DDT

Summary

DDT (D-dopachrome tautomerase, HGNC:2732) is a protein-coding gene on chromosome 22q11.23, encoding D-dopachrome decarboxylase (P30046). Tautomerization of D-dopachrome with decarboxylation to give 5,6-dihydroxyindole (DHI).

D-dopachrome tautomerase converts D-dopachrome into 5,6-dihydroxyindole. The DDT gene is related to the migration inhibitory factor (MIF) in terms of sequence, enzyme activity, and gene structure. DDT and MIF are closely linked on chromosome 22.

Source: NCBI Gene 1652 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 5 total
• Druggable target: yes
• MANE Select transcript: NM_001084392

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2732
Approved symbol	DDT
Name	D-dopachrome tautomerase
Location	22q11.23
Locus type	gene with protein product
Status	Approved
Aliases	DDCT, MIF2, MIF-2, D-DT
Ensembl gene	ENSG00000099977
Ensembl biotype	protein_coding
OMIM	602750
Entrez	1652

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 2 retained_intron

ENST00000350608, ENST00000398344, ENST00000403754, ENST00000428792, ENST00000430101, ENST00000444947, ENST00000703965, ENST00000703966, ENST00000897329, ENST00000938492, ENST00000938493, ENST00000938494

RefSeq mRNA: 4 — MANE Select: NM_001084392 NM_001084392, NM_001355, NM_001381852, NM_001397485

CCDS: CCDS13820, CCDS93131

Canonical transcript exons

ENST00000398344 — 3 exons

Exon	Start	End
ENSE00000879495	23971370	23971623
ENSE00001895724	23974307	23974441
ENSE00003837199	23973768	23973943

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.6200 / max 100.4801, expressed in 1807 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
209420	12.6200	1807

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	99.27	gold quality
mucosa of transverse colon	UBERON:0004991	99.01	gold quality
liver	UBERON:0002107	98.92	gold quality
body of pancreas	UBERON:0001150	98.67	gold quality
adult mammalian kidney	UBERON:0000082	98.31	gold quality
apex of heart	UBERON:0002098	98.12	gold quality
body of stomach	UBERON:0001161	98.11	gold quality
transverse colon	UBERON:0001157	97.62	gold quality
heart left ventricle	UBERON:0002084	97.61	gold quality
fundus of stomach	UBERON:0001160	97.59	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.54	gold quality
right adrenal gland	UBERON:0001233	97.45	gold quality
right atrium auricular region	UBERON:0006631	97.40	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.31	gold quality
right adrenal gland cortex	UBERON:0035827	97.21	gold quality
heart	UBERON:0000948	97.12	gold quality
duodenum	UBERON:0002114	97.09	gold quality
left adrenal gland	UBERON:0001234	97.02	gold quality
stomach	UBERON:0000945	97.01	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.94	gold quality
lower esophagus	UBERON:0013473	96.93	gold quality
substantia nigra	UBERON:0002038	96.89	gold quality
left adrenal gland cortex	UBERON:0035825	96.87	gold quality
omental fat pad	UBERON:0010414	96.85	gold quality
prostate gland	UBERON:0002367	96.83	gold quality
esophagus mucosa	UBERON:0002469	96.83	gold quality
cortex of kidney	UBERON:0001225	96.75	gold quality
prefrontal cortex	UBERON:0000451	96.73	gold quality
small intestine	UBERON:0002108	96.73	gold quality
esophagus	UBERON:0001043	96.68	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-9	yes	59.25
E-ANND-3	yes	11.62
E-MTAB-6524	no	106.64

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

14 targeting DDT, 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-MIR-3185	99.99	68.12	1959
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-5007-3P	99.51	68.14	1242
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-518C-5P	98.53	69.20	1640
HSA-MIR-6764-3P	98.44	67.64	1153
HSA-MIR-6824-3P	98.44	67.62	1154
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-3679-5P	94.75	66.46	862

Literature-anchored findings (GeneRIF, showing 24)

• role of tautomerase active site of macrophage migration inhibitory factor as a potential target for discovery of novel anti-inflammatory agents (PMID:11997397)
• DDT is for the first time demonstrated in the skin and can be related to inflammation, and its covariation with MIF strengthens this observation. (PMID:12823441)
• D-dopachrome tautomerase (D-DT) and macrophage migration inhibitory factor, individually and additively, promote vascular endothelial growth factor and CXCL8 expression in human lung adenocarcinoma cell lines. (PMID:18684922)
• D-DT-dependent beta-catenin stabilization is regulated by COX-2 expression, suggesting the existence of an amplification loop between COX-2- and beta-catenin-mediated transcription in these cells (PMID:21071513)
• These data indicate that D-DT is a MIF-like cytokine. (PMID:21817065)
• DDT acts on adipocytes to regulate lipid metabolism through AMPK and/or PKA pathway(s) and improves glucose intolerance caused by obesity. (PMID:22428043)
• D-dopachrome tautomerase secreted from adipocytes acts on preadipocytes to promote IL-6 expression and to inhibit adipogenesis by suppressing the induction of genes encoding adipogenic regulators (PMID:22951300)
• findings identify DDT as a functionally redundant but more potent cytokine to MIF in cancer and suggest that current attempts to inhibit MIF signaling may fail because of DDT compensation. (PMID:24356968)
• Both p53 wildtype and mutant human lung adenocarcinoma tumors rely on MIF family members for maximal cell growth and survival. (PMID:24932684)
• High MIF-2 levels are predictive of the development of organ dysfunction in myocardial ischemia reperfusion injury. (PMID:26234719)
• Gene expression level of DDT is significantly higher in AD patients when compared to normal controls. (PMID:26943237)
• DDT was increased in burn patients. (PMID:27209369)
• Study demonstrated that DDT was over- expressed in pancreatic ductal adenocarcinoma (PDAC) tissues and cell lines in a pattern correlated with MIF, and knockdown of DDT and MIF in PANC- 1 cells cooperatively inhibited cell proliferation, invasion and tumor formation. The tautomerase activities of both MIF and DDT are required for their negative regulatory role in p53 and their tumor-promoting functions. (PMID:27434219)
• These results have implications for the manner in which D-DT and MIF compete with each other for binding to the CD74 receptor and for the relative potency of DRa1-MOG-35-55 and RTL1000 for competitive inhibition of D-DT and MIF binding and activation through CD74. (PMID:27573366)
• The knockdown of D-DT and MIF, individually and additively, inhibited the proliferation, migration, and invasion in HeLa and SiHa cells and restrained the growth of xenograft tumor. (PMID:28338494)
• D-dopachrome tautomerase transcription may be regulated in a cell-dependent manner, and was enhanced by AMPK activation in SGBS adipocytes through inhibiting the mTOR signaling (PMID:28445821)
• results show that the minor allele frequency of rs755622 and expression of DDT are significantly increased in males for MS subjects and this minor allele variant can significantly upregulate DDT expression for males but not females, which suggests that the regulation of DDT expression level by rs755622 can affect MS progression in males. (PMID:30140701)
• Cardiomyocyte d-dopachrome tautomerase protects against heart failure. (PMID:31484822)
• Genetic regulation of gene expression of MIF family members in lung tissue. (PMID:33046825)
• Macrophage Migration Inhibitory Factor (MIF) and Its Homologue d-Dopachrome Tautomerase (DDT) Inversely Correlate with Inflammation in Discoid Lupus Erythematosus. (PMID:33401503)
• D-dopachrome tautomerase contributes to lung epithelial repair via atypical chemokine receptor 3-dependent Akt signaling. (PMID:34098338)
• Knockdown of D-dopachrome Tautomerase Inhibits Cell Proliferation in Human HepG2 Cell Line. (PMID:34281877)
• A structurally preserved allosteric site in the MIF superfamily affects enzymatic activity and CD74 activation in D-dopachrome tautomerase. (PMID:34384784)
• D-dopachrome tautomerase in cardiovascular and inflammatory diseases-A new kid on the block or just another MIF? (PMID:36269019)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ddt	ENSDARG00000044751
mus_musculus	Ddt	ENSMUSG00000001666
rattus_norvegicus		ENSRNOG00000083406

Paralogs (2): DDTL (ENSG00000099974), MIF (ENSG00000240972)

Protein

Protein identifiers

D-dopachrome decarboxylase — P30046 (reviewed: P30046)

Alternative names: D-dopachrome tautomerase, Phenylpyruvate tautomerase II

All UniProt accessions (5): P30046, B5MC82, H7C342, J3KQ18, Q53Y51

UniProt curated annotations — full annotation on UniProt →

Function. Tautomerization of D-dopachrome with decarboxylation to give 5,6-dihydroxyindole (DHI).

Subunit / interactions. Homotrimer.

Subcellular location. Cytoplasm.

Tissue specificity. Highly expressed in the liver and at lower levels in the heart, lung and pancreas.

Similarity. Belongs to the MIF family.

Isoforms (2)

UniProt ID	Names	Canonical?
P30046-1	1	yes
P30046-2	2

RefSeq proteins (4): NP_001077861, NP_001346, NP_001368781, NP_001384414 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001398	Macrophage_inhib_fac	Family
IPR014347	Tautomerase/MIF_sf	Homologous_superfamily
IPR019829	Macrophage_inhib_fac_CS	Conserved_site

Pfam: PF01187

Enzyme classification (BRENDA):

• EC 4.1.1.84 — D-dopachrome decarboxylase (BRENDA: 5 organisms, 9 substrates, 15 inhibitors, 7 Km, 4 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
D-DOPACHROME	0.42–1.5	3
4-CHLOROPHENYLPYRUVATE	2.17	1
4-HYDROXYPHENYLPYRUVATE	3.6	1
4-METHOXYPHENYLPYRUVATE	6.7	1
PHENYLPYRUVATE	2.4	1

Catalyzed reactions (Rhea), 1 shown:

• D-dopachrome + H(+) = 5,6-dihydroxyindole + CO2 (RHEA:18441)

UniProt features (20 total): helix 7, strand 6, modified residue 2, initiator methionine 1, chain 1, splice variant 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

23 structures.

PDB	Method	Resolution (Å)
9BB0	X-RAY DIFFRACTION	0.98
7MW7	X-RAY DIFFRACTION	1.1
3KAN	X-RAY DIFFRACTION	1.13
8VFL	X-RAY DIFFRACTION	1.23
8VG7	X-RAY DIFFRACTION	1.24
7MSE	X-RAY DIFFRACTION	1.27
8VFN	X-RAY DIFFRACTION	1.29
8DBB	X-RAY DIFFRACTION	1.3
8VFW	X-RAY DIFFRACTION	1.31
7MRU	X-RAY DIFFRACTION	1.33
8VG8	X-RAY DIFFRACTION	1.33
8VFO	X-RAY DIFFRACTION	1.35
6C5F	X-RAY DIFFRACTION	1.4
9O3U	X-RAY DIFFRACTION	1.49
8VG5	X-RAY DIFFRACTION	1.5
9O3T	X-RAY DIFFRACTION	1.53
9O3R	X-RAY DIFFRACTION	1.54
1DPT	X-RAY DIFFRACTION	1.54
7MRV	X-RAY DIFFRACTION	1.57
8VFK	X-RAY DIFFRACTION	1.59
9O3S	X-RAY DIFFRACTION	1.64
4Q3F	X-RAY DIFFRACTION	1.8
8VDY	X-RAY DIFFRACTION	2.44

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30046-F1	97.99	1.00

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): 2, 33

Mutagenesis-validated functional residues (1):

Position	Phenotype
2	loss of enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 204 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, MODULE_52, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_PHENOL_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, HSIAO_HOUSEKEEPING_GENES, MODULE_335, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION, GOBP_POSITIVE_REGULATION_OF_TUMOR_NECROSIS_FACTOR_SUPERFAMILY_CYTOKINE_PRODUCTION

GO Biological Process (5): negative regulation of macrophage chemotaxis (GO:0010760), positive regulation of tumor necrosis factor production (GO:0032760), melanin biosynthetic process (GO:0042438), positive regulation of inflammatory response (GO:0050729), positive regulation of ERK1 and ERK2 cascade (GO:0070374)

GO Molecular Function (5): dopachrome isomerase activity (GO:0004167), cytokine receptor binding (GO:0005126), D-dopachrome decarboxylase activity (GO:0033981), phenylpyruvate tautomerase activity (GO:0050178), lyase activity (GO:0016829)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of leukocyte chemotaxis	1
regulation of macrophage chemotaxis	1
macrophage chemotaxis	1
negative regulation of macrophage migration	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
melanin metabolic process	1
secondary metabolite biosynthetic process	1
pigment biosynthetic process	1
phenol-containing compound biosynthetic process	1
inflammatory response	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
regulation of inflammatory response	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
intramolecular oxidoreductase activity, transposing C=C bonds	1
signaling receptor binding	1
carboxy-lyase activity	1
intramolecular oxidoreductase activity, interconverting keto- and enol-groups	1
catalytic activity	1
intracellular anatomical structure	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

508 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DDT	CD74	P04233	965
DDT	DCT	P40126	696
DDT	CXCR4	P30991	542
DDT	CXCR2	P25025	505
DDT	CD44	P16070	501
DDT	COPS5	Q92905	453
DDT	GSTT2B	P0CG30	417
DDT	GSTT4	A0A1W2PR19	380
DDT	LRRC75B	Q2VPJ9	371
DDT	C22orf15	Q8WYQ4	350
DDT	CXCR1	P25024	317
DDT	AMH	P03971	304
DDT	ITGAL	P20701	303
DDT	GAPDH	P00354	295
DDT	ATP5MGL	Q7Z4Y8	279

IntAct

13 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
	TK2	psi-mi:“MI:0915”(physical association)	0.400
MAD2L2		psi-mi:“MI:0914”(association)	0.350
ZDHHC5	HACD3	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
SLC12A3	ILVBL	psi-mi:“MI:0914”(association)	0.350
VHL	DDT	psi-mi:“MI:0915”(physical association)	0.000
EIF1B	DDT	psi-mi:“MI:0915”(physical association)	0.000
IKBKE	DDT	psi-mi:“MI:0915”(physical association)	0.000
HLA-B	DDT	psi-mi:“MI:0915”(physical association)	0.000
DSTYK	DDT	psi-mi:“MI:0915”(physical association)	0.000
DDT	dsbD	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (38): DDT (Affinity Capture-RNA), DDT (Affinity Capture-MS), DDT (Two-hybrid), DDT (Affinity Capture-MS), TRIM24 (Affinity Capture-MS), ARHGDIA (Affinity Capture-MS), MTPN (Affinity Capture-MS), MDH1 (Affinity Capture-MS), TBCA (Affinity Capture-MS), CYCS (Affinity Capture-MS), CSTB (Affinity Capture-MS), RPS28 (Affinity Capture-MS), DDT (Affinity Capture-MS), DDTL (Proximity Label-MS), DDTL (Proximity Label-MS)

ESM2 similar proteins: A0A1X9QHJ0, A4XTM7, A5PK65, B9FFD2, O24210, O32183, O34882, O35215, O44786, O75891, O86237, P12928, P22989, P30046, P30613, P53657, P55434, P80254, P81529, P84172, P90835, P91850, P94502, Q05354, Q0APT7, Q0VFN1, Q18785, Q1GTY6, Q28J83, Q29536, Q2G6R7, Q2IZ07, Q2NAA7, Q2W6A0, Q3MHY6, Q5NQB9, Q5ZMG0, Q640C5, Q68FI3, Q7G764

