MAPDA

Summary

MAPDA (N6-Methyl-AMP deaminase, HGNC:31853) is a protein-coding gene on chromosome 15q15.3, encoding N6-Methyl-AMP deaminase (Q6DHV7). Deaminase involved in the detoxification of modified adenosines containing N(6)-methylated adenine (m6A) post-transcriptional modification.

Predicted to enable adenosine deaminase activity. Predicted to be involved in adenosine catabolic process and inosine biosynthetic process. Predicted to act upstream of or within response to alcohol. Predicted to be located in cytosol.

Source: NCBI Gene 161823 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 32 total
• Druggable target: yes
• MANE Select transcript: NM_001324366

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31853
Approved symbol	MAPDA
Name	N6-Methyl-AMP deaminase
Location	15q15.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000168803
Ensembl biotype	protein_coding
OMIM	619346
Entrez	161823

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 17 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000389651, ENST00000422466, ENST00000428046, ENST00000562188, ENST00000563551, ENST00000565555, ENST00000566154, ENST00000610420, ENST00000908745, ENST00000908746, ENST00000908747, ENST00000908748, ENST00000908749, ENST00000930894, ENST00000930895, ENST00000952037, ENST00000952038, ENST00000952039, ENST00000952040

RefSeq mRNA: 7 — MANE Select: NM_001324366 NM_001012969, NM_001159280, NM_001324364, NM_001324365, NM_001324366, NM_001324367, NM_001324368

CCDS: CCDS32214, CCDS53936, CCDS81868

Canonical transcript exons

ENST00000562188 — 13 exons

Exon	Start	End
ENSE00001147255	43345854	43345980
ENSE00001147300	43347016	43347096
ENSE00001325198	43336626	43336686
ENSE00001377415	43334945	43335170
ENSE00001526968	43333311	43333434
ENSE00001729308	43348907	43349045
ENSE00001749120	43350941	43351041
ENSE00002276760	43331900	43332000
ENSE00002622419	43351751	43354569
ENSE00003471045	43335696	43335826
ENSE00003547337	43340265	43340352
ENSE00003579827	43342994	43343075
ENSE00003827711	43330672	43330859

Expression profiles

Bgee: expression breadth ubiquitous, 205 present calls, max score 93.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.7328 / max 114.8289, expressed in 1609 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146297	5.7328	1609

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.59	gold quality
left ventricle myocardium	UBERON:0006566	92.03	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	87.46	silver quality
kidney epithelium	UBERON:0004819	86.81	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.37	gold quality
muscle of leg	UBERON:0001383	85.07	gold quality
calcaneal tendon	UBERON:0003701	85.03	gold quality
gastrocnemius	UBERON:0001388	84.78	gold quality
heart left ventricle	UBERON:0002084	84.49	gold quality
cardiac ventricle	UBERON:0002082	84.14	gold quality
hindlimb stylopod muscle	UBERON:0004252	83.77	gold quality
tibialis anterior	UBERON:0001385	83.73	silver quality
cardiac atrium	UBERON:0002081	83.18	gold quality
right atrium auricular region	UBERON:0006631	83.00	gold quality
apex of heart	UBERON:0002098	82.82	gold quality
heart	UBERON:0000948	82.80	gold quality
muscle tissue	UBERON:0002385	82.42	gold quality
skeletal muscle tissue	UBERON:0001134	81.67	gold quality
parotid gland	UBERON:0001831	81.41	silver quality
vastus lateralis	UBERON:0001379	81.08	silver quality
cortical plate	UBERON:0005343	80.99	gold quality
deltoid	UBERON:0001476	80.75	silver quality
quadriceps femoris	UBERON:0001377	80.49	silver quality
metanephros cortex	UBERON:0010533	80.31	gold quality
anterior cingulate cortex	UBERON:0009835	79.79	gold quality
right frontal lobe	UBERON:0002810	79.73	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.73	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	79.72	gold quality
nucleus accumbens	UBERON:0001882	79.17	gold quality
putamen	UBERON:0001874	79.16	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.45
E-MTAB-6142	no	90.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

87 targeting MAPDA, 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-340-5P	100.00	72.50	4437
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-2681-5P	99.75	67.64	1655

Literature-anchored findings (GeneRIF, showing 3)

