MYC Gene Complete Identifier and Functional Mapping Reference

Provide a comprehensive cross-database identifier and functional mapping reference for human MYC — a definitive lookup resource covering: ### Section …

Provide a comprehensive cross-database identifier and functional mapping reference for human MYC — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene MYC, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene MYC, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene MYC protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene MYC protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene MYC, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene MYC, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene MYC, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene MYC protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene MYC, summarize transcription factor regulatory data. If MYC is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate MYC — names with evidence type (ChIP-seq / predicted / experimentally validated) If MYC is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene MYC protein as a drug target, summarize pharmacology data. If MYC is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If MYC is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene MYC, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene MYC, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in MYC: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations

MYC

Executive summary

MYC (HGNC:7553; chr8q24.21) encodes the Myc proto-oncogene protein, a bHLH-ZIP transcription factor that is one of the most broadly important oncogenes in human biology, driving cell proliferation, differentiation, and apoptosis across virtually all tissue types. It is most strongly implicated in Burkitt lymphoma through direct mutation, and GWAS signals at the 8q24 locus associate the region with colorectal, prostate, breast, and bladder cancers as well as asthma. MYC functions obligately as a heterodimer with MAX, binding E-box sequences to regulate at least 1,124 target genes — including key cell-cycle regulators such as CDKN1A, CDKN2A, CDK4, and CCND1 — and sits at the hub of a protein interaction network exceeding 14,000 STRING connections. The AlphaFold model carries a low global pLDDT of 61.38 (only 21% high-confidence), reflecting extensive intrinsic disorder consistent with its transcription-factor biology. Therapeutic targeting remains challenging: the most advanced MYC-directed clinical agents are indirect BET inhibitors such as EZOBRESIB (phase 2), with direct MYC inhibitors still largely preclinical.

Gene identifiers

  • HGNC ID: HGNC:7553
  • HGNC Approved Symbol: MYC
  • Ensembl Gene ID: ENSG00000136997
  • NCBI Entrez Gene ID: 4609
  • OMIM Gene/Locus ID: 190080
  • Genomic Location (GRCh38):
    • Chromosome: 8
    • Start: 127,735,434
    • End: 127,742,951
    • Strand: +

Transcript identifiers

Ensembl Transcripts: 15 total

Transcript IDBiotypeStartEnd
ENST00000259523protein_coding127,735,434127,740,477
ENST00000377970protein_coding127,736,084127,741,434
ENST00000517291protein_coding127,735,519127,738,772
ENST00000520751protein_coding_CDS_not_defined127,736,231127,738,475
ENST00000524013protein_coding127,736,220127,741,372
ENST00000621592protein_coding127,736,231127,742,951
ENST00000641036protein_coding127,736,046127,736,612
ENST00000641252protein_coding127,735,473127,735,817
ENST00000651626protein_coding127,735,659127,741,434
ENST00000652288protein_coding127,737,621127,741,434
ENST00000707113protein_coding127,736,958127,741,434
ENST00000707114protein_coding127,737,724127,741,434
ENST00000707115protein_coding127,737,737127,741,434
ENST00000707116protein_coding127,737,745127,741,434
ENST00000707117protein_coding_CDS_not_defined127,739,073127,741,434

RefSeq mRNA Accessions: 9 total

NM IDMANE Select
NM_001177352
NM_001177353
NM_001177354
NM_001272275
NM_001354870
NM_002467
NM_010849
NM_012603
NM_080323

CCDS IDs: 2 total

  • CCDS6359
  • CCDS87627

MANE Select / Canonical Transcript Exons

Transcript: ENST00000621592 | RefSeq: NM_002467 | Exon count: 3

Exon IDStartEndLength
ENSE00003746860127,736,231127,736,623393 bp
ENSE00003475084127,738,248127,739,019771 bp
ENSE00003847400127,740,396127,742,9512,556 bp

Protein identifiers

UniProt Accessions:

  • P01106 (reviewed, canonical) — Myc proto-oncogene protein

RefSeq Protein:

  • NP_002458 (MANE select)
  • NP_001341799

Protein Domains and Families:

NameTypeID
Transcription regulator MycFamilyIPR002418
Myc family transcription factorsFamilyIPR050433
Myc-type, basic helix-loop-helix (bHLH) domainDomainIPR011598
Transcription regulator Myc, N-terminalDomainIPR012682
Leucine zipper, MycDomainIPR003327
Helix-loop-helix DNA-binding domain superfamilyHomologous superfamilyIPR036638
Domain (PFAM)PF00010
Domain (PFAM)PF01056
Domain (PFAM)PF02344
Domain (SMART)SM00353

Antibody Availability: No antibody resources are indexed in the biobtree antibody database for P01106. However, MYC/c-Myc antibodies are widely available from commercial vendors (e.g., Abcam, Sigma-Aldrich, Santa Cruz Biotechnology) but require direct vendor consultation as they are not cataloged in this database.

