MPG

Summary

MPG (N-methylpurine DNA glycosylase, HGNC:7211) is a protein-coding gene on chromosome 16p13.3, encoding DNA-3-methyladenine glycosylase (P29372). Hydrolysis of the deoxyribose N-glycosidic bond to excise 3-methyladenine, and 7-methylguanine from the damaged DNA polymer formed by alkylation lesions.

Enables DNA binding activity. Predicted to be involved in base-excision repair. Located in cytosol and nucleoplasm.

Source: NCBI Gene 4350 — RefSeq curated summary.

At a glance

• Gene–disease (curated): schizophrenia (No Known Disease Relationship, GenCC)
• GWAS associations: 10
• Clinical variants (ClinVar): 84 total — 5 pathogenic
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001015052

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7211
Approved symbol	MPG
Name	N-methylpurine DNA glycosylase
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	MDG
Ensembl gene	ENSG00000103152
Ensembl biotype	protein_coding
OMIM	156565
Entrez	4350

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000219431, ENST00000356432, ENST00000397817, ENST00000436333, ENST00000475280

RefSeq mRNA: 3 — MANE Select: NM_001015052 NM_001015052, NM_001015054, NM_002434

CCDS: CCDS32345, CCDS32346, CCDS42087

Canonical transcript exons

ENST00000356432 — 4 exons

Exon	Start	End
ENSE00000663759	83052	83256
ENSE00001852360	85401	85846
ENSE00001924635	78225	78333
ENSE00003570985	79425	79700

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 96.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 58.5921 / max 394.2493, expressed in 1819 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151849	56.2863	1819
151850	2.3057	1119

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ascending aorta	UBERON:0001496	96.64	gold quality
thoracic aorta	UBERON:0001515	96.64	gold quality
descending thoracic aorta	UBERON:0002345	96.43	gold quality
right coronary artery	UBERON:0001625	96.27	gold quality
stromal cell of endometrium	CL:0002255	96.02	gold quality
left coronary artery	UBERON:0001626	95.96	gold quality
aorta	UBERON:0000947	95.93	gold quality
popliteal artery	UBERON:0002250	95.54	gold quality
tibial artery	UBERON:0007610	95.54	gold quality
coronary artery	UBERON:0001621	95.31	gold quality
mucosa of stomach	UBERON:0001199	95.15	gold quality
left adrenal gland cortex	UBERON:0035825	94.88	gold quality
left adrenal gland	UBERON:0001234	94.77	gold quality
right lung	UBERON:0002167	94.49	gold quality
right adrenal gland	UBERON:0001233	94.45	gold quality
right adrenal gland cortex	UBERON:0035827	94.32	gold quality
adrenal cortex	UBERON:0001235	94.16	gold quality
endocervix	UBERON:0000458	94.03	gold quality
body of pancreas	UBERON:0001150	93.84	gold quality
left uterine tube	UBERON:0001303	93.82	gold quality
body of stomach	UBERON:0001161	93.70	gold quality
right ovary	UBERON:0002118	93.61	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.57	gold quality
adenohypophysis	UBERON:0002196	93.56	gold quality
lower esophagus	UBERON:0013473	93.55	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.52	gold quality
gastrocnemius	UBERON:0001388	93.50	gold quality
right lobe of liver	UBERON:0001114	93.44	gold quality
right lobe of thyroid gland	UBERON:0001119	93.40	gold quality
apex of heart	UBERON:0002098	93.30	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.77
E-CURD-122	yes	9.55
E-GEOD-70580	no	257.12

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): APEX1, GATA4, NR3C1, SP1, TFAP2A, TP53

Literature-anchored findings (GeneRIF, showing 40)

