MAFK

Summary

MAFK (MAF bZIP transcription factor K, HGNC:6782) is a protein-coding gene on chromosome 7p22.3, encoding Transcription factor MafK (O60675). Since they lack a putative transactivation domain, the small Mafs behave as transcriptional repressors when they dimerize among themselves.

The developmentally regulated expression of the globin genes depends on upstream regulatory elements termed locus control regions (LCRs). LCRs are associated with powerful enhancer activity that is mediated by the transcription factor NFE2 (nuclear factor erythroid-2). NFE2 recognition sites are also present in the gene promoters of 2 heme biosynthetic enzymes, porphobilinogen deaminase (PBGD; MIM 609806) and ferrochelatase (FECH; MIM 612386). NFE2 DNA-binding activity consists of a heterodimer containing an 18-kD Maf protein (MafF, MafG (MIM 602020), or MafK) and p45 (MIM 601490). Both subunits are members of the activator protein-1 superfamily of basic leucine zipper (bZIP) proteins (see MIM 165160). Maf homodimers suppress transcription at NFE2 sites.

Source: NCBI Gene 7975 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 17 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Transcription factor: yes — 24 downstream targets (CollecTRI)
• MANE Select transcript: NM_002360

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6782
Approved symbol	MAFK
Name	MAF bZIP transcription factor K
Location	7p22.3
Locus type	gene with protein product
Status	Approved
Aliases	P18, NFE2U
Ensembl gene	ENSG00000198517
Ensembl biotype	protein_coding
OMIM	600197
Entrez	7975

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 nonsense_mediated_decay

ENST00000343242, ENST00000403150, ENST00000406174, ENST00000885490, ENST00000947296, ENST00000947297, ENST00000947298

RefSeq mRNA: 1 — MANE Select: NM_002360 NM_002360

CCDS: CCDS5325

Canonical transcript exons

ENST00000343242 — 3 exons

Exon	Start	End
ENSE00001034948	1539149	1539228
ENSE00001034951	1530702	1530898
ENSE00001294126	1539941	1543043

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 98.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.3068 / max 174.1737, expressed in 1778 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
76929	8.1770	1738
76930	2.1190	901
76934	0.7977	366
76932	0.6187	329
76931	0.4378	245
76935	0.1006	43
76933	0.0559	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	98.16	gold quality
ascending aorta	UBERON:0001496	96.79	gold quality
thoracic aorta	UBERON:0001515	96.61	gold quality
aorta	UBERON:0000947	96.41	gold quality
right coronary artery	UBERON:0001625	96.29	gold quality
popliteal artery	UBERON:0002250	96.29	gold quality
tibial artery	UBERON:0007610	96.29	gold quality
mucosa of stomach	UBERON:0001199	95.92	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.63	gold quality
lower esophagus	UBERON:0013473	95.59	gold quality
right lung	UBERON:0002167	95.57	gold quality
saphenous vein	UBERON:0007318	95.56	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.31	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.29	gold quality
coronary artery	UBERON:0001621	95.01	gold quality
left coronary artery	UBERON:0001626	94.97	gold quality
right atrium auricular region	UBERON:0006631	94.75	gold quality
heart left ventricle	UBERON:0002084	94.55	gold quality
cardiac ventricle	UBERON:0002082	94.43	gold quality
descending thoracic aorta	UBERON:0002345	94.39	gold quality
gastrocnemius	UBERON:0001388	94.10	gold quality
upper lobe of left lung	UBERON:0008952	93.77	gold quality
metanephros cortex	UBERON:0010533	93.70	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.56	gold quality
tibial nerve	UBERON:0001323	93.49	gold quality
left uterine tube	UBERON:0001303	93.45	gold quality
upper lobe of lung	UBERON:0008948	93.37	gold quality
sigmoid colon	UBERON:0001159	93.12	gold quality
omental fat pad	UBERON:0010414	93.04	gold quality
peritoneum	UBERON:0002358	92.97	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.59

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

24 targets.

