MYCN

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

Basic information

Region (hg38): 2:15940550-15947007

Previous symbols: [ "NMYC" ]

Links

ENSG00000134323 ∙ NCBI:4613 ∙ OMIM:164840 ∙ HGNC:7559 ∙ Uniprot:P04198 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Feingold syndrome type 1 (Definitive), mode of inheritance: AD
• Feingold syndrome type 1 (Definitive), mode of inheritance: AD
• Feingold syndrome type 1 (Strong), mode of inheritance: AD
• Feingold syndrome type 1 (Supportive), mode of inheritance: AD
• Feingold syndrome type 1 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Feingold syndrome 1; Megalencephaly-polydactyly syndrome	AD	Cardiovascular; Oncologic	Feingold syndrome can involve congenital cardiac anomalies, and awareness may allow early management; Megalencephaly-polydactyly syndrome may involve, among other findings, increased risk of neuroblastoma, and awareness may allow prompt recognition and management	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Oncologic; Renal	9096752; 14518066; 15821734; 16906565; 18671284; 18470948; 19852433; 20301770; 21224895; 22842076; 30573562; 37710961
The condition can include multiple congenital anomalies

ClinVar

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

• not_provided (170 variants)
• Feingold_syndrome_type_1 (111 variants)
• Megalencephaly-polydactyly_syndrome (61 variants)
• Inborn_genetic_diseases (57 variants)
• MYCN-related_disorder (25 variants)
• not_specified (17 variants)
• Intellectual_disability (3 variants)
• Feingold_syndrome (2 variants)
• Isolated_agenesis_of_gallbladder (1 variants)
• Double_outlet_right_ventricle (1 variants)
• Ventricular_septal_defect (1 variants)
• See_cases (1 variants)
• Bilateral_cleft_palate (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYCN gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005378.6. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	46	3	52
missense	2	14	149	18	1	184
nonsense	10	5	1			16
start loss			2			2
frameshift	18	18	2			38
splice donor/acceptor (+/-2bp)	1					1
Total	31	37	157	64	4

Highest pathogenic variant AF is 0.000013683298

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYCN	protein_coding	protein_coding	ENST00000281043	2	6444

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.889	0.111	125721	0	18	125739	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.41	181	243	0.746	0.0000141	2970
Missense in Polyphen		77	118.34	0.65068		1385
Synonymous	-1.50	128	108	1.18	0.00000661	974
Loss of Function	2.87	1	11.5	0.0867	6.79e-7	128

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000373	0.000373
Ashkenazi Jewish	0.00	0.00
East Asian	0.000113	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000197	0.0000176
Middle Eastern	0.000113	0.000109
South Asian	0.0000353	0.0000327
Other	0.000174	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Positively regulates the transcription of MYCNOS in neuroblastoma cells. {ECO:0000269|PubMed:24391509}.
• Disease: DISEASE: Note=Amplification of the N-MYC gene is associated with a variety of human tumors, most frequently neuroblastoma, where the level of amplification appears to increase as the tumor progresses. {ECO:0000269|PubMed:2834684}.; DISEASE: Feingold syndrome 1 (FGLDS1) [MIM:164280]: A syndrome characterized by variable combinations of esophageal and duodenal atresias, microcephaly, learning disability, mental retardation, and limb malformations. Hand and foot abnormalities may include hypoplastic thumbs, clinodactyly of second and fifth fingers, syndactyly (characteristically between second and third and fourth and fifth toes), and shortened or absent middle phalanges. Cardiac and renal malformations, vertebral anomalies, and deafness have also been described. {ECO:0000269|PubMed:15821734, ECO:0000269|PubMed:16906565}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Transcriptional misregulation in cancer - Homo sapiens (human);miR-targeted genes in lymphocytes - TarBase;Pathways Affected in Adenoid Cystic Carcinoma (Consensus)

Recessive Scores

• pRec: 0.671

Intolerance Scores

• loftool: 0.0238
• rvis_EVS: -0.38
• rvis_percentile_EVS: 27.42

Haploinsufficiency Scores

• pHI: 0.994
• hipred: Y
• hipred_score: 0.880
• ghis: 0.652

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.981

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mycn
• Phenotype: muscle phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; digestive/alimentary phenotype; limbs/digits/tail 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); vision/eye phenotype; skeleton phenotype; renal/urinary system phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; respiratory 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; normal 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)

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;positive regulation of gene expression;negative regulation of gene expression;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;positive regulation of production of miRNAs involved in gene silencing by miRNA
• Cellular component: chromatin;nucleus;nucleolus
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;protein binding;kinase binding;protein dimerization activity