• The human alkyl-N-purine-DNA glycosylase (ANPG or MPG) excises both 1,N(6)-ethenoadenine and 1,N(2)-ethenoguanine adducts, exocyclic DNA adducts generated by lipid peroxidation, when present in DNA. (PMID:12016206)
• Effects of hydrogen bonding within a damaged base pair on the activity of wild type and DNA-intercalating mutants of the human alkyladenine DNA glycosylase. (PMID:12077143)
• MPG mRNA expression was slightly higher in astrocytic tumors than in adjacent tissue, suggesting a role in astrocytic tumors & the possibility that the altered MPG expression & intracellular localization could be associated with astrocytic tumorigenesis. (PMID:12820404)
• Methylated DNA-binding domain 1 cooperates with this enzyme for transcriptional repression and DNA repair. (PMID:14555760)
• alkyladenine DNA-glycosylase activates neutral lesions by protonation of the nucleobase leaving group (PMID:14567703)
• analysis of substrate specificity of human 3-methyladenine-DNA glycosylase (PMID:14688248)
• The human alkyl-N-purine-DNA glycosylase (ANPG or MPG) binds tightly to ethenocytosine adduct when present in DNA. Unlike the ethenopurines, ANPG does not excise ethenocytosine but prevents its repair by forming an abortive protein-DNA complex. (PMID:14761949)
• plays a role in maintaining integrity of the genome by recruiting DNA repair proteins to actively transcribing DNA [3-methyladenine DNA glycosylase] (PMID:14761960)
• AAG is a mammalian enzyme that can act on all three purine deamination bases, hypoxanthine, xanthine, and oxanine (PMID:15247209)
• C147G and C342G missense mutations and a 5’-UTR 1-27 insT were found in familial colorectal cancer DNA suggesting a limited role for this gene in the devlopment of CRC. (PMID:17029639)
• this newly purified full-length hMPG is appreciably stable at high temperature, such as 50 degrees C. (PMID:18191412)
• The mutability of the AAG substrate binding pocket, and the essentiality of individual binding pocket amino acids for survival of methylation damage, was assessed. (PMID:18706524)
• Although the amino terminus of the protein is dispensable for glycosylase activity at a single site, we find that deletion of the 80 amino-terminal amino acids significantly decreases the processivity of AAG. (PMID:18839966)
• Results suggest the possible significance of repair of the frequent lesions in single-stranded DNA transiently generated during replication and transcription. (PMID:19219989)
• evidence that the excised base rather than AP-site could be rate-limiting for DNA-glycosylase reactions (PMID:19616486)
• RNS-induced posttranslational modification of AAG is one mechanism of base excision repair dysregulation (PMID:19864471)
• AAG uses hopping to effectively search both strands of a DNA duplex in a single binding encounter. (PMID:20201599)
• AAG and its mutants bind DNA containing one and two base-pair loops with significant affinity, thus shielding them from mismatch repair; the strength of such binding correlates with their ability to induce the mutator phenotype. (PMID:20347426)
• AAG can make damaged DNA by catalyzing formation of an N-glycosyl bond between 1,N(6)-ethenoadenine (epsilonA) and abasic DNA. We attribute the reversibility of this reaction to the tight binding and slow subsequent hydrolysis of DNA containing an epsilonA lesion. (PMID:20873830)
• rs710079 and rs2858056 polymorphisms and the GCGC haplotype in the MPG gene are associated with the risk of rheumatoid arthritis progression. (PMID:21063071)
• Substitution of active site tyrosines with tryptophan alters the free energy for nucleotide flipping by human alkyladenine DNA glycosylase (PMID:21244040)
• Structural basis for the inhibition of human alkyladenine DNA glycosylase (AAG) by 3,N4-ethenocytosine-containing DNA. (PMID:21349833)
• The use of a concerted mechanism supports previous speculations that AAG uses a nonspecific strategy to excise both neutral 1,N(6)-ethenoadenine and cationic N(3)-methyladenine lesions. (PMID:21877721)
• The non-enzymatic binding of AAG to 3,N(4)-ethenocytosine specifically blocks ALKBH2-catalyzed repair of 3,N(4)-ethenocytosine but not that of methylated ALKBH2 substrates. (PMID:22079122)
• Novel structures of AAG presented here help provide an understanding of this intriguing DNA repair protein, both in terms of understanding how AAG can recognize different types of DNA damage and in terms of how it may search the genome for DNA damage. (PMID:22148158)
• Evaluation of APNG protein levels in several clinical datasets demonstrated that in patients, high nuclear APNG expression correlated with poorer overall survival compared with patients lacking APNG expression. (PMID:22156195)
• Elevated MPG activity is associated with lung cancer, possibly by creating an imbalance in the base excision repair pathway. (PMID:22266085)
• Investigated the expression of MPG gene and protein in 128 glioma and 10 non-neoplastic brain tissues. Found MPG gene expression level in glioma tissues was significantly higher than that in non-neoplastic brain tissues (P < 0.001). (PMID:22496614)
• N-methylpurine DNA glycosylase negatively regulates p53-mediated cell cycle arrest. (PMID:22801474)
• A functional footprinting approach was used to define the binding site of alkyladenine DNA glycosylase used for the repair of deaminated purines. (PMID:23074184)
• disease-stage-specific alterations in the expression of MPG may highlight a potential role for MPG in determining EAC onset and thus potentially be of clinical relevance for early disease detection and increased patient survival. (PMID:23137018)
• Mitochondrial single-stranded binding protein (mtSSB) as a novel interacting partner of AAG. (PMID:23290262)
• UHRF1 interacts with N-methylpurine DNA glycosylase (MPG) in cancer cells in vitro and displays a co-localization with MPG in the nucleoplasm. (PMID:23537643)
• AAG removes both methanol and 1,N(6)-ethenoadenine from DNA with single-turnover rate constants that are significantly greater than the corresponding uncatalyzed rates. (PMID:23688261)
• AAG has a flexible amino terminus that tunes its affinity for nonspecific DNA, but we find that it is not required for intersegmental transfer. As AAG has only a single DNA binding site, this argues against the bridging model for intersegmental transfer (PMID:23839988)
• In the case of alkyladenine DNA glycosylase, DNA intercalation contributes to the specific binding of a damaged nucleotide, but this enhanced specificity comes at the cost of reduced speed of nucleotide flipping. (PMID:25324304)
• High MPG DNA repair assays for two different oxidative DNA lesions reveal associations with increased lung cancer risk. (PMID:25355292)
• results suggest that individuals carrying R120C and R141Q MPG variants may be at risk for genomic instability and associated diseases as a consequence. (PMID:25538240)
• Rheumatoid arthritis is associated with a polymorphism in the MPG gene (rs2858056) and increased serum level of the MPG protein. (PMID:25757089)
• Role of MPG protein in the DNA damage response through the base excision repair pathway (PMID:26025911)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mpg	ENSDARG00000069729
mus_musculus	Mpg	ENSMUSG00000020287
rattus_norvegicus	Mpg	ENSRNOG00000020571