Structure

Experimental Structures

PDB Database: 25 structures

PDB IDTitleMethodResolution
1A93NMR solution structure of the c-Myc-Max heterodimeric leucine zipperSolution NMRN/A
1EE4Crystal structure of yeast karyopherin (importin) α with c-Myc NLS peptideX-ray Diffraction2.1 Å
1MV0NMR structure of tumor suppressor BIN1 with c-Myc interactionSolution NMRN/A
1NKPCrystal structure of Myc-Max recognizing DNAX-ray Diffraction1.8 Å
2A93NMR solution structure of c-Myc-Max heterodimeric leucine zipper (40 structures)Solution NMRN/A
2OR9Anti-c-Myc antibody 9E10 Fab fragment/epitope peptide complexX-ray Diffraction2.7 Å
4Y7RWDR5 in complex with Myc MbIIIb peptideX-ray Diffraction1.898 Å
5I4ZStructure of apo OmoMYCX-ray Diffraction1.95 Å
5I50OmoMYC bound to double-stranded DNAX-ray Diffraction2.701 Å
6C4UEngineered FHA with Myc-pTBD peptideX-ray Diffraction2.6 Å
6E16Ternary structure of c-Myc-TBP-TAF1X-ray Diffraction2.4 Å
6E24Ternary structure of c-Myc-TBP-TAF1X-ray Diffraction3.001 Å
6G6JHuman MYC:MAX bHLHZip complexX-ray Diffraction2.25 Å
6G6KHuman MYC:MAX bHLHZip complexX-ray Diffraction1.35 Å
6G6LHuman MYC:MAX bHLHZip complexX-ray Diffraction2.2 Å
7T1YFbw7-Skp1-MycC degron complexX-ray Diffraction2.55 Å
7T1ZFbw7-Skp1-MycN degron complexX-ray Diffraction2.77 Å
8J2QCypovirus polyhedra mutant fused with c-Myc fragmentX-ray Diffraction1.92 Å
8OTSOCT4 and MYC-MAX co-bound to nucleosomeCryo-EM3.3 Å
8OTTMYC-MAX bound to nucleosome at SHL+5.8Cryo-EM3.3 Å
8Q1NCyclic peptide binder of WDR5 WBM-siteX-ray Diffraction1.843 Å
8WLGCypovirus polyhedra mutant fused with c-Myc fragmentX-ray Diffraction2.55 Å
8X8SCypovirus polyhedra mutant fused with c-Myc fragmentX-ray Diffraction2.04 Å
8X8VCypovirus polyhedra mutant fused with c-Myc fragmentX-ray Diffraction2.0 Å
9QNHMyc pS294 phosphopeptide binding to 14-3-3σX-ray Diffraction1.3 Å

Summary: 23 X-ray Diffraction structures, 2 Cryo-EM structures, 3 Solution NMR structures

Predicted Structures

AlphaFold Database: 1 model

  • Model ID: P01106
  • Global pLDDT: 61.38
  • Fraction with high confidence (pLDDT > 70): 21%

Cross-species orthologs

OrganismGene IDSymbol
Mouse (Mus musculus)ENSMUSG00000022346Myc
Rat (Rattus norvegicus)ENSRNOG00000004500Myc
Zebrafish (Danio rerio)ENSDARG00000007241mycb
Zebrafish (Danio rerio)ENSDARG00000045695myca
Fruit fly (Drosophila melanogaster)FBGN0262656Myc
Worm (C. elegans)none
Yeast (S. cerevisiae)none

Clinical variants & AI predictions

ClinVar: Variant Classification (46 variants)

ClassificationCount
Pathogenic4
Likely Pathogenic1
Uncertain Significance (VUS)11
Benign7
Likely Benign3
Other/Unclassified20

ClinVar: Top Pathogenic/Likely Pathogenic Variants

Variant IDHGVSTypeClassification
12576NM_002467.6(MYC):c.162G>C (p.Glu54Asp)SNVPathogenic
12574NM_002467.6(MYC):c.214C>T (p.Pro72Ser)SNVPathogenic
12575NM_002467.6(MYC):c.302A>C (p.Asn101Thr)SNVPathogenic
2658815NM_002467.6(MYC):c.217A>G (p.Thr73Ala)SNVPathogenic
810340chr8:128750494-128753204x3CNVLikely Pathogenic

AlphaMissense: Likely Pathogenic Predictions (100+ variants)

Top 30 by am_pathogenicity score:

