MYC

protein-coding

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

Gene summary

This gene is a proto-oncogene and encodes a nuclear phosphoprotein that plays a role in cell cycle progression, apoptosis and cellular transformation. The encoded protein forms a heterodimer with the related transcription factor MAX. This complex binds to the E box DNA consensus sequence and regulates the transcription of specific target genes. Amplification of this gene is frequently observed in numerous human cancers. Translocations involving this gene are associated with Burkitt lymphoma and multiple myeloma in human patients. There is evidence to show that translation initiates both from an upstream, in-frame non-AUG (CUG) and a downstream AUG start site, resulting in the production of two isoforms with distinct N-termini. [provided by RefSeq, Aug 2017]

MANE transcript

NM_002467.6

Inheritance

—

ClinVar variants

P:4U:28B:4

Top phenotype

Burkitt lymphoma

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr8:127,735,434-127,742,951

External References & Databases

Ensembl (ENSG00000136997)

Transcript & Mutation Effects

hg38 • Region Span ~7.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Burkitt lymphomaNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0007243

Submitter: Labcorp Genetics (formerly Invitae)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MYC variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 9

not providedTotal: 7

Burkitt lymphomaTotal: 4

Cholesteatoma of middle earTotal: 2

Premature ovarian failureTotal: 1

MYC-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002467.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar	1 clinvar	2
missense	4 clinvar		26 clinvar	2 clinvar		32
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	4	0	28	3	1	36

Highest pathogenic variant AF is 0.0000065660743

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002467.6	RefSeq	NP_002458.2	3	MANE Select
ENST00000621592.8	Ensembl	ENSP00000478887.2	3	MANE Select
NM_001354870.1	RefSeq	NP_001341799.1	3	Standard
ENST00000259523.10	Ensembl	ENSP00000259523.6	2	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
myca	Danio rerio	Structure: intersegmental vessel Quality: decreased branchiness abnormal

Gene / Model

Organism

Observed Phenotype

myca

Danio rerio

Structure: intersegmental vessel

Quality: decreased branchiness

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

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

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

Cellular Component

nuclear chromatin
nucleus
nucleoplasm
nucleolus
protein-containing complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377970
Coding exons: 3
Length: 5995
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.22	208	264	0.788	0.0000140	2964
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.987

Intolerance Scores

RVIS EVS: 0
RVIS percentile EVS: 53.73

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

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