MAFG

Summary

MAFG (MAF bZIP transcription factor G, HGNC:6781) is a protein-coding gene on chromosome 17q25.3, encoding Transcription factor MafG (O15525). Since they lack a putative transactivation domain, the small Mafs behave as transcriptional repressors when they dimerize among themselves.

Globin gene expression is regulated through nuclear factor erythroid-2 (NFE2) elements located in enhancer-like locus control regions positioned many kb upstream of alpha- and beta-gene clusters (summarized by Blank et al., 1997 [PubMed 9166829]). NFE2 DNA-binding activity consists of a heterodimer containing a ubiquitous small Maf protein (MafF, MIM 604877; MafG; or MafK, MIM 600197) and the tissue-restricted protein p45 NFE2 (MIM 601490). Both subunits are members of the activator protein-1-like superfamily of basic leucine zipper (bZIP) proteins (see MIM 165160).

Source: NCBI Gene 4097 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 17 total
• Druggable target: yes
• Transcription factor: yes — 10 downstream targets (CollecTRI)
• MANE Select transcript: NM_002359

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6781
Approved symbol	MAFG
Name	MAF bZIP transcription factor G
Location	17q25.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC13090, MGC20149
Ensembl gene	ENSG00000197063
Ensembl biotype	protein_coding
OMIM	602020
Entrez	4097

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 20 protein_coding

ENST00000357736, ENST00000392366, ENST00000574686, ENST00000899697, ENST00000899698, ENST00000899699, ENST00000899700, ENST00000899701, ENST00000899702, ENST00000899703, ENST00000932389, ENST00000932390, ENST00000953147, ENST00000953148, ENST00000953149, ENST00000953150, ENST00000953151, ENST00000953152, ENST00000953153, ENST00000953154

RefSeq mRNA: 2 — MANE Select: NM_002359 NM_002359, NM_032711

CCDS: CCDS11793

Canonical transcript exons

ENST00000357736 — 3 exons

Exon	Start	End
ENSE00001404808	81918270	81923057
ENSE00001780776	81923150	81923214
ENSE00002640218	81927528	81927735

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 95.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.8783 / max 148.7481, expressed in 1813 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
168862	11.6710	1803
168861	1.4337	787
168858	1.1928	513
168863	0.9279	605
168860	0.3169	115
168857	0.1800	80
168859	0.1560	73

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	95.94	gold quality
oocyte	CL:0000023	94.81	gold quality
substantia nigra pars compacta	UBERON:0001965	93.57	silver quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	93.21	gold quality
substantia nigra pars reticulata	UBERON:0001966	93.19	silver quality
amniotic fluid	UBERON:0000173	92.35	gold quality
nipple	UBERON:0002030	92.23	gold quality
ventral tegmental area	UBERON:0002691	92.14	silver quality
middle temporal gyrus	UBERON:0002771	92.05	gold quality
pons	UBERON:0000988	91.97	silver quality
superior vestibular nucleus	UBERON:0007227	91.89	gold quality
body of tongue	UBERON:0011876	91.80	silver quality
cartilage tissue	UBERON:0002418	91.76	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.70	gold quality
medulla oblongata	UBERON:0001896	91.48	silver quality
pylorus	UBERON:0001166	91.46	silver quality
vena cava	UBERON:0004087	91.46	silver quality
subthalamic nucleus	UBERON:0001906	91.16	silver quality
lateral globus pallidus	UBERON:0002476	91.09	silver quality
lateral nuclear group of thalamus	UBERON:0002736	90.98	silver quality
inferior vagus X ganglion	UBERON:0005363	90.98	gold quality
pharyngeal mucosa	UBERON:0000355	90.83	gold quality
dorsal root ganglion	UBERON:0000044	90.64	gold quality
gastrocnemius	UBERON:0001388	90.44	gold quality
pericardium	UBERON:0002407	90.33	silver quality
cerebellar vermis	UBERON:0004720	90.21	gold quality
dorsal plus ventral thalamus	UBERON:0001897	89.76	silver quality
tongue	UBERON:0001723	89.36	silver quality
muscle of leg	UBERON:0001383	89.26	gold quality
stromal cell of endometrium	CL:0002255	89.22	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.98

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

10 targets.

