ADI1

Summary

ADI1 (acireductone dioxygenase 1, HGNC:30576) is a protein-coding gene on chromosome 2p25.3, encoding Acireductone dioxygenase (Q9BV57). Catalyzes 2 different reactions between oxygen and the acireductone 1,2-dihydroxy-3-keto-5-methylthiopentene (DHK-MTPene) depending upon the metal bound in the active site.

This gene encodes an enzyme that belongs to the aci-reductone dioxygenase family of metal-binding enzymes, which are involved in methionine salvage. This enzyme may regulate mRNA processing in the nucleus, and may carry out different functions depending on its localization. Related pseudogenes have been defined on chromosomes 8 and 20. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 55256 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 48 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_018269

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30576
Approved symbol	ADI1
Name	acireductone dioxygenase 1
Location	2p25.3
Locus type	gene with protein product
Status	Approved
Aliases	SIPL, MTCBP-1, ARD, APL1, FLJ10913, HMFT1638, mtnD
Ensembl gene	ENSG00000182551
Ensembl biotype	protein_coding
OMIM	613400
Entrez	55256

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 12 protein_coding

ENST00000327435, ENST00000382093, ENST00000415131, ENST00000879401, ENST00000879402, ENST00000879403, ENST00000879404, ENST00000879405, ENST00000879406, ENST00000879407, ENST00000879408, ENST00000879409

RefSeq mRNA: 2 — MANE Select: NM_018269 NM_001306077, NM_018269

CCDS: CCDS1653, CCDS77380

Canonical transcript exons

ENST00000327435 — 4 exons

Exon	Start	End
ENSE00001303509	3513857	3513976
ENSE00001307713	3497366	3499082
ENSE00001321384	3500814	3500993
ENSE00001328051	3519368	3519531

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 61.1718 / max 846.2116, expressed in 1826 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
26710	55.6068	1826
26711	3.1295	1586
26712	2.4354	1479

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.06	gold quality
liver	UBERON:0002107	98.64	gold quality
adult mammalian kidney	UBERON:0000082	97.99	gold quality
descending thoracic aorta	UBERON:0002345	97.84	gold quality
thoracic aorta	UBERON:0001515	97.79	gold quality
ascending aorta	UBERON:0001496	97.75	gold quality
right atrium auricular region	UBERON:0006631	97.68	gold quality
duodenum	UBERON:0002114	97.61	gold quality
heart left ventricle	UBERON:0002084	97.51	gold quality
right coronary artery	UBERON:0001625	97.46	gold quality
left coronary artery	UBERON:0001626	97.40	gold quality
heart	UBERON:0000948	97.38	gold quality
right adrenal gland cortex	UBERON:0035827	97.34	gold quality
right adrenal gland	UBERON:0001233	97.18	gold quality
gall bladder	UBERON:0002110	97.06	gold quality
fundus of stomach	UBERON:0001160	96.96	gold quality
body of stomach	UBERON:0001161	96.74	gold quality
left adrenal gland	UBERON:0001234	96.74	gold quality
apex of heart	UBERON:0002098	96.70	gold quality
left adrenal gland cortex	UBERON:0035825	96.60	gold quality
prostate gland	UBERON:0002367	96.59	gold quality
kidney	UBERON:0002113	96.52	gold quality
popliteal artery	UBERON:0002250	96.46	gold quality
tibial artery	UBERON:0007610	96.45	gold quality
adrenal gland	UBERON:0002369	96.43	gold quality
gastrocnemius	UBERON:0001388	96.42	gold quality
muscle of leg	UBERON:0001383	96.36	gold quality
adrenal tissue	UBERON:0018303	96.17	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.00	gold quality
cortex of kidney	UBERON:0001225	95.70	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-10553	yes	38.27
E-GEOD-134144	yes	8.71
E-GEOD-125970	yes	7.08
E-GEOD-86618	no	193.94
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

57 targeting ADI1, 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-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-383-3P	99.85	65.84	1359
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-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-12131	99.48	68.72	1673

Literature-anchored findings (GeneRIF, showing 10)

• MTCBP-1 is a new member of the Cupin superfamily with a role as an invasion suppressor down-regulated in tumors (PMID:14718544)
• nucleo-cytoplasmic transport of hADI1 is regulated by a non-canonical nuclear export signal (NES) located in the N-terminal region of hADI1. (PMID:17212658)
• ADI1 may check prostate cancer progression through apoptosis by an activity that does not require metal binding. (PMID:17786183)
• 293-ADI1-CD81 cells are permissive for serum-derived HCV infection. (PMID:19626614)
• Data elucidate a new role for MTCBP-1 regulating the intracellular function of MT1-MMP-mediated autophagy. Their inverse expression correlation with brain tumor grades could also contribute to the decreased autophagic index observed in high-grade tumors. (PMID:25640948)
• In summary, clinical and cell-based experiments suggested that physical interaction between MT1-MMP and ADI1 led to suppression of hepatitis C virus infection. This inhibitory effect could be reversed by ADI1 overexpression. (PMID:26537061)
• The thermal stability of the HsARD isozymes is a function of the metal ion identity, with Ni2+-bound HsARD being the most stable followed by Co2+ and Fe2+, and Mn2+-bound HsARD being the least stable. (PMID:28062648)
• High ADI1 expression is associated with malignant glioma. (PMID:30066900)
• Pancreatic tumor cell metastasis is restricted by MT1-MMP binding protein MTCBP-1. (PMID:30487181)
• Acireductone dioxygenase 1 (ADI1) is regulated by cellular iron by a mechanism involving the iron chaperone, PCBP1, with PCBP2 acting as a potential co-chaperone. (PMID:32480040)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	adi1	ENSDARG00000020448
mus_musculus	Adi1	ENSMUSG00000020629
rattus_norvegicus	Adi1	ENSRNOG00000008950
drosophila_melanogaster	Adi1	FBGN0052068
caenorhabditis_elegans		WBGENE00019489
caenorhabditis_elegans		WBGENE00020149

Protein

Protein identifiers

Acireductone dioxygenase — Q9BV57 (reviewed: Q9BV57)

Alternative names: Acireductone dioxygenase (Fe(2+)-requiring), Acireductone dioxygenase (Ni(2+)-requiring), Membrane-type 1 matrix metalloproteinase cytoplasmic tail-binding protein 1, Submergence-induced protein-like factor

All UniProt accessions (2): Q9BV57, H7C382

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes 2 different reactions between oxygen and the acireductone 1,2-dihydroxy-3-keto-5-methylthiopentene (DHK-MTPene) depending upon the metal bound in the active site. Fe-containing acireductone dioxygenase (Fe-ARD) produces formate and 2-keto-4-methylthiobutyrate (KMTB), the alpha-ketoacid precursor of methionine in the methionine recycle pathway. Ni-containing acireductone dioxygenase (Ni-ARD) produces methylthiopropionate, carbon monoxide and formate, and does not lie on the methionine recycle pathway. Also down-regulates cell migration mediated by MMP14. Necessary for hepatitis C virus replication in an otherwise non-permissive cell line.

Subunit / interactions. Monomer. Interacts with MMP14.

Subcellular location. Cytoplasm. Nucleus. Cell membrane.

Tissue specificity. Detected in heart, colon, lung, stomach, brain, spleen, liver, skeletal muscle and kidney.

Cofactor. Binds either 1 Fe or Ni cation per monomer. Iron-binding promotes an acireductone dioxygenase reaction producing 2-keto-4-methylthiobutyrate, while nickel-binding promotes an acireductone dioxygenase reaction producing 3-(methylsulfanyl)propanoate.

Pathway. Amino-acid biosynthesis; L-methionine biosynthesis via salvage pathway; L-methionine from S-methyl-5-thio-alpha-D-ribose 1-phosphate: step 5/6.

Similarity. Belongs to the acireductone dioxygenase (ARD) family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BV57-1	1	yes
Q9BV57-2	2

RefSeq proteins (2): NP_001293006, NP_060739* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004313	ARD	Family
IPR011051	RmlC_Cupin_sf	Homologous_superfamily
IPR014710	RmlC-like_jellyroll	Homologous_superfamily
IPR027496	ARD_euk	Family

Pfam: PF03079

Enzyme classification (BRENDA):

• EC 1.13.11.53 — acireductone dioxygenase (Ni2+-requiring) (BRENDA: 9 organisms, 30 substrates, 1 inhibitors, 8 Km, 4 kcat entries)
• EC 1.13.11.54 — acireductone dioxygenase [iron(II)-requiring] (BRENDA: 11 organisms, 15 substrates, 0 inhibitors, 7 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

10 substrates with measured Km, best-characterized 10. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
O2	0.047–210	3
(1Z)-1,2-DIHYDROXYHEX-1-EN-3-ONE	0.0493–0.2871	2
1,2-DIHYDROXY-5-(METHYLTHIO)PENT-1-EN-3-ONE	0.044–500	2
O2	0.11–500	2
1,2-DIHYDROXY-3-KETO-1-HEXENE	0.05	1
1-PHOSPHONOOXY-2,2-DIHYDROXY-3-OXO-3-PHENYLPROPA	0.0392	1
(1Z)-1,2-DIHYDROXYHEX-1-EN-3-ONE	0.1185	1
1,2-DIHYDROXY-3-OXOPENT-1-ENE	25.9	1
1,2-DIHYDROXY-5-(METHYLTHIO)PENT-1-EN-3-ONE	210	1
1,2-DIHYDROXYHEX-1-EN-3-ONE	0.052	1

Catalyzed reactions (Rhea), 2 shown:

• 1,2-dihydroxy-5-(methylsulfanyl)pent-1-en-3-one + O2 = 3-(methylsulfanyl)propanoate + CO + formate + 2 H(+) (RHEA:14161)
• 1,2-dihydroxy-5-(methylsulfanyl)pent-1-en-3-one + O2 = 4-methylsulfanyl-2-oxobutanoate + formate + 2 H(+) (RHEA:24504)

UniProt features (40 total): strand 13, helix 8, binding site 8, turn 4, sequence conflict 3, chain 1, region of interest 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4QGN	X-RAY DIFFRACTION	3.05
7JXG	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BV57-F1	96.78	0.97

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 (8): 88; 88; 90; 90; 94; 94; 133; 133

Mutagenesis-validated functional residues (1):

Position	Phenotype
94	loss of aci-reductone dioxygenase activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1237112	Methionine salvage pathway
R-HSA-1430728	Metabolism
R-HSA-1614635	Sulfur amino acid metabolism
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 203 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, chr2p25, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, KEGG_CYSTEINE_AND_METHIONINE_METABOLISM, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_AMINO_ACID_BIOSYNTHETIC_PROCESS, GOBP_ASPARTATE_FAMILY_AMINO_ACID_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, BOYAULT_LIVER_CANCER_SUBCLASS_G12_DN, ONKEN_UVEAL_MELANOMA_UP, GOBP_SULFUR_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_METHIONINE_BIOSYNTHETIC_PROCESS, GOBP_METHIONINE_METABOLIC_PROCESS

GO Biological Process (4): L-methionine metabolic process (GO:0006555), obsolete L-methionine salvage from methylthioadenosine (GO:0019509), amino acid biosynthetic process (GO:0008652), obsolete methionine biosynthetic process (GO:0009086)

GO Molecular Function (8): iron ion binding (GO:0005506), acireductone dioxygenase (Ni2+-requiring) activity (GO:0010308), acireductone dioxygenase [iron(II)-requiring] activity (GO:0010309), nickel cation binding (GO:0016151), oxidoreductase activity (GO:0016491), protein binding (GO:0005515), metal ion binding (GO:0046872), dioxygenase activity (GO:0051213)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Sulfur amino acid metabolism	1
Metabolism of amino acids and derivatives	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
transition metal ion binding	2
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen	2
sulfur amino acid metabolic process	1
L-amino acid metabolic process	1
proteinogenic amino acid metabolic process	1
amino acid metabolic process	1
biosynthetic process	1
catalytic activity	1
binding	1
cation binding	1
oxidoreductase activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

962 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADI1	MMP14	P50281	930
ADI1	ENOPH1	Q9UHY7	811
ADI1	MRI1	Q9BV20	775
ADI1	MT-ND1	P03886	763
ADI1	MT-ND6	P03923	714
ADI1	MT-ND5	P03915	702
ADI1	APIP	Q96GX9	595
ADI1	APLP1	P51693	570
ADI1	APLP2	Q06481	507
ADI1	SRM	P19623	501
ADI1	MTAP	Q13126	489
ADI1	MAT1A	Q00266	474
ADI1	MAT2A	P31153	472
ADI1	COLEC11	Q9BWP8	446
ADI1	APPL1	Q9UKG1	443

IntAct

14 interactions, top by confidence:

A	B	Type	Score
MMP14	ADI1	psi-mi:“MI:0915”(physical association)	0.600
ADI1	MMP14	psi-mi:“MI:0915”(physical association)	0.600
ADI1	MMP14	psi-mi:“MI:0403”(colocalization)	0.600
ADI1	APPL1	psi-mi:“MI:0915”(physical association)	0.560
ADI1	SRPK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
ADI1	TRAPPC10	psi-mi:“MI:0914”(association)	0.350
CFTR	UBA6	psi-mi:“MI:2364”(proximity)	0.270
ADI1	DBT	psi-mi:“MI:0915”(physical association)	0.000
ADI1	OSTF1	psi-mi:“MI:0915”(physical association)	0.000
ADI1	APPL1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (43): ADI1 (Co-fractionation), ADI1 (Co-fractionation), ADI1 (Co-fractionation), ADI1 (Co-fractionation), ADI1 (Co-fractionation), ADI1 (Co-fractionation), ADI1 (Co-fractionation), ADI1 (Co-fractionation), ALDOA (Co-fractionation), ALDOC (Co-fractionation), GBE1 (Co-fractionation), NIT1 (Co-fractionation), PGK1 (Co-fractionation), ADI1 (Affinity Capture-RNA), DBT (Affinity Capture-MS)

ESM2 similar proteins: A1L4T4, A2XCT8, A2Z7C4, A7RIT9, A8BQB4, A9SCJ6, A9SDW6, A9SS00, A9VCM7, B7PRF6, C3ZAH2, C5WWY0, C5X1F5, D7T737, E0W481, F6HDT7, F6QS54, F6W3G8, F7FKV1, O48707, P35573, P35574, P46952, P46953, Q0VCA8, Q10RE5, Q28FT4, Q2LZI9, Q2PQH8, Q3B8C8, Q3ZBL1, Q562C9, Q5U3F8, Q5ZL43, Q6AWN0, Q6DIY2, Q6DIZ0, Q6P7I0, Q6PBX5, Q75HE6

Diamond homologs: A1L4T4, A2XCT8, A2Z7C4, A4HYT9, A4VM82, A7E4S9, A7HU87, A7Z3X7, A8FCH1, A8N4R7, A8N4R8, A8WMD5, A8X409, A8XHQ1, A9BVZ7, A9SCJ6, A9SDW6, A9SS00, A9VCM7, B0SFU6, B0SP94, B0U3A5, B1YIX9, B2I5X3, B2VAA3, B3QG72, B7PRF6, C0NZU2, C3ZAH2, C4YCU0, C5WWY0, C5X1F5, C7Z9Z4, D3BH90, D5GE59, D7T737, E0W481, E3KY53, E9AIE8, E9EUE8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	35
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
980458	GRCh37/hg19 2p25.3(chr2:2074335-3934366)x3	Pathogenic

SpliceAI

760 predictions. Top by Δscore:

Variant	Effect	Δscore
2:3499080:GTT:G	acceptor_gain	1.0000
2:3499081:TT:T	acceptor_gain	1.0000
2:3499083:C:CC	acceptor_gain	1.0000
2:3499083:C:T	acceptor_loss	1.0000
2:3499084:T:C	acceptor_loss	1.0000
2:3500869:C:CA	donor_gain	1.0000
2:3500989:TTAAT:T	acceptor_gain	1.0000
2:3500992:AT:A	acceptor_gain	1.0000
2:3500993:TCT:T	acceptor_loss	1.0000
2:3500994:C:CC	acceptor_gain	1.0000
2:3500997:G:C	acceptor_gain	1.0000
2:3500997:G:GC	acceptor_gain	1.0000
2:3499078:TAGTT:T	acceptor_gain	0.9900
2:3499079:AGTT:A	acceptor_gain	0.9900
2:3500821:TCC:T	donor_gain	0.9900
2:3500990:TAAT:T	acceptor_gain	0.9900
2:3500990:TAATC:T	acceptor_gain	0.9900
2:3500991:AAT:A	acceptor_gain	0.9900
2:3500991:AATC:A	acceptor_gain	0.9900
2:3500992:ATCTA:A	acceptor_gain	0.9900
2:3500993:TCTA:T	acceptor_gain	0.9900
2:3500994:C:G	acceptor_gain	0.9900
2:3500995:T:G	acceptor_gain	0.9900
2:3501000:C:CT	acceptor_gain	0.9900
2:3501001:A:T	acceptor_gain	0.9900
2:3513852:CTTA:C	donor_loss	0.9900
2:3513853:TTACC:T	donor_loss	0.9900
2:3513854:TACCT:T	donor_loss	0.9900
2:3513855:ACCTT:A	donor_loss	0.9900
2:3513992:C:CT	acceptor_gain	0.9900

AlphaMissense

1191 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:3499056:A:C	F149L	0.999
2:3499056:A:T	F149L	0.999
2:3499058:A:G	F149L	0.999
2:3500837:G:C	H133D	0.999
2:3500829:G:C	F135L	0.998
2:3500829:G:T	F135L	0.998
2:3500831:A:G	F135L	0.998
2:3500966:G:C	H90D	0.998
2:3500894:A:G	W114R	0.997
2:3500894:A:T	W114R	0.997
2:3500964:G:C	H90Q	0.997
2:3500964:G:T	H90Q	0.997
2:3500833:C:G	R134P	0.996
2:3500837:G:T	H133N	0.996
2:3500926:C:T	G103E	0.996
2:3500953:T:A	E94V	0.996
2:3500966:G:T	H90N	0.996
2:3500970:A:C	H88Q	0.996
2:3500970:A:T	H88Q	0.996
2:3500972:G:C	H88D	0.996
2:3500830:A:G	F135S	0.995
2:3500887:C:G	R116P	0.995
2:3500910:C:A	R108S	0.995
2:3500910:C:G	R108S	0.995
2:3500919:G:C	F105L	0.995
2:3500919:G:T	F105L	0.995
2:3500921:A:G	F105L	0.995
2:3500932:C:A	G101V	0.995
2:3513904:C:G	D65H	0.995
2:3499040:A:G	W155R	0.994

dbSNP variants (sampled 300 via entrez): RS1000066146 (2:3506512 C>A,T), RS1000067355 (2:3514289 G>T), RS1000180619 (2:3506278 A>G), RS1000410082 (2:3512966 C>G), RS1000412964 (2:3518203 T>C), RS1000451168 (2:3501279 G>A), RS1000476714 (2:3497271 A>C,G), RS1000525016 (2:3514604 A>G), RS1000636982 (2:3518125 T>A,C), RS1000796168 (2:3505921 T>C), RS1000848447 (2:3506290 G>A), RS1001067845 (2:3502337 G>C,T), RS1001131562 (2:3512969 G>A,C), RS1001139113 (2:3509014 A>G), RS1001328699 (2:3518634 A>C)

Disease associations

OMIM: gene MIM:613400 | disease phenotypes: MIM:612563

GenCC curated gene-disease

Mondo (1): Diamond-Blackfan anemia 8 (MONDO:0012939)

Orphanet (1): Diamond-Blackfan anemia (Orphanet:124)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005514_3	Neuritic plaques or neurofibrillary tangles or cerebral amyloid angiopathy (pleiotropy)	6.000000e-07
GCST008161_97	Waist circumference adjusted for body mass index	3.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006797	neurofibrillary tangles measurement
EFO:0006798	neuritic plaque measurement
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567253	Diamond-Blackfan Anemia 8 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3817720 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects expression, decreases expression	4
bisphenol A	affects expression, increases expression	3
Vorinostat	decreases expression	3
bisphenol S	increases methylation, increases expression, affects cotreatment	2
(+)-JQ1 compound	increases expression	2
Cisplatin	affects expression, affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	decreases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
bismuth tripotassium dicitrate	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
beta-lapachone	increases expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
potassium chromate(VI)	decreases expression	1
CGP 52608	affects binding, increases reaction	1
mibolerone	increases expression	1
entinostat	decreases expression	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
pyrimidifen	increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
belinostat	decreases expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3821391	ADMET	Binding affinity to ADL1 in human HepG2 assessed as intensity fold change of cumulated normalized intensity of protein between capture and competition assay at 100 uM after 1 hr in presence of active Tcp-CC-13 by differential competition ca	Identification of Potential Off-target Toxicity Liabilities of Catechol-O-methyltransferase Inhibitors by Differential Competition Capture Compound Mass Spectrometry. — J Med Chem

Clinical trials (associated diseases)

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