Target	Regulation
CD44
CDK2
CDK6
CDKN1B
CDKN2A
CDKN2B
CDKN2C
CRYZ
CXCL8	Activation
GSTP1
H2AC18
HBB
HDC
HMOX1	Unknown
HPGDS
IL10	Activation
IL12B	Activation
IL2	Activation
IL4	Activation
IL6	Activation
MEN1
NQO1	Unknown
PRDM1	Unknown
TNF	Activation

JASPAR motifs

Motif	Name	Family
MA0496.1	MAFK	Maf-related
MA0496.2	MAFK	Maf-related
MA0496.3	MAFK	Maf-related
MA0496.4	MAFK	Maf-related

JASPAR matrix evidence (PMIDs): PMID:8264639

Upstream regulators (CollecTRI, top): GATA1, GATA2, GATA4, GATA6, NFE2L2

miRNA regulators (miRDB)

89 targeting MAFK, 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-5692A	100.00	74.40	6850
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798

Literature-anchored findings (GeneRIF, showing 9)

• These findings demonstrate that a combination of p45NF-E2, Maf G, and Maf K is a key determinant of both megakaryopoiesis and thrombopoiesis. (PMID:22855609)
• Data indicate that transcription factors MafK and Bach1 regulate expression of heme oxygenase-1 (HO-1). (PMID:23737527)
• Results suggest that JDP2 is an integral component of the Nrf2-MafK complex and that it modulates antioxidant and detoxification programs by acting via the ARE. (PMID:24232097)
• MafK mediated p65 acetylation by CBP upon LPS stimulation, thereby facilitating recruitment of p65 to NF-kappaB promoters such as IL-8 and TNFalpha. (PMID:24247732)
• Results suggested that Wnt1-induced MAFK expression promoted cell proliferation in MG63 cells, and that the role of MAFK in osteosarcoma might be closely linked to the Wnt signaling pathway. (PMID:26214410)
• Findings suggest that MAFK and its target gene GPNMB play important roles in the malignant progression of triple-negative breast cancer (TNBC) cells, offering potentially new therapeutic targets for TNBC patients. (PMID:28400538)
• MAFK genetic polymorphisms are significantly associated with susceptibility to ulcerative colitis development in Japan. (PMID:28839436)
• MAFK Polymorphisms Located in 3’-UTR are Associated with Severity of Atrophy and CDKN2A Methylation Status in the Gastric Mucosa. (PMID:33877894)
• MafK accelerates Salmonella mucosal infection through caspase-3 activation. (PMID:35260530)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	mafk	ENSDARG00000100947
mus_musculus	Mafk	ENSMUSG00000018143
rattus_norvegicus	Mafk	ENSRNOG00000065794
drosophila_melanogaster	tj	FBGN0000964
drosophila_melanogaster	maf-S	FBGN0034534
caenorhabditis_elegans	maf-1	WBGENE00077521

Paralogs (6): NRL (ENSG00000129535), MAF (ENSG00000178573), MAFA (ENSG00000182759), MAFF (ENSG00000185022), MAFG (ENSG00000197063), MAFB (ENSG00000204103)

Protein

Protein identifiers

Transcription factor MafK — O60675 (reviewed: O60675)

Alternative names: Erythroid transcription factor NF-E2 p18 subunit

All UniProt accessions (1): O60675

UniProt curated annotations — full annotation on UniProt →

Function. Since they lack a putative transactivation domain, the small Mafs behave as transcriptional repressors when they dimerize among themselves. However, they act as transcriptional activators by dimerizing with other (usually larger) basic-zipper proteins, such as NFE2, NFE2L1/NRF1, NFE2L2/NRF2 and NFE2L3/NRF3, and recruiting them to specific DNA-binding sites. Small Maf proteins heterodimerize with Fos and may act as competitive repressors of the NF-E2 transcription factor.

Subunit / interactions. Homodimer or heterodimer. It can form high affinity heterodimers with members of the CNC-bZIP family such as NFE2, NFE2L1/NRF1, NFE2L2/NRF2 and NFE2L3/NRF3.