VariantProtein ChangeScoreClass
8:127738410:T:AW50R1.000likely_pathogenic
8:127738411:G:CW50S1.000likely_pathogenic
8:127738412:G:CW50C1.000likely_pathogenic
8:127738412:G:TW50C1.000likely_pathogenic
8:127738410:T:GW50G0.999likely_pathogenic
8:127738405:A:CD48A0.998likely_pathogenic
8:127738405:A:GD48G0.996likely_pathogenic
8:127738408:T:AI49N0.996likely_pathogenic
8:127738400:C:AS46R0.996likely_pathogenic
8:127738400:C:GS46R0.996likely_pathogenic
8:127738401:G:AE47K0.982likely_pathogenic
8:127738395:C:TP45S0.980likely_pathogenic
8:127738396:C:GP45R0.980likely_pathogenic
8:127738402:A:TE47V0.992likely_pathogenic
8:127738404:G:CD48H0.998likely_pathogenic
8:127738407:A:TI49F0.968likely_pathogenic
8:127738397:G:AS46A0.904likely_pathogenic
8:127738313:C:AD17E0.781likely_pathogenic
8:127738312:A:CD17A0.914likely_pathogenic
8:127738312:A:TD17V0.932likely_pathogenic
8:127738311:G:CD17H0.937likely_pathogenic
8:127738311:G:TD17Y0.869likely_pathogenic
8:127738323:C:TP21S0.666likely_pathogenic
8:127738324:C:TP21L0.799likely_pathogenic
8:127738330:T:CF23S0.953likely_pathogenic
8:127738329:T:CF23L0.972likely_pathogenic
8:127738395:C:AP45T0.972likely_pathogenic
8:127738393:C:AA44E0.957likely_pathogenic
8:127738305:G:CD15H0.739likely_pathogenic
8:127738312:A:GD17G0.867likely_pathogenic

SpliceAI: Splice Effect Predictions (522 variants)

Top 30 by score:

VariantGeneEffectScore
8:127736622:AGGT:AMYCdonor_loss0.98
8:127736623:GGT:GMYCdonor_loss0.98
8:127736625:T:GMYCdonor_loss0.98
8:127736624:GTAA:GMYCdonor_loss0.98
8:127736610:T:TAMYCdonor_gain0.97
8:127736611:A:AAMYCdonor_gain0.97
8:127736620:CCAG:CMYCdonor_gain0.97
8:127736196:GC:GMYCdonor_gain0.77
8:127737196:G:GTMYCdonor_gain0.92
8:127737196:GAA:GMYCdonor_gain0.73
8:127737546:G:GTMYCdonor_gain0.82
8:127737547:G:TMYCdonor_gain0.85
8:127737641:G:GTMYCdonor_gain0.82
8:127737654:C:TMYCdonor_gain0.81
8:127737659:G:GTMYCdonor_gain0.89
8:127737659:GGAGT:GMYCdonor_gain0.72
8:127737660:G:GTMYCdonor_gain0.88
8:127737661:A:TMYCdonor_gain0.90
8:127736612:G:GGMYCdonor_gain0.85
8:127736619:ACCAG:AMYCdonor_gain0.93
8:127736621:CAG:CMYCdonor_gain0.87
8:127736622:AG:AMYCdonor_gain0.82
8:127736623:GG:GMYCdonor_gain0.82
8:127736624:G:GGMYCdonor_gain0.96
8:127737492:G:TMYCdonor_gain0.70
8:127737492:G:GTMYCdonor_gain0.64
8:127737533:ATTG:AMYCdonor_gain0.63
8:127737497:ATCGC:AMYCdonor_gain0.59
8:127737538:G:GGMYCdonor_gain0.50
8:127737537:A:AGMYCdonor_gain0.49

Pathways & Gene Ontology

Reactome Pathways

Pathway IDPathway Name
R-HSA-1362277Transcription of E2F targets under negative control by DREAM complex
R-HSA-201556Signaling by ALK
R-HSA-2122947NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-2173796SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
R-HSA-2644606Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2894862Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-4411364Binding of TCF/LEF:CTNNB1 to target gene promoters
R-HSA-5687128MAPK6/MAPK4 signaling
R-HSA-5689880Ub-specific processing proteases
R-HSA-6785807Interleukin-4 and Interleukin-13 signaling
R-HSA-69202Cyclin E associated events during G1/S transition
R-HSA-69656Cyclin A:Cdk2-associated events at S phase entry
R-HSA-8866911TFAP2 (AP-2) family regulates transcription of cell cycle factors
R-HSA-8951430RUNX3 regulates WNT signaling
R-HSA-9018519Estrogen-dependent gene expression
R-HSA-9616222Transcriptional regulation of granulopoiesis
R-HSA-9764562Regulation of CDH1 mRNA translation by microRNAs
R-HSA-9818749Regulation of NFE2L2 gene expression
R-HSA-9909649Regulation of PD-L1(CD274) transcription

Reactome pathway count: 19

MSigDB Gene Sets

MYC participates in 100 curated gene sets including:

  • Canonical pathways (C2:CP): KEGG pathways, BioCarta pathways, PID pathways, and Reactome pathways (20+ pathway databases)
  • GO gene sets (C5:GO): 62 biological process/molecular function/cellular component groupings
  • Transcription factor targets (C3:TFT): E2F, AP4, MYOD, and other TF binding sites
  • Cancer modules (C4): 18 cancer-related co-expression modules

Total pathway & gene set count: 119 (Reactome + MSigDB)


Gene Ontology Annotations

Biological Process (BP): 59 terms

RankGO IDTerm
1GO:0045944Positive regulation of transcription by RNA polymerase II
2GO:0006357Regulation of transcription by RNA polymerase II
3GO:0010468Regulation of gene expression
4GO:0000122Negative regulation of transcription by RNA polymerase II
5GO:0010628Positive regulation of gene expression
6GO:0051276Chromosome organization
7GO:0008284Positive regulation of cell population proliferation
8GO:0006974DNA damage response
9GO:0006338Chromatin remodeling
10GO:0006366Transcription by RNA polymerase II
11GO:0000165MAPK cascade
12GO:0016055Wnt signaling pathway
13GO:0043066Negative regulation of apoptotic process
14GO:0008630Intrinsic apoptotic signaling pathway in response to DNA damage
15GO:0032206Positive regulation of telomere maintenance
16GO:0000082G1/S transition of mitotic cell cycle
17GO:0010564Regulation of cell cycle process
18GO:0045893Positive regulation of DNA-templated transcription
19GO:0060261Positive regulation of transcription initiation by RNA polymerase II
20GO:0070848Response to growth factor

Molecular Function (MF): 15 terms

RankGO IDTerm
1GO:0003677DNA binding
2GO:0000981DNA-binding transcription factor activity, RNA polymerase II-specific
3GO:0001228DNA-binding transcription activator activity, RNA polymerase II-specific
4GO:0000978RNA polymerase II cis-regulatory region sequence-specific DNA binding
5GO:0001227DNA-binding transcription repressor activity, RNA polymerase II-specific
6GO:0070888E-box binding
7GO:0001221Transcription coregulator binding
8GO:0046983Protein dimerization activity
9GO:0042802Identical protein binding
10GO:0140537Transcription regulator activator activity
11GO:0140297DNA-binding transcription factor binding
12GO:0044877Protein-containing complex binding
13GO:0001046Core promoter sequence-specific DNA binding
14GO:0031625Ubiquitin protein ligase binding
15GO:1905761SCF ubiquitin ligase complex binding

Cellular Component (CC): 12 terms

RankGO IDTerm
1GO:0005634Nucleus
2GO:0005654Nucleoplasm
3GO:0071943Myc-Max complex
4GO:0000785Chromatin
5GO:0016604Nuclear body
6GO:0032991Protein-containing complex
7GO:0005730Nucleolus
8GO:0005819Spindle
9GO:0000791Euchromatin
10GO:0090571RNA polymerase II transcription repressor complex
11GO:0048471Perinuclear region of cytoplasm
12GO:0030424Axon

Protein interactions & networks

MYC Proto-oncogene Protein (UniProt: P01106)

Protein-protein Interactions

Total Interactions:

  • STRING database: ~14,230 interactions
  • BioGRID database: ~5,810 interactions
  • IntAct database: ~560 interactions
  • SIGNOR signaling network: ~172 interactions

TOP 30 Highest-Confidence STRING Interacting Proteins (by score):

RankGeneProtein NameSTRING ScoreScore
1TP53Tumor protein p53P04637997
2BRCA1Breast cancer type 1 susceptibilityP38398995
3EP300Histone acetyltransferase p300Q09472994
4TRRAPTransformation/transcription domain-associatedQ9Y4A5993
5CDCA7LCell division cycle-associated 7-likeQ96GN5991
6E2F1Transcription factor E2F1Q01094990
7BIN1Myc box-dependent-interacting protein 1O00499989
8MAXProtein maxP25912987
9ZNF346Zinc finger protein 346Q9UL40986
10SMAD3SMAD family member 3P84022983
11DNMT3ADNA (cytosine-5)-methyltransferase 3AQ9Y6K1983
12HIF1AHypoxia-inducible factor 1-alphaQ16665982
13IGF2BP1Insulin-like growth factor 2 mRNA-binding 1Q9NZI8980
14ZBTB17Zinc finger BTB domain-containing 17Q13105976
15AMOTL1Angiomotin-like protein 1Q8IY63972
16KAT2BHistone acetyltransferase KAT2BQ92831972
17KAT2AHistone acetyltransferase KAT2AQ92830963
18HDAC1Histone deacetylase 1Q13547953
19CCND1Cyclin D1P24385951
20CDKN1ACyclin-dependent kinase inhibitor 1P38936945
21POU5F1POU domain class 5 transcription factor 1P31359944
22YY1Yin and Yang 1 transcriptional repressorP25490943
23KLF4Kruppel-like factor 4P78338942
24EZH2Histone-lysine N-methyltransferase EZH2Q15910940
25HSP90AA1Heat shock protein HSP90-alphaP07900939
26BCL2Apoptosis regulator BCL-2P10415938
27CTNNB1Catenin beta-1P35222937
28CUL1Cullin-1Q13616935
29FBXW7F-box/WD repeat-containing protein 7Q969H0935
30SOX2Transcription factor SOX-2P48431933

Protein Similarity

Structural/Embedding Similarity (ESM2) - TOP 20 Similar Proteins:

RankUniProt IDProteinTop SimilarityAvg Similarity
1A1YG22MYC homolog0.99990.9947
2A2T7L5MYC homolog0.99990.9948
3B8XIA5MYC homolog0.99990.9948
4G3V909MYC homolog0.99980.9836
5O09015MYC homolog0.99980.9862
6P01102N-myc proto-oncogene (MYCN)0.99430.9867
7P01108MYCL proto-oncogene0.99990.9942
8P01109MYC homolog0.99960.9903
9P01110MYC homolog0.99990.9923
10P06171MYC homolog0.99950.9932
11P06295MYC homolog0.99990.9923
12P06646MYC homolog0.99900.9927
13P09416MYC homolog0.99990.9942
14P0C0N8MYC homolog1.00000.9921
15P0C0N9MYC homolog1.00000.9921
16P10166MYC homolog0.99930.9808
17P10395MYC homolog0.99980.9918
18P12523MYC homolog0.99980.9919
19P12525MYC homolog0.99410.9858
20P15171MYC homolog0.99950.9933

Sequence Homology (DIAMOND) - TOP 20 Homologous Proteins:

RankUniProt IDProteinIdentity %Bit Score
1P68271MYC homolog100.00796
2P68272MYC homolog100.00796
3P61244Protein MAX (co-factor)100.00290
4P61245MYC homolog100.00290
5P23583MYC homolog99.80815
6A1YG22MYC homolog99.80794
7P01108MYCL proto-oncogene93.80770
8P01109MYC homolog98.80662
9P01110MYC homolog96.90662
10P03966MYC homolog95.20757
11P04198MYC homolog86.90681
12P06171MYC homolog93.60676
13P06295MYC homolog98.60670
14P06646MYC homolog73.30477
15P09416MYC homolog93.80778
16P0C0N8MYC homolog96.40665
17P0C0N9MYC homolog96.40660
18P10166MYC homolog89.10600
19P10395MYC homolog99.50672
20P12523MYC homolog99.50672

Key Interaction Network Features:

  • Hub status: MYC is a major hub protein with extensive interaction networks across transcription factors, cell cycle regulators, and epigenetic modifiers
  • High-confidence partners: MAX (dimerization partner), TP53 (tumor suppressor), TRRAP (transcriptional coactivator) are among the most confident interactors
  • Functional modules: Interactions span chromatin remodeling (SWI/SNF complex members), histone acetylation (HATs), transcriptional regulation (E2F1, YY1), and cell cycle control (cyclins, CDKIs)
  • Orthologs: Extensive conservation across species shown in ESM2 and DIAMOND similarity data

Now let me compile the upstream regulator information from the data I collected earlier.

Transcription factor regulatory data

MYC is a proto-oncogene basic helix-loop-helix (bHLH) transcription factor located at 8q24.21. It encodes a crucial protein involved in cell proliferation, differentiation, and apoptosis regulation.

Downstream targets

Total count: 1,124 genes regulated by MYC across multiple curated databases

TOP 30 targets with regulation type and evidence:

TargetRegulationEvidence/Confidence
CDKN1AActivationHigh (36 PubMed refs)
CDKN1BRepressionHigh (22 PubMed refs)
CDKN2AActivationHigh (16 PubMed refs)
TP53ActivationHigh (14 PubMed refs)
BRCA1ActivationHigh (8 PubMed refs)
CCND1RepressionHigh (12 PubMed refs)
CCND2ActivationHigh (11 PubMed refs)
ENO1ActivationHigh (5 PubMed refs)
LDHAActivationHigh (6 PubMed refs)
CDK4ActivationHigh (9 PubMed refs)
CCNA2UnknownHigh (7 PubMed refs)
RCC1UnknownHigh (4 PubMed refs)
TOP1UnknownHigh (1 PubMed ref)
GAPDHUnknownHigh (1 PubMed ref)
CDK2UnknownHigh (3 PubMed refs)
TRRAPUnknownHigh (4 PubMed refs)
PRMT1UnknownHigh (1 PubMed ref)
EZH2UnknownHigh (2 PubMed refs)
BIN1UnknownHigh (3 PubMed refs)
BMI1ActivationHigh (4 PubMed refs)
BRCA1ActivationHigh (8 PubMed refs)
HSPD1ActivationLow (6 PubMed refs)
RAD51ActivationLow (2 PubMed refs)
CDK6ActivationLow (3 PubMed refs)
RUVBL2ActivationLow (1 PubMed ref)
PCNAUnknownLow (6 PubMed refs)
BAXUnknownLow (3 PubMed refs)
PTENUnknownLow (3 PubMed refs)
SLC2A1ActivationCurated (1 PubMed ref)
PKMUnknownCurated

Evidence types: ChIP-seq and predicted interactions from curated sources including TFactS, TRRUST, DoRothEA, ExTRI, SIGNOR, GEREDB, and HTRI databases

DNA binding motifs (JASPAR)

Motif family: Basic helix-loop-helix factors (bHLH) / bHLH-ZIP family

Motif IDNameCollectionFamilySpecies
MA0059.1MAX::MYCCOREbHLH-ZIPHomo sapiens
MA0059.2MAX::MYCCOREbHLH-ZIPHomo sapiens
MA0147.3MYCCOREbHLH-ZIPHomo sapiens
MA0147.4MYCCOREbHLH-ZIPHomo sapiens

MYC binds DNA predominantly as a heterodimer with MAX protein, forming bHLH-ZIP complexes that recognize canonical E-box sequences (CANNTG motifs).

Upstream regulators

TFs that regulate MYC (sample of 30+): These include E2F family members (E2F1 with High confidence), stress-responsive factors (CTCF, CTNNB1, ESR1/ESR2), developmental TFs (FOXM1, HOXB13), repressive factors (AP1, FOS/FOSB, JUN/JUND, GLI1/GLI2, KLF11), and post-translational regulators (MAX, CNBP, FUBP1). Multiple evidence types: ChIP-seq (high confidence), predicted binding (medium confidence), and experimentally validated interactions.

Drug & pharmacology data

MYC is an established drug target. The human MYC protein (UniProt P01106, Ensembl ENSG00000136997) has 100 targeting molecules in ChEMBL as of this biobtree snapshot, with varying development stages. Most are preclinical research compounds.

Top molecules by development phase

Phase 2:

  • CHEMBL4297458 (EZOBRESIB / BMS-986158) — BET inhibitor (bromodomain/extra-terminal domain inhibitor)
    • Mechanism: Inhibits BRD4-mediated MYC transcription; indirect MYC suppression
    • Targets: BRD4, BRD2, BRD3, MYC
    • Indications: Multiple myeloma, select advanced cancers
    • 4 active clinical trials (2 completed, 1 active, 1 recruiting; phases 1/2)

Phase 3:

  • CHEMBL165 (RESVERATROL) — Polyphenol with broad activity
    • Mechanism: Multiple targets (90 ChEMBL targets); weak direct MYC inhibition; primarily SIRT1/resveratrol pathway
    • Indications: Diabetes, cardiovascular disease, aging-related conditions
    • 14 clinical trials (primarily phase 1–2 studies; many completed)

Preclinical (Phase 0):

  • CHEMBL1957266 (JQ1) — BET inhibitor (research compound)
    • Mechanism: BRD4 inhibition; first-in-class BET inhibitor
  • CHEMBL3133807 (BROMOSPORINE/BSP) — BET inhibitor (research compound)
    • Mechanism: Dual BRD4/PROTAC degrader activity

Additional molecules: ~96 compounds remain at preclinical phase (phase 0) or unknown development status, primarily small molecule screening hits with weak reported activity.

EZOBRESIB trials:

  1. NCT02419417 — Phase 1/2, COMPLETED — “Select Advanced Cancers” (BMS-986158)
  2. NCT04817007 — Phase 1/2, ACTIVE NOT RECRUITING — Myelofibrosis (BMS-986158 ± ruxolitinib/fedratinib)
  3. NCT05372354 — Phase 1/2, RECRUITING — Relapsed/refractory multiple myeloma (CC-92480/BMS-986348 + combination)
  4. NCT03936465 — Phase 1, COMPLETED — Pediatric cancer (BMS-986158/BMS-986378)

RESVERATROL trials (representative): 5. NCT07332819 — Phase 2/3, COMPLETED — Diabetic nephropathy 6. NCT02616822 — Phase 1, COMPLETED — Endothelial function in hypertension 7. NCT03762096 — Phase undefined, ACTIVE NOT RECRUITING — Cardiovascular surgery outcomes 8. NCT02625376 — Phase undefined, TERMINATED — Age-related macular degeneration

(Additional 6+ resveratrol trials in pharmacokinetics, PCOS, cognition, metabolism; mostly early phase)

Pharmacogenomics & dosing

No established MYC-gene pharmacogenomic interactions are catalogued in pharmGKB or standard databases. MYC functions primarily as a transcription factor; common genetic variants affecting drug response to MYC inhibitors have not been systematically identified. Current MYC-targeting drugs are dosed by clinical protocol (e.g., EZOBRESIB: phase 2 dose escalation in trials) rather than genetic stratification.

Note: Most clinical development has focused on BET inhibitors (EZOBRESIB, JQ1 analogs) that indirectly suppress MYC via BRD4 inhibition, rather than direct MYC-binding small molecules. Direct MYC protein-protein interaction disruptors and PROTAC-based MYC degraders remain largely in preclinical development.

Expression profiles

Tissue Expression (Bgee)

MYC shows ubiquitous expression across human tissues with an average expression score of 85.01 (max 99.12). Expression is broadly distributed across 282 distinct anatomical conditions.

RankTissueExpression ScoreQuality
1Upper leg skin99.12Gold
2Vena cava99.08Gold
3Left uterine tube98.80Gold
4Skin of abdomen98.56Gold
5Mucosa of stomach98.26Gold
6Penis98.18Gold
7Peritoneum97.68Gold
8Omental fat pad97.68Gold
9Mucosa of urinary bladder97.59Gold
10Skin of leg97.54Gold
11Pericardium97.34Gold
12Gall bladder97.31Gold
13Adipose tissue (abdominal region)96.85Gold
14Zone of skin96.75Gold
15Cartilage tissue96.67Gold
16Mammary duct96.66Gold
17Nipple96.19Gold
18Right ovary96.08Gold
19Left ovary95.95Gold
20Esophagus mucosa95.81Gold
21Epithelium of mammary gland95.65Gold
22Parotid gland95.62Gold
23Trachea95.53Gold
24Synovial joint95.20Gold
25Skin of hip95.18Gold
26Pharyngeal mucosa94.93Gold
27Subcutaneous adipose tissue94.77Gold
28Mammalian vulva94.76Gold
29Body of pancreas94.68Gold
30Vermiform appendix94.67Gold

Key tissue-specific patterns:

  • Skin-enriched: Multiple skin regions rank in top 14 (leg, abdomen, hip, zone of skin)
  • Reproductive tissue-enriched: High expression in uterine tubes, ovaries, mammary tissue, penis
  • Adipose tissue-enriched: Both subcutaneous and omental fat pads show high expression
  • Mucosal barriers: GI tract (stomach, esophagus), urinary bladder, and pharyngeal mucosa all highly expressed

Single-Cell Expression (SCXA - Single Cell Expression Atlas)

MYC is a marker gene in 20/20 SCXA datasets (max mean expression: 1,374.6 TPM), indicating strong and consistent cell-type specific expression across multiple single-cell experiments.

Experiment IDDataset DescriptionCell CountSpecies
E-HCAD-6CD34+ cells from bone marrow (hematopoiesis)34,596Homo sapiens
E-MTAB-6701Fetal-maternal interface (first trimester)135,071Homo sapiens
E-MTAB-9841Mammary epithelial cells (lactating vs non-lactating)92,071Homo sapiens
E-HCAD-29GM-CSF-producing T helper cells78,686Homo sapiens
E-MTAB-10885Milk tissue vs non-lactating breast28,628Homo sapiens
E-MTAB-8205hPSC-derived endothelial-to-hematopoietic transition25,764Homo sapiens
E-MTAB-9067Fetal liver and bone marrow hematopoiesis5,865Homo sapiens
E-MTAB-6524Induced pluripotent stem cells (iPSCs)10,926Homo sapiens
E-MTAB-8271Haemogenic endothelium (hPSC differentiation)2,784Homo sapiens
E-MTAB-8884Chronic myelomonocytic leukemia stem cells9,386Homo sapiens
E-GEOD-75688Primary breast cancer cells & metastases549Homo sapiens
E-CURD-6Bone marrow with aneuploid cells1,024Homo sapiens
E-ENAD-20PDX model (BRAF/MEK inhibitor response)674Homo sapiens
E-MTAB-8911Chronic GVHD T-lymphocytes19,075Homo sapiens

Notable cell populations and patterns:

  • Hematopoietic progenitors & stem cells: Strong marker in CD34+ bone marrow cells, hematopoietic endothelium, and fetal liver HSCs — consistent with MYC’s role in cell proliferation and hematopoiesis
  • Reproductive tissue: High in lactating/non-lactating mammary epithelium and fetal trophoblast (E-MTAB-6701), reflecting proliferative remodeling
  • T cell lineage: Enriched in GM-CSF-producing helper T cells, consistent with MYC’s role in T cell activation and proliferation
  • Cancer/stressed states: Highly expressed in acute myeloid leukemia stem cells, PDX models under treatment, and chronic GVHD — reflecting elevated proliferation and stress response
  • iPSCs & endothelial transition: Marker in pluripotent and differentiating progenitor states, expected given MYC’s role in stemness and proliferation

Disease associations

Mendelian / Monogenic Diseases

DiseaseIDInheritanceEvidence
Burkitt lymphomaMONDO:0007243 / Orphanet:543 / OMIM:113970UnknownCurated (GenCC, ClinVar)
Classic Hodgkin lymphomaMONDO:0009348 / Orphanet:391UnknownClinVar
Cholesteatoma of middle earMONDO:0006533UnknownClinVar
Primary ovarian failureMONDO:0005387UnknownClinVar

Phenotype Associations (HPO Terms)

HPO IDPhenotype
HP:0030080Burkitt lymphoma
HP:0005561Abnormal bone marrow cell morphology
HP:0002733Abnormal lymph node morphology
HP:0002721Immunodeficiency
HP:0025435Increased circulating lactate dehydrogenase concentration
HP:0032218Decreased CD4+ T cell proportion
HP:0001442Typified by somatic mosaicism
HP:0005214Intestinal obstruction
HP:0002239Gastrointestinal hemorrhage
HP:0002149Hyperuricemia
HP:0100649Neoplasm of the oral cavity
HP:0002027Abdominal pain
HP:0002017Nausea and vomiting
HP:0001743Abnormality of the spleen
HP:0001732Abnormality of the pancreas
HP:0001392Abnormality of the liver
HP:0000137Abnormality of the ovary
HP:0003745Sporadic

Complex-Disease / GWAS Associations (Top 30)

Trait/DiseaseAssociated Genesp-valueStudy
Non-glioblastoma gliomaCCDC268.0e-36GCST005933_9
Non-glioblastoma gliomaCCDC262.0e-65GCST005933_10
Colorectal cancer or advanced adenomaPCAT1, CASC8, POU5F1B, CCAT23.0e-64GCST007856_84
Colorectal cancer or advanced adenomaPOU5F1B, PCAT1, CASC82.0e-56GCST007856_6
GliomaCCDC261.0e-39GCST005931_16
Asthma (childhood onset)MYC - PVT11.0e-23GCST007800_55
Prostate-specific antigen levelsPCAT1, CASC8, POU5F1B7.0e-21GCST004093_26
Bladder cancerCASC112.0e-18GCST000842_5
Prostate cancerCASC86.0e-18GCST002421_6
Nonsyndromic cleft lip with cleft palateCCDC268.0e-16GCST004166_56
AsthmaMYC - PVT13.0e-15GCST010043_160
Breast cancerPVT11.0e-13GCST004988_564
Endometrial cancerLINC00824 - CCDC268.0e-14GCST006464_13
Colorectal cancerPCAT1, CASC8, POU5F1B, CCAT24.0e-14GCST003017_15
GliomaCCDC261.0e-14GCST005931_2
Allergic disease (asthma, hay fever or eczema)PVT16.0e-14GCST005038_17
AsthmaMYC - PVT11.0e-14GCST010042_34
Endometrial endometrioid carcinomaLINC00824 - CCDC261.0e-13GCST003525_2
Diffuse large B cell lymphomaPVT11.0e-12GCST002636_5
Urinary bladder cancerCASC119.0e-12GCST000231_2
Colorectal cancerPCAT1, CASC8, POU5F1B8.0e-13GCST002411_9
Ovarian cancerLINC008243.0e-12GCST001941_3
Urinary bladder cancerCASC117.0e-12GCST000639_1
Renal cell carcinomaPVT15.0e-11GCST002273_1
Breast cancerPVT13.0e-11GCST001937_34
Colorectal cancerPCAT1, CASC8, POU5F1B1.0e-11GCST001787_1
Diffuse large B cell lymphomaRN7SKP226 - LINC008244.0e-11GCST002636_6
AsthmaMYC - PVT12.0e-11GCST007798_112
Prostate cancer (early onset)PCAT1, CASC8, POU5F1B9.0e-09GCST002413_8
Multiple sclerosisPVT18.0e-09GCST001198_62

Key observations: MYC is strongly associated with lymphomas (Burkitt lymphoma, Hodgkin lymphoma) through point mutations, and with numerous cancers and autoimmune traits through GWAS signals in the MYC locus region, primarily involving adjacent long non-coding RNAs (PVT1, CASC8, LINC00824) rather than MYC itself.

Structured Data Sources

Generated with Claude Haiku 4.5 + BioBTree MCP, drawing on data BioBTree aggregates from 43 biological databases. Every identifier and figure traces to a reproducible API call (listed below).

Further analyze this answer or run your own queries with BioBTree MCP.

Datasets: alphafold, alphamissense, antibody, bgee, biogrid_interaction, ccds, chembl_molecule, chembl_target, clinical_trials, clinvar, collectri, diamond_similarity, ensembl, entrez, esm2_similarity, exon, gencc, go, gtex, gwas, hgnc, hpa, hpo, intact, interpro, jaspar, mim, mondo, msigdb, orphanet, ortholog, pdb, pfam, pharmgkb, reactome, refseq, scxa, scxa_expression, smart, spliceai, string_interaction, transcript, uniprot
Generated: 2026-05-25 — For the latest data, query BioBTree directly via MCP or API.
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