MAX

Summary

MAX (MYC associated transcriptional regulator X, HGNC:6913) is a protein-coding gene on chromosome 14q23.3, encoding Protein max (P61244). Transcription regulator. It is a selective cancer dependency (DepMap: 89.3% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene is a member of the basic helix-loop-helix leucine zipper (bHLHZ) family of transcription factors. It is able to form homodimers and heterodimers with other family members, which include Mad, Mxi1 and Myc. Myc is an oncoprotein implicated in cell proliferation, differentiation and apoptosis. The homodimers and heterodimers compete for a common DNA target site (the E box) and rearrangement among these dimer forms provides a complex system of transcriptional regulation. Mutations of this gene have been reported to be associated with hereditary pheochromocytoma. A pseudogene of this gene is located on the long arm of chromosome 7. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 4149 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary pheochromocytoma-paraganglioma (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 37
• Clinical variants (ClinVar): 573 total — 33 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 70
• Druggable target: yes
• Cancer driver (intOGen): activating (oncogene-like) across 8 cancer types
• Cancer dependency (DepMap): dependent in 89.3% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 55 downstream targets (CollecTRI)
• MANE Select transcript: NM_002382

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6913
Approved symbol	MAX
Name	MYC associated transcriptional regulator X
Location	14q23.3
Locus type	gene with protein product
Status	Approved
Aliases	bHLHd4, bHLHd5, bHLHd6, bHLHd7, bHLHd8
Ensembl gene	ENSG00000125952
Ensembl biotype	protein_coding
OMIM	154950
Entrez	4149

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 15 protein_coding, 3 nonsense_mediated_decay, 3 retained_intron

ENST00000246163, ENST00000284165, ENST00000341653, ENST00000358402, ENST00000358664, ENST00000394606, ENST00000553928, ENST00000553951, ENST00000554709, ENST00000555419, ENST00000555667, ENST00000555932, ENST00000556443, ENST00000556702, ENST00000556892, ENST00000556979, ENST00000557277, ENST00000557746, ENST00000651648, ENST00000937807, ENST00000937808

RefSeq mRNA: 28 — MANE Select: NM_002382 NM_001271068, NM_001271069, NM_001320415, NM_001407094, NM_001407095, NM_001407096, NM_001407097, NM_001407098, NM_001407099, NM_001407100, NM_001407101, NM_001407102, NM_001407103, NM_001407104, NM_001407105, NM_001407106, NM_001407107, NM_001407108, NM_001407109, NM_001407110, NM_001407111, NM_001407112, NM_001407113, NM_002382, NM_145112, NM_145113, NM_145114, NM_197957

CCDS: CCDS41965, CCDS81813, CCDS9770, CCDS9771, CCDS9772, CCDS9774

Canonical transcript exons

ENST00000358664 — 5 exons

Exon	Start	End
ENSE00001884996	65075127	65076663
ENSE00003459724	65077913	65078036
ENSE00003470068	65101546	65101572
ENSE00003500404	65102304	65102517
ENSE00003507137	65093708	65093815

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 98.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 68.6606 / max 911.8037, expressed in 1821 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
143704	52.8752	1819
143705	10.1555	1786
143703	3.4559	1205
143701	1.3121	358
143702	0.5533	207
143700	0.3086	149

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.81	gold quality
mononuclear cell	CL:0000842	98.80	gold quality
leukocyte	CL:0000738	98.70	gold quality
tendon of biceps brachii	UBERON:0008188	98.56	gold quality
oocyte	CL:0000023	98.19	gold quality
cervix squamous epithelium	UBERON:0006922	98.01	gold quality
secondary oocyte	CL:0000655	97.95	gold quality
epithelium of nasopharynx	UBERON:0001951	97.83	gold quality
blood	UBERON:0000178	97.79	gold quality
olfactory bulb	UBERON:0002264	97.49	gold quality
tendon	UBERON:0000043	97.45	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	97.43	gold quality
lower esophagus mucosa	UBERON:0035834	97.41	gold quality
calcaneal tendon	UBERON:0003701	97.32	gold quality
granulocyte	CL:0000094	97.28	gold quality
nipple	UBERON:0002030	97.19	gold quality
mammary duct	UBERON:0001765	97.17	gold quality
trigeminal ganglion	UBERON:0001675	97.13	gold quality
germinal epithelium of ovary	UBERON:0001304	97.12	gold quality
squamous epithelium	UBERON:0006914	97.12	gold quality
epithelium of mammary gland	UBERON:0003244	97.07	gold quality
esophagus squamous epithelium	UBERON:0006920	97.04	gold quality
urethra	UBERON:0000057	96.94	gold quality
epithelium of esophagus	UBERON:0001976	96.92	gold quality
hair follicle	UBERON:0002073	96.73	gold quality
medial globus pallidus	UBERON:0002477	96.71	gold quality
superficial temporal artery	UBERON:0001614	96.69	gold quality
trabecular bone tissue	UBERON:0002483	96.68	gold quality
palpebral conjunctiva	UBERON:0001812	96.67	gold quality
gingival epithelium	UBERON:0001949	96.67	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	35.50
E-CURD-122	yes	23.98
E-HCAD-10	yes	17.43
E-MTAB-6379	no	459.59
E-ENAD-17	no	188.01
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

55 targets.