Subcellular location. Nucleus.

Similarity. Belongs to the bZIP family. Maf subfamily.

RefSeq proteins (1): NP_002351* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004826	bZIP_Maf	Domain
IPR004827	bZIP	Domain
IPR008917	TF_DNA-bd_sf	Homologous_superfamily
IPR024874	Transcription_factor_Maf_fam	Family
IPR046347	bZIP_sf	Homologous_superfamily

Pfam: PF03131

UniProt features (6 total): region of interest 2, chain 1, domain 1, modified residue 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60675-F1	84.67	0.65

Functional residue map

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

Post-translational modifications (2): 25, 130

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-9707587	Regulation of HMOX1 expression and activity
R-HSA-9707616	Heme signaling
R-HSA-9708530	Regulation of BACH1 activity
R-HSA-9759194	Nuclear events mediated by NFE2L2
R-HSA-9818026	NFE2L2 regulating inflammation associated genes
R-HSA-9818027	NFE2L2 regulating anti-oxidant/detoxification enzymes
R-HSA-9818030	NFE2L2 regulating tumorigenic genes
R-HSA-9818032	NFE2L2 regulating MDR associated enzymes
R-HSA-9818035	NFE2L2 regulating ER-stress associated genes
R-HSA-9818749	Regulation of NFE2L2 gene expression
R-HSA-983231	Factors involved in megakaryocyte development and platelet production
R-HSA-9943962	CHD6, CHD7, CHD8, CHD9 subfamily
R-HSA-109582	Hemostasis
R-HSA-2262752	Cellular responses to stress
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9707564	Cytoprotection by HMOX1
R-HSA-9711123	Cellular response to chemical stress
R-HSA-9755511	KEAP1-NFE2L2 pathway

MSigDB gene sets: 189 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, chr7p22, GERY_CEBP_TARGETS, CATTTCA_MIR203, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, FOSTER_TOLERANT_MACROPHAGE_UP, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, SHIN_B_CELL_LYMPHOMA_CLUSTER_8, WELCH_GATA1_TARGETS, BIOCARTA_ARENRF2_PATHWAY, RICKMAN_TUMOR_DIFFERENTIATED_MODERATELY_VS_POORLY_UP, NIKOLSKY_BREAST_CANCER_7P22_AMPLICON, DURCHDEWALD_SKIN_CARCINOGENESIS_DN, GOCC_RNA_POLYMERASE_II_TRANSCRIPTION_REGULATOR_COMPLEX

GO Biological Process (3): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (8): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription factor activity (GO:0003700), sequence-specific DNA binding (GO:0043565), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), RNA polymerase II transcription regulator complex (GO:0090575)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Nuclear events mediated by NFE2L2	6
Cellular responses to stress	2
KEAP1-NFE2L2 pathway	2
Cellular response to chemical stress	2
Cytoprotection by HMOX1	1
Hemostasis	1
CHD chromatin remodelers	1
Cellular responses to stimuli	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
regulation of DNA-templated transcription	2
cellular anatomical structure	2
negative regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
DNA binding	1
nucleic acid binding	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
transcription regulator complex	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

1134 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAFK	NFE2	Q16621	973
MAFK	BACH2	Q9BYV9	940
MAFK	NFE2L1	Q14494	933
MAFK	NFE2L2	Q16236	933
MAFK	MAFG	O15525	875
MAFK	NFE2L3	Q9Y4A8	873
MAFK	HDAC3	O15379	796
MAFK	MAFF	Q9ULX9	775
MAFK	FOS	P01100	764
MAFK	HHAT	Q5VTY9	699
MAFK	GATA1	P15976	676
MAFK	JUN	P05412	672
MAFK	EP300	Q09472	601
MAFK	FOSL2	P15408	601
MAFK	KEAP1	Q14145	588

IntAct

24 interactions, top by confidence:

