MYC

MYC proto-oncogene, bHLH transcription factor, the group of Basic helix-loop-helix proteins

Basic information

Region (hg38): 8:127735433-127742951

Links

ENSG00000136997 ∙ NCBI:4609 ∙ OMIM:190080 ∙ HGNC:7553 ∙ Uniprot:P01106 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Burkitt lymphoma (No Known Disease Relationship), mode of inheritance: Unknown

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYC gene.

• not provided (9 variants)
• Inborn genetic diseases (3 variants)
• Cholesteatoma of middle ear (2 variants)
• Premature ovarian failure (1 variants)
• Burkitt lymphoma (1 variants)
• Classic Hodgkin lymphoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYC gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense	1		5	1	1	8
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding				1	3	4
Total	1	0	5	2	5

Variants in MYC

This is a list of pathogenic ClinVar variants found in the MYC region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-127736331-G-A			Likely benign (Sep 01, 2023)
8-127736498-C-T			Benign (Mar 01, 2023)
8-127736627-A-T			Uncertain significance (Sep 01, 2023)
8-127737223-C-T			Benign (Oct 01, 2023)
8-127738076-G-A			Benign (Nov 01, 2022)
8-127738281-T-C			Benign/Likely benign (Jan 01, 2023)
8-127738294-A-G		Classic Hodgkin lymphoma • MYC-related disorder	Conflicting classifications of pathogenicity (Oct 01, 2021)
8-127738361-G-A			Benign (May 31, 2018)
8-127738379-G-C		Burkitt lymphoma	Pathogenic (Sep 01, 1993)
8-127738386-C-T		Neoplasm	Likely pathogenic (Jul 14, 2015)
8-127738390-C-T		Non-Hodgkin lymphoma • Lung adenocarcinoma • Carcinoma of esophagus • Neuroblastoma • Malignant melanoma of skin	Likely pathogenic (May 31, 2016)
8-127738393-C-T		Neoplasm	Likely pathogenic (Jul 14, 2015)
8-127738431-C-T		Burkitt lymphoma	Pathogenic (Sep 01, 1993)
8-127738434-A-C		Neuroblastoma • Non-Hodgkin lymphoma • Malignant melanoma of skin • Carcinoma of esophagus • Lung adenocarcinoma	Likely pathogenic (May 31, 2016)
8-127738434-A-G		Acute myeloid leukemia	Pathogenic (Jul 01, 2023)
8-127738435-C-T		Non-Hodgkin lymphoma • Neoplasm • Lung adenocarcinoma • Carcinoma of esophagus • Malignant melanoma of skin • Neuroblastoma	Likely pathogenic (May 31, 2016)
8-127738437-C-G		Burkitt lymphoma • Cholesteatoma of middle ear	other (-)
8-127738440-C-A		Cholesteatoma of middle ear	other (-)
8-127738447-C-T		Neoplasm	Likely pathogenic (Jul 14, 2015)
8-127738519-A-C		Burkitt lymphoma • Neoplasm	Pathogenic/Likely pathogenic (Jul 14, 2015)
8-127738626-G-C		not specified	Uncertain significance (May 01, 2022)
8-127738655-G-A		MYC-related disorder	Likely benign (Feb 22, 2019)
8-127738695-G-A		Premature ovarian failure	Uncertain significance (Mar 02, 2020)
8-127738888-C-T		not specified	Uncertain significance (Apr 19, 2023)
8-127738955-G-A		MYC-related disorder	Benign (Sep 06, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYC	protein_coding	protein_coding	ENST00000377970	3	5995

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00199	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.22	208	264	0.788	0.0000140	2964
Missense in Polyphen		68	122.37	0.55568		1374
Synonymous	-0.546	122	115	1.06	0.00000632	909
Loss of Function	3.95	0	18.2	0.00	0.00000116	176

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'- CAC[GA]TG-3'. Activates the transcription of growth-related genes. Binds to the VEGFA promoter, promoting VEGFA production and subsequent sprouting angiogenesis (PubMed:24940000). {ECO:0000269|PubMed:24940000, ECO:0000269|PubMed:25956029}.
• Disease: DISEASE: Note=A chromosomal aberration involving MYC may be a cause of a form of B-cell chronic lymphocytic leukemia. Translocation t(8;12)(q24;q22) with BTG1. {ECO:0000269|PubMed:2069907}.; DISEASE: Burkitt lymphoma (BL) [MIM:113970]: A form of undifferentiated malignant lymphoma commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. {ECO:0000269|PubMed:2166998, ECO:0000269|PubMed:8220424}. Note=The gene represented in this entry is involved in disease pathogenesis. Chromosomal aberrations involving MYC are usually found in Burkitt lymphoma. Translocations t(8;14), t(8;22) or t(2;8) which juxtapose MYC to one of the heavy or light chain immunoglobulin gene loci.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Chronic myeloid leukemia - Homo sapiens (human);Gastric cancer - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);TGF-beta signaling pathway - Homo sapiens (human);Central carbon metabolism in cancer - Homo sapiens (human);Bladder cancer - Homo sapiens (human);Cell cycle - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Acute myeloid leukemia - Homo sapiens (human);Breast cancer - Homo sapiens (human);ErbB signaling pathway - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Thyroid cancer - Homo sapiens (human);Busulfan Pathway, Pharmacodynamics;Endometrial cancer - Homo sapiens (human);Colorectal cancer - Homo sapiens (human);EGFR Inhibitor Pathway, Pharmacodynamics;Vemurafenib Pathway, Pharmacodynamics;update your name in edit mode;Glutaminolysis and Cancer;EGF-Core;TGF-Core;IL-5 Signaling Pathway;miRNA Regulation of DNA Damage Response;miRNAs involved in DNA damage response;TP53 Network;Integrated Cancer Pathway;Integrated Breast Cancer Pathway;Signaling by NOTCH1;Transcriptional activity of SMAD2-SMAD3-SMAD4 heterotrimer;Human Thyroid Stimulating Hormone (TSH) signaling pathway;Prolactin Signaling Pathway;IL-7 Signaling Pathway;Neural Crest Differentiation;Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway;Metastatic brain tumor;Androgen Receptor Network in Prostate Cancer;B Cell Receptor Signaling Pathway;Gastric Cancer Network 2;Spinal Cord Injury;Retinoblastoma (RB) in Cancer;Apoptosis;Polycystic Kidney Disease Pathway;Aryl Hydrocarbon Receptor;JAK-STAT;Structural Pathway of Interleukin 1 (IL-1);Degradation of beta-catenin by the destruction complex;Hair Follicle Development- Induction (Part 1 of 3);Mammary gland development pathway - Involution (Stage 4 of 4);Bladder Cancer;Ectoderm Differentiation;Vitamin D Receptor Pathway;PPAR Alpha Pathway;Nuclear Receptors Meta-Pathway;let-7 inhibition of ES cell reprogramming;Rac1-Pak1-p38-MMP-2 pathway;TCF dependent signaling in response to WNT;Beta-catenin independent WNT signaling;Wnt Signaling Pathway;Apoptotic Signaling Pathway;Imatinib and Chronic Myeloid Leukemia;Hepatitis C and Hepatocellular Carcinoma;Pathways Affected in Adenoid Cystic Carcinoma;TGF-beta Signaling Pathway;Association Between Physico-Chemical Features and Toxicity Associated Pathways;MAPK Signaling Pathway;Regulation of Apoptosis by Parathyroid Hormone-related Protein;Wnt Signaling Pathway and Pluripotency;p38 MAPK Signaling Pathway;Interleukin-4 and 13 signaling;Transcriptional regulation by RUNX3;PI3K-AKT-mTOR - VitD3 Signalling;Endometrial cancer;PI3K-Akt Signaling Pathway;Chromosomal and microsatellite instability in colorectal cancer;Wnt Signaling Pathway;G1 to S cell cycle control;IL-2 Signaling Pathway;Notch Signaling Pathway;ErbB Signaling Pathway;DNA Damage Response;DNA Damage Response (only ATM dependent);Degradation of beta-catenin by the destruction complex;Disease;Signaling by WNT;Signal Transduction;Gene expression (Transcription);RUNX3 regulates WNT signaling;Transcriptional regulation by RUNX3;mechanism of gene regulation by peroxisome proliferators via ppara;inhibition of cellular proliferation by gleevec;telomeres telomerase cellular aging and immortality;role of egf receptor transactivation by gpcrs in cardiac hypertrophy;wnt signaling pathway;tumor suppressor arf inhibits ribosomal biogenesis;p38 mapk signaling pathway;cadmium induces dna synthesis and proliferation in macrophages;overview of telomerase protein component gene htert transcriptional regulation;erk1/erk2 mapk signaling pathway;ctcf: first multivalent nuclear factor;mapkinase signaling pathway;Generic Transcription Pathway;Repression of WNT target genes;MAPK6/MAPK4 signaling;Post-translational protein modification;Metabolism of proteins;RNA Polymerase II Transcription;p73 transcription factor network;Cyclin E associated events during G1/S transition ;Signaling by NOTCH1;Mitotic G1-G1/S phases;Signaling by NOTCH;TGF_beta_Receptor;EGFR1;Ca2+ pathway;Beta-catenin independent WNT signaling;Ub-specific processing proteases;MAPK family signaling cascades;Deubiquitination;G1/S Transition;Signaling by Nuclear Receptors;C-MYB transcription factor network;IL2-mediated signaling events;C-MYC pathway;Notch signaling pathway;TFAP2 (AP-2) family regulates transcription of cell cycle factors;Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors;Estrogen-dependent gene expression;Cell Cycle;Constitutive Signaling by NOTCH1 PEST Domain Mutants;Signaling by NOTCH1 PEST Domain Mutants in Cancer;Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants;Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer;Signaling by NOTCH1 in Cancer;Cell Cycle, Mitotic;ESR-mediated signaling;Regulation of nuclear beta catenin signaling and target gene transcription;IL2 signaling events mediated by STAT5;CD40/CD40L signaling;Diseases of signal transduction;Validated nuclear estrogen receptor alpha network;Validated targets of C-MYC transcriptional repression;Validated targets of C-MYC transcriptional activation;Regulation of Telomerase;AP-1 transcription factor network;IL2 signaling events mediated by PI3K;Binding of TCF/LEF:CTNNB1 to target gene promoters;Formation of the beta-catenin:TCF transactivating complex;TCF dependent signaling in response to WNT;FOXM1 transcription factor network;PDGFR-beta signaling pathway;NOTCH1 Intracellular Domain Regulates Transcription;Regulation of nuclear SMAD2/3 signaling;IL6-mediated signaling events;Presenilin action in Notch and Wnt signaling;E2F transcription factor network;Ceramide signaling pathway;LKB1 signaling events (Consensus)

Recessive Scores

• pRec: 0.987

Intolerance Scores

• rvis_EVS: 0
• rvis_percentile_EVS: 53.73

Haploinsufficiency Scores

• pHI: 0.701
• ghis: 0.549

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Myc
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; craniofacial phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; embryo phenotype; neoplasm; pigmentation phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; digestive/alimentary phenotype; skeleton phenotype

Zebrafish Information Network

• Gene name: myca
• Affected structure: intersegmental vessel
• Phenotype tag: abnormal
• Phenotype quality: decreased branchiness

Gene ontology

• Biological process: G1/S transition of mitotic cell cycle;negative regulation of transcription by RNA polymerase II;MAPK cascade;branching involved in ureteric bud morphogenesis;positive regulation of mesenchymal cell proliferation;energy reserve metabolic process;chromatin remodeling;regulation of transcription by RNA polymerase II;cellular iron ion homeostasis;cellular response to DNA damage stimulus;cell cycle arrest;Notch signaling pathway;positive regulation of cell population proliferation;response to gamma radiation;regulation of gene expression;positive regulation of gene expression;oxygen transport;protein deubiquitination;cytokine-mediated signaling pathway;regulation of telomere maintenance;negative regulation of stress-activated MAPK cascade;protein-DNA complex disassembly;cellular response to UV;cellular response to drug;response to drug;negative regulation of apoptotic process;positive regulation of cysteine-type endopeptidase activity involved in apoptotic process;fibroblast apoptotic process;negative regulation of monocyte differentiation;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;positive regulation of fibroblast proliferation;negative regulation of fibroblast proliferation;positive regulation of epithelial cell proliferation;chromosome organization;negative regulation of cell division;positive regulation of telomerase activity;ERK1 and ERK2 cascade;response to growth factor;cellular response to hypoxia;positive regulation of metanephric cap mesenchymal cell proliferation;beta-catenin-TCF complex assembly;positive regulation of DNA methylation;positive regulation of DNA biosynthetic process;positive regulation of response to DNA damage stimulus
• Cellular component: nuclear chromatin;nucleus;nucleoplasm;nucleolus;protein-containing complex
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;protein binding;transcription factor binding;activating transcription factor binding;protein-containing complex binding;protein dimerization activity;repressing transcription factor binding;E-box binding