Target	Regulation
CRYZ
DDIT3	Activation
HMOX1	Activation
LITAF
MAF
MAFG
MLH1	Unknown
NFE2L1	Repression
NOS2
NQO1	Unknown

JASPAR motifs

Motif	Name	Family
MA0089.2	MAFG::NRF1	Maf-related::NRF
MA0089.3	MAFG::NRF1	Maf-related::NRF
MA0659.1	MAFG	Maf-related
MA0659.2	MAFG	Maf-related

JASPAR matrix evidence (PMIDs): PMID:9421508, PMID:9224592, PMID:8264639

Upstream regulators (CollecTRI, top): LITAF, MAFG, NFE2L2

miRNA regulators (miRDB)

189 targeting MAFG, 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-6873-3P	100.00	71.42	2626
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-340-5P	100.00	72.50	4437
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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4666A-3P	99.96	71.71	3434

Literature-anchored findings (GeneRIF, showing 19)

• This study thus manifests that a clear set of rules pertaining to the cis-acting element determine whether a given Maf-recognition elements preferentially associates with MafG homodimer or with MafG:Nrf2 heterodimer. (PMID:16716189)
• the up-regulation of TCF11/MafG binding could be suppressed by overexpression of the TGF-beta inhibitor Smad7, and a small interfering RNA to TCF11 blocked the suppression of iNOS by TGF-beta. (PMID:17928287)
• MAFG is a target gene of the BACH1 transcription factor according to ChIP-seq analysis in HEK 293 cells. (PMID:21555518)
• 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)
• MAF genes have different levels of biological and genetic relevance. Besides, MAFF and MAFG could be associated with the susceptibility to develop CML. (PMID:24118457)
• PARP-1 serves as a transcriptional coactivator, upregulating the transcriptional activity of Nrf2 by enhancing the interaction among Nrf2, MafG, and the the antioxidant response element. (PMID:24140708)
• Results show that BRAF(V600E)-mediated upregulation of MAFG is required for transcriptional silencing of MLH1 in colorectal neoplasm. (PMID:25219500)
• In condition of hypoxia, MAFG induction correlated with reduced levels of miR-128. This lead to increased mRNA levels of HMOX-1 and x-CT for blunting stress. Overall, these findings identify MAFG as novel direct target of miR-128. (PMID:29138682)
• MAFG is a direct target gene of miRNA-7.The direct regulation of MAFG through miR-7 and their involvement in the development of cisplatin resistance in human tumor cells. (PMID:29158814)
• Expression of MAFG increases in cells and tissues with cholestasis, as well as in human cholangiocarcinoma and hepatocellular carcinoma specimens; high expression levels correlate with tumor progression and reduced survival time. (PMID:29733835)
• musculoaponeurotic fibrosarcoma oncogene family, protein G (MAFG) modulates the redox response and confers cell protection against free radicals generated after platinum administration thus also being a promising therapeutic target in non-small-cell lung cancer drug therapy (PMID:30053382)
• Over-expression of MAFG-AS1 significantly decreased the level of miR-339-5p in NSCLC cell. Moreover, the matrix metalloproteinase 15 (MMP15) was identified to be a target of miR-339-5p. (PMID:30599080)
• LncRNA MAFG-AS1 boosts the proliferation of lung adenocarcinoma cells via regulating miR-744-5p/MAFG axis (PMID:31211984)
• MAFG-lncRNA controlled hepatic glucose metabolism in health and metabolic disease. (PMID:32005828)
• identification of astrocytes in EAE and multiple sclerosis that were characterized by decreased expression of NRF2 and increased expression of MAFG, which cooperates with MAT2alpha to promote DNA methylation and represses antioxidant and anti-inflammatory transcriptional programs (PMID:32051591)
• High-expression of LncRNA MAFG-AS1 is associated with the prognostic of patients with colorectal cancer. (PMID:33295405)
• The small protein MafG plays a critical role in MC3T3-E1 cell apoptosis induced by simulated microgravity and radiation. (PMID:33819748)
• LncRNA MAFG-AS1 Upregulates Polo-Like Kinase-1 by Sponging miR-505 to Promote Gastric Adenocarcinoma Cell Proliferation. (PMID:34591387)
• MAFG-AS1/MAFG positive feedback loop contributes to cisplatin resistance in bladder urothelial carcinoma through antagonistic ferroptosis. (PMID:36654385)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	mafga	ENSDARG00000018109
danio_rerio	mafgb	ENSDARG00000100097
mus_musculus	Mafg	ENSMUSG00000051510
rattus_norvegicus		ENSRNOG00000072854
drosophila_melanogaster	tj	FBGN0000964
drosophila_melanogaster	maf-S	FBGN0034534
caenorhabditis_elegans	maf-1	WBGENE00077521