A	B	Type	Score
BACH1	MAFG	psi-mi:“MI:0914”(association)	0.870
MAFK	NFE2L2	psi-mi:“MI:0915”(physical association)	0.810
NFE2L2	MAFK	psi-mi:“MI:0915”(physical association)	0.810
NFE2L3	MAFG	psi-mi:“MI:0914”(association)	0.780
MAFK	BACH2	psi-mi:“MI:0915”(physical association)	0.740
MAFK	BACH1	psi-mi:“MI:0914”(association)	0.730
Bach1	BACH1	psi-mi:“MI:0915”(physical association)	0.400
Bach1	SYNM	psi-mi:“MI:0914”(association)	0.350
BACH1		psi-mi:“MI:0914”(association)	0.350
CUL4A	DDX39A	psi-mi:“MI:0914”(association)	0.350
DCAF4	IGLL5	psi-mi:“MI:0914”(association)	0.350
BACH2	ENC1	psi-mi:“MI:0914”(association)	0.350
ZBTB24	BACH1	psi-mi:“MI:0914”(association)	0.350
MAFK	MAFG	psi-mi:“MI:0914”(association)	0.350
MAFK	NFE2L2	psi-mi:“MI:0915”(physical association)	0.000
MAFK	BACH2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (54): MAFK (Affinity Capture-MS), MAFK (Affinity Capture-MS), MAFK (Reconstituted Complex), MAFK (Affinity Capture-MS), MAFK (Affinity Capture-MS), MAFK (Affinity Capture-MS), MAFK (Affinity Capture-Western), MAFK (Affinity Capture-Western), MAFK (Affinity Capture-MS), MAFK (Affinity Capture-Western), MAFK (Affinity Capture-MS), MAFK (Affinity Capture-MS), MAFK (Two-hybrid), MAFK (Two-hybrid), NFE2L2 (Reconstituted Complex)

ESM2 similar proteins: A5PJV0, A7YY73, F1QW76, O15525, O43150, O54790, O54791, O57337, O60675, P13096, P13097, P13098, P35428, P50538, P97496, Q01068, Q01069, Q01070, Q01071, Q01664, Q04666, Q05195, Q07291, Q07E41, Q108T9, Q14469, Q14582, Q16206, Q16520, Q3ZBG4, Q5FWS6, Q5PPM5, Q61827, Q674X7, Q6IRB2, Q6PBD4, Q76MX4, Q7Z3E5, Q8AVU4, Q8BHR2

Diamond homologs: A3KMR8, A5PJV0, A7YY73, A7Z017, D3ZNT6, O15525, O42290, O54790, O54791, O57342, O60675, O75444, P23091, P54841, P54842, P54843, P54844, P54845, P54846, Q0V9K1, Q2PFS4, Q4U1U2, Q504L8, Q61827, Q6DE84, Q76MX4, Q789F3, Q8CF90, Q8NHW3, Q90370, Q90595, Q90596, Q90888, Q90889, Q98UK4, Q98UK5, Q9ULX9, Q9Y5Q3

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
BACH1	“up-regulates activity”	MAFK	binding
HOXD12	“down-regulates activity”	MAFK	binding
PRRX1	“down-regulates activity”	MAFK	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

718 predictions. Top by Δscore:

Variant	Effect	Δscore
7:1539937:CCAG:C	acceptor_loss	1.0000
7:1539938:CAG:C	acceptor_loss	1.0000
7:1530894:GCCAG:G	donor_gain	0.9900
7:1530900:T:G	donor_loss	0.9900
7:1539139:T:G	acceptor_gain	0.9900
7:1539224:TAAAG:T	donor_loss	0.9900
7:1539225:AAAG:A	donor_loss	0.9900
7:1539226:AAGGT:A	donor_loss	0.9900
7:1539227:AGGTA:A	donor_loss	0.9900
7:1539228:GGTA:G	donor_loss	0.9900
7:1539229:G:GA	donor_loss	0.9900
7:1539230:T:G	donor_loss	0.9900
7:1539939:A:AG	acceptor_gain	0.9900
7:1539940:G:GG	acceptor_gain	0.9900
7:1530899:G:GG	donor_gain	0.9800
7:1539138:A:AG	acceptor_gain	0.9800
7:1539138:AT:A	acceptor_gain	0.9800
7:1539139:T:TA	acceptor_gain	0.9800
7:1539143:TTCCA:T	acceptor_loss	0.9800
7:1539145:CCAGC:C	acceptor_loss	0.9800
7:1539146:CA:C	acceptor_loss	0.9800
7:1539147:A:AG	acceptor_gain	0.9800
7:1539147:AGCT:A	acceptor_loss	0.9800
7:1539148:G:GA	acceptor_loss	0.9800
7:1539148:G:GG	acceptor_gain	0.9800
7:1539148:GCT:G	acceptor_gain	0.9800
7:1539930:T:TA	acceptor_gain	0.9800
7:1539931:G:A	acceptor_gain	0.9800
7:1537686:G:GT	donor_gain	0.9700
7:1539148:GCTAC:G	acceptor_gain	0.9700

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000144443 (7:1540571 C>T), RS1000186244 (7:1533257 G>A,T), RS1000260687 (7:1540975 C>A,T), RS1000587956 (7:1533982 C>G), RS1000689717 (7:1534169 T>C,G), RS1000741561 (7:1534318 C>T), RS1000930204 (7:1530460 G>A), RS1001013017 (7:1541131 T>G), RS1001041449 (7:1537969 G>A), RS1001148255 (7:1541258 C>T), RS1001153488 (7:1537560 T>G), RS1001235830 (7:1540828 G>A,C), RS1001266863 (7:1540681 C>T), RS1001473636 (7:1537321 G>A), RS1001509726 (7:1529412 C>T)

Disease associations

OMIM: gene MIM:600197 | 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
GCST90000025_143	Appendicular lean mass	3.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2346484 (SINGLE PROTEIN), CHEMBL4523627 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 7,981 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL48802	SULFORAPHANE	3	7,981

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs4720833	Toxicity	3	isoniazid	Drug-induced liver injury;Toxic liver disease

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4720833	MAFK	3	0.75	1	isoniazid

ChEMBL bioactivities

1 potent at pChembl≥5 of 2 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.50	IC50	3162	nM	CHEMBL4474353

PubChem BioAssay actives

1 with measured affinity, of 5 total; 1 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
3-(dimethylamino)-4-[3-isothiocyanatopropyl(methyl)amino]cyclobut-3-ene-1,2-dione	1536358: Inhibition of Bach1-Mafk interaction (unknown origin) by luciferase reporter gene based enzyme fragment complementation assay	ic50	3.1623	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	affects cotreatment, increases expression, decreases methylation	4
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression, increases expression	3
bisphenol A	affects expression, decreases expression	2
sodium arsenite	increases expression	2
nickel sulfate	increases expression	2
Cisplatin	affects cotreatment, decreases expression	2
Dinitrochlorobenzene	increases expression	2
Ozone	increases oxidation, increases abundance, affects expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	increases expression, increases methylation	2
aristolochic acid I	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
kojic acid	decreases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
cinnamyl alcohol	increases expression	1
coumarin	increases phosphorylation	1
cupric oxide	increases expression	1
isoeugenol	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
Bandrowski’s base	increases expression	1
nefazodone	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
hexyl cinnamic aldehyde	increases expression	1
2-palmitoylglycerol	increases expression	1
monomethylarsonous acid	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2351429	Binding	Inhibition of JAK2-JH1-JH2 (unknown origin) assessed as remaining activity at 10 uM relative to control	Use of core modification in the discovery of CC214-2, an orally available, selective inhibitor of mTOR kinase. — Bioorg Med Chem Lett

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A4A1	SEES3-1V human MAFK, clone1	Embryonic stem cell	Male
CVCL_A4A2	SEES3-1V human MAFK, clone2	Embryonic stem cell	Male
CVCL_A4A3	SEES3-1V human MAFK, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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