setting of ischemic left ventricular dysfunction. (PMID:15309698)
• Primary myoadenylate-deaminase deficiency was diagnosed based upon elevated creatine-kinase, absent staining for MAD on muscle biopsy, markedly reduced MAD activity in the muscle homogenate, and C34T mutation within exon 2 of AMPD1 gene. (PMID:15368811)
• In conclusion, although the frequency distribution of the mutant T allele of the AMPD1 genotype is lower in Caucasian elite endurance athletes than in controls, the C34T mutation does not significantly impair endurance performance. (PMID:15677729)
• In this study, the metabolic clearance rate of insulin was associated with AMPD1 SNPs and haplotypes. (PMID:15793265)
• a C34T mutation in AMP deaminase is found more frequently in healthy donor hearts than in healthy controls or donors with failing hearts (PMID:16021915)
• the AMPD1 mutation decreases the activity of AMP-deaminase in the heart without changing the activity of any other enzymes of adenine nucleotide metabolism (PMID:16021918)
• The interpretation of the significance of these observations suggests a physiological mutual dependence between skeletal muscle HPRG and AMPD polypeptides with regard to their stability. (PMID:16570231)
• Genes are associated with good clinical response of rheumatoid arthritis to methotrexate treatment. (PMID:16947783)
• We did not demonstrate any effect of the C34T polymorphism of the AMPD1 gene on major congestive heart failure parameters and on survival. (PMID:16996850)
• The 34C > T variant of AMPD1 augments vasodilation and reduces tissue injury in response to forearm ischaemia. These mechanisms could contribute to the survival benefit of cardiovascular patients with this variant allele. (PMID:17376785)
• Reveals a functional role for skeletal muscle AMPD1 enzyme in sprint exercise. (PMID:17463303)
• C34T and G468T variations in the adenosine monophosphate deaminase-1 (AMPD1) gene were associated with intima-media thickness of the carotid and brachial artery, endothelial function of the brachial artery in patients with coronary heart disease. (PMID:17565237)
• Results suggest a better circulatory adaptation to exercise in individuals with diminished AMPD1 activity, probably due to an AMPD1 genotype-dependent increase in adenosine formation. (PMID:18224333)
• may control the systemic metabolic status by changing AMPK activity through the AMP level. (PMID:18409530)
• C34T AMPD1 polymorphism may be associated with reduced frequency of obesity in coronary artery disease(CAD) patients and of hyperglycaemia and diabetes in both CAD and heart failure patients. (PMID:18855224)
• We found statistical significance for ACE ID and II genotypes in soccer players than in runners; Statistical significance was also reached for AMPD1 (with higher frequency of CT genotype in soccer players than in runners [chi(2)((2))=7.538, P=0.006]) (PMID:19277943)
• Possession of AMPD1 T allele is associated with decreased inotropic requirements before heart donation. Incidence of graft dysfunction was significantly higher in recipients who received AMPD1 T-allele-possessing organs resulting in worse 1-year survival. (PMID:19427446)
• some physico-chemical properties of AMP-deaminase isolated from cardiac muscle of a 10-year-old boy heterozygote for this mutation (PMID:20544536)
• AMPD1 gene mutations are associated with obesity and diabetes in Polish patients with cardiovascular diseases. (PMID:21108053)
• There was a lower frequency of the AMPD1 exon 2 T34 allele in elite Polish power-oriented athletes. The data suggested that the C allele may help athletes to attain elite status in power-oriented sports. (PMID:22017426)
• The researchers found evidence that the T allele polymorphism of the AMPD1 gene is associated with negative factor in athletic performance (PMID:22105616)
• In a study of a Spanish and 2 North African cohorts, frequency of the AMPD1 C34T mutation was lower in Berbers compared with the Alpujarra cohort. The GDF8 K153R substitution showed little variability among the three cohorts. (PMID:22324844)
• AMPD1 gene polymorphism C34T can be considered as a marker of liability to the high-speed and strength muscular activity. (PMID:23486588)
• Alpinists show significantly higher frequencies of T allele compared to controls. (PMID:24058088)
• Our other studies on the metabolic impact of AMPD1 C34T mutation revealed decrease in AMPD activity. (PMID:24431031)
• The present study demonstrated a positive effect of C34T AMPD1 gene polymorphism in aortic stiffness and in inflammatory status in a high risk population of CAD subjects. (PMID:24508110)
• Mutational variants in AMPD1 contribute to autism risk in Han Chinese population, via mitochondria dysfunction and cell necrosis. (PMID:25155876)
• The best response to creatine in terms of physical performance was presented by AMPD1 CC genotype. (PMID:25665401)
• AMPD1 could have a profound influence on cholinergic neurotransmission and sleep; further studies are mandatory (PMID:26439223)
• AMPD1 34C>T variant is associated with higher infection susceptibility to community acquired pneumonia but not to ventilator associated pneumonia in sepsis pateints (PMID:26529652)
• Common polymorphism of the AMPD1 gene (C34T) is strongly associated with essential hypertension. (PMID:27323204)
• Variations in AMPD1, CPT2, and PGYM genes are not associated with the onset, susceptibility, or severity of chronic fatigue syndrome. (PMID:27525900)
• T allele of AMPD1 gene C34T polymorphism may be correlated with LVEF, LVEDD and SBP, which plays a protective role in the cardiac functions and blood pressure in cardiovascular disease patients. (PMID:28673246)
• The metabolic-chronotropic response is decreased in skeletal muscle MAD deficiency, suggesting a biological mechanism by which AMPD1 gene exerts cardiac effect (PMID:29095874)
• Ultrastructural Localization of Histidine-rich Glycoprotein in Skeletal Muscle Fibers: Colocalization With AMP Deaminase. (PMID:31880188)
• AMPD1 C34T Polymorphism (rs17602729) Is Not Associated with Post-Exercise Changes of Body Weight, Body Composition, and Biochemical Parameters in Caucasian Females. (PMID:32429460)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ampd1	ENSDARG00000033832
mus_musculus	Ampd1	ENSMUSG00000070385
rattus_norvegicus	Ampd1	ENSRNOG00000018656

Paralogs (2): AMPD2 (ENSG00000116337), AMPD3 (ENSG00000133805)

Protein

Protein identifiers

AMP deaminase 1 — P23109 (reviewed: P23109)

Alternative names: AMP deaminase isoform M, Myoadenylate deaminase

All UniProt accessions (2): P23109, A0A1B0GTL6

UniProt curated annotations — full annotation on UniProt →

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

Subunit / interactions. Homotetramer.

Disease relevance. Myopathy due to myoadenylate deaminase deficiency (MMDD) [MIM:615511] A metabolic disorder resulting in exercise-related myopathy. It is characterized by exercise-induced muscle aches, cramps, and early fatigue. 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 (2)

UniProt ID	Names	Canonical?
P23109-1	1	yes
P23109-2	2

RefSeq proteins (2): NP_000027, NP_001166097 (=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 (25 total): binding site 8, sequence variant 5, sequence conflict 5, modified residue 4, chain 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23109-F1	86.84	0.73

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): 594 (proton acceptor)

Ligand- & substrate-binding residues (8): 303; 305; 305; 374–379; 572; 575; 649; 650–653

Post-translational modifications (4): 81, 85, 216, 441

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: 172 (showing top): ZHAN_LATE_DIFFERENTIATION_GENES_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, MEF2_02, 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, SHAFFER_IRF4_TARGETS_IN_PLASMA_CELL_VS_MATURE_B_LYMPHOCYTE, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, MODULE_99, GOBP_NUCLEOSIDE_MONOPHOSPHATE_BIOSYNTHETIC_PROCESS, KEGG_PURINE_METABOLISM, MODULE_113, SABATES_COLORECTAL_ADENOMA_DN

GO Biological Process (7): IMP biosynthetic process (GO:0006188), GMP salvage (GO:0032263), IMP salvage (GO:0032264), AMP metabolic process (GO:0046033), nucleoside phosphate metabolic process (GO:0006753), nucleotide metabolic process (GO:0009117), purine ribonucleoside monophosphate biosynthetic process (GO:0009168)

GO Molecular Function (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 salvage	2
purine ribonucleoside monophosphate 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
purine ribonucleotide metabolic process	1
organophosphate metabolic process	1
nucleobase-containing small molecule metabolic process	1
nucleoside phosphate metabolic process	1
purine nucleoside monophosphate biosynthetic process	1
ribonucleoside monophosphate biosynthetic process	1
adenosine-phosphate deaminase activity	1
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

1798 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AMPD1	ADSS2	P30520	924
AMPD1	ADA	P00813	894
AMPD1	ADSL	P30566	745
AMPD1	PNP	P00491	717
AMPD1	ATIC	P31939	695
AMPD1	ADK	P55263	694
AMPD1	APRT	P07741	686
AMPD1	ALDOB	P05062	669
AMPD1	AK1	P00568	665
AMPD1	ITPA	Q9BY32	654
AMPD1	GMPS	P49915	637
AMPD1	ADSS1	Q8N142	607
AMPD1	ACTN3	Q08043	604
AMPD1	MB	P02144	601
AMPD1	IMPDH2	P12268	588

IntAct

19 interactions, top by confidence:

A	B	Type	Score
AMPD1	AMPD3	psi-mi:“MI:0915”(physical association)	0.560
AMPD1	AMPD2	psi-mi:“MI:0915”(physical association)	0.560
AMPD1	AMPD1	psi-mi:“MI:0915”(physical association)	0.560
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
CUL1	LGALS8	psi-mi:“MI:0914”(association)	0.350
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
MAP1LC3A		psi-mi:“MI:0914”(association)	0.350
MAP1LC3B		psi-mi:“MI:0914”(association)	0.350
GABARAPL1		psi-mi:“MI:0914”(association)	0.350
GABARAP		psi-mi:“MI:0914”(association)	0.350
AMPD1	AMPD3	psi-mi:“MI:0915”(physical association)	0.000
AMPD2	AMPD1	psi-mi:“MI:0915”(physical association)	0.000
AMPD1	AMPD1	psi-mi:“MI:0915”(physical association)	0.000
C1QTNF9	AMPD1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (13): AMPD1 (Affinity Capture-MS), AMPD1 (Two-hybrid), AMPD1 (Two-hybrid), AMPD3 (Two-hybrid), AMPD1 (Two-hybrid), AMPD1 (Proximity Label-MS), AMPD1 (Affinity Capture-MS), EEA1 (Cross-Linking-MS (XL-MS)), AMPD1 (Affinity Capture-MS), AMPD1 (Affinity Capture-MS), AMPD1 (Affinity Capture-MS), AMPD1 (Affinity Capture-MS), AMPD1 (Affinity Capture-MS)

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

Diamond homologs: 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

7 interactions.

A	Effect	B	Mechanism
AMPD1	“down-regulates quantity”	“adenosine 5’-monophosphate”	“chemical modification”
AMPD1	“up-regulates quantity”	IMP	“chemical modification”
AMPD1	“up-regulates quantity”	ammonium	“chemical modification”
AMPD1	“down-regulates quantity”	AMP	“chemical modification”
AMPD1	“down-regulates quantity”	water	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	3
Uncertain significance	340
Likely benign	163
Benign	47

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
2425617	NC_000001.10:g.(?112318699)(115576848_?)del	Pathogenic
3247662	NC_000001.10:g.(?115231162)(115238191_?)del	Pathogenic
4277942	NM_000036.3(AMPD1):c.1679+2T>C	Pathogenic
1030545	NM_000036.3(AMPD1):c.2181T>A (p.Tyr727Ter)	Likely pathogenic
4845819	NM_000036.3(AMPD1):c.1957C>T (p.Gln653Ter)	Likely pathogenic
814118	GRCh37/hg19 1p13.2-13.1(chr1:114024461-116189135)x1	Likely pathogenic

SpliceAI

2158 predictions. Top by Δscore:

Variant	Effect	Δscore
1:114673671:T:A	donor_gain	1.0000
1:114673704:G:C	donor_gain	1.0000
1:114673756:T:C	acceptor_gain	1.0000
1:114673756:T:TC	acceptor_gain	1.0000
1:114673758:A:AC	acceptor_gain	1.0000
1:114673758:A:C	acceptor_gain	1.0000
1:114673761:T:TC	acceptor_gain	1.0000
1:114674747:CTCA:C	donor_loss	1.0000
1:114674748:TCA:T	donor_loss	1.0000
1:114674749:CA:C	donor_loss	1.0000
1:114674750:A:AC	donor_gain	1.0000
1:114674750:A:AG	donor_loss	1.0000
1:114674750:AC:A	donor_gain	1.0000
1:114674751:C:CC	donor_gain	1.0000
1:114674751:CC:C	donor_gain	1.0000
1:114674751:CCT:C	donor_gain	1.0000
1:114674751:CCTT:C	donor_gain	1.0000
1:114674871:CC:C	acceptor_gain	1.0000
1:114674872:CC:C	acceptor_gain	1.0000
1:114674873:C:CC	acceptor_gain	1.0000
1:114674874:T:A	acceptor_loss	1.0000
1:114675525:CTTA:C	donor_gain	1.0000
1:114675526:TTACT:T	donor_loss	1.0000
1:114675527:TACT:T	donor_loss	1.0000
1:114675528:A:AC	donor_gain	1.0000
1:114675528:AC:A	donor_loss	1.0000
1:114675529:C:CC	donor_gain	1.0000
1:114675529:CT:C	donor_gain	1.0000
1:114675529:CTT:C	donor_gain	1.0000
1:114675529:CTTT:C	donor_gain	1.0000

AlphaMissense

5225 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:114677935:C:A	G433V	1.000
1:114677936:C:A	G433W	1.000
1:114678009:G:C	F408L	1.000
1:114678009:G:T	F408L	1.000
1:114678011:A:G	F408L	1.000
1:114678346:A:G	L393P	1.000
1:114678481:A:G	L348P	1.000
1:114673937:T:A	D682V	0.999
1:114673940:G:A	T681I	0.999
1:114674005:A:C	F659L	0.999
1:114674005:A:T	F659L	0.999
1:114674007:A:G	F659L	0.999
1:114677935:C:T	G433E	0.999
1:114677963:A:C	Y424D	0.999
1:114677974:A:G	L420P	0.999
1:114678010:A:G	F408S	0.999
1:114678018:A:C	F405L	0.999
1:114678018:A:T	F405L	0.999
1:114678020:A:G	F405L	0.999
1:114678346:A:T	L393Q	0.999
1:114678361:A:G	L388P	0.999
1:114678471:A:C	F351L	0.999
1:114678471:A:T	F351L	0.999
1:114678473:A:G	F351L	0.999
1:114678478:A:G	L349P	0.999
1:114678512:G:C	H338D	0.999
1:114679691:C:G	R295P	0.999
1:114673175:C:G	R761P	0.998
1:114673666:A:C	S719R	0.998
1:114673666:A:T	S719R	0.998

dbSNP variants (sampled 300 via entrez): RS1000084763 (1:114678988 A>G), RS1000095522 (1:114678840 G>A), RS1000432275 (1:114696197 G>T), RS1000527650 (1:114689335 G>A), RS1000669363 (1:114688306 T>A,G), RS1000737090 (1:114689769 A>G), RS1000755410 (1:114695563 A>T), RS1000838352 (1:114677706 T>A,C), RS1001019159 (1:114683609 C>T), RS1001089733 (1:114695104 A>C,G), RS1001352117 (1:114683195 T>C), RS1001376319 (1:114677786 TTTCCCTCTCTCCCTCC>T), RS1001423542 (1:114691701 G>A,C), RS1001499498 (1:114680708 T>C), RS1001622625 (1:114674124 A>G)

Disease associations

OMIM: gene MIM:102770 | disease phenotypes: MIM:615511, MIM:144010, MIM:614066, MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
myopathy due to myoadenylate deaminase deficiency	Strong	Autosomal recessive
adenosine monophosphate deaminase deficiency	Supportive	Autosomal recessive

Mondo (6): myopathy due to myoadenylate deaminase deficiency (MONDO:0014220), hypercholesterolemia, autosomal dominant, type B (MONDO:0007751), hereditary spastic paraplegia 47 (MONDO:0013551), RASopathy (MONDO:0021060), autism (MONDO:0005260), adenosine monophosphate deaminase deficiency (MONDO:0013028)

Orphanet (3): Adenosine monophosphate deaminase deficiency (Orphanet:45), Severe intellectual disability and progressive spastic paraplegia (Orphanet:280763), RASopathy (Orphanet:536391)

HPO phenotypes

16 total (17 of 16 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001252	Hypotonia
HP:0001284	Areflexia
HP:0001324	Muscle weakness
HP:0002151	Increased circulating lactate concentration
HP:0003198	Myopathy
HP:0003201	Rhabdomyolysis
HP:0003202	Skeletal muscle atrophy
HP:0003326	Myalgia
HP:0003394	Muscle spasm
HP:0003690	Limb muscle weakness
HP:0003738	Exercise-induced myalgia
HP:0003750	Increased muscle fatiguability
HP:0008331	Elevated creatine kinase after exercise
HP:0009020	Exercise-induced muscle fatigue
HP:0034529	Reduced muscle myoadenylate deaminase activity
HP:0000717	Autism

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002268_1	Autism	3.000000e-08
GCST002268_10	Autism	4.000000e-08
GCST002268_2	Autism	9.000000e-08
GCST010989_181	Body size at age 10	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009819	comparative body size at age 10, self-reported

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
C538234	Adenosine monophosphate deaminase deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2869 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs17602729	Toxicity	3	regadenoson
rs17602729	Efficacy,Toxicity	4	methotrexate	Rheumatoid arthritis

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs17602729	AMPD1	3	4.50	2	methotrexate;regadenoson

Binding affinities (BindingDB)

2 measured of 4 human assays (4 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
4-[4-({[(1R)-1-(isoquinolin-8-yl)ethyl]amino}methyl)phenyl]-2-methoxybenzoic acid (Compound 4)	IC50	24 nM
6-[4-({[(1S)-1-(isoquinolin-8-yl)ethyl]amino}methyl)phenyl]pyridine-3-carboxylic acid (Compound 3)	IC50	38 nM

ChEMBL bioactivities

3 potent at pChembl≥5 of 6 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.30	IC50	500	nM	CHEMBL346040
5.10	Ki	8000	nM	CHEMBL38305
5.00	Ki	1e+04	nM	CHEMBL38218

PubChem BioAssay actives

7 with measured affinity, of 12 total; 7 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
4-[4-[[[(1R)-1-isoquinolin-8-ylethyl]amino]methyl]phenyl]-2-methoxybenzoic 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	0.0240	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	0.0380	uM
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	668711: Inhibition of human skeletal muscle AMPD1	ic50	0.5000	uM
6-[4-[[[(1R)-1-naphthalen-1-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	0.6200	uM
8-(8-hydroxy-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-3-yl)octanoic acid	34764: Evaluated for the inhibition of porcine heart or human L-type Adenosine 5’-monophosphate deaminase (AMPDA)	ki	8.0000	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	9.2000	uM
3-heptyl-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-8-ol	34764: Evaluated for the inhibition of porcine heart or human L-type Adenosine 5’-monophosphate deaminase (AMPDA)	ki	10.0000	uM

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Methotrexate	affects response to substance	2
aristolochic acid I	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
epigallocatechin gallate	increases expression, affects cotreatment	1
(+)-JQ1 compound	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Air Pollutants	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression	1
Curcumin	decreases reaction, increases activity	1
Hypochlorous Acid	decreases reaction, increases activity	1
Aflatoxin B1	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2044563	Binding	Inhibition of human skeletal muscle AMPD1	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)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms