MTARC1

Summary

MTARC1 (mitochondrial amidoxime reducing component 1, HGNC:26189) is a protein-coding gene on chromosome 1q41, encoding Mitochondrial amidoxime-reducing component 1 (Q5VT66). Catalyzes the reduction of N-oxygenated molecules, acting as a counterpart of cytochrome P450 and flavin-containing monooxygenases in metabolic cycles.

Enables molybdenum ion binding activity; molybdopterin cofactor binding activity; and oxidoreductase activity, acting on other nitrogenous compounds as donors. Contributes to nitrite reductase (NO-forming) activity. Involved in cellular detoxification of nitrogen compound; nitrate metabolic process; and nitric oxide biosynthetic process. Located in mitochondrion. Part of nitric-oxide synthase complex.

Source: NCBI Gene 64757 — RefSeq curated summary.

At a glance

• GWAS associations: 46
• Clinical variants (ClinVar): 53 total
• Druggable target: yes
• MANE Select transcript: NM_022746

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26189
Approved symbol	MTARC1
Name	mitochondrial amidoxime reducing component 1
Location	1q41
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22390
Ensembl gene	ENSG00000186205
Ensembl biotype	protein_coding
OMIM	614126
Entrez	64757

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 9 protein_coding, 5 retained_intron, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000366910, ENST00000407981, ENST00000443880, ENST00000463976, ENST00000472269, ENST00000492847, ENST00000496110, ENST00000694918, ENST00000694919, ENST00000694920, ENST00000694921, ENST00000694922, ENST00000694923, ENST00000694924, ENST00000694925, ENST00000694926, ENST00000865599, ENST00000865600, ENST00000865601

RefSeq mRNA: 1 — MANE Select: NM_022746 NM_022746

CCDS: CCDS1526

Canonical transcript exons

ENST00000366910 — 7 exons

Exon	Start	End
ENSE00001068935	220786913	220787219
ENSE00003511124	220791491	220791664
ENSE00003613359	220796643	220796805
ENSE00003644685	220805203	220805274
ENSE00003669175	220805052	220805113
ENSE00003670977	220797874	220798014
ENSE00003737576	220813292	220819659

Expression profiles

Bgee: expression breadth ubiquitous, 209 present calls, max score 95.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.2764 / max 832.9894, expressed in 1105 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8660	11.0636	1096
8659	0.2128	118

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adipose tissue	UBERON:0001013	95.73	gold quality
adipose tissue of abdominal region	UBERON:0007808	95.37	gold quality
omental fat pad	UBERON:0010414	95.26	gold quality
peritoneum	UBERON:0002358	95.21	gold quality
right lobe of liver	UBERON:0001114	94.95	gold quality
right lobe of thyroid gland	UBERON:0001119	94.92	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.91	gold quality
connective tissue	UBERON:0002384	94.65	gold quality
left lobe of thyroid gland	UBERON:0001120	94.36	gold quality
monocyte	CL:0000576	93.95	gold quality
thyroid gland	UBERON:0002046	93.93	gold quality
mononuclear cell	CL:0000842	93.92	gold quality
leukocyte	CL:0000738	93.46	gold quality
liver	UBERON:0002107	92.39	gold quality
olfactory bulb	UBERON:0002264	92.38	silver quality
type B pancreatic cell	CL:0000169	91.56	gold quality
mucosa of transverse colon	UBERON:0004991	91.25	gold quality
parotid gland	UBERON:0001831	90.68	gold quality
diaphragm	UBERON:0001103	89.90	gold quality
ventricular zone	UBERON:0003053	89.72	gold quality
blood	UBERON:0000178	89.55	gold quality
tibial nerve	UBERON:0001323	89.32	gold quality
bone marrow	UBERON:0002371	89.22	gold quality
rectum	UBERON:0001052	88.82	gold quality
thoracic mammary gland	UBERON:0005200	88.05	gold quality
mammary gland	UBERON:0001911	87.96	gold quality
cervix squamous epithelium	UBERON:0006922	87.78	gold quality
bone marrow cell	CL:0002092	87.20	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	86.73	silver quality
prostate gland	UBERON:0002367	86.55	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.83
E-GEOD-99795	no	344.18
E-GEOD-75367	no	136.69

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

71 targeting MTARC1, 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-513A-5P	100.00	69.77	2465
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4446-5P	99.72	69.19	2544

Literature-anchored findings (GeneRIF, showing 20)

• molybdoprotein mARC1 is involved in the activation of N-hydroxylated prodrugs. (PMID:19053771)
• 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)
• The transmembrane domain of mARC1 shown to be sufficient for mitochondrial targeting and the N-terminal targeting signal to function as a supportive receptor for the outer mitochondrial membrane. (PMID:23086957)
• 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)
• identification of a series of additional MARC1 alleles that also associated with lower cholesterol levels, liver enzyme levels and reduced risk of cirrhosis, suggesting that deficiency of the MARC1 enzyme may lower blood cholesterol levels and protect against cirrhosis (PMID:32282858)
• Genome-Wide Association Study for Alcohol-Related Cirrhosis Identifies Risk Loci in MARC1 and HNRNPUL1. (PMID:32561361)
• A genome-first approach to mortality and metabolic phenotypes in MTARC1 p.Ala165Thr (rs2642438) heterozygotes and homozygotes. (PMID:34258604)
• MARC1 p.A165T variant is associated with decreased markers of liver injury and enhanced antioxidant capacity in autoimmune hepatitis. (PMID:34949757)
• Variants in mitochondrial amidoxime reducing component 1 and hydroxysteroid 17-beta dehydrogenase 13 reduce severity of nonalcoholic fatty liver disease in children and suppress fibrotic pathways through distinct mechanisms. (PMID:35411667)
• Association of MARC1, ADCY5, and BCO1 Variants with the Lipid Profile, Suggests an Additive Effect for Hypertriglyceridemia in Mexican Adult Men. (PMID:36233117)
• MTARC1 and HSD17B13 Variants Have Protective Effects on Non-Alcoholic Fatty Liver Disease in Patients Undergoing Bariatric Surgery. (PMID:36555467)
• Fatty liver disease protective MTARC1 p.A165T variant reduces the protein stability of MTARC1. (PMID:38340654)
• Mitochondrial amidoxime-reducing component 1 p.Ala165Thr increases protein degradation mediated by the proteasome. (PMID:38375985)
• Divergent role of Mitochondrial Amidoxime Reducing Component 1 (MARC1) in human and mouse. (PMID:38437227)
• mARC1 in MASLD: Modulation of lipid accumulation in human hepatocytes and adipocytes. (PMID:38619429)
• Biochemical and functional characterization of the p.A165T missense variant of mitochondrial amidoxime-reducing component 1. (PMID:38723751)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	marc1	ENSDARG00000070487
mus_musculus	Mtarc1	ENSMUSG00000026621
rattus_norvegicus	Mtarc1	ENSRNOG00000037850
drosophila_melanogaster	Marc	FBGN0033451
caenorhabditis_elegans		WBGENE00009049
caenorhabditis_elegans		WBGENE00018758
caenorhabditis_elegans		WBGENE00018925

Paralogs (2): MOCOS (ENSG00000075643), MTARC2 (ENSG00000117791)

Protein

Protein identifiers

Mitochondrial amidoxime-reducing component 1 — Q5VT66 (reviewed: Q5VT66)

Alternative names: Molybdenum cofactor sulfurase C-terminal domain-containing protein 1

All UniProt accessions (6): Q5VT66, A0A8Q3SHG3, A0A8Q3SHL7, H0YDX4, H7BYZ9, X6RIL1

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 and MTARC1.

Subcellular location. Mitochondrion outer membrane. Membrane.

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

Domain organisation. Comprises two structural domains, the molybdenum cofactor/Moco sulfurase C-terminal (MOSC) domain and the MOSC N-terminal region, forming a cleft that accommodates Moco. The MOSC domain, which contains a large seven-stranded mostly antiparallel beta-barrel, engages multiple interactions with Moco both pterin ring and phosphate group, allowing for a tight coordination of Moco within the core of the enzyme.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5VT66-1	1	yes
Q5VT66-2	2
Q5VT66-3	3

RefSeq proteins (1): NP_073583* (*=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 (60 total): strand 20, binding site 11, helix 9, sequence variant 7, turn 3, splice variant 2, topological domain 2, initiator methionine 1, chain 1, lipid moiety-binding region 1, transmembrane region 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7P41	X-RAY DIFFRACTION	1.6
29AJ	X-RAY DIFFRACTION	1.63
6FW2	X-RAY DIFFRACTION	1.78

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VT66-F1	91.66	0.83

Functional residue map

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

Ligand- & substrate-binding residues (11): 210; 211; 238; 240; 271; 272; 273; 317; 67; 68; 92

Post-translational modifications (1): 2

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: 135 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_BIOLOGICAL_OXIDATIONS, PRAMOONJAGO_SOX4_TARGETS_DN, ONDER_CDH1_TARGETS_3_DN, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE, GOBP_REACTIVE_NITROGEN_SPECIES_METABOLIC_PROCESS, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, CASORELLI_APL_SECONDARY_VS_DE_NOVO_UP, GOBP_DETOXIFICATION, GOCC_MITOCHONDRIAL_ENVELOPE, MCBRYAN_PUBERTAL_BREAST_5_6WK_UP, GOZGIT_ESR1_TARGETS_UP, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, GOBP_ORGANIC_ACID_METABOLIC_PROCESS

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 (11): 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), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872), nitrite reductase (NO-forming) activity (GO:0050421)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), nitric-oxide synthase complex (GO:1903958), 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
binding	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
molecular_function	1
catalytic activity	1
cation binding	1
oxidoreductase activity, acting on other nitrogenous compounds as donors, cytochrome as acceptor	1
nitrite reductase activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrial membrane	1
organelle outer membrane	1
oxidoreductase complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

604 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MTARC1	HSD17B13	Q7Z5P4	667
MTARC1	SUOX	P51687	664
MTARC1	TM6SF2	Q9BZW4	582
MTARC1	PNPLA3	Q9NST1	541
MTARC1	TYW1B	Q6NUM6	519
MTARC1	MBOAT7	Q96N66	507
MTARC1	CYB5B	O43169	494
MTARC1	RNF214	Q8ND24	434
MTARC1	CYB5R3	P00387	403
MTARC1	AOX1	Q06278	403
MTARC1	MOCS1	Q9NZB8	399
MTARC1	OSBPL7	Q9BZF2	394
MTARC1	CYB5A	P00167	389
MTARC1	LUZP2	Q86TE4	374
MTARC1	TRIB1	Q96RU8	358
MTARC1	CLPSL2	Q6UWE3	358

IntAct

55 interactions, top by confidence:

A	B	Type	Score
	TOMM70	psi-mi:“MI:0914”(association)	0.980
CHST15	CANX	psi-mi:“MI:0914”(association)	0.670
EPHB6	MTARC1	psi-mi:“MI:0915”(physical association)	0.560
MTARC1	NAA11	psi-mi:“MI:0915”(physical association)	0.560
rep	AGPS	psi-mi:“MI:0914”(association)	0.530
SPINT2	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
LRRTM1	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
ZNRF4	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
GDPD5	GOLIM4	psi-mi:“MI:0914”(association)	0.530
SRPRB	CTDNEP1	psi-mi:“MI:0914”(association)	0.530
SIDT2	AP3D1	psi-mi:“MI:0914”(association)	0.530
MTARC1	HSPD1	psi-mi:“MI:0915”(physical association)	0.400
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
rep	STXBP3	psi-mi:“MI:0914”(association)	0.350
rep	CEBPZOS	psi-mi:“MI:0914”(association)	0.350
ADCK2	ILVBL	psi-mi:“MI:0914”(association)	0.350
KCNA2	TMEM129	psi-mi:“MI:0914”(association)	0.350
TTMP	TMEM223	psi-mi:“MI:0914”(association)	0.350
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
CHRNB2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SIDT2	KLRG2	psi-mi:“MI:0914”(association)	0.350
MAGEA8	METTL15	psi-mi:“MI:0914”(association)	0.350
KCNMB3	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
PCDHGC4		psi-mi:“MI:0914”(association)	0.350
TMEM30A	TLCD2	psi-mi:“MI:0914”(association)	0.350
MARCHF4	C2CD2L	psi-mi:“MI:0914”(association)	0.350
PCDHGA5	AREL1	psi-mi:“MI:0914”(association)	0.350
H2AP	GNPAT	psi-mi:“MI:0914”(association)	0.350
UGT1A7	FGFR1	psi-mi:“MI:0914”(association)	0.350

BioGRID (90): MARC1 (Affinity Capture-MS), MARC1 (Affinity Capture-MS), MARC1 (Affinity Capture-MS), MARC1 (Affinity Capture-MS), MARC1 (Affinity Capture-MS), MARC1 (Affinity Capture-MS), MARC1 (Affinity Capture-MS), MARC1 (Affinity Capture-MS), MARC1 (Affinity Capture-MS), MARC1 (Affinity Capture-MS), TFB2M (Affinity Capture-MS), SLC25A29 (Affinity Capture-MS), MARC1 (Affinity Capture-MS), PGM3 (Affinity Capture-MS), MYBBP1A (Affinity Capture-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, 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, P00254

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MTARC1	“up-regulates quantity”	“nitric oxide”	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	1
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1631 predictions. Top by Δscore:

Variant	Effect	Δscore
1:220796629:T:TA	acceptor_gain	1.0000
1:220797870:TCA:T	acceptor_loss	1.0000
1:220797871:CAG:C	acceptor_loss	1.0000
1:220797873:GATT:G	acceptor_gain	1.0000
1:220798248:GCTTC:G	donor_gain	1.0000
1:220787216:ACAG:A	donor_loss	0.9900
1:220787217:CAGGT:C	donor_loss	0.9900
1:220787218:AGGTA:A	donor_loss	0.9900
1:220787219:GGTAC:G	donor_loss	0.9900
1:220787220:GT:G	donor_loss	0.9900
1:220787221:T:A	donor_loss	0.9900
1:220791666:T:G	donor_loss	0.9900
1:220796641:A:AG	acceptor_gain	0.9900
1:220796642:G:GG	acceptor_gain	0.9900
1:220796642:GA:G	acceptor_gain	0.9900
1:220797870:TCAGA:T	acceptor_gain	0.9900
1:220797871:CAGA:C	acceptor_gain	0.9900
1:220797872:A:AG	acceptor_gain	0.9900
1:220797872:AGATT:A	acceptor_gain	0.9900
1:220797873:G:GG	acceptor_gain	0.9900
1:220797873:GAT:G	acceptor_gain	0.9900
1:220797873:GATTG:G	acceptor_gain	0.9900
1:220805046:CCCTA:C	acceptor_loss	0.9900
1:220805047:CCTA:C	acceptor_loss	0.9900
1:220805048:CTAG:C	acceptor_loss	0.9900
1:220805049:TAGGA:T	acceptor_loss	0.9900
1:220805050:A:AG	acceptor_gain	0.9900
1:220805050:A:G	acceptor_loss	0.9900
1:220805050:AG:A	acceptor_gain	0.9900
1:220805051:G:GG	acceptor_gain	0.9900

AlphaMissense

2151 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:220787144:A:T	K67I	0.993
1:220787145:A:C	K67N	0.992
1:220787145:A:T	K67N	0.992
1:220797974:G:C	R238T	0.992
1:220787219:G:T	R92M	0.991
1:220813296:C:A	R298S	0.989
1:220791499:T:C	L95P	0.985
1:220813348:G:A	G315E	0.985
1:220787219:G:C	R92T	0.983
1:220813297:G:C	R298P	0.983
1:220797974:G:T	R238M	0.982
1:220805058:T:A	W254R	0.982
1:220805058:T:C	W254R	0.982
1:220805204:T:C	C273R	0.982
1:220797932:T:C	L224P	0.981
1:220791495:T:A	W94R	0.980
1:220791495:T:C	W94R	0.980
1:220797880:T:G	Y207D	0.980
1:220797975:G:C	R238S	0.980
1:220797975:G:T	R238S	0.980
1:220797983:T:A	I241N	0.980
1:220805113:G:C	R272T	0.980
1:220791532:C:A	A106D	0.978
1:220797971:T:C	F237S	0.978
1:220787146:T:C	S68P	0.977
1:220796695:T:A	W168R	0.977
1:220796695:T:C	W168R	0.977
1:220805268:T:C	L294P	0.977
1:220813347:G:T	G315W	0.977
1:220787216:A:C	D91A	0.976

dbSNP variants (sampled 300 via entrez): RS1000054294 (1:220818204 A>C,G), RS1000216514 (1:220802024 A>G), RS1000241338 (1:220806466 C>T), RS1000242670 (1:220800699 G>A,T), RS1000363843 (1:220790425 C>T), RS1000465612 (1:220796949 A>G), RS1000541469 (1:220818107 G>A), RS1000561041 (1:220785729 A>T), RS1000724350 (1:220784939 C>G), RS1000844394 (1:220806248 G>T), RS1000879056 (1:220812566 C>G,T), RS1000985148 (1:220790904 A>G), RS1001033828 (1:220796532 A>G), RS1001116750 (1:220806479 G>A), RS1001139827 (1:220812803 C>A)

Disease associations

OMIM: gene MIM:614126 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

46 associations (top):

Study	Trait	p-value
GCST000759_5	LDL cholesterol	6.000000e-11
GCST000760_38	Cholesterol, total	5.000000e-13
GCST000982_9	F-cell distribution in sickle cell anaemia	2.000000e-06
GCST001048_2	Monocyte early outgrowth colony forming units	3.000000e-07
GCST002221_22	Cholesterol, total	3.000000e-11
GCST002222_55	LDL cholesterol	5.000000e-11
GCST002896_19	Cholesterol, total	5.000000e-10
GCST004233_48	LDL cholesterol levels	1.000000e-19
GCST004235_31	Total cholesterol levels	1.000000e-22
GCST004235_5	Total cholesterol levels	5.000000e-06
GCST006016_11	Serum alkaline phosphatase levels	2.000000e-08
GCST008059_173	Estimated glomerular filtration rate	3.000000e-13
GCST008070_37	HDL cholesterol levels	5.000000e-09
GCST008070_97	HDL cholesterol levels	3.000000e-07
GCST008074_11	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	3.000000e-07
GCST008074_161	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	7.000000e-09
GCST008075_107	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	8.000000e-18
GCST008075_127	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	9.000000e-06
GCST008075_51	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2.000000e-13
GCST008077_76	LDL cholesterol levels	5.000000e-08
GCST008078_11	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	3.000000e-15
GCST008078_68	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	6.000000e-22
GCST008079_141	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-22
GCST008079_17	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	7.000000e-15
GCST008079_95	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	7.000000e-06
GCST008083_122	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	3.000000e-10
GCST008083_30	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	6.000000e-07
GCST008084_225	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	1.000000e-21
GCST008084_50	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	3.000000e-17
GCST008085_32	HDL cholesterol levels in current drinkers	6.000000e-11

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0004576	fetal hemoglobin measurement
EFO:0004506	monocyte early outgrowth colony forming unit
EFO:0004533	alkaline phosphatase measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004329	alcohol drinking
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004736	aspartate aminotransferase measurement
EFO:0010821	liver fat measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3706559 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	7
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	3
Cyclosporine	decreases expression	3
sodium arsenite	decreases expression	2
entinostat	increases expression, affects cotreatment	2
NAD	affects cotreatment, increases reduction, affects reaction	2
Nickel	decreases expression	2
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
trimethyloxamine	increases reduction, increases chemical synthesis, affects reaction	1
glycidyl methacrylate	increases expression	1
N(4)-hydroxycytidine	affects cotreatment, increases reduction	1
terbufos	increases methylation	1
N(4)-hydroxycytosine	affects cotreatment, increases reduction	1
trimethylamine	increases chemical synthesis, increases reduction	1
potassium chromate(VI)	increases expression	1
benzamidoxime	affects cotreatment, increases reduction	1
sulfamethoxazole hydroxylamine	affects cotreatment, increases reduction	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
bisphenol B	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
Pioglitazone	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Azathioprine	decreases expression	1

ChEMBL screening assays

25 unique, capped per target: 12 binding, 11 admet, 2 unclassified

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1014425	Binding	Specific activity at molybdenum cofactor/metal-free precursor molybopterin bound human recombinant mARC1 expressed in Escherichia coli TP1000 assessed as reduction to melagatran in complete reconstituted system containing microsomal cyt b5,	The fourth molybdenum containing enzyme mARC: cloning and involvement in the activation of N-hydroxylated prodrugs. — J Med Chem
CHEMBL1686549	Unclassified	Activation of prodrug into benzamidine per mg of recombinant hmARC1 in 20 mM MES buffer of pH 6.0 for 30 mins	Synthesis and biological evaluation of L-valine-amidoximeesters as double prodrugs of amidines. — Bioorg Med Chem
CHEMBL4380148	ADMET	Substrate activity at human recombinant mARC1 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

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_E3V5	EXSURGi001-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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