• Data indicated that ADAL1 specifically acts at the 6-position of purine and 2-aminopurine nucleoside monophosphates. (PMID:21755941)
• Mutations in adenosine deaminase-like (ADAL) protein confer drug resistance in Uterine Cervical Neoplasms. (PMID:23645737)
• ADGR: Admixture-Informed Differential Gene Regulation. (PMID:36672888)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mapda	ENSDARG00000012986
mus_musculus	Adal	ENSMUSG00000027259
rattus_norvegicus	Adal	ENSRNOG00000012166
drosophila_melanogaster	Ada	FBGN0037661
caenorhabditis_elegans		WBGENE00016632

Paralogs (2): ADA2 (ENSG00000093072), ADA (ENSG00000196839)

Protein

Protein identifiers

N6-Methyl-AMP deaminase — Q6DHV7 (reviewed: Q6DHV7)

Alternative names: Adenosine deaminase-like protein, N6,N6-dimethyl-AMP deaminase, N6-isopentenyl-AMP deaminase, N6-mAMP deaminase, N6-methyl-AMP aminohydrolase

All UniProt accessions (3): Q6DHV7, H3BQR9, H3BUD6

UniProt curated annotations — full annotation on UniProt →

Function. Deaminase involved in the detoxification of modified adenosines containing N(6)-methylated adenine (m6A) post-transcriptional modification. Modified nucleosides are derived from the degradation of RNAs (mRNAs, rRNAs and tRNAs) and possess intrinsic cytotoxicity and must be cleared to prevent metabolic dysfunction. Acts downstream of ADK and catalyzes the hydrolysis of the free cytosolic methylated adenosine nucleotides N(6)-methyl-AMP (m6AMP), N(6),N(6)-dimethyl-AMP (m6,6AMP) and N(6)-isopentenyl-AMP (i6AMP) to produce inositol monophosphate (IMP). Catalyzes the removal of different alkyl groups not only from N6-substituted purine or 2-aminopurine nucleoside monophosphates but also from O6-substituted compounds in vitro.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm. Cytosol.

Cofactor. Binds 1 zinc ion per subunit.

Miscellaneous. Involved in the activation pathway of bemnifosbuvir (AT-527) and its epimer, AT-752. AT-527 and AT-752 are two guanosine analogs tested in clinical trials against several RNA viruses, which are activated into their common 5’-triphosphate AT-9010 in human cells. Mediates the third activation step by catalyzing transformation of AT-8003 into AT-8001.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q6DHV7-1	1	yes
Q6DHV7-2	2
Q6DHV7-3	3

RefSeq proteins (7): NP_001012987, NP_001152752, NP_001311293, NP_001311294, NP_001311295, NP_001311296, NP_001311297 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001365	A_deaminase_dom	Domain
IPR006330	Ado/ade_deaminase	Family
IPR032466	Metal_Hydrolase	Homologous_superfamily

Pfam: PF00962

Catalyzed reactions (Rhea), 3 shown:

• N(6)-methyl-AMP + H2O + H(+) = IMP + methylamine (RHEA:16001)
• N(6),N(6)-dimethyl-AMP + H2O + H(+) = dimethylamine + IMP (RHEA:86223)
• N(6)-(dimethylallyl)adenosine 5’-phosphate + H2O + H(+) = dimethylallylamine + IMP (RHEA:86227)

UniProt features (57 total): helix 21, binding site 13, strand 10, turn 6, splice variant 2, sequence conflict 2, chain 1, active site 1, site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8QCH	X-RAY DIFFRACTION	2.44

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6DHV7-F1	93.50	0.86

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 (2): 211 (proton donor); 232 (important for catalytic activity)

Ligand- & substrate-binding residues (13): 208; 211; 293; 293; 294; 24; 26; 26; 28; 74; 106–109; 148 …

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-2161541	Abacavir metabolism
R-HSA-74217	Purine salvage
R-HSA-1430728	Metabolism
R-HSA-15869	Metabolism of nucleotides
R-HSA-2161522	Abacavir ADME
R-HSA-8956321	Nucleotide salvage
R-HSA-9748784	Drug ADME

MSigDB gene sets: 105 (showing top): GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_DETOXIFICATION, GOBP_PURINE_NUCLEOSIDE_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS, DOUGLAS_BMI1_TARGETS_DN, GOBP_PURINE_NUCLEOSIDE_CATABOLIC_PROCESS, GOBP_RESPONSE_TO_TOXIC_SUBSTANCE, GOBP_PURINE_CONTAINING_COMPOUND_METABOLIC_PROCESS

GO Biological Process (4): adenosine catabolic process (GO:0006154), nucleotide metabolic process (GO:0009117), inosine biosynthetic process (GO:0046103), response to alcohol (GO:0097305)

GO Molecular Function (6): adenosine deaminase activity (GO:0004000), metal ion binding (GO:0046872), N6-methyl-AMP deaminase activity (GO:0062154), 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-5 pathways:

Category	Pathways
Abacavir ADME	1
Nucleotide salvage	1
Metabolism	1
Drug ADME	1
Metabolism of nucleotides	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
deaminase activity	2
adenosine metabolic process	1
purine ribonucleoside catabolic process	1
nucleoside phosphate metabolic process	1
inosine metabolic process	1
purine ribonucleoside biosynthetic process	1
response to oxygen-containing compound	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amidines	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

1152 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAPDA	HINT1	P49773	615
MAPDA	GUK1	Q16774	613
MAPDA	CTSA	P10619	530
MAPDA	CES1	P23141	476
MAPDA	HNRNPU	Q00839	442
MAPDA	IGF2BP2	Q9Y6M1	441
MAPDA	ZNF835	Q9Y2P0	440
MAPDA	TAOK3	Q9H2K8	439
MAPDA	ADK	P55263	421
MAPDA	VSIG10L	Q86VR7	414
MAPDA	ANKRD36B	Q8N2N9	404
MAPDA	GMPS	P49915	373
MAPDA	GART	P22102	353
MAPDA	LIPH	Q8WWY8	352
MAPDA	WRAP73	Q9P2S5	348
MAPDA	ADARB1	P78555	348

IntAct

1 interactions, top by confidence:

BioGRID (7): ADAL (Affinity Capture-RNA), ADAL (Affinity Capture-RNA), ADAL (Affinity Capture-RNA), ADAL (Two-hybrid), ADAL (Affinity Capture-RNA), GGA2 (Co-fractionation), ADAL (Protein-RNA)

ESM2 similar proteins: A0A1P8AWH8, A2Y8B9, F1QR43, F4JG10, F4JVN6, F4KFT7, O18756, O22975, O23617, O80574, O80596, O80738, O94923, Q06402, Q0VC13, Q0WUI9, Q10MJ1, Q1PET6, Q3U1V6, Q43093, Q43847, Q5IH13, Q5IH14, Q5MAU8, Q5VS72, Q6DHV7, Q6YXW6, Q6ZHE5, Q80SY6, Q8L7N4, Q8LB01, Q8VYP9, Q8VZF3, Q8W4K1, Q8W519, Q94AH8, Q94AS5, Q94E75, Q96DG6, Q99683

Diamond homologs: Q0VC13, Q295P6, Q4V831, Q4V9P6, Q6DHV7, Q80SY6, Q82K09, Q8IG39, Q8LPL7, Q9VHH7, Q839J4, A4TEW1, B5ZXI3

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
MAPDA	“down-regulates quantity”	N(6)-methyl-AMP(2-)	“chemical modification”
MAPDA	“down-regulates quantity”	water	“chemical modification”
MAPDA	“down-regulates quantity”	hydron	“chemical modification”
MAPDA	“up-regulates quantity”	IMP	“chemical modification”
MAPDA	“up-regulates quantity”	methylammonium	“chemical modification”
MAPDA	“down-regulates quantity”	N(6)-methyl-dAMP(2-)	“chemical modification”
MAPDA	“up-regulates quantity”	“2’-deoxyinosine 5’-phosphate(2-)”	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	0
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1827 predictions. Top by Δscore:

Variant	Effect	Δscore
15:43335805:G:T	donor_gain	1.0000
15:43335822:GAAGA:G	donor_gain	1.0000
15:43335823:AAGA:A	donor_gain	1.0000
15:43335823:AAGAG:A	donor_loss	1.0000
15:43335824:AGA:A	donor_gain	1.0000
15:43335824:AGAGT:A	donor_loss	1.0000
15:43335825:GA:G	donor_gain	1.0000
15:43335825:GAG:G	donor_gain	1.0000
15:43335827:G:GG	donor_gain	1.0000
15:43335827:GTAA:G	donor_loss	1.0000
15:43335829:AAGT:A	donor_loss	1.0000
15:43336623:CAGA:C	acceptor_loss	1.0000
15:43336624:A:AG	acceptor_gain	1.0000
15:43336624:AG:A	acceptor_loss	1.0000
15:43336625:G:GG	acceptor_gain	1.0000
15:43336625:GAT:G	acceptor_gain	1.0000
15:43336682:TAATG:T	donor_loss	1.0000
15:43336685:TGGT:T	donor_loss	1.0000
15:43336688:T:A	donor_loss	1.0000
15:43339665:G:GT	donor_gain	1.0000
15:43340347:C:G	donor_gain	1.0000
15:43342979:ATGT:A	acceptor_gain	1.0000
15:43342980:T:G	acceptor_gain	1.0000
15:43342988:TTCTA:T	acceptor_loss	1.0000
15:43342989:TCTA:T	acceptor_loss	1.0000
15:43342990:CTAGG:C	acceptor_loss	1.0000
15:43342992:A:AG	acceptor_gain	1.0000
15:43342992:A:C	acceptor_loss	1.0000
15:43342992:AG:A	acceptor_gain	1.0000
15:43342993:G:GG	acceptor_gain	1.0000

AlphaMissense

2351 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:43340325:A:C	S106R	0.998
15:43340327:C:A	S106R	0.998
15:43340327:C:G	S106R	0.998
15:43351755:A:T	D293V	0.998
15:43351041:T:G	C291W	0.997
15:43351756:T:A	D293E	0.997
15:43351756:T:G	D293E	0.997
15:43351754:G:C	D293H	0.996
15:43335708:C:G	H26D	0.995
15:43336639:T:C	F70L	0.995
15:43336641:T:A	F70L	0.995
15:43336641:T:G	F70L	0.995
15:43340314:T:C	L102P	0.995
15:43350948:T:G	C260W	0.995
15:43335710:C:A	H26Q	0.994
15:43335710:C:G	H26Q	0.994
15:43340289:T:C	F94L	0.994
15:43340291:T:A	F94L	0.994
15:43340291:T:G	F94L	0.994
15:43340323:G:T	R105M	0.994
15:43351755:A:C	D293A	0.994
15:43351758:A:T	D294V	0.994
15:43351759:T:A	D294E	0.994
15:43351759:T:G	D294E	0.994
15:43348960:A:C	R229S	0.993
15:43348960:A:T	R229S	0.993
15:43351754:G:T	D293Y	0.993
15:43335718:G:A	G29E	0.992
15:43340323:G:C	R105T	0.992
15:43340324:G:C	R105S	0.992

dbSNP variants (sampled 300 via entrez): RS1000074569 (15:43341615 G>T), RS1000136086 (15:43341023 CCT>C), RS1000151571 (15:43341780 A>G), RS1000218851 (15:43352299 G>A), RS1000277097 (15:43348714 A>G,T), RS1000472481 (15:43342164 A>G), RS1000488798 (15:43350250 G>A,T), RS1000496994 (15:43347513 C>G,T), RS1000547209 (15:43342381 T>C), RS1001037015 (15:43336154 A>G), RS1001137405 (15:43339246 G>A), RS1001212805 (15:43339567 G>A), RS1001419426 (15:43345819 TA>T), RS1001536599 (15:43329894 G>A,C), RS1001757263 (15:43332342 T>A)

Disease associations

OMIM: gene MIM:619346 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002382_240	Eosinophil percentage of white cells	5.000000e-17

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1795150 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation	2
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	decreases expression	1
manganese chloride	increases abundance, increases expression	1
CGP 52608	increases reaction, affects binding	1
jinfukang	affects cotreatment, increases expression	1
2,6-dichloro-(1,4)benzoquinone	decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Cisplatin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Manganese	increases abundance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Cyclosporine	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1817385	Binding	Kcat/Km ratio of recombinant human ADAL1 expressed in Escherichia coli	Adenosine deaminase-like protein 1 (ADAL1): characterization and substrate specificity in the hydrolysis of N(6)- or O(6)-substituted purine or 2-aminopurine nucleoside monophosphates. — J Med Chem

Clinical trials (associated diseases)

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