MYCN (N-myc proto-oncogene protein) variants and mutations
MYCN (also known as N-myc proto-oncogene protein) is a human protein-coding gene encoding a n-myc proto-oncogene protein. It drives transcriptional programs for growth, metabolism, and proliferation during neural and other embryonic development. Amplification is a major adverse prognostic feature in neuroblastoma, while germline dysregulation can cause developmental syndromes with abnormal growth. This analysis covers 1,371 MYCN variants and mutations. Of these, 62% have computational variant effect predictions. Disease context includes Feingold syndrome type 1, Feingold syndrome, and megalencephaly-polydactyly syndrome. Example MYCN variants include M1?, P2L, and P2R.
Variant analysis overview
- Gene: MYCN
- Protein: N-myc proto-oncogene protein
- UniProt accession: P04198
- Organism: Homo sapiens
- Variants analyzed: 1371
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 1,102 unspecified-consequence records; 129 missense variants; 105 synonymous variants; 15 frameshift variants; 8 stop-gained variants; 4 in-frame insertions; 7 in-frame deletions; 1 substitution
- Prediction scores: 855 variants have prediction scores (62% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Feingold syndrome type 1, Feingold syndrome, megalencephaly-polydactyly syndrome, basal cell carcinoma, neurodegenerative disease, hereditary disease, prostate carcinoma, non-melanoma skin carcinoma, melanoma, skin basal cell carcinoma, cutaneous melanoma, skin squamous cell carcinoma.
Protein structure and variant hotspots
- Protein features: 1 domains; 3 post-translational modification sites.
- Structural context: 112 variants have structural context.
- PTM context: 10 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable MYCN variants
Examples include M1?, P2L, P2R, P2S, P2P, S3I, S3N, S3R. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, NCI-TCGA Cosmic COSV5525, Variant assessed as somatic; high impact.
- P2L (p.Pro2Leu), ESP rs370558211, ExAC rs370558211, TOPMed rs370558211, gnomAD rs370558211, REVEL 0.24, MetaLR 0.17
- P2R (p.Pro2Arg), ESP rs370558211, ExAC rs370558211, TOPMed rs370558211, gnomAD rs370558211, REVEL 0.22, MetaLR 0.19
- P2S (p.Pro2Ser), Ensembl rs2103323084
- P2P (p.Pro2Pro), rs936259634, gnomAD 2-15940601-T-A, CADD 18.50
- S3I (p.Ser3Ile), NCI-TCGA Cosmic COSV9980, REVEL 0.22, MetaLR 0.32, Variant assessed as somatic; moderate impact.
- S3N (p.Ser3Asn), 1000Genomes rs373683425, ESP rs373683425, ExAC rs373683425, TOPMed rs373683425, REVEL 0.30, MetaLR 0.29, Likely benign
- S3R (p.Ser3Arg), ExAC rs780064642, gnomAD rs780064642
- S3T (p.Ser3Thr), rs373683425, ClinGen CA1538099, ClinVar RCV000591265, ClinVar RCV003925767, REVEL 0.29, MetaLR 0.30, Conflicting interpretations, not provided
- S3S (p.Ser3Ser), rs780064642, gnomAD 2-15942073-C-T, CADD 14.10
- C4F (p.Cys4Phe), ExAC rs756249997, TOPMed rs756249997, gnomAD rs756249997, REVEL 0.27, MetaLR 0.42, Uncertain significance, Feingold syndrome type 1; Megalencephaly-polydactyly syndrome
- C4G (p.Cys4Gly), ExAC rs748156396, gnomAD rs748156396, REVEL 0.28, MetaLR 0.34
- C4Y (p.Cys4Tyr), ExAC rs756249997, TOPMed rs756249997, gnomAD rs756249997, REVEL 0.28, MetaLR 0.40, Uncertain significance
- p.Cys4 Cys14del, gnomAD 2-15942071-AGCTGC, CADD 22.10
- C4C (p.Cys4Cys), rs2103323120, gnomAD 2-15942076-C-T, CADD 13.60
- S5T (p.Ser5Thr), rs868623724, NCI-TCGA Cosmic COSV9980, Ensembl rs868623724, REVEL 0.26, MetaLR 0.12, Variant assessed as somatic; moderate impact.
- S5F (p.Ser5Phe), gnomAD 2-15942078-C-T, REVEL 0.38, MetaLR 0.28
- S5S (p.Ser5Ser), rs2103323135, gnomAD 2-15942079-C-T, CADD 9.21
- T6M (p.Thr6Met), gnomAD rs1311546727, REVEL 0.32, MetaLR 0.20
- T6S (p.Thr6Ser), Ensembl rs2103323138
- T6A (p.Thr6Ala), gnomAD 2-15942080-A-G, REVEL 0.22, MetaLR 0.23
- T6K (p.Thr6Lys), gnomAD 2-15942081-C-A, REVEL 0.24, MetaLR 0.33
- T6T (p.Thr6Thr), rs199929021, gnomAD 2-15942082-G-A, CADD 10.80
- S7F (p.Ser7Phe), rs1395093741, NCI-TCGA Cosmic COSV9980, TOPMed rs1395093741, MutPred 0.23, Uncertain significance, not provided
- S7Y (p.Ser7Tyr), gnomAD 2-15942084-C-A, REVEL 0.37, MetaLR 0.52
- S7S (p.Ser7Ser), rs2103323154, gnomAD 2-15942085-C-T, CADD 13.70
- T8A (p.Thr8Ala), Ensembl rs2103323162
- T8I (p.Thr8Ile), ESP rs371517719, ExAC rs371517719, TOPMed rs371517719, gnomAD rs371517719, REVEL 0.30, MetaLR 0.42
- T8S (p.Thr8Ser), ESP rs371517719, ExAC rs371517719, TOPMed rs371517719, gnomAD rs371517719
- T8N (p.Thr8Asn), gnomAD 2-15940654-C-A, CADD 17.30, SIFT 0.03
- T8P (p.Thr8Pro), gnomAD 2-15942086-A-C, REVEL 0.35, MetaLR 0.39
- T8T (p.Thr8Thr), rs2103323174, gnomAD 2-15942088-C-T, CADD 14.20
- M9I (p.Met9Ile), Ensembl rs2103323190
- M9K (p.Met9Lys), Ensembl rs2103323183
- M9T (p.Met9Thr), Ensembl rs2103323183
- M9V (p.Met9Val), gnomAD rs1260613770, REVEL 0.35, MetaLR 0.20
- P10Q (p.Pro10Gln), Ensembl rs1572216812
- P10R (p.Pro10Arg), Ensembl rs1572216812
- P10S (p.Pro10Ser), 1000Genomes rs577079213, ExAC rs577079213, gnomAD rs577079213, REVEL 0.37, MetaLR 0.16
- P10T (p.Pro10Thr), 1000Genomes rs577079213, ExAC rs577079213, gnomAD rs577079213, REVEL 0.39, MetaLR 0.22
- P10L (p.Pro10Leu), gnomAD 2-15942093-C-T, REVEL 0.34, MetaLR 0.18
- P10P (p.Pro10Pro), rs201009439, gnomAD 2-15942094-G-C, CADD 11.60
- G11A (p.Gly11Ala), ExAC rs772399455, gnomAD rs772399455, REVEL 0.17, MetaLR 0.09
- G11D (p.Gly11Asp), ExAC rs772399455, gnomAD rs772399455
- G11R (p.Gly11Arg), Ensembl rs2103323221
- G11S (p.Gly11Ser), Ensembl rs2103323221, REVEL 0.22, MetaLR 0.06
- G11V (p.Gly11Val), ExAC rs772399455, gnomAD rs772399455
- G11W (p.Gly11Trp), gnomAD 2-15940593-G-T, CADD 19.60, SIFT 0.00
- G11E (p.Gly11Glu), gnomAD 2-15940594-G-A, CADD 20.80, SIFT 0.00
- G11G (p.Gly11Gly), rs1051172316, gnomAD 2-15940595-G-A, CADD 21.20
- G11* (p.Gly11Ter), rs2103319726, gnomAD 2-15940614-G-T, CADD 21.10
- M12I (p.Met12Ile), NCI-TCGA Cosmic COSV9980, REVEL 0.02, MetaLR 0.05, Variant assessed as somatic; moderate impact.
- M12R (p.Met12Arg), rs776147637, ClinGen CA345930003, ClinVar RCV003415508, MutPred 0.54, Uncertain significance, not provided
- M12T (p.Met12Thr), ExAC rs776147637, gnomAD rs776147637, REVEL 0.20, MetaLR 0.09
- M12V (p.Met12Val), NCI-TCGA Cosmic COSV5525, Variant assessed as somatic; moderate impact.
- p.Met12 Cys14del, rs1048058262, gnomAD 2-15942095-GGCATG, CADD 21.60
- I13I (p.Ile13Ile), rs1662611231, gnomAD 2-15940664-C-A, CADD 18.60
- C14R (p.Cys14Arg), Ensembl rs2103323256
- C14Y (p.Cys14Tyr), TOPMed rs886765376, gnomAD rs886765376, REVEL 0.15, MetaLR 0.06
- C14F (p.Cys14Phe), gnomAD 2-15942105-G-T, REVEL 0.16, MetaLR 0.08
- K15N (p.Lys15Asn), Ensembl rs2103323276
- K15R (p.Lys15Arg), gnomAD rs1429263576, REVEL 0.09, MetaLR 0.06
- K15E (p.Lys15Glu), gnomAD 2-15940641-A-G, CADD 18.50, SIFT 0.26
- N16D (p.Asn16Asp), Ensembl rs2103323286
- N16I (p.Asn16Ile), Ensembl rs2103323292
- N16K (p.Asn16Lys), Ensembl rs2103323297
- N16T (p.Asn16Thr), gnomAD 2-15940601-TG-T, CADD 18.60
- N16S (p.Asn16Ser), rs1007593827, gnomAD 2-15940606-A-G, CADD 19.60, SIFT 0.05
- P17A (p.Pro17Ala), TOPMed rs1168585029
- P17L (p.Pro17Leu), ExAC rs760258394, gnomAD rs760258394
- P17R (p.Pro17Arg), ExAC rs760258394, gnomAD rs760258394, REVEL 0.10, MetaLR 0.07
- P17T (p.Pro17Thr), TOPMed rs1168585029
- D18A (p.Asp18Ala), Ensembl rs2103323319
- D18H (p.Asp18His), Ensembl rs2103323315
- D18V (p.Asp18Val), Ensembl rs2103323319
- L19F (p.Leu19Phe), ExAC rs763755133, TOPMed rs763755133, gnomAD rs763755133
- L19H (p.Leu19His), Ensembl rs2103323337
- L19I (p.Leu19Ile), ExAC rs763755133, TOPMed rs763755133, gnomAD rs763755133
- L19V (p.Leu19Val), ExAC rs763755133, TOPMed rs763755133, gnomAD rs763755133, REVEL 0.17, MetaLR 0.15
- L19L (p.Leu19Leu), gnomAD 2-15940629-C-T, CADD 20.20
- L19Q (p.Leu19Gln), rs1662607722, gnomAD 2-15940630-T-A, CADD 19.40, SIFT 0.00
- E20* (p.Glu20Ter), Ensembl rs2103323352
- E20D (p.Glu20Asp), TOPMed rs1662699303
- E20K (p.Glu20Lys), Ensembl rs2103323352
- E20Q (p.Glu20Gln), NCI-TCGA Cosmic COSV5525, Ensembl rs2103323352, Variant assessed as somatic; moderate impact.
- E20V (p.Glu20Val), Ensembl rs2103323358
- E20S (p.Glu20Ser), gnomAD 2-15940619-CG-C, CADD 18.90
- E20E (p.Glu20Glu), rs1662606963, gnomAD 2-15940622-G-A, CADD 19.60
- E20A (p.Glu20Ala), gnomAD 2-15942123-A-C, REVEL 0.45, MetaLR 0.13
- F21C (p.Phe21Cys), Ensembl rs2103323385
- F21I (p.Phe21Ile), Ensembl rs2103323376
- F21L (p.Phe21Leu), TOPMed rs1477455904, gnomAD rs1477455904, Uncertain significance, not provided
- F21V (p.Phe21Val), Ensembl rs2103323376
- F21Y (p.Phe21Tyr), Ensembl rs2103323385, REVEL 0.24, MetaLR 0.04
- D22A (p.Asp22Ala), Ensembl rs2103323402
- D22E (p.Asp22Glu), Ensembl rs2103323406
- D22G (p.Asp22Gly), Ensembl rs2103323402
- D22H (p.Asp22His), Ensembl rs2103323397
- D22V (p.Asp22Val), Ensembl rs2103323402
- D22Y (p.Asp22Tyr), Ensembl rs2103323397
- S23* (p.Ser23Ter), NCI-TCGA Cosmic COSV5526, ExAC rs776400798, TOPMed rs776400798, gnomAD rs776400798, Variant assessed as somatic; high impact.
- S23L (p.Ser23Leu), ExAC rs776400798, TOPMed rs776400798, gnomAD rs776400798
- S23W (p.Ser23Trp), ExAC rs776400798, TOPMed rs776400798, gnomAD rs776400798, REVEL 0.27, MetaLR 0.15
- S23S (p.Ser23Ser), rs141260022, gnomAD 2-15942133-G-C, CADD 12.30
- L24I (p.Leu24Ile), gnomAD rs1464331307
- L24P (p.Leu24Pro), Ensembl rs2103323435, REVEL 0.54, MetaLR 0.16
- L24Q (p.Leu24Gln), Ensembl rs2103323435
- L24V (p.Leu24Val), gnomAD rs1464331307
- L24L (p.Leu24Leu), rs1464331307, gnomAD 2-15942134-C-T, CADD 14.50
- Q25* (p.Gln25Ter), rs886041290, ClinGen CA10602808, ClinVar RCV000403531, Ensembl rs886041290, MutPred 0.73, Pathogenic
- Q25E (p.Gln25Glu), Ensembl rs886041290, Pathogenic
- Q25H (p.Gln25His), ExAC rs764975322, TOPMed rs764975322, gnomAD rs764975322, REVEL 0.27, MetaLR 0.16
- Q25K (p.Gln25Lys), Ensembl rs886041290, Pathogenic
- Q25L (p.Gln25Leu), Ensembl rs2103323450
- Q25P (p.Gln25Pro), rs1662607045, gnomAD 2-15940624-A-C, CADD 17.30, SIFT 0.08
- Q25Q (p.Gln25Gln), rs1662607166, gnomAD 2-15940625-A-G, CADD 19.90
- Q25D (p.Gln25Asp), rs1558532321, gnomAD 2-15940647-GCA-G, CADD 18.40
- Q25R (p.Gln25Arg), gnomAD 2-15940651-A-G, CADD 16.40, SIFT 0.41
- P26L (p.Pro26Leu), rs1662700407, ClinGen CA345930101, ClinVar RCV002226846, TOPMed rs1662700407, REVEL 0.44, MetaLR 0.29, Likely pathogenic, Feingold syndrome type 1
- P26S (p.Pro26Ser), Ensembl rs2103323461
- P26T (p.Pro26Thr), Ensembl rs2103323461
- P26P (p.Pro26Pro), rs1237986262, gnomAD 2-15942142-C-T, CADD 15.20
- C27* (p.Cys27Ter), Ensembl rs2103323489
- C27F (p.Cys27Phe), Ensembl rs2103323483
- C27R (p.Cys27Arg), Ensembl rs2103323479
- C27S (p.Cys27Ser), Ensembl rs2103323479
- C27Y (p.Cys27Tyr), Ensembl rs2103323483, REVEL 0.29, MetaLR 0.05
- C27W (p.Cys27Trp), gnomAD 2-15942145-C-G, REVEL 0.31, MetaLR 0.12
- C27C (p.Cys27Cys), rs2103323489, gnomAD 2-15942145-C-T, CADD 15.20
- F28L (p.Phe28Leu), Ensembl rs2103323499
- Y29* (p.Tyr29Ter), Ensembl rs2103323520
- Y29C (p.Tyr29Cys), Ensembl rs2103323516
- Y29F (p.Tyr29Phe), Ensembl rs2103323516
- Y29H (p.Tyr29His), Ensembl rs1662700729
- Y29N (p.Tyr29Asn), Ensembl rs1662700729
- Y29S (p.Tyr29Ser), Ensembl rs2103323516
- P30L (p.Pro30Leu), gnomAD rs1662700836, CADD 19.70, SIFT 0.01
- P30Q (p.Pro30Gln), gnomAD rs1662700836
- P30R (p.Pro30Arg), gnomAD rs1662700836, REVEL 0.29, MetaLR 0.12
- p.Pro30 Arg31insProProProProProP, gnomAD 2-15940667-A-AGGA, CADD 16.30
- P30A (p.Pro30Ala), gnomAD 2-15940673-C-CG, CADD 18.40
- P30T (p.Pro30Thr), gnomAD 2-15940674-C-A, CADD 18.60, SIