MTARC2

Summary

MTARC2 (mitochondrial amidoxime reducing component 2, HGNC:26064) is a protein-coding gene on chromosome 1q41, encoding Mitochondrial amidoxime reducing component 2 (Q969Z3). Catalyzes the reduction of N-oxygenated molecules, acting as a counterpart of cytochrome P450 and flavin-containing monooxygenases in metabolic cycles.

The protein encoded by this gene is an enzyme found in the outer mitochondrial membrane that reduces N-hydroxylated substrates. The encoded protein uses molybdenum as a cofactor and cytochrome b5 type B and NADH cytochrome b5 reductase as accessory proteins. One type of substrate used is N-hydroxylated nucleotide base analogues, which can be toxic to a cell. Other substrates include N(omega)-hydroxy-L-arginine (NOHA) and amidoxime prodrugs, which are activated by the encoded enzyme. Multiple transcript variants encoding the different isoforms have been found for this gene.

Source: NCBI Gene 54996 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 52 total
• Druggable target: yes
• MANE Select transcript: NM_017898

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26064
Approved symbol	MTARC2
Name	mitochondrial amidoxime reducing component 2
Location	1q41
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20605
Ensembl gene	ENSG00000117791
Ensembl biotype	protein_coding
OMIM	614127
Entrez	54996

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000359316, ENST00000366913, ENST00000425560, ENST00000469583, ENST00000472447, ENST00000496078, ENST00000866789, ENST00000866790, ENST00000866791, ENST00000956460, ENST00000956461

RefSeq mRNA: 3 — MANE Select: NM_017898 NM_001317338, NM_001331042, NM_017898

CCDS: CCDS1525, CCDS81425

Canonical transcript exons

ENST00000366913 — 8 exons

Exon	Start	End
ENSE00000792556	220761658	220761820
ENSE00000801893	220754947	220755120
ENSE00001000175	220762910	220763050
ENSE00001068931	220780018	220780079
ENSE00001068934	220780168	220780239
ENSE00001442977	220748322	220748803
ENSE00001868967	220783919	220784815
ENSE00003667771	220781778	220781932

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 98.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.3595 / max 302.6508, expressed in 1342 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8655	4.3610	1180
8653	1.4440	752
8654	0.5545	278

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.92	gold quality
left lobe of thyroid gland	UBERON:0001120	97.31	gold quality
liver	UBERON:0002107	97.19	gold quality
right lobe of thyroid gland	UBERON:0001119	97.04	gold quality
thyroid gland	UBERON:0002046	96.74	gold quality
adult mammalian kidney	UBERON:0000082	96.72	gold quality
right lung	UBERON:0002167	96.61	gold quality
nephron tubule	UBERON:0001231	96.31	gold quality
kidney epithelium	UBERON:0004819	95.66	gold quality
metanephros cortex	UBERON:0010533	95.57	gold quality
parotid gland	UBERON:0001831	95.47	gold quality
duodenum	UBERON:0002114	95.47	gold quality
body of pancreas	UBERON:0001150	95.44	gold quality
jejunal mucosa	UBERON:0000399	95.24	gold quality
upper lobe of left lung	UBERON:0008952	95.12	gold quality
upper lobe of lung	UBERON:0008948	94.96	gold quality
kidney	UBERON:0002113	94.94	gold quality
right coronary artery	UBERON:0001625	94.88	gold quality
gall bladder	UBERON:0002110	94.82	gold quality
mucosa of stomach	UBERON:0001199	94.76	gold quality
left ovary	UBERON:0002119	94.75	gold quality
right ovary	UBERON:0002118	94.63	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.51	gold quality
left coronary artery	UBERON:0001626	94.45	gold quality
body of stomach	UBERON:0001161	94.40	gold quality
right atrium auricular region	UBERON:0006631	94.34	gold quality
descending thoracic aorta	UBERON:0002345	94.23	gold quality
small intestine	UBERON:0002108	94.10	gold quality
cortex of kidney	UBERON:0001225	94.06	gold quality
renal glomerulus	UBERON:0000074	94.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

76 targeting MTARC2, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-200A-5P	99.76	69.10	949

Literature-anchored findings (GeneRIF, showing 9)

• Arc1(MOSC-1) and Arc2(MOSC-2) proteins are monomeric in their active forms. (PMID:20861021)
• results provide the first hints that mARC might be involved in mitochondrial N(omega)-hydroxy-L-arginine reduction and could be of physiological significance in affecting endogenous nitric oxide levels. (PMID:21029045)
• Chlamydomonas reinhardtii ARC has a Zn-dependent activity and protein partners similar to human MARC1 and MARC2. (PMID:21803866)
• analysis of the nature of ligands in the Mo(V) state of the active site of mARC-2 (PMID:21916412)
• Data indicate that mitochondrial amidoxime reducing components 1 and 2 together with the electron transport proteins NADH-cytochrome b5 reductase (CYB5R) and cytochrome b5 (CYB5) catalyze the reduction of N-hydroxylated compounds such as amidoximes. (PMID:23703616)
• Functional characteristics of protein variants encoded by nonsynonymous single nucleotide polymorphisms in MARC1 and MARC2 in healthy Caucasians were determined. (PMID:24423752)
• human mARC-1 and mARC-2 are capable of catalyzing reduction of nitrite to NO through reaction with its molybdenum cofactor (PMID:24500710)
• mARC2 has a pivotal role in protecting human cells against apoptotic effects of the base analog N6-hydroxylaminopurine. (PMID:25713076)
• CIRC-MARC2 SILENCING PROTECTS HUMAN CARDIOMYOCYTES FROM HYPOXIA/REOXYGENATION-INDUCED INJURY BY MODULATING MIR-335-5P/TRPM7 AXIS. (PMID:38010085)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mtarc2	ENSMUSG00000073481
rattus_norvegicus	Mtarc2	ENSRNOG00000077900
caenorhabditis_elegans		WBGENE00009049
caenorhabditis_elegans		WBGENE00018758

Paralogs (2): MOCOS (ENSG00000075643), MTARC1 (ENSG00000186205)

Protein

Protein identifiers

Mitochondrial amidoxime reducing component 2 — Q969Z3 (reviewed: Q969Z3)

Alternative names: Molybdenum cofactor sulfurase C-terminal domain-containing protein 2

All UniProt accessions (3): Q969Z3, F6V6Z1, X1WI34

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the reduction of N-oxygenated molecules, acting as a counterpart of cytochrome P450 and flavin-containing monooxygenases in metabolic cycles. As a component of prodrug-converting system, reduces a multitude of N-hydroxylated prodrugs particularly amidoximes, leading to increased drug bioavailability. May be involved in mitochondrial N(omega)-hydroxy-L-arginine (NOHA) reduction, regulating endogenous nitric oxide levels and biosynthesis. Postulated to cleave the N-OH bond of N-hydroxylated substrates in concert with electron transfer from NADH to cytochrome b5 reductase then to cytochrome b5, the ultimate electron donor that primes the active site for substrate reduction.

Subunit / interactions. Component of a complex composed of cytochrome b5, NADH-cytochrome b5 reductase (CYB5R3) and MTARC2.

Subcellular location. Mitochondrion outer membrane. Peroxisome.

Post-translational modifications. Ubiquitinated by PRKN during mitophagy, leading to its degradation and enhancement of mitophagy. Deubiquitinated by USP30.

Cofactor. Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit.

Isoforms (2)

UniProt ID	Names	Canonical?
Q969Z3-1	1	yes
Q969Z3-2	2

RefSeq proteins (3): NP_001304267, NP_001317971, NP_060368* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005302	MoCF_Sase_C	Domain
IPR005303	MOCOS_middle	Domain
IPR011037	Pyrv_Knase-like_insert_dom_sf	Homologous_superfamily

Pfam: PF03473, PF03476

Enzyme classification (BRENDA):

• EC 1.16.98.B1 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)
• EC 1.7.2.1 — nitrite reductase (NO-forming) (BRENDA: 51 organisms, 98 substrates, 32 inhibitors, 100 Km, 86 kcat entries)

Substrate kinetics (BRENDA)

16 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NITRITE	0.0001–416	41
O2	0.027–1	14
NO2-	0.0015–0.8	12
FERRICYTOCHROME C551	0.0018–0.079	6
HYDROXYLAMINE	0.43–2.5	5
NH2OH	0.434–2.5	5
REDUCED PSEUDOAZURIN	0.067–0.16	5
AZURIN	0.0008–0.049	3
FERROCYTOCHROME C-551	0.0018–0.0075	3
FERRICYTOCHROME C	0.0305–0.046	2
REDUCED METHYL VIOLOGEN	0.41	1
FERRICYTOCHROME C B0428	—	0
FERROCYTOCHROME C2	—	0
FERROCYTOCHROME V(GAMMA)	—	0
NO	—	0

Catalyzed reactions (Rhea), 1 shown:

• N(omega)-hydroxy-L-arginine + 2 Fe(II)-[cytochrome b5] + 2 H(+) = L-arginine + 2 Fe(III)-[cytochrome b5] + H2O (RHEA:61644)

UniProt features (19 total): cross-link 9, sequence variant 3, splice variant 2, transit peptide 1, chain 1, sequence conflict 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q969Z3-F1	91.52	0.85

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 (10): 187, 287, 294, 156, 59, 138, 144, 156, 166, 173

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-211945	Phase I - Functionalization of compounds
R-HSA-1430728	Metabolism
R-HSA-211859	Biological oxidations

MSigDB gene sets: 149 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_BIOLOGICAL_OXIDATIONS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE, AMIT_EGF_RESPONSE_120_HELA, GOBP_REACTIVE_NITROGEN_SPECIES_METABOLIC_PROCESS, GOBP_DETOXIFICATION, GOCC_MITOCHONDRIAL_ENVELOPE, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_RESPONSE_TO_TOXIC_SUBSTANCE, ROSS_AML_WITH_PML_RARA_FUSION, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN

GO Biological Process (4): nitric oxide biosynthetic process (GO:0006809), nitrate metabolic process (GO:0042126), detoxification of nitrogen compound (GO:0051410), cellular detoxification of nitrogen compound (GO:0070458)

GO Molecular Function (8): nitrate reductase activity (GO:0008940), oxidoreductase activity, acting on other nitrogenous compounds as donors (GO:0016661), molybdenum ion binding (GO:0030151), pyridoxal phosphate binding (GO:0030170), molybdopterin cofactor binding (GO:0043546), nitrite reductase activity (GO:0098809), catalytic activity (GO:0003824), oxidoreductase activity (GO:0016491)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), peroxisome (GO:0005777), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Biological oxidations	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
oxidoreductase activity, acting on other nitrogenous compounds as donors	2
biosynthetic process	1
nitric oxide metabolic process	1
oxoacid metabolic process	1
reactive nitrogen species metabolic process	1
detoxification	1
response to nitrogen compound	1
cellular response to stress	1
detoxification of nitrogen compound	1
cellular detoxification	1
oxidoreductase activity	1
transition metal ion binding	1
anion binding	1
vitamin B6 binding	1
binding	1
molecular_function	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrial membrane	1
organelle outer membrane	1
microbody	1
cellular anatomical structure	1

Protein interactions and networks

STRING

516 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MTARC2	MOCS2	O96007	910
MTARC2	MOCS1	Q9NZB8	895
MTARC2	GPHN	Q9NQX3	760
MTARC2	SUOX	P51687	571
MTARC2	CYB5B	O43169	495
MTARC2	CYB5R3	P00387	425
MTARC2	ATAD1	Q8NBU5	415
MTARC2	PTGR3	Q8N4Q0	410
MTARC2	CYB5A	P00167	401
MTARC2	ACBD5	Q5T8D3	383
MTARC2	OXCT1	P55809	368
MTARC2	PXMP4	Q9Y6I8	361
MTARC2	FAR2	Q96K12	351
MTARC2	RBBP8NL	Q8NC74	340
MTARC2	C11orf52	Q96A22	339

IntAct

29 interactions, top by confidence:

A	B	Type	Score
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
PEX19	FAM20B	psi-mi:“MI:0914”(association)	0.530
PEX19	MYO1D	psi-mi:“MI:0914”(association)	0.530
HTRA2	HAX1	psi-mi:“MI:2364”(proximity)	0.420
PPP4R1L	IFT56	psi-mi:“MI:0914”(association)	0.350
KCNA2	TMEM129	psi-mi:“MI:0914”(association)	0.350
CRELD1	TMEM223	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
RP2	QSOX1	psi-mi:“MI:0914”(association)	0.350
SAAL1	QSOX1	psi-mi:“MI:0914”(association)	0.350
SYBU	SNPH	psi-mi:“MI:0914”(association)	0.350
TDRKH	ESPL1	psi-mi:“MI:0914”(association)	0.350
MTHFD1L	TRAPPC6B	psi-mi:“MI:0914”(association)	0.350
PEX19	KCNN4	psi-mi:“MI:0914”(association)	0.350
MTCH1	IPO5	psi-mi:“MI:0914”(association)	0.350
MTCH2	IPO5	psi-mi:“MI:0914”(association)	0.350
FECH	GTPBP10	psi-mi:“MI:0914”(association)	0.350
RP2	STOM	psi-mi:“MI:0914”(association)	0.350
SAAL1	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC30A10	GOLIM4	psi-mi:“MI:0914”(association)	0.350
SLC39A11	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC39A4	ESYT2	psi-mi:“MI:0914”(association)	0.350
COX14	NUDT19	psi-mi:“MI:2364”(proximity)	0.270
MGST3	DNM1L	psi-mi:“MI:2364”(proximity)	0.270
TOMM20	NUDT19	psi-mi:“MI:2364”(proximity)	0.270
TOMM22	DNM1L	psi-mi:“MI:2364”(proximity)	0.270
IMMP2L	MRPL45	psi-mi:“MI:2364”(proximity)	0.270
LACTB	NUDT19	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (67): MARC2 (Affinity Capture-MS), MARC2 (Affinity Capture-MS), MARC2 (Affinity Capture-MS), MARC2 (Affinity Capture-MS), MARC2 (Affinity Capture-MS), MARC2 (Affinity Capture-MS), MARC2 (Affinity Capture-MS), MARC2 (Proximity Label-MS), MARC2 (Proximity Label-MS), MARC2 (Proximity Label-MS), MARC2 (Proximity Label-MS), MARC2 (Proximity Label-MS), MARC2 (Proximity Label-MS), MARC2 (Proximity Label-MS), MARC2 (Proximity Label-MS)

ESM2 similar proteins: A2VD33, A4IF87, A4IHY0, A6QQV6, B8JMH0, E1BCH6, E1BVR9, E9PYK3, O15228, O46504, O77480, O88994, P09838, P47823, P79106, P83006, P98192, Q14CH1, Q1LWG4, Q1LZH1, Q3U3W5, Q503J2, Q58EJ9, Q5E9H9, Q5I0C5, Q5I0L3, Q5R5S1, Q5RFM7, Q5U534, Q5VT66, Q6PE15, Q7T0X7, Q8BYI6, Q8BYL4, Q8L5Z4, Q8VDG7, Q8VDH1, Q90678, Q91ZW6, Q922Q1

Diamond homologs: O88994, P75863, Q1LZH1, Q21657, Q58EJ9, Q5U534, Q5VT66, Q922Q1, Q969Z3, Q9C5X8, Q9CW42, Q9GKW0, P0C2C3, A2YQD9, O04166, O78510, O80429, O98450, P00220, P00221, P00222, P00224, P00225, P00226, P00227, P00228, P00229, P00230, P00233, P00234, P00235, P00241, P00242, P00243, P00244, P00247, P00248, P00250, P00252, P00253

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1746 predictions. Top by Δscore:

Variant	Effect	Δscore
1:220755157:GC:G	donor_gain	1.0000
1:220761656:AG:A	acceptor_gain	1.0000
1:220761657:GG:G	acceptor_gain	1.0000
1:220761657:GGAT:G	acceptor_gain	1.0000
1:220761817:CCAG:C	donor_loss	1.0000
1:220761820:GGT:G	donor_loss	1.0000
1:220761821:GT:G	donor_loss	1.0000
1:220761822:T:A	donor_loss	1.0000
1:220762907:AAGGT:A	acceptor_gain	1.0000
1:220762908:A:G	acceptor_gain	1.0000
1:220781898:GT:G	donor_gain	1.0000
1:220781904:A:G	donor_gain	1.0000
1:220748757:GC:G	donor_gain	0.9900
1:220748800:ACAGG:A	donor_loss	0.9900
1:220748801:CAG:C	donor_loss	0.9900
1:220748802:AG:A	donor_loss	0.9900
1:220748803:GGTAC:G	donor_loss	0.9900
1:220748804:GT:G	donor_loss	0.9900
1:220748805:T:C	donor_loss	0.9900
1:220754941:CTGCA:C	acceptor_loss	0.9900
1:220754942:TGCA:T	acceptor_loss	0.9900
1:220754943:GCA:G	acceptor_loss	0.9900
1:220754944:CAGGT:C	acceptor_loss	0.9900
1:220755085:C:T	donor_gain	0.9900
1:220755158:C:T	donor_gain	0.9900
1:220759456:G:T	donor_gain	0.9900
1:220761653:TCCA:T	acceptor_loss	0.9900
1:220761655:CA:C	acceptor_loss	0.9900
1:220761656:A:AG	acceptor_gain	0.9900
1:220761656:A:AT	acceptor_loss	0.9900

AlphaMissense

2187 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:220748729:A:C	K66N	0.993
1:220748729:A:T	K66N	0.993
1:220748803:G:T	R91M	0.993
1:220780024:T:A	W253R	0.993
1:220780024:T:C	W253R	0.993
1:220781782:C:A	R297S	0.992
1:220763010:G:C	R237T	0.991
1:220748803:G:C	R91T	0.990
1:220748728:A:T	K66I	0.989
1:220780079:G:T	R271M	0.989
1:220781783:G:C	R297P	0.989
1:220781833:G:T	G314W	0.989
1:220781834:G:A	G314E	0.989
1:220761710:T:A	W167R	0.988
1:220761710:T:C	W167R	0.988
1:220761750:T:A	V180D	0.988
1:220754991:G:C	R106P	0.987
1:220748730:T:C	S67P	0.986
1:220762916:T:G	Y206D	0.986
1:220761680:G:C	G157R	0.985
1:220780079:G:C	R271T	0.985
1:220780169:T:C	C272R	0.985
1:220780168:G:C	R271S	0.984
1:220780168:G:T	R271S	0.984
1:220780233:T:C	L293P	0.984
1:220754947:G:C	R91S	0.983
1:220754947:G:T	R91S	0.983
1:220754951:T:A	W93R	0.983
1:220754951:T:C	W93R	0.983
1:220754955:T:C	L94P	0.983

dbSNP variants (sampled 300 via entrez): RS1000093371 (1:220756913 A>AT), RS1000282621 (1:220751392 G>A), RS1000293942 (1:220763319 T>C), RS1000364219 (1:220751584 C>T), RS1000395389 (1:220774304 G>A), RS1000468320 (1:220768500 C>G), RS1000475874 (1:220755848 A>C,G,T), RS1000644434 (1:220763569 C>T), RS1000666527 (1:220747309 G>T), RS1000724350 (1:220784939 C>G), RS1000881521 (1:220752717 T>C), RS1000929602 (1:220779828 A>G), RS1000951738 (1:220773525 G>A), RS1000974014 (1:220757887 A>G), RS1001049043 (1:220758199 G>A,C)

Disease associations

OMIM: gene MIM:614127 | 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
GCST000514_4	Response to antipsychotic therapy (extrapyramidal side effects)	6.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523423 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
entinostat	affects cotreatment, increases expression	2
bisphenol S	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Nickel	decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	affects expression, increases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
bisphenol F	affects cotreatment, increases expression	1
fluorene-9-bisphenol	decreases expression	1
bisphenol A	increases expression	1
N(4)-hydroxycytidine	affects cotreatment, increases reduction	1
N(4)-hydroxycytosine	affects cotreatment, increases reduction	1
perfluorooctanoic acid	decreases expression	1
nickel sulfate	increases expression	1
benzamidoxime	affects cotreatment, increases reduction	1
sulfamethoxazole hydroxylamine	affects cotreatment, increases reduction	1
CGP 52608	affects binding, increases reaction	1
corosolic acid	decreases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
bisphenol AF	increases expression	1
Acetaminophen	increases expression	1

ChEMBL screening assays

13 unique, capped per target: 11 admet, 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4380149	ADMET	Substrate activity at human recombinant mARC2 expressed in Escherichia coli assessed as enzyme-mediated N-(4-Aminobutyl)-N’-(2-methoxyethyl)guanidine formation at 3 mM and pH 6 preincubated for 3 mins followed by NADH addition measured afte	Discovery of N-(4-Aminobutyl)-N’-(2-methoxyethyl)guanidine as the First Selective, Nonamino Acid, Catalytic Site Inhibitor of Human Dimethylarginine Dimethylaminohydrolase-1 (hDDAH-1). — J Med Chem
CHEMBL6130557	Binding	Binding affinity to human recombinant mARC2 extracted from Escherichia coli assessed as Km by Michaelis-menten based analysis	mARC1 Is the Main Contributor to Metabolic Reduction of N-Hydroxyurea. — J Med Chem

Clinical trials (associated diseases)

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