Paralogs (6): NRL (ENSG00000129535), MAF (ENSG00000178573), MAFA (ENSG00000182759), MAFF (ENSG00000185022), MAFK (ENSG00000198517), MAFB (ENSG00000204103)

Protein

Protein identifiers

Transcription factor MafG — O15525 (reviewed: O15525)

Alternative names: V-maf musculoaponeurotic fibrosarcoma oncogene homolog G, hMAF

All UniProt accessions (2): O15525, I3L2F8

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 seem to serve as transcriptional activators by dimerizing with other (usually larger) basic-zipper proteins, such as NFE2, NFE2L1 and NFE2L2, and recruiting them to specific DNA-binding sites. Small Maf proteins heterodimerize with Fos and may act as competitive repressors of the NFE2L2 transcription factor. Transcription factor, component of erythroid-specific transcription factor NFE2L2. Activates globin gene expression when associated with NFE2L2. May be involved in signal transduction of extracellular H(+).

Subunit / interactions. Homodimer or heterodimer. Homodimerization leads to transcriptional repression. Forms high affinity heterodimers with members of the CNC-bZIP family such as NFE2, NFE2L1/NRF1, NFE2L2/NRF2 and NFE2L3/NRF3. Interacts with CREBBP; the interaction leads to acetylation of the basic region of MAFG and stimulation of NFE2 transcriptional activity through increased DNA binding.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in skeletal muscle. Also expressed in heart and brain.

Post-translational modifications. Acetylated in erythroid cells by CREB-binding protein (CBP). Acetylation augments the DNA-binding activity of NFE2, but has no effect on binding NFE2. Sumoylation at Lys-14 is required for active transcriptional repression.

Similarity. Belongs to the bZIP family. Maf subfamily.

RefSeq proteins (2): NP_002350, NP_116100 (=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 (20 total): modified residue 5, mutagenesis site 4, helix 4, region of interest 3, cross-link 2, chain 1, domain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7X5E	X-RAY DIFFRACTION	2.3
7X5G	X-RAY DIFFRACTION	2.3
7X5F	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15525-F1	81.14	0.63

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 (7): 14, 14, 53, 60, 71, 76, 124

Mutagenesis-validated functional residues (4):

Position	Phenotype
53	abolishes acetylation. has no effect on binding to nfe2 but impairs the dna binding and transcriptional activities of nf
60	abolishes acetylation. has no effect on binding to nfe2 but impairs the dna binding and transcriptional activities of nf
71	abolishes acetylation. has no effect on binding to nfe2 but impairs the dna binding and transcriptional activities of nf
76	abolishes acetylation. has no effect on binding to nfe2 but impairs the dna binding and transcriptional activities of nf

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-9759194	Nuclear events mediated by NFE2L2
R-HSA-9818028	NFE2L2 regulates pentose phosphate pathway genes
R-HSA-983231	Factors involved in megakaryocyte development and platelet production
R-HSA-109582	Hemostasis
R-HSA-2262752	Cellular responses to stress
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9711123	Cellular response to chemical stress
R-HSA-9755511	KEAP1-NFE2L2 pathway

MSigDB gene sets: 257 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_BEHAVIOR, DORSAM_HOXA9_TARGETS_UP, GOBP_REGULATION_OF_EPIDERMIS_DEVELOPMENT, GOBP_ADULT_BEHAVIOR, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, RACCACAR_AML_Q6, ADDYA_ERYTHROID_DIFFERENTIATION_BY_HEMIN, CACCAGC_MIR138, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP

GO Biological Process (9): negative regulation of transcription by RNA polymerase II (GO:0000122), in utero embryonic development (GO:0001701), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of gene expression (GO:0010628), adult behavior (GO:0030534), regulation of cell population proliferation (GO:0042127), regulation of epidermal cell differentiation (GO:0045604), regulation of DNA-templated transcription (GO:0006355), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (8): 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 activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), identical protein binding (GO:0042802), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), RNA polymerase II transcription regulator complex (GO:0090575)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
KEAP1-NFE2L2 pathway	1
Nuclear events mediated by NFE2L2	1
Hemostasis	1
Cellular responses to stimuli	1
Cellular responses to stress	1
Cellular response to chemical stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
regulation of gene expression	2
negative regulation of DNA-templated transcription	1
chordate embryonic development	1
gene expression	1
positive regulation of macromolecule biosynthetic process	1
behavior	1
cell population proliferation	1
regulation of cellular process	1
epidermal cell differentiation	1
regulation of epithelial cell differentiation	1
regulation of epidermis development	1
DNA-templated transcription	1
regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
protein binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
transcription regulator complex	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

922 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAFG	NFE2L1	Q14494	993
MAFG	NFE2L2	Q16236	993
MAFG	NFE2	Q16621	993
MAFG	BACH2	Q9BYV9	944
MAFG	DNMT3B	Q9UBC3	936
MAFG	MAFK	O60675	875
MAFG	CHD8	Q9HCK8	826
MAFG	MAFF	Q9ULX9	770
MAFG	FOS	P01100	740
MAFG	HHAT	Q5VTY9	737
MAFG	JUN	P05412	688
MAFG	JUND	P17535	654
MAFG	FOSB	P53539	642
MAFG	NEIL1	Q96FI4	641
MAFG	JUNB	P17275	620

IntAct

101 interactions, top by confidence:

A	B	Type	Score
MAFG	NFE2L2	psi-mi:“MI:0915”(physical association)	0.940
NFE2L2	MAFG	psi-mi:“MI:0915”(physical association)	0.940
NFE2L2	MAFG	psi-mi:“MI:0407”(direct interaction)	0.940
MAFG	NFE2L2	psi-mi:“MI:0407”(direct interaction)	0.940
NFE2L2	MAFG	psi-mi:“MI:0914”(association)	0.940
MAFG	BACH1	psi-mi:“MI:0407”(direct interaction)	0.870
BACH1	MAFG	psi-mi:“MI:0407”(direct interaction)	0.870
BACH1	MAFG	psi-mi:“MI:0914”(association)	0.870
NFE2L3	MAFG	psi-mi:“MI:0407”(direct interaction)	0.780
NFE2L3	MAFG	psi-mi:“MI:0914”(association)	0.780
MAFG	NFE2L3	psi-mi:“MI:0407”(direct interaction)	0.780
MAFG	BACH2	psi-mi:“MI:0915”(physical association)	0.760
BACH2	MAFG	psi-mi:“MI:0407”(direct interaction)	0.760
MAFG	BACH2	psi-mi:“MI:0407”(direct interaction)	0.760

BioGRID (77): MAFG (Affinity Capture-MS), MAFG (Affinity Capture-MS), MAFG (Affinity Capture-MS), MAFG (Affinity Capture-MS), MAFG (Affinity Capture-MS), MAFG (Affinity Capture-MS), MAFG (Affinity Capture-MS), MAFG (Affinity Capture-MS), BACH1 (Affinity Capture-Western), CHD8 (Affinity Capture-Western), DNMT3B (Affinity Capture-Western), MAFG (Affinity Capture-Western), MAFG (Affinity Capture-Western), MAFG (Affinity Capture-Western), MAFG (Biochemical Activity)

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
MAPK3	“up-regulates quantity”	MAFG	phosphorylation
HOXD12	“down-regulates activity”	MAFG	binding
PRRX1	“down-regulates activity”	MAFG	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 45 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Factors involved in megakaryocyte development and platelet production	7	16.0×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
integrated stress response signaling	5	83.6×	1e-06

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	14
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

709 predictions. Top by Δscore:

Variant	Effect	Δscore
17:81923058:C:CA	acceptor_loss	1.0000
17:81923146:TCA:T	donor_loss	1.0000
17:81923147:CA:C	donor_loss	1.0000
17:81923210:GCTCT:G	acceptor_gain	1.0000
17:81923211:CTCT:C	acceptor_gain	1.0000
17:81923211:CTCTC:C	acceptor_gain	1.0000
17:81923212:TCT:T	acceptor_gain	1.0000
17:81923212:TCTCT:T	acceptor_gain	1.0000
17:81923213:CT:C	acceptor_gain	1.0000
17:81923213:CTC:C	acceptor_gain	1.0000
17:81923214:TCT:T	acceptor_gain	1.0000
17:81923215:C:CC	acceptor_gain	1.0000
17:81923215:C:T	acceptor_loss	1.0000
17:81927527:CCACA:C	donor_gain	1.0000
17:81923053:TTCAC:T	acceptor_gain	0.9900
17:81923055:CAC:C	acceptor_gain	0.9900
17:81923058:C:CC	acceptor_gain	0.9900
17:81923148:A:AC	donor_gain	0.9900
17:81923149:C:CC	donor_gain	0.9900
17:81923149:CCTT:C	donor_gain	0.9900
17:81923215:C:G	acceptor_gain	0.9900
17:81927521:CACT:C	donor_loss	0.9900
17:81927524:TCA:T	donor_loss	0.9900
17:81927526:A:AC	donor_gain	0.9900
17:81927527:C:CC	donor_gain	0.9900
17:81927527:C:T	donor_loss	0.9900
17:81927527:CCA:C	donor_gain	0.9900
17:81923064:C:CT	acceptor_gain	0.9800
17:81927522:A:AC	donor_gain	0.9800
17:81927522:ACTC:A	donor_loss	0.9800

AlphaMissense

1022 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:81922837:A:G	L86P	1.000
17:81922858:A:G	L79P	1.000
17:81922889:G:T	R69S	1.000
17:81922891:C:T	C68Y	1.000
17:81922892:A:G	C68R	1.000
17:81922898:C:G	A66P	1.000
17:81922900:G:T	A65D	1.000
17:81922903:T:C	Y64C	1.000
17:81922904:A:G	Y64H	1.000
17:81922909:C:G	R62P	1.000
17:81922910:G:C	R62G	1.000
17:81922910:G:T	R62S	1.000
17:81922911:G:C	N61K	1.000
17:81922911:G:T	N61K	1.000
17:81922912:T:A	N61I	1.000
17:81922912:T:C	N61S	1.000
17:81922912:T:G	N61T	1.000
17:81922913:T:C	N61D	1.000
17:81922913:T:G	N61H	1.000
17:81922914:C:A	K60N	1.000
17:81922914:C:G	K60N	1.000
17:81922915:T:A	K60M	1.000
17:81922916:T:C	K60E	1.000
17:81922918:A:G	L59P	1.000
17:81922918:A:T	L59H	1.000
17:81922924:C:G	R57P	1.000
17:81922925:G:T	R57S	1.000
17:81922930:C:G	R55P	1.000
17:81922931:G:T	R55S	1.000
17:81922935:C:A	K53N	1.000

dbSNP variants (sampled 300 via entrez): RS1000041849 (17:81919917 A>G), RS1000129030 (17:81930705 A>G), RS1000195754 (17:81925763 G>A,C), RS1000195845 (17:81924020 G>A,T), RS1000254063 (17:81931007 T>G), RS1000360344 (17:81921536 C>T), RS1000573932 (17:81923986 T>G), RS1000692725 (17:81920443 C>T), RS1000936718 (17:81924876 C>A), RS1000962824 (17:81933173 GAA>G), RS1001048844 (17:81921080 G>A,C), RS1001487206 (17:81921913 G>A,T), RS1001909276 (17:81927733 CATG>C), RS1001989055 (17:81923066 C>T), RS1002001150 (17:81927596 G>A)

Disease associations

OMIM: gene MIM:602020 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (1): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL5465260 (SINGLE PROTEIN), CHEMBL5483087 (PROTEIN COMPLEX)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.47	Kd	337	nM	CHEMBL5437633
5.72	IC50	1900	nM	CHEMBL1479098

PubChem BioAssay actives

2 with measured affinity, of 8 total; 2 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
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,5S,8S,11R,15Z,20R)-20-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(3S)-2-[6-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]hexanoylamino]-3-methylpentanoyl]amino]-3-methylbutanoyl]amino]-4-carboxybutanoyl]amino]-4-methylpentanoyl]amino]-4-carboxybutanoyl]amino]-2,8-bis(carboxymethyl)-11,20-dimethyl-5-(2-methylpropyl)-3,6,9,21-tetraoxo-1,4,7,10-tetrazacyclohenicos-15-ene-11-carbonyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-3-carboxypropanoyl]amino]-4-carboxybutanoyl]amino]-6-aminohexanoyl]amino]-5-amino-5-oxopentanoic acid	1988076: Binding affinity to human His-tagged MafG assessed as dissociation constant incubated for 10 mins by SPR analysis	kd	0.3370	uM
2-(1,3-benzodioxol-5-yl)-N-[5-methyl-4-[1-(2-methylbenzoyl)-2,3-dihydroindol-5-yl]-1,3-thiazol-2-yl]acetamide	2130465: Inhibition of NRF2/MAFG (unknown origin) heterodimerization using fluorescein-labeled ARE DNA duplex as substrate preincubated for 1 hr followed by substrate addition measured after 1 hr by FP assay	ic50	1.9000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, increases activity, affects expression, affects binding, increases reaction (+1 more)	9
Tobacco Smoke Pollution	increases expression	7
Air Pollutants	decreases expression, affects cotreatment, increases abundance, affects expression, increases expression	5
Cyclosporine	affects cotreatment, increases expression	5
bisphenol A	affects expression, decreases expression, increases expression, affects cotreatment, increases abundance	3
Benzo(a)pyrene	increases expression, increases methylation	3
Valproic Acid	affects expression, increases expression, increases methylation	3
Cadmium Chloride	increases expression	3
Particulate Matter	increases abundance, increases expression, affects cotreatment	3
methylmercuric chloride	increases expression	2
diethyl maleate	increases expression	2
sulforaphane	affects expression, increases expression	2
cupric chloride	increases expression	2
cadmium sulfate	increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
bardoxolone methyl	affects expression, decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Aerosols	increases expression	2
Amiodarone	increases expression	2
Copper	affects binding, increases expression	2
Hydrogen Peroxide	affects expression, increases expression	2
Lead	decreases expression, increases expression	2
Ozone	affects cotreatment, decreases expression, increases abundance, affects expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Rotenone	decreases expression, increases expression	2
Tunicamycin	increases expression	2
beta-Naphthoflavone	increases expression	2
tert-Butylhydroperoxide	increases expression, increases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
Vitamin K 3	affects expression, increases expression	2