Protein

Protein identifiers

DNA-3-methyladenine glycosylase — P29372 (reviewed: P29372)

Alternative names: 3-alkyladenine DNA glycosylase, 3-methyladenine DNA glycosidase, ADPG, N-methylpurine-DNA glycosylase

All UniProt accessions (3): P29372, A2IDA3, Q1W6H1

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolysis of the deoxyribose N-glycosidic bond to excise 3-methyladenine, and 7-methylguanine from the damaged DNA polymer formed by alkylation lesions.

Subunit / interactions. Binds MBD1. Binds SSBP1.

Subcellular location. Cytoplasm. Mitochondrion matrix. Mitochondrion nucleoid. Nucleus.

Activity regulation. Binding to SSBP1 in mitochondria inhibits glycosylase activity in the context of a single-stranded DNA (ssDNA), but not a double-stranded DNA (dsDNA) substrates.

Similarity. Belongs to the DNA glycosylase MPG family.

Isoforms (4)

UniProt ID	Names	Canonical?
P29372-1	1	yes
P29372-2	2
P29372-4	3
P29372-5	4

RefSeq proteins (3): NP_001015052, NP_001015054, NP_002425 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003180	MPG	Family
IPR011034	Formyl_transferase-like_C_sf	Homologous_superfamily
IPR036995	MPG_sf	Homologous_superfamily

Pfam: PF02245

Enzyme classification (BRENDA):

• EC 3.2.2.21 — DNA-3-methyladenine glycosylase II (BRENDA: 13 organisms, 96 substrates, 22 inhibitors, 17 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ALKYLATED DNA	—	5
DUPLEX OLIGONUCLEOTIDE SUBSTRATE CONTAINING ETHE	—	4
ALKYLATED DNA, TREATED WITH N-METHYL-N’-NITRO-N-	—	2
1,N6-ETHENOADENINE RESIDUES IN ALKYLATED DNA	—	1
3-METHYLADENINE RESIDUES IN ALKYLATED DNA	—	1
7-METHYLGUANINE RESIDUES IN ALKYLATED DNA	—	1
HYPOXANTHINE	—	1

UniProt features (53 total): strand 13, helix 10, sequence variant 8, sequence conflict 7, turn 6, splice variant 3, modified residue 2, transit peptide 1, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
3UBY	X-RAY DIFFRACTION	2
1EWN	X-RAY DIFFRACTION	2.1
3QI5	X-RAY DIFFRACTION	2.2
1F4R	X-RAY DIFFRACTION	2.4
1F6O	X-RAY DIFFRACTION	2.4
1BNK	X-RAY DIFFRACTION	2.7
7XFH	ELECTRON MICROSCOPY	2.9
7XFJ	ELECTRON MICROSCOPY	3
7XFM	ELECTRON MICROSCOPY	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P29372-F1	82.08	0.65

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 78, 252

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-110330	Recognition and association of DNA glycosylase with site containing an affected purine
R-HSA-110331	Cleavage of the damaged purine
R-HSA-110357	Displacement of DNA glycosylase by APEX1
R-HSA-73884	Base Excision Repair
R-HSA-73894	DNA Repair
R-HSA-73927	Depurination
R-HSA-73929	Base-Excision Repair, AP Site Formation
R-HSA-73933	Resolution of Abasic Sites (AP sites)

MSigDB gene sets: 134 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, ENK_UV_RESPONSE_KERATINOCYTE_UP, KAUFFMANN_DNA_REPAIR_GENES, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_DNA_MODIFICATION, WANG_RESPONSE_TO_BEXAROTENE_UP, GOBP_DNA_DAMAGE_RESPONSE, AFFAR_YY1_TARGETS_UP, REACTOME_DNA_REPAIR, MODULE_568, MODULE_60, MODULE_491, MILI_PSEUDOPODIA_CHEMOTAXIS_DN, CARDOSO_RESPONSE_TO_GAMMA_RADIATION_AND_3AB, KOKKINAKIS_METHIONINE_DEPRIVATION_48HR_DN

GO Biological Process (5): base-excision repair (GO:0006284), DNA alkylation repair (GO:0006307), depurination (GO:0045007), DNA repair (GO:0006281), DNA damage response (GO:0006974)

GO Molecular Function (7): DNA binding (GO:0003677), damaged DNA binding (GO:0003684), alkylbase DNA N-glycosylase activity (GO:0003905), DNA N-glycosylase activity (GO:0019104), catalytic activity (GO:0003824), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (7): nucleoplasm (GO:0005654), mitochondrion (GO:0005739), cytosol (GO:0005829), mitochondrial nucleoid (GO:0042645), nucleus (GO:0005634), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Depurination	2
Base Excision Repair	2
Resolution of Abasic Sites (AP sites)	1
DNA Repair	1
Base-Excision Repair, AP Site Formation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
DNA repair	2
cytoplasm	2
intracellular membrane-bounded organelle	2
base-excision repair, AP site formation	1
DNA modification	1
DNA metabolic process	1
DNA damage response	1
cellular response to stress	1
nucleic acid binding	1
DNA binding	1
DNA N-glycosylase activity	1
hydrolase activity, hydrolyzing N-glycosyl compounds	1
catalytic activity, acting on DNA	1
molecular_function	1
binding	1
catalytic activity	1
nuclear lumen	1
mitochondrion	1
mitochondrial matrix	1
nucleoid	1
intracellular membraneless organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

740 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MPG	OGG1	P78554	840
MPG	VPS18	Q9P253	830
MPG	MGMT	P16455	814
MPG	APEX1	P27695	787
MPG	NTHL1	P78549	768
MPG	HBZ	P02008	768
MPG	UNG	P13051	743
MPG	NEIL2	Q969S2	708
MPG	PGC	P20142	680
MPG	MBD4	O95243	669
MPG	TDG	Q13569	658
MPG	XRCC1	P18887	657
MPG	CACNA1S	Q13698	649
MPG	NEIL3	Q8TAT5	647
MPG	LIG1	P18858	638

IntAct

105 interactions, top by confidence:

A	B	Type	Score
MPG	HSD17B14	psi-mi:“MI:0915”(physical association)	0.670
HSD17B14	MPG	psi-mi:“MI:0915”(physical association)	0.670
PRNP	MPG	psi-mi:“MI:0915”(physical association)	0.570
PRNP	MPG	psi-mi:“MI:0403”(colocalization)	0.570
GHITM	MFN2	psi-mi:“MI:0914”(association)	0.530
ZNRD2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
MPG	HSPD1	psi-mi:“MI:0915”(physical association)	0.400
MPG	XRCC1	psi-mi:“MI:0915”(physical association)	0.400
TERF2IP	MPG	psi-mi:“MI:0915”(physical association)	0.370
MPG	GPR182	psi-mi:“MI:0915”(physical association)	0.370
OTUB1		psi-mi:“MI:0914”(association)	0.350
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
Eif3a	RPSA	psi-mi:“MI:0914”(association)	0.350
RPL10	RPS6	psi-mi:“MI:0914”(association)	0.350
Srp72		psi-mi:“MI:0914”(association)	0.350
Rrbp1	PIPSL	psi-mi:“MI:0914”(association)	0.350
NPM1	RPSA	psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
	DDX3Y	psi-mi:“MI:0914”(association)	0.350
TP53	HGS	psi-mi:“MI:0914”(association)	0.350
CHD8	IGLV4-60	psi-mi:“MI:0914”(association)	0.350
HCN1	USP27X	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (138): HSD17B14 (Two-hybrid), IKBKAP (Affinity Capture-MS), ELP3 (Affinity Capture-MS), ELP2 (Affinity Capture-MS), KBTBD4 (Affinity Capture-MS), EIF2A (Co-fractionation), KIFC1 (Co-fractionation), MPG (Two-hybrid), MPG (Proximity Label-MS), MPG (Affinity Capture-MS), MPG (Affinity Capture-MS), MPG (Affinity Capture-MS), MPG (Affinity Capture-MS), MPG (Affinity Capture-MS), MPG (Affinity Capture-MS)

ESM2 similar proteins: A1L3C1, A2AWP8, A2RRU4, A6QM06, A6QNS9, E1BBQ2, F1LQY6, G3V9M2, O43189, O94827, P29372, P29590, P41155, P97260, Q01113, Q02833, Q04841, Q0P5I0, Q12770, Q13387, Q13505, Q29RM4, Q32L49, Q3V1H9, Q5MNU5, Q5R5M3, Q66T02, Q69Z89, Q6GQT6, Q6IPT2, Q6RFZ7, Q6ZN54, Q70EL4, Q7Z6G3, Q8BQB4, Q8C4U2, Q8N1F8, Q8N554, Q8WWW0, Q8WXF8

Diamond homologs: A0AH42, A0PZK9, A0RAB9, A3CTY6, A4IY77, A4J510, A5I1A3, A5IG48, A5IVC5, A6LPI2, A6QJI5, A6U471, A7FTE3, A7GCV4, A7GLP0, A7HIL2, A7NBW2, A7X5V7, A7ZA84, A8MF35, A8Z534, A9VGI8, B1IJE7, B1KZY0, B2A7A8, B2THZ1, B2UXQ2, B3EN08, B4S4K5, B7HEV9, B7HXM9, B7IJ32, B7J1Z1, B7JSE3, B8DEK7, B9IRB4, C1EZP2, C1FKZ0, C1L1K0, C3KTV2

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
MPG	“down-regulates quantity by destabilization”	IGBP1	monoubiquitination
ATM	“up-regulates activity”	MPG	phosphorylation
UBE2D1	“up-regulates activity”	MPG	binding
UBE2D3	“up-regulates activity”	MPG	binding
UBE2E1	“up-regulates activity”	MPG	binding
MPG	“down-regulates quantity by destabilization”	PPP2CA	polyubiquitination
MPG	“down-regulates quantity by destabilization”	STK36	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 83 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
Autodegradation of the E3 ubiquitin ligase COP1	5	21.8×	4e-04
Defective CFTR causes cystic fibrosis	5	18.0×	8e-04
Degradation of CDH1	5	16.1×	1e-03
Regulation of RUNX2 expression and activity	5	14.9×	1e-03
Activation of STAT3 by cadherin engagement	5	13.4×	2e-03
The role of GTSE1 in G2/M progression after G2 checkpoint	5	13.2×	2e-03
MAPK6/MAPK4 signaling	5	11.1×	2e-03
G2/M Checkpoints	5	11.0×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	67
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
3243550	NC_000016.9:g.(?97132)(143343_?)del	Pathogenic
3243554	NC_000016.9:g.(?97132)(167394_?)del	Pathogenic
3243555	NC_000016.9:g.(?97132)(150527_?)del	Pathogenic
3339966	NC_000016.9:g.(?_135384)_139739del	Pathogenic
3770232	GRCh37/hg19 16p13.3(chr16:80000-180000)x1	Pathogenic

SpliceAI

931 predictions. Top by Δscore:

Variant	Effect	Δscore
16:79423:A:AG	acceptor_gain	1.0000
16:79424:G:GG	acceptor_gain	1.0000
16:83254:AGGGT:A	donor_loss	1.0000
16:83255:GG:G	donor_gain	1.0000
16:83255:GGGTG:G	donor_loss	1.0000
16:83256:GG:G	donor_gain	1.0000
16:83256:GGTGA:G	donor_loss	1.0000
16:83257:G:GG	donor_gain	1.0000
16:83258:T:G	donor_loss	1.0000
16:79420:TACA:T	acceptor_loss	0.9900
16:79422:CAGT:C	acceptor_loss	0.9900
16:79424:GT:G	acceptor_gain	0.9900
16:79424:GTT:G	acceptor_gain	0.9900
16:79424:GTTT:G	acceptor_gain	0.9900
16:79424:GTTTT:G	acceptor_gain	0.9900
16:79697:ACAG:A	donor_loss	0.9900
16:79698:CAG:C	donor_loss	0.9900
16:79699:AG:A	donor_loss	0.9900
16:79700:GG:G	donor_loss	0.9900
16:79701:GT:G	donor_loss	0.9900
16:79702:T:G	donor_loss	0.9900
16:80510:T:G	donor_gain	0.9900
16:83047:CACA:C	acceptor_loss	0.9900
16:83049:CAG:C	acceptor_loss	0.9900
16:83050:A:AG	acceptor_gain	0.9900
16:83050:AGGTC:A	acceptor_loss	0.9900
16:83051:G:GG	acceptor_gain	0.9900
16:83225:C:T	donor_gain	0.9900
16:83259:GA:G	donor_loss	0.9900
16:85398:CAGGG:C	acceptor_loss	0.9900

AlphaMissense

1872 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:83184:T:C	F150L	0.991
16:83186:C:A	F150L	0.991
16:83186:C:G	F150L	0.991
16:83130:G:C	D132H	0.987
16:83250:A:C	S172R	0.986
16:83252:C:A	S172R	0.986
16:83252:C:G	S172R	0.986
16:83243:C:A	N169K	0.984
16:83243:C:G	N169K	0.984
16:83104:A:T	E123V	0.983
16:83237:C:G	C167W	0.980
16:85709:T:C	F277L	0.978
16:85711:C:A	F277L	0.978
16:85711:C:G	F277L	0.978
16:85416:T:A	V179D	0.976
16:85546:C:G	C222W	0.976
16:85550:G:C	A224P	0.972
16:85706:C:A	R276S	0.972
16:85736:A:C	S286R	0.972
16:85738:T:A	S286R	0.972
16:85738:T:G	S286R	0.972
16:85427:G:C	A183P	0.971
16:85523:T:C	C215R	0.971
16:85545:G:A	C222Y	0.970
16:83110:A:T	E125V	0.969
16:83111:G:C	E125D	0.969
16:83111:G:T	E125D	0.969
16:83236:G:A	C167Y	0.968
16:83092:G:A	G119D	0.967
16:85525:C:G	C215W	0.967

dbSNP variants (sampled 300 via entrez): RS1000087335 (16:75536 G>A,C), RS1000251699 (16:82400 A>G), RS1001042935 (16:78998 T>A,C), RS1001470245 (16:79567 G>C), RS1001673947 (16:78709 C>G,T), RS1001901891 (16:78401 C>T), RS1001945021 (16:83178 G>A,C), RS1002458136 (16:78597 G>A), RS1002531974 (16:76062 G>A), RS1002910347 (16:77566 A>C), RS1002971155 (16:82293 C>T), RS1003101892 (16:86045 C>A,G), RS1003350485 (16:82498 G>A), RS1003501584 (16:84955 C>G), RS1003761125 (16:75826 G>A,C)

Disease associations

OMIM: gene MIM:156565 | disease phenotypes: MIM:617118, MIM:604364

GenCC curated gene-disease

Disease	Classification	Inheritance
schizophrenia	No Known Disease Relationship	Unknown

Mondo (3): epilepsy, familial focal, with variable foci 3 (MONDO:0014925), epilepsy, familial focal, with variable foci 1 (MONDO:0024556), schizophrenia (MONDO:0005090)

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001873_3	Red blood cell traits	3.000000e-23
GCST001873_5	Red blood cell traits	9.000000e-48
GCST001873_6	Red blood cell traits	2.000000e-34
GCST001873_8	Red blood cell traits	4.000000e-22
GCST003122_1	Hemoglobin levels	6.000000e-18
GCST004349_4	Glioblastoma	2.000000e-08
GCST006585_5	Blood protein levels	1.000000e-12
GCST90002390_430	Mean corpuscular hemoglobin	1.000000e-22
GCST90002391_153	Mean corpuscular hemoglobin concentration	1.000000e-13
GCST90002392_443	Mean corpuscular volume	6.000000e-20

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0004527	mean corpuscular hemoglobin
EFO:0007629	hemoglobin A1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3396943 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 83,905 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1417019	MITOXANTRONE HYDROCHLORIDE	4	69,932
CHEMBL51483	GOSSYPOL	3	13,973

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

ChEMBL bioactivities

5 potent at pChembl≥5 of 8 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.70	IC50	200	nM	AURINTRICARBOXYLIC ACID
5.60	IC50	2500	nM	MITOXANTRONE HYDROCHLORIDE
5.58	IC50	2600	nM	CHEMBL1512355
5.58	IC50	2600	nM	MORIN
5.52	IC50	3000	nM	GOSSYPOL

PubChem BioAssay actives

5 with measured affinity, of 29 total; 5 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
5-[(3-carboxy-4-hydroxyphenyl)-(3-carboxy-4-oxocyclohexa-2,5-dien-1-ylidene)methyl]-2-hydroxybenzoic acid	1191749: Inhibition of human purified MPG pre-incubated with compound for 10 mins followed by addition of 1,N6 ethenoadenine containing 32P-labeled duplex oligonucleotide substrates by gel-based excision activity assay	ic50	0.2000	uM
Mitoxantrone Hydrochloride	1191749: Inhibition of human purified MPG pre-incubated with compound for 10 mins followed by addition of 1,N6 ethenoadenine containing 32P-labeled duplex oligonucleotide substrates by gel-based excision activity assay	ic50	2.5000	uM
2-(2,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one;hydrate	1191749: Inhibition of human purified MPG pre-incubated with compound for 10 mins followed by addition of 1,N6 ethenoadenine containing 32P-labeled duplex oligonucleotide substrates by gel-based excision activity assay	ic50	2.6000	uM
2-(2,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one	1720122: Inhibition of human AAG using HXO2/Loop01 oligonucleotide as substrate incubated for 2 hrs by colorimetric based microplate assay	ic50	2.6000	uM
7-(8-formyl-1,6,7-trihydroxy-3-methyl-5-propan-2-ylnaphthalen-2-yl)-2,3,8-trihydroxy-6-methyl-4-propan-2-ylnaphthalene-1-carbaldehyde	1191749: Inhibition of human purified MPG pre-incubated with compound for 10 mins followed by addition of 1,N6 ethenoadenine containing 32P-labeled duplex oligonucleotide substrates by gel-based excision activity assay	ic50	3.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Temozolomide	increases reaction, increases response to substance, decreases response to substance, decreases reaction	4
Methyl Methanesulfonate	increases reaction, increases response to substance, decreases response to substance	4
sodium arsenite	decreases expression, decreases reaction, increases abundance, affects cotreatment, increases expression	3
Methylnitrosourea	decreases response to substance, increases response to substance	3
1,N(6)-ethenoadenine	increases metabolic processing	2
methoxyamine	increases reaction, increases response to substance, decreases reaction	2
Arsenic	affects cotreatment, affects methylation, decreases expression, decreases reaction, increases abundance	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Cisplatin	affects cotreatment, increases expression, affects activity, affects binding	2
Doxorubicin	affects response to substance, increases expression, affects expression	2
Ethyl Methanesulfonate	increases expression, affects response to substance, increases response to substance	2
Valproic Acid	affects expression, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
dimethyl sulfate	increases response to substance	1
bromoacetate	increases expression	1
3-methyladenine	increases metabolic processing	1
Ginkgo biloba extract	decreases expression, decreases reaction, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CPG-oligonucleotide	increases expression	1
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride	increases reaction, increases response to substance	1
fenbuconazole	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	increases expression, decreases reaction	1
BIX 01294	increases abundance, decreases expression, decreases reaction	1
veliparib	increases reaction, increases response to substance	1
jinfukang	affects cotreatment, increases expression	1
Vehicle Emissions	decreases reaction, increases expression	1
Caffeine	decreases phosphorylation	1
Carmustine	decreases response to substance	1

ChEMBL screening assays

12 unique, capped per target: 11 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3398686	Binding	Inhibition of human purified MPG pre-incubated with compound for 10 mins followed by addition of 1,N6 ethenoadenine containing 32P-labeled duplex oligonucleotide substrates by gel-based excision activity assay	Naturally occurring polyphenol, morin hydrate, inhibits enzymatic activity of N-methylpurine DNA glycosylase, a DNA repair enzyme with various roles in human disease. — Bioorg Med Chem
CHEMBL5665445	Functional	Inhibition of MPG by quantifying inhibition of MPG-mediated cleavage and dissociation of quenched duplex DNA oligonucleotides, measured as fluorescence at 594 nm. To generate a functional strand incision and increase turn-over this assay is	Enzyme Inhibitor Single Concentration assay results for EUbOPEN Chemogenomics Library

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1NU	Abcam K-562 MPG KO	Cancer cell line	Female
CVCL_D2KF	Abcam Raji MPG KO	Cancer cell line	Male
CVCL_SY79	HAP1 MPG (-) 1	Cancer cell line	Male
CVCL_SY80	HAP1 MPG (-) 2	Cancer cell line	Male
CVCL_UQ96	Abcam Jurkat MPG KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety