MYCN

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

Basic information

Region (hg38): 2:15940549-15947007

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 (Supportive), mode of inheritance: AD
• Feingold syndrome type 1 (Strong), 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	AD	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Renal	9096752; 14518066; 15821734; 16906565; 18671284; 18470948; 19852433; 20301770; 21224895; 22842076
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 (116 variants)
• Feingold syndrome type 1 (39 variants)
• Inborn genetic diseases (26 variants)
• not specified (13 variants)
• MYCN-related condition (7 variants)
• megalencephaly-polydactyly syndrome (1 variants)
• Feingold syndrome (1 variants)
• Isolated agenesis of gallbladder;Ventricular septal defect;Double outlet right ventricle;Bilateral cleft palate (1 variants)
• See cases (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.

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			2	29	2	33
missense	1	8	59	7	2	77
nonsense	8	4	1			13
start loss						0
frameshift	17	13				30
inframe indel		2	3			5
splice donor/acceptor (+/-2bp)	1					1
splice region						0
non coding			4	7	2	13
Total	27	27	69	43	6

Highest pathogenic variant AF is 0.00000657

Variants in MYCN

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

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

Position	Type	Phenotype	Significance	ClinVar
2-15940646-CG-C		Feingold syndrome type 1	Likely benign (-)
2-15940647-G-T		MYCN-related disorder	Benign/Likely benign (Sep 01, 2022)
2-15940650-C-T		Feingold syndrome type 1	not provided (-)
2-15940683-C-A		MYCN-related disorder	Uncertain significance (Apr 09, 2023)
2-15940684-C-T		MYCN-related disorder	Likely benign (Jun 09, 2022)
2-15940691-A-C			Likely benign (Jan 01, 2023)
2-15940712-A-G			Likely benign (Dec 14, 2020)
2-15940728-C-T		MYCN-related disorder	Likely benign (Sep 21, 2021)
2-15941822-G-A			Likely benign (Jun 29, 2018)
2-15941939-C-T		not specified	Likely benign (Jul 20, 2017)
2-15941964-C-T		MYCN-related disorder	Likely benign (Jun 03, 2019)
2-15941967-C-T			Likely benign (Jun 05, 2018)
2-15941981-G-T		Feingold syndrome type 1	Uncertain significance (Jul 02, 2020)
2-15942038-C-T		MYCN-related disorder	Uncertain significance (Dec 28, 2023)
2-15942048-G-C		not specified	Likely benign (May 25, 2017)
2-15942066-T-C		Feingold syndrome type 1	Likely benign (-)
2-15942072-G-C		MYCN-related disorder	Conflicting classifications of pathogenicity (Apr 04, 2022)
2-15942082-G-A		not specified • Feingold syndrome type 1 • MYCN-related disorder	Likely benign (Dec 26, 2023)
2-15942084-C-T			Uncertain significance (Jun 11, 2023)
2-15942099-T-G			Uncertain significance (Sep 01, 2022)
2-15942129-A-ACTCG		Feingold syndrome type 1	Pathogenic (Jan 12, 2016)
2-15942133-G-T		Feingold syndrome type 1	Benign/Likely benign (Aug 12, 2022)
2-15942137-C-T			Pathogenic (Aug 20, 2015)
2-15942141-C-T		Feingold syndrome type 1	Likely pathogenic (Aug 01, 2021)
2-15942154-G-C			Likely benign (Nov 01, 2023)

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