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5340993	Binding	Binding affinity to human His-tagged MafG expressed in Escherichia coli Rosetta (DE3) by immunoprecipitation assay	Stapled Peptides as Direct Inhibitors of Nrf2-sMAF Transcription Factors. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_AW34	K562 eGFP-MAFG	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results
NCT00005095	Not specified	RECRUITING	Specimen and Data Study for Ovarian Cancer Early Detection and Prevention
NCT00609505	Not specified	COMPLETED	Telemedicine vs. Face-to-Face Cancer Genetic Counseling
NCT01273909	Not specified	UNKNOWN	Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment
NCT01445275	Not specified	WITHDRAWN	Cost of Cancer Risk Management in Women at Elevated Genetic Risk for Ovarian Cancer Who Participated on GOG-0199
NCT01608074	Not specified	ACTIVE_NOT_RECRUITING	Radical Fimbriectomy for Young BRCA Mutation Carriers
NCT02087592	Not specified	COMPLETED	Feasibility of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02302742	Not specified	RECRUITING	Triple Negative Breast Cancer and Germline Hereditary Breast and Ovarian Cancer Mutation Carrier Registry
NCT02324062	Not specified	COMPLETED	Cancer Genetics Hereditary Cancer Panel Testing
NCT02516540	Not specified	UNKNOWN	Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02653105	Not specified	ACTIVE_NOT_RECRUITING	Women at Risk of Breast Cancer and OLFM4
NCT02705924	Not specified	TERMINATED	Impact of a Psychoeducational Intervention on Expectations and Coping in Young Women Exposed to a High HBOC Risk
NCT02760849	Not specified	ACTIVE_NOT_RECRUITING	Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations
NCT02786147	Not specified	COMPLETED	Identification and Referral of Women at Risk for Hereditary Breast/Ovarian Cancer
NCT02956681	Not specified	COMPLETED	Statewide Communication to Reach Diverse Low Income Women
NCT03015376	Not specified	UNKNOWN	Inherited Susceptible Genes Among Epithelial Ovarian Cancer
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03075540	Not specified	COMPLETED	Enhancing At-risk Latina Women’s Use of Genetic Counseling for Hereditary Breast and Ovarian Cancer
NCT03124212	Not specified	RECRUITING	Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland
NCT03246841	Not specified	ACTIVE_NOT_RECRUITING	Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.
NCT03294343	Not specified	UNKNOWN	Risk-Reducing Surgeries for Hereditary Ovarian Cancer
NCT03421327	Not specified	COMPLETED	Genetic Risk: Whether, When, and How to Tell Adolescents
NCT03510689	Not specified	COMPLETED	Genetics and Heart Health After Cancer Therapy
NCT03511690	Not specified	COMPLETED	Testing an Intelligent Tutoring System to Enhance Genetic Risk Assessment
NCT03784859	Not specified	COMPLETED	Tissue Expansion in Breast Reconstruction Without Drains
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04197856	Not specified	ACTIVE_NOT_RECRUITING	Direct Information to At-risk Relatives
NCT04407611	Not specified	COMPLETED	Scalable Communication Modalities for Returning Genetic Research Results
NCT04508764	Not specified	TERMINATED	Implementation of the Families Accelerating Cascade Testing Toolkit (FACTT) for Hereditary Breast and Ovarian Cancer and Lynch Syndrome