Target	Regulation
BRD7	Unknown
CAT
CCNB1	Repression
CCND1	Activation
CCND2
CD74
CD80
CDKN1B
CEBPA
CEBPD
CHI3L1	Activation
CSF3R
CXCR4	Activation
DDIT3
DDR2
FASLG	Unknown
FMR1
GADD45A
GNG3
GPT
HNRNPU
ID2
IL6
MAPK1
MAX
MIR22
MLXIPL	Activation
MXD1
MYC	Unknown
MYCT1

JASPAR motifs

Motif	Name	Family
MA0058.1	MAX	bHLH-ZIP
MA0058.2	MAX	bHLH-ZIP
MA0058.3	MAX	bHLH-ZIP
MA0058.4	MAX	bHLH-ZIP
MA0059.1	MAX::MYC	bHLH-ZIP
MA0059.2	MAX::MYC	bHLH-ZIP

JASPAR matrix evidence (PMIDs): PMID:8265351, PMID:22955619

Upstream regulators (CollecTRI, top): MAX, MNT, MXD1, MXI1, MYC, ZBTB16

miRNA regulators (miRDB)

8 targeting MAX, 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-4715-3P	99.98	66.03	670
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-4528	99.18	69.77	1936
HSA-MIR-4711-3P	98.97	66.87	1020
HSA-MIR-599	98.32	66.99	1037
HSA-MIR-1243	97.07	65.44	719
HSA-MIR-3654	96.43	66.55	646

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 89.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• X-ray structures of Myc-Max and Mad-Max recognizing DNA. Molecular bases of regulation by proto-oncogenic transcription factors. (PMID:12553908)
• downregulation of MYCN was reflected in a decreased MYCN/Max DNA-binding activity while the Mnt/Max binding did not change during differentiation (PMID:15258910)
• High levels of Max and stress-induced NFkappaB activation may result in elevated expression of Fas ligand in human lung cancer cells and possibly contribute to Fas ligand-associated immune escape mechanisms. (PMID:15302589)
• C6-cer inhibited the DNA-binding function of the c-Myc/Max oncogene (PMID:16201965)
• Binding affinities & thermodynamics of dimerization of Max-Max homodimer & c-Myc-Max & Mad-Max heterodimers were determined.c-Myc & Max form most stable heterodimer.Polylysine had little effect, polyglutamic acid stabilized both heterodimers & homodimers. (PMID:16475822)
• Max as a novel co-activator of C/EBPalpha functions, thereby suggesting a possible link between C/EBPalpha and Myc-Max-Mad network. (PMID:17082780)
• results uncover novel post-translational modifications of Max and suggest the potential regulation of specific Max complexes by p300 and reversible acetylation (PMID:17217336)
• The switch from Mnt-Max to Myc-Max during bile duct ligation (cholestasis) and in hepatocytes treated with lithocholic acid is responsible for the induction in p53 and cyclin D1 expression and contributes to apoptosis. (PMID:19086036)
• Enforced miR-22 expression presumably lowers Max levels available for Myc binding, which differentially influenced the transcription of downstream targets of the Myc-Max complex. (PMID:20214878)
• The transcription factors Max and RXRalpha bind directly to the miR-193a promoter and inhibit miR-193a expression during transformation, thereby activating the PLAU and K-Ras oncogenes. (PMID:21670079)
• MAX mutations are associated with hereditary pheochromocytoma. (PMID:21685915)
• The E-box binding factors Max/Mnt, MITF, and USF1 act coordinately with FoxO to regulate expression of proapoptotic and cell cycle control genes by phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3 signaling. (PMID:21873430)
• Genetic variants in MAX does not contribute to the development of Lynch syndrome. (PMID:22086303)
• Max b-HLH-LZ can transduce into cells and inhibit c-Myc transcriptional activities (PMID:22384171)
• germline mutations in MAX are responsible for 1.12% of hereditary and sporadic pheochromocytoma and paraganglioma in patients without evidence of other known mutations (PMID:22452945)
• Data show that Sirt1, p53, and p38(MAPK) are involved in the detrimental phenotype of Max-null ESCs. Analyses revealed these proteins are involved at varying levels to one another in the hierarchy of the pathway leading to cell death in Max-null ESCs. (PMID:22696478)
• New structural determinants for c-Myc specific heterodimerization with Max and development of a novel homodimeric c-Myc b-HLH-LZ. (PMID:22733550)
• Delta Max, but not full-length Max, rescues Myc-dependent glycolytic gene expression upon induced EGFRvIII loss, and correlates with hnRNPA1 expression and downstream Myc-dependent gene transcription in patients. (PMID:23707073)
• MAX mutations remain unusual events in Swedish patients with pheochromocytoma and paraganglioma tumours. (PMID:23743562)
• Genetic and molecular findings provide powerful evidence that MAX is a tumor-suppressor gene involved in SCLC development. (PMID:24362264)
• Myc and its obligate heterodimeric partner, Max, are integral to the coordinated recruitment and post-translational modification of components of the core transcriptional machinery. (PMID:24657798)
• Max mutation is associated with pheochromocytomas and paragangliomas. (PMID:24676840)
• Here we review the activities of MYC, MNT and other MAX interacting proteins in the setting of T and B cell activation and oncogenesis (PMID:24731854)
• MYC is part of a network of bHLHLZ proteins centered on the MYC heterodimeric partner MAX and its counterpart, the MAX-like protein MLX. (PMID:24857747)
• Hypoxia reduces MAX expression in endothelial cells by unproductive splicing (PMID:25451222)
• We confirmed that these dimeric inhibitors directly bind to Myc blocking its interaction with Max and affect transcription of MYC dependent genes. (PMID:25875098)
• The introduction of wild-type MAX cDNA into PC12 cells significantly decreased MYC’s ability to bind to canonical E-boxes, while pathogenic MAX proteins were not able to fully repress MYC activity. Further clinical and molecular evaluation of variant carriers corroborated the results obtained with the functional assessment. (PMID:26070438)
• Celastrol and some of its quinone methidecontaining analogs directly inhibit c-Myc-Max heterodimers in tumor cells. (PMID:26474287)
• In addition, loss of function mutation of the MAX gene was identified for the first time in GIST, and a broader role for MAX in GIST progression was suggested. mechanism for a subset of sporadic gastrointestinal stromal tumors (PMID:26555092)
• our results confirm that MAX is a tumor suppressor gene for renal oncocytomas (PMID:26670126)
• To our knowledge, this is the first report of an association between dysregulation of the MAX-MYC network in the brain and a behavior, suggesting a novel approach for exploiting the neuroplasticity associated with depression (PMID:27727240)
• The mechanism of inhibition of c-Myc transcriptional activity by Miz-1 that binds c-Myc while competing for binding with Max has been described. (PMID:27859590)
• evidence that MAX can ‘sense’ the oxidation status of 5mCpGs, and that cancer-associated mutations in MAX differentially affect binding to these features (PMID:27903915)
• MAX inactivation is a common event in GIST progression, fostering cell cycle activity in early GISTs. (PMID:28270683)
• These results suggest that the wild type Max homodimer is important for attenuating the binding of c-Myc to specific and non-specific DNA, whereas alternative splicing (e.g. DeltaMax) is unable to do so. Conversely, the splicing of Max into DeltaMax could provoke an increase in overall chromatin bound c-Myc. (PMID:28350847)
• The SDHA, TMEM127, MAX, and SDHAF2 genes contribute to hereditary pheochromocytoma and paraganglioma. (PMID:28384794)
• Sequence-specific DNA binding by MYC/MAX to low-affinity non-E-box motifs (PMID:28719624)
• Importance of MAX mutations in Endometrial cancer, pointing to increased vascularity as one mechanism contributing to clinical aggressiveness of endometrial cancer. (PMID:29155953)
• MAX to MYCN ratio that can account for tumour progression and clinical outcome in neuroblastoma. (PMID:29408445)
• Using isothermal calorimetry, the study found that Myc phosphorylation destabilizes this ternary protein-DNA complex by decreasing Myc’s affinity for Max by 2 orders of magnitude, suggesting a major effect of phosphorylation on this complex. (PMID:29695509)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	max	ENSDARG00000024844
mus_musculus	Max	ENSMUSG00000059436
rattus_norvegicus	Max	ENSRNOG00000008049
drosophila_melanogaster	Max	FBGN0017578
caenorhabditis_elegans		WBGENE00003509
caenorhabditis_elegans		WBGENE00003511

Protein

Protein identifiers

Protein max — P61244 (reviewed: P61244)

Alternative names: Class D basic helix-loop-helix protein 4, Myc-associated factor X

All UniProt accessions (9): P61244, A0A494C130, G3V2N4, G3V2R5, G3V302, G3V563, G3V570, G3V5L1, Q6V3B1

UniProt curated annotations — full annotation on UniProt →

Function. Transcription regulator. Forms a sequence-specific DNA-binding protein complex with MYC or MAD which recognizes the core sequence 5’-CAC[GA]TG-3’. The MYC:MAX complex is a transcriptional activator, whereas the MAD:MAX complex is a repressor. May repress transcription via the recruitment of a chromatin remodeling complex containing H3 ‘Lys-9’ histone methyltransferase activity. Represses MYC transcriptional activity from E-box elements.

Subunit / interactions. Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a heterodimer with MYC or MAD. Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EUHMTASE1, RING1, RNF2, MBLR, L3MBTL2 and YAF2. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BACC1, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Interacts with SPAG9. The heterodimer MYC:MAX interacts with ABI1; the interaction may enhance MYC:MAX transcriptional activity.

Subcellular location. Nucleus. Cell projection. Dendrite.

Tissue specificity. High levels found in the brain, heart and lung while lower levels are seen in the liver, kidney and skeletal muscle.

Post-translational modifications. Reversible lysine acetylation might regulate the nuclear-cytoplasmic shuttling of specific Max complexes.

Disease relevance. Pheochromocytoma (PCC) [MIM:171300] A catecholamine-producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent. Disease susceptibility is associated with variants affecting the gene represented in this entry. Polydactyly-macrocephaly syndrome (PDMCS) [MIM:620712] An autosomal dominant syndrome characterized by progressive macrocephaly and post-axial polydactyly, a condition defined by the occurrence of supernumerary digits affecting the fifth finger and/or toe. Additional variable features include ocular anomalies, global developmental delay and autistic traits. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the MAX family.

Isoforms (6)

UniProt ID	Names	Canonical?
P61244-1	1, Long	yes
P61244-2	2, Short
P61244-3	3, Delta-Max
P61244-4	4
P61244-5	5
P61244-6	6

RefSeq proteins (28): NP_001257997, NP_001257998, NP_001307344, NP_001394023, NP_001394024, NP_001394025, NP_001394026, NP_001394027, NP_001394028, NP_001394029, NP_001394030, NP_001394031, NP_001394032, NP_001394033, NP_001394034, NP_001394035, NP_001394036, NP_001394037, NP_001394038, NP_001394039, NP_001394040, NP_001394041, NP_001394042, NP_002373, NP_660087, NP_660088, NP_660089, NP_932061 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011598	bHLH_dom	Domain
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily

Pfam: PF00010

UniProt features (53 total): sequence variant 17, modified residue 10, mutagenesis site 6, splice variant 5, region of interest 3, helix 3, compositionally biased region 3, initiator methionine 2, chain 1, domain 1, turn 1, short sequence motif 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
6G6K	X-RAY DIFFRACTION	1.35
1NKP	X-RAY DIFFRACTION	1.8
1NLW	X-RAY DIFFRACTION	2
6G6L	X-RAY DIFFRACTION	2.2
6G6J	X-RAY DIFFRACTION	2.25
5EYO	X-RAY DIFFRACTION	2.39
7RCU	X-RAY DIFFRACTION	2.69
1HLO	X-RAY DIFFRACTION	2.8
1AN2	X-RAY DIFFRACTION	2.9
8OTS	ELECTRON MICROSCOPY	3.3
8OTT	ELECTRON MICROSCOPY	3.3
1R05	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P61244-F1	82.07	0.55

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 (10): 2, 2, 11, 66, 107, 153, 154, 2, 2, 11

Mutagenesis-validated functional residues (6):

Position	Phenotype
66	kept nuclear localization. loss of nuclear localization; when associated with q-153 and q-154.
66	loss of acetylation, kept nuclear localization; when associated with r-153 and r-154.
153	loss of nuclear localization; when associated with q-66 and q-154. kept nuclear localization; when associated with q-154
153	loss of acetylation, kept nuclear localization; when associated with r-66 and r-154.
154	loss of nuclear localization; when associated with q-66 and q-153. kept nuclear localization; when associated with q-153
154	loss of acetylation, kept nuclear localization; when associated with r-66 and r-153.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-1362277	Transcription of E2F targets under negative control by DREAM complex
R-HSA-69202	Cyclin E associated events during G1/S transition
R-HSA-69656	Cyclin A:Cdk2-associated events at S phase entry
R-HSA-8953750	Transcriptional Regulation by E2F6
R-HSA-1538133	G0 and Early G1
R-HSA-1640170	Cell Cycle
R-HSA-212436	Generic Transcription Pathway
R-HSA-453279	Mitotic G1 phase and G1/S transition
R-HSA-69206	G1/S Transition
R-HSA-69242	S Phase
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 0 (showing top):

GO Biological Process (5): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (12): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), identical protein binding (GO:0042802), protein dimerization activity (GO:0046983), E-box binding (GO:0070888), DNA-binding transcription factor binding (GO:0140297), sequence-specific double-stranded DNA binding (GO:1990837), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), protein binding (GO:0005515)

GO Cellular Component (10): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), dendrite (GO:0030425), protein-DNA complex (GO:0032993), Mad-Max complex (GO:0070443), MLL1 complex (GO:0071339), Myc-Max complex (GO:0071943), RNA polymerase II transcription regulator complex (GO:0090575), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Mitotic G1 phase and G1/S transition	2
Cell Cycle, Mitotic	2
G0 and Early G1	1
G1/S Transition	1
S Phase	1
Generic Transcription Pathway	1
RNA Polymerase II Transcription	1
Cell Cycle	1
Gene expression (Transcription)	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
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
DNA-templated transcription	2
transcription cis-regulatory region binding	2
protein binding	2
negative regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	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
nucleic acid binding	1
transcription regulator activity	1
RNA polymerase II cis-regulatory region sequence-specific DNA binding	1
transcription factor binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
neuron projection	1
dendritic tree	1
protein-containing complex	1
RNA polymerase II transcription repressor complex	1
MLL1/2 complex	1
RNA polymerase II transcription regulator complex	1
transcription regulator complex	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

252 interactions, top by confidence:

A	B	Type	Score
MAX	MYC	psi-mi:“MI:2364”(proximity)	0.980
MAX	MYC	psi-mi:“MI:0914”(association)	0.980
MYC	MAX	psi-mi:“MI:2364”(proximity)	0.980
MAX	MYC	psi-mi:“MI:0915”(physical association)	0.980
MYC	MAX	psi-mi:“MI:0915”(physical association)	0.980
MYC	MAX	psi-mi:“MI:0914”(association)	0.980
MAX	MXI1	psi-mi:“MI:0915”(physical association)	0.900
MXI1	MAX	psi-mi:“MI:0915”(physical association)	0.900
PRDM14	CBFA2T2	psi-mi:“MI:0914”(association)	0.860
L3MBTL2	MAX	psi-mi:“MI:0915”(physical association)	0.850

BioGRID (529): USP37 (Affinity Capture-Western), MAX (Affinity Capture-MS), MXI1 (Two-hybrid), BANP (Two-hybrid), UNC45A (Two-hybrid), MAX (Affinity Capture-MS), PLEKHF2 (Two-hybrid), MXI1 (Two-hybrid), MAX (Affinity Capture-Western), MAX (Reconstituted Complex), MXD1 (Reconstituted Complex), MAX (Affinity Capture-MS), MAX (Affinity Capture-MS), MAX (Affinity Capture-MS), MAX (Co-localization)

ESM2 similar proteins: A4IGK3, B7ZAP0, O08609, O54941, O55047, O60519, P18847, P26801, P28574, P29596, P37285, P52161, P52162, P52164, P60762, P61244, P61245, P97875, Q07016, Q07866, Q08CW1, Q08DJ0, Q0VCP9, Q0VD32, Q13330, Q28772, Q2KII1, Q32KT0, Q32M00, Q3T0B9, Q56A18, Q5BJU6, Q5R581, Q5ZIL4, Q60765, Q62599, Q642H2, Q6PH81, Q78E65, Q7TMY4

Diamond homologs: A1YG22, A2T7L5, B8XIA5, P01106, P01108, P01109, P01110, P03966, P04198, P06171, P06295, P06646, P09416, P0C0N8, P0C0N9, P10166, P10395, P12523, P12524, P15063, P15171, P18444, P20389, P21438, P22555, P23583, P23999, P24793, P26014, P28574, P49032, P49033, P49709, P52160, P52161, P52162, P52164, P61244, P61245, P68271

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
MAX	“up-regulates activity”	MXD4	binding
MAX	“up-regulates activity”	MGA	binding
MAX	“up-regulates activity”	MXI1	binding
MAX	“up-regulates activity”	MNT	binding
MAX	“up-regulates activity”	MAD1L1	binding
MAX	“up-regulates activity”	MXD3	binding
MAPK14	down-regulates	MAX	phosphorylation
CSNK2A1	down-regulates	MAX	phosphorylation
MAX	up-regulates	MYC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 149 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
Transcriptional Regulation by E2F6	7	19.2×	3e-05
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	5	14.0×	2e-03
AURKA Activation by TPX2	6	8.5×	5e-03
Regulation of PLK1 Activity at G2/M Transition	7	8.3×	2e-03
Cellular responses to stress	11	3.8×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of double-strand break repair via homologous recombination	6	16.5×	3e-04
regulation of DNA repair	6	11.9×	1e-03
cellular response to UV	5	10.6×	8e-03
positive regulation of miRNA transcription	5	10.4×	8e-03
regulation of cell cycle	11	5.9×	4e-04
chromatin remodeling	9	4.7×	9e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 8 cancer types — BRCA, GIST, LGGNOS, MBL, PAST, PCM, SIC, UCEC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	33
Likely pathogenic	9
Uncertain significance	279
Likely benign	185
Benign	28

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1436106	NM_002382.5(MAX):c.205_206del (p.Glu69fs)	Pathogenic
1454157	NM_002382.5(MAX):c.91del (p.Leu31fs)	Pathogenic
1458939	NM_002382.5(MAX):c.295+1G>T	Pathogenic
1778793	NM_002382.5(MAX):c.172-2A>G	Pathogenic
1779169	NM_002382.5(MAX):c.173del (p.Ala58fs)	Pathogenic
1791462	NM_002382.5(MAX):c.244C>T (p.Gln82Ter)	Pathogenic
1795169	NM_002382.5(MAX):c.271C>T (p.Gln91Ter)	Pathogenic
186993	NM_002382.5(MAX):c.295+1G>A	Pathogenic
2125867	NM_002382.5(MAX):c.183_195del (p.Gln62fs)	Pathogenic
232919	NM_002382.5(MAX):c.320C>A (p.Ser107Ter)	Pathogenic
2568116	NM_002382.5(MAX):c.210T>G (p.Tyr70Ter)	Pathogenic
2709522	NM_002382.5(MAX):c.37_38del (p.Glu13fs)	Pathogenic
2851942	NM_002382.5(MAX):c.234_235dup (p.His79fs)	Pathogenic
29785	NM_002382.5(MAX):c.1A>G (p.Met1Val)	Pathogenic
29786	NM_002382.5(MAX):c.223C>T (p.Arg75Ter)	Pathogenic
3222151	NM_002382.5(MAX):c.124dup (p.Ser42fs)	Pathogenic
3243969	NC_000014.8:g.(?65543194)(65569057_?)del	Pathogenic
3243970	NC_000014.8:g.(?65543194)(65544764_?)del	Pathogenic
3543698	NM_002382.5(MAX):c.179_182dup (p.Gln62fs)	Pathogenic
3543700	NM_002382.5(MAX):c.171+2T>G	Pathogenic
3644266	NM_002382.5(MAX):c.112del (p.His38fs)	Pathogenic
404110	NM_002382.5(MAX):c.211_221del (p.Ile71fs)	Pathogenic
4731849	NM_145112.3(MAX):c.36+732del	Pathogenic
4759298	NM_002382.5(MAX):c.146C>G (p.Ser49Ter)	Pathogenic
480770	NM_002382.5(MAX):c.98dup (p.Arg35fs)	Pathogenic
532507	NM_002382.5(MAX):c.219T>A (p.Tyr73Ter)	Pathogenic
532511	NM_002382.5(MAX):c.228del (p.Asn78fs)	Pathogenic
652863	NM_002382.5(MAX):c.120del (p.Asp41fs)	Pathogenic
658608	NM_002382.5(MAX):c.289C>T (p.Gln97Ter)	Pathogenic
821060	NM_002382.5(MAX):c.22G>T (p.Glu8Ter)	Pathogenic

SpliceAI

3273 predictions. Top by Δscore:

Variant	Effect	Δscore
14:65011739:G:GT	donor_gain	1.0000
14:65011775:GGGCT:G	donor_gain	1.0000
14:65011776:GGCTG:G	donor_gain	1.0000
14:65012316:GGCTT:G	acceptor_gain	1.0000
14:65012385:ATGAG:A	donor_loss	1.0000
14:65012386:TGAG:T	donor_loss	1.0000
14:65012387:GAGGT:G	donor_loss	1.0000
14:65012388:AG:A	donor_loss	1.0000
14:65012388:AGGTA:A	donor_loss	1.0000
14:65012389:GGTAA:G	donor_loss	1.0000
14:65012390:G:GA	donor_loss	1.0000
14:65012390:GT:G	donor_loss	1.0000
14:65012391:T:A	donor_loss	1.0000
14:65015715:GA:G	donor_gain	1.0000
14:65015717:G:GG	donor_gain	1.0000
14:65027438:T:TA	acceptor_gain	1.0000
14:65027451:A:AG	acceptor_gain	1.0000
14:65027452:G:GG	acceptor_gain	1.0000
14:65027452:GTGT:G	acceptor_gain	1.0000
14:65032608:A:AG	acceptor_gain	1.0000
14:65032609:G:GG	acceptor_gain	1.0000
14:65040785:CTTA:C	acceptor_loss	1.0000
14:65040786:TTA:T	acceptor_loss	1.0000
14:65040787:TAG:T	acceptor_loss	1.0000
14:65040787:TAGGT:T	acceptor_loss	1.0000
14:65040788:A:AG	acceptor_gain	1.0000
14:65040789:G:GG	acceptor_gain	1.0000
14:65040789:G:GT	acceptor_loss	1.0000
14:65040789:GGT:G	acceptor_gain	1.0000
14:65040915:TATTA:T	donor_gain	1.0000

AlphaMissense

1066 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:65077915:T:G	Q98P	1.000
14:65077924:A:G	L95P	1.000
14:65077936:T:G	Q91P	1.000
14:65077945:A:G	L88P	1.000
14:65077945:A:T	L88H	1.000
14:65077984:C:G	R75P	1.000
14:65077996:A:C	I71S	1.000
14:65077996:A:G	I71T	1.000
14:65077996:A:T	I71N	1.000
14:65078008:G:T	A67D	1.000
14:65078009:C:G	A67P	1.000
14:65078017:A:C	L64R	1.000
14:65078017:A:G	L64P	1.000
14:65078017:A:T	L64Q	1.000
14:65078020:A:C	I63S	1.000
14:65078020:A:G	I63T	1.000
14:65078020:A:T	I63N	1.000
14:65078021:T:A	I63F	1.000
14:65078026:G:T	A61D	1.000
14:65078027:C:G	A61P	1.000
14:65078029:C:A	R60L	1.000
14:65078029:C:G	R60P	1.000
14:65078029:C:T	R60Q	1.000
14:65078030:G:A	R60W	1.000
14:65078030:G:C	R60G	1.000
14:65078032:G:A	S59F	1.000
14:65078032:G:T	S59Y	1.000
14:65093727:G:T	P51Q	1.000
14:65093730:A:T	V50D	1.000
14:65093734:A:G	S49P	1.000

dbSNP variants (sampled 300 via entrez): RS1000004064 (14:65102517 T>C), RS1000009374 (14:65039915 G>A), RS1000029483 (14:65011742 A>G,T), RS1000089134 (14:65059549 ATTGTT>A), RS1000120893 (14:65061045 T>C), RS1000162937 (14:65037376 T>A,C,G), RS1000173519 (14:65052765 T>C), RS1000174220 (14:65095250 C>A), RS1000182871 (14:65073799 C>T), RS1000225434 (14:65013556 C>G,T), RS1000232677 (14:65088099 G>A), RS1000283969 (14:65045926 A>C,T), RS1000308802 (14:65082101 C>T), RS1000323746 (14:65033911 C>T), RS1000331368 (14:65058382 A>T)

Disease associations

OMIM: gene MIM:154950 | disease phenotypes: MIM:168000, MIM:171300, MIM:620712

GenCC curated gene-disease

Disease	Classification	Inheritance
pheochromocytoma	Definitive	Autosomal dominant
hereditary pheochromocytoma-paraganglioma	Definitive	Autosomal dominant
syndromic disease	Strong	Autosomal dominant
polydactyly-macrocephaly syndrome	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
hereditary pheochromocytoma-paraganglioma	Definitive	AD

Mondo (6): hereditary neoplastic syndrome (MONDO:0015356), hereditary pheochromocytoma-paraganglioma (MONDO:0017366), pheochromocytoma (MONDO:0008233), polydactyly-macrocephaly syndrome (MONDO:0958227), retinoblastoma (MONDO:0008380), syndromic disease (MONDO:0002254)

Orphanet (3): Inherited cancer-predisposing syndrome (Orphanet:140162), Hereditary pheochromocytoma-paraganglioma (Orphanet:29072), Retinoblastoma (Orphanet:790)

HPO phenotypes

70 total (30 of 70 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000047	Hypospadias
HP:0000093	Proteinuria
HP:0000096	Glomerular sclerosis
HP:0000104	Renal agenesis
HP:0000256	Macrocephaly
HP:0000405	Conductive hearing impairment
HP:0000518	Cataract
HP:0000519	Developmental cataract
HP:0000526	Aniridia
HP:0000567	Chorioretinal coloboma
HP:0000568	Microphthalmia
HP:0000729	Autistic behavior
HP:0000740	Episodic paroxysmal anxiety
HP:0000768	Pectus carinatum
HP:0000790	Hematuria
HP:0000875	Episodic hypertension
HP:0000957	Cafe-au-lait spot
HP:0000975	Hyperhidrosis
HP:0000980	Pallor
HP:0001028	Hemangioma
HP:0001069	Episodic hyperhidrosis
HP:0001095	Hypertensive retinopathy
HP:0001162	Postaxial hand polydactyly
HP:0001195	Single umbilical artery
HP:0001263	Global developmental delay
HP:0001293	Cranial nerve compression
HP:0001337	Tremor
HP:0001342	Cerebral hemorrhage
HP:0001605	Vocal cord paralysis

GWAS associations

37 associations (top):

Study	Trait	p-value
GCST000327_10	Anthropometric traits	4.000000e-06
GCST001762_791	Obesity-related traits	4.000000e-07
GCST001765_13	Red blood cell traits	2.000000e-12
GCST002040_9	Blood trace element (Zn levels)	1.000000e-07
GCST004599_165	Mean platelet volume	7.000000e-12
GCST004601_174	Red blood cell count	2.000000e-14
GCST004602_204	Mean corpuscular volume	4.000000e-52
GCST004603_134	Platelet count	1.000000e-11
GCST004605_3	Mean corpuscular hemoglobin concentration	9.000000e-26
GCST004630_200	Mean corpuscular hemoglobin	2.000000e-74
GCST005992_18	Mean corpuscular hemoglobin concentration	2.000000e-11
GCST006585_2699	Blood protein levels	3.000000e-06
GCST008839_293	Height	8.000000e-10
GCST010083_251	Hemoglobin levels	1.000000e-11
GCST90000025_537	Appendicular lean mass	1.000000e-23
GCST90002381_601	Eosinophil count	4.000000e-10
GCST90002382_225	Eosinophil percentage of white cells	6.000000e-10
GCST90002384_340	Hemoglobin	4.000000e-11
GCST90002385_28	High light scatter reticulocyte count	2.000000e-22
GCST90002386_172	High light scatter reticulocyte percentage of red cells	2.000000e-30
GCST90002387_144	Immature fraction of reticulocytes	1.000000e-14
GCST90002390_265	Mean corpuscular hemoglobin	2.000000e-140
GCST90002390_266	Mean corpuscular hemoglobin	4.000000e-27
GCST90002391_143	Mean corpuscular hemoglobin concentration	4.000000e-16
GCST90002391_144	Mean corpuscular hemoglobin concentration	8.000000e-35
GCST90002392_452	Mean corpuscular volume	3.000000e-26
GCST90002392_453	Mean corpuscular volume	1.000000e-12
GCST90002392_454	Mean corpuscular volume	9.000000e-12
GCST90002395_201	Mean platelet volume	2.000000e-23
GCST90002396_567	Mean reticulocyte volume	3.000000e-16

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0004302	anthropometric measurement
EFO:0005188	CCL11 measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0004305	erythrocyte count
EFO:0004309	platelet count
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0004509	hemoglobin measurement
EFO:0004980	appendicular lean mass
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0007986	reticulocyte count
EFO:0010701	mean reticulocyte volume
EFO:0004833	neutrophil count

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D010673	Pheochromocytoma	C04.557.465.625.650.700.725; C04.557.580.625.650.700.725
D012175	Retinoblastoma	C04.557.465.625.600.725; C04.557.470.670.725; C04.557.580.625.600.725; C04.588.364.818.760; C11.270.862; C11.319.475.760; C11.768.717.760
D013577	Syndrome	C23.550.288.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL1250363 (SINGLE PROTEIN), CHEMBL3301395 (PROTEIN COMPLEX), CHEMBL4106127 (PROTEIN-PROTEIN INTERACTION)

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

ChEMBL bioactivities

10 potent at pChembl≥5 of 51 total, top 9 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.19	Kd	6.5	nM	CHEMBL4238599
7.87	Kd	13.4	nM	CHEMBL4238599
5.75	IC50	1800	nM	CHEMBL4796663
5.39	IC50	4100	nM	CHEMBL201467
5.34	IC50	4600	nM	CHEMBL4093782
5.25	IC50	5600	nM	CHEMBL3427016
5.19	IC50	6500	nM	CHEMBL4086023
5.05	IC50	8900	nM	CHEMBL4467662
5.00	IC50	1e+04	nM	CHEMBL4103943

PubChem BioAssay actives

5 with measured affinity, of 206 total; 4 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
4-[2-(furan-2-yl)-6-(4-nitrophenyl)-4-pyridinyl]benzamide	2001631: Inhibition of c-Myc to Max protein dimerization (unknown origin) by fluorescence polarization assay	kd	0.0065	uM
benzo[a]phenazin-5-ol	2074198: Binding affinity to MYC/MAX (unknown origin) by PCA analysis	ic50	1.8000	uM
4-[[4-[(2-ethoxy-2-oxoacetyl)amino]-3-(2-methylpropoxy)benzoyl]amino]-3-(2-methylpropoxy)benzoic acid	1205230: Disruption of human recombinant c-Myc-Max/DNA (unknown origin) binding assessed as complex level by electrophoretic mobility shift assay relative to control	ic50	5.6000	uM
1-benzyl-3-[3,5-bis(trifluoromethyl)phenyl]thiourea	1585071: Inhibition of Myc-Max (unknown origin) expressed in human LNCAP cells assessed as reduction in transcriptional activity after 1 day by luciferase reporter gene assay	ic50	8.9000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
Estradiol	increases expression, increases reaction	4
Copper	affects binding, increases expression	2
FR900359	increases phosphorylation	1
beta-lapachone	decreases expression, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
perfluorooctane sulfonic acid	increases expression	1
4-methoxycinnamate methyl ester	decreases expression, increases reaction	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, decreases reaction	1
dorsomorphin	affects cotreatment, increases expression	1
NSC 689534	affects binding, increases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	increases expression	1
Arsenic Trioxide	affects methylation, decreases expression	1
Fulvestrant	increases methylation	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	increases expression	1
Vehicle Emissions	decreases expression, decreases reaction	1
Chelating Agents	affects binding, increases expression	1
Coumestrol	increases expression	1
Doxorubicin	decreases expression	1
Drugs, Chinese Herbal	decreases expression, increases reaction	1
Endosulfan	increases expression	1
Lead	increases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Methylnitronitrosoguanidine	increases expression	1

ChEMBL screening assays

97 unique, capped per target: 97 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2318155	Binding	Inhibition of His6-tagged Max (151 amino acid residues) (unknown origin) assessed as disruption of Max-Max dimerization by electrophoretic mobility shift assay	Pharmacophore identification of c-Myc inhibitor 10074-G5. — Bioorg Med Chem Lett

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A4A4	SEES3-1V human MAX, clone1	Embryonic stem cell	Male
CVCL_A4A5	SEES3-1V human MAX, clone2	Embryonic stem cell	Male
CVCL_A4A6	SEES3-1V human MAX, clone3	Embryonic stem cell	Male
CVCL_A656	MZ-CRC-1	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01379898	PHASE4	COMPLETED	Phenoxybenzamine Versus Doxazosin in PCC Patients
NCT01959711	PHASE4	COMPLETED	Randomized Clinical Trial of Posterior Retroperitoneoscopic Adrenalectomy Versus Lateral Laparoscopic Adrenalectomy
NCT05702944	PHASE4	RECRUITING	The Effect and Safety of Omitting Preoperative Alpha-adrenergic Blockade for Normotensive Pheochromocytoma
NCT00002641	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Soft Tissue Sarcoma
NCT00002764	PHASE3	COMPLETED	Surgery With or Without Combination Chemotherapy in Treating Patients With Lung Metastases From Soft Tissue Sarcoma
NCT00126412	PHASE3	COMPLETED	Meta-Iodobenzylguanidine (123I mIBG) Scintigraphy in Patients Being Evaluated for Phaeochromocytoma or Neuroblastoma
NCT01373736	PHASE3	UNKNOWN	123I-MIBG Scintigraphy in Patients Being Evaluated for Neuroendocrine Tumors
NCT03176693	PHASE3	COMPLETED	Preoperative Alpha Blockade for Pheochromocytoma
NCT00002608	PHASE2	COMPLETED	Combination Chemotherapy and Tamoxifen in Treating Patients With Solid Tumors
NCT00028106	PHASE2	COMPLETED	131MIBG to Treat Malignant Pheochromocytoma
NCT00107289	PHASE2	RECRUITING	Iodine I 131 Metaiodobenzylguanidine in Treating Patients With Recurrent, Progressive, or Refractory Neuroblastoma or Malignant Pheochromocytoma or Paraganglioma
NCT00466856	PHASE2	TERMINATED	Internal Radiation Therapy in Treating Patients With Liver Metastases From Neuroendocrine Tumors
NCT00843037	PHASE2	COMPLETED	Study Of Sunitinib In Patients With Recurrent Paraganglioma/Pheochromocytoma
NCT00874614	PHASE2	UNKNOWN	A Study Evaluating Ultratrace Iobenguane I131 in Patients With Malignant Relapsed/Refractory Pheochromocytoma/Paraganglioma
NCT00923481	PHASE2	COMPLETED	A Broad Multi-histology Phase II Study of the Multi-Kinase Inhibitor R935788 (Fostamatinib Disodium) in Advanced Colorectal, Non-small Cell Lung, Head and Neck Hepatocellular and Renal Cell Carcinomas, and Pheochromocytoma and Thyroid Tumors (Multi-H…
NCT01152827	PHASE2	COMPLETED	RAD001 in Pheochromocytoma or Nonfunctioning Carcinoid
NCT01413503	PHASE2	COMPLETED	A Phase II Study of 131I- Metaiodobenzylguanidine (MIBG) for Treatment of Metastatic or Unresectable Pheochromocytoma and Related Tumors
NCT01635907	PHASE2	COMPLETED	Dovitinib in Neuroendocrine Tumors
NCT01967576	PHASE2	COMPLETED	Phase II Study of Axitinib (AG-013736) With Evaluation of the VEGF-pathway in Metastatic, Recurrent or Primary Unresectable Pheochromocytoma/Paraganglioma
NCT03165721	PHASE2	TERMINATED	A Phase II Trial of the DNA Methyl Transferase Inhibitor, Guadecitabine (SGI-110), in Children and Adults With Wild Type GIST,Pheochromocytoma and Paraganglioma Associated With Succinate Dehydrogenase Deficiency and HLRCC-associated Kidney Cancer
NCT03206060	PHASE2	RECRUITING	Lu-177-DOTATATE (Lutathera) in Therapy of Inoperable Pheochromocytoma/ Paraganglioma
NCT03839498	PHASE2	ACTIVE_NOT_RECRUITING	Study of Axitinib (AG-013736) With Evaluation of the VEGF-pathway in Pheochromocytoma/Paraganglioma
NCT03946527	PHASE2	ACTIVE_NOT_RECRUITING	LAnreotide in Metastatic Pheochromocytoma / PARAganglioma (LAMPARA)
NCT04276597	PHASE2	WITHDRAWN	Phase-II Study of Lu177DOTATOC in Adults With STTR(+)Pulmonary, Pheochromocytoma, Paraganglioma, Unknown Primary, Thymus NETs (PUTNET), or Any Other Non-.GEP-NET.
NCT04320589	PHASE2	COMPLETED	the Effect of Dexmedetomidine and Magnesium Sulfate in Open Resection of Pheochromocytoma
NCT04400474	PHASE2	COMPLETED	Trial of Cabozantinib Plus Atezolizumab in Advanced and Progressive Neoplasms of the Endocrine System. The CABATEN Study
NCT04711135	PHASE2	ACTIVE_NOT_RECRUITING	Study to Evaluate Safety and Dosimetry of Lutathera in Adolescent Patients With GEP-NETs and PPGLs
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