Diamond homologs: A5PK65, A6NHG4, O35215, O55052, P14174, P30046, P80177, P80254, P80928, P81529, P91850, Q1ZZU7, Q28J83, Q4R549, Q5ZMG0, Q640C5, Q68FI3, Q6DN04, A9JSE7, P30904, P34884, Q02960, Q18785, O44786, P81748, Q76BK2, P90835

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

556 predictions. Top by Δscore:

Variant	Effect	Δscore
22:23974308:T:TA	donor_gain	1.0000
22:23980304:TCA:T	donor_gain	1.0000
22:23980305:CAAAG:C	donor_loss	1.0000
22:23980307:AAG:A	donor_loss	1.0000
22:23980308:AGGT:A	donor_loss	1.0000
22:23980309:GGTG:G	donor_loss	1.0000
22:23980310:GT:G	donor_loss	1.0000
22:23980311:T:G	donor_loss	1.0000
22:23973789:T:TA	donor_gain	0.9900
22:23973806:A:AC	donor_gain	0.9900
22:23973940:CGCG:C	acceptor_gain	0.9900
22:23973942:CG:C	acceptor_gain	0.9900
22:23974302:CTTA:C	donor_loss	0.9900
22:23974303:TTA:T	donor_loss	0.9900
22:23974304:TAC:T	donor_loss	0.9900
22:23974305:A:AC	donor_gain	0.9900
22:23974305:ACGT:A	donor_gain	0.9900
22:23974306:C:CC	donor_gain	0.9900
22:23974306:C:CG	donor_loss	0.9900
22:23974306:CGT:C	donor_gain	0.9900
22:23974306:CGTC:C	donor_gain	0.9900
22:23974309:C:A	donor_gain	0.9900
22:23980285:C:G	donor_gain	0.9900
22:23980306:AAAG:A	donor_gain	0.9900
22:23973807:A:C	donor_gain	0.9800
22:23973944:C:CC	acceptor_gain	0.9800
22:23974305:ACGTC:A	donor_gain	0.9800
22:23974306:CG:C	donor_gain	0.9800
22:23974306:CGTCC:C	donor_gain	0.9800
22:23980263:G:GT	donor_gain	0.9800

AlphaMissense

756 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:23971557:A:C	F117L	0.965
22:23971557:A:T	F117L	0.965
22:23971559:A:G	F117L	0.965
22:23973768:C:G	R95P	0.964
22:23973818:G:C	S78R	0.963
22:23973818:G:T	S78R	0.963
22:23973820:T:G	S78R	0.963
22:23971608:A:C	F100L	0.962
22:23971608:A:T	F100L	0.962
22:23971610:A:G	F100L	0.962
22:23974388:A:C	N9K	0.956
22:23974388:A:T	N9K	0.956
22:23971582:C:T	G109D	0.947
22:23973867:A:T	I62N	0.943
22:23974398:A:T	L6Q	0.929
22:23974316:T:A	K33N	0.928
22:23974316:T:G	K33N	0.928
22:23974410:G:T	P2Q	0.924
22:23971621:A:T	I96K	0.921
22:23973862:A:G	S64P	0.921
22:23973879:G:T	A58E	0.919
22:23971609:A:G	F100S	0.916
22:23973873:A:C	L60R	0.916
22:23973798:A:T	L85H	0.915
22:23973873:A:G	L60P	0.914
22:23973798:A:C	L85R	0.912
22:23973942:C:G	R37P	0.911
22:23974347:A:T	L23H	0.911
22:23973865:A:G	S63P	0.910
22:23974406:G:C	F3L	0.909

dbSNP variants (sampled 300 via entrez): RS1000959418 (22:23982069 C>G), RS1001149768 (22:23971758 C>T), RS1004855495 (22:23980808 G>T), RS1005087550 (22:23972396 C>A,T), RS1005118772 (22:23975444 T>G), RS1006771 (22:23971817 G>T), RS1007882230 (22:23982230 T>G), RS1008893621 (22:23972111 T>A,C), RS1008924555 (22:23972290 T>C), RS1010778120 (22:23971869 G>A,C), RS1012380559 (22:23975792 C>T), RS1012870914 (22:23980857 G>A,C), RS1015920945 (22:23971125 G>A), RS1016950282 (22:23971156 C>A,T), RS1017043746 (22:23970965 C>T)

Disease associations

OMIM: gene MIM:602750 | 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
GCST001277_19	Liver enzyme levels (gamma-glutamyl transferase)	2.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004532	serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL5724909 (SINGLE PROTEIN), CHEMBL6066044 (PROTEIN-PROTEIN INTERACTION)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Macrophage migration inhibitory factor (MIF) family proteins

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 10b [PMID: 41766566]	Inhibition	5.82	pIC50

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
6.30	IC50	500	nM	CHEMBL5618599
5.57	IC50	2700	nM	CHEMBL5619655
5.51	IC50	3100	nM	CHEMBL5618860
5.41	IC50	3900	nM	CHEMBL5620288
5.23	IC50	5900	nM	CHEMBL5618597

PubChem BioAssay actives

5 with measured affinity, of 15 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
1-[4-[[3-methoxy-5-(trifluoromethyl)phenyl]carbamoyl]phenyl]-N-[(3-methylphenyl)methyl]triazole-4-carboxamide	2128385: Non-competitive inhibition of DDT (unknown origin) using pyruvic acid as substrate incubated for 10 mins by absorbance based analysis	ic50	0.5000	uM
N-[4-chloro-3-(trifluoromethyl)phenyl]-1-(3,4-dimethylphenyl)triazole-4-carboxamide	2128385: Non-competitive inhibition of DDT (unknown origin) using pyruvic acid as substrate incubated for 10 mins by absorbance based analysis	ic50	2.7000	uM
N-[(3-methylphenyl)methyl]-1-[4-[[3-(trifluoromethyl)phenyl]carbamoyl]phenyl]triazole-4-carboxamide	2128385: Non-competitive inhibition of DDT (unknown origin) using pyruvic acid as substrate incubated for 10 mins by absorbance based analysis	ic50	3.1000	uM
N-[(3-methylphenyl)methyl]-1-[3-(trifluoromethyl)phenyl]triazole-4-carboxamide	2128385: Non-competitive inhibition of DDT (unknown origin) using pyruvic acid as substrate incubated for 10 mins by absorbance based analysis	ic50	3.9000	uM
4-[4-[[[2-[1-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]-2-oxoethyl]cyclopentyl]acetyl]amino]methyl]triazol-1-yl]-N-[3-methoxy-5-(trifluoromethyl)phenyl]benzamide	2128385: Non-competitive inhibition of DDT (unknown origin) using pyruvic acid as substrate incubated for 10 mins by absorbance based analysis	ic50	5.9000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, increases expression, affects expression	4
Smoke	decreases expression, increases abundance	3
Aflatoxin B1	affects expression, decreases expression, increases methylation	3
Air Pollutants	decreases expression, increases abundance	2
Benzo(a)pyrene	decreases expression	2
2,4,6-tribromophenol	decreases expression	1
methyleugenol	decreases expression	1
bisphenol A	decreases expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
decabromobiphenyl ether	decreases expression	1
arsenite	affects binding, increases reaction	1
tetrabromobisphenol A	decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
diallyl trisulfide	decreases expression	1
chloropicrin	increases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol AF	increases expression	1
Rosiglitazone	decreases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Acetaminophen	decreases expression	1
Cannabidiol	decreases expression	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Copper	affects binding	1
Dichlorodiphenyl Dichloroethylene	increases methylation	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5615200	Binding	Non-competitive inhibition of DDT (unknown origin) using pyruvic acid as substrate incubated for 10 mins by absorbance based analysis	The synthesis of 1,2,3-triazoles as binders of D-dopachrome tautomerase (D-DT) for the development of dual-targeting inhibitors. — Eur J Med Chem

Clinical trials (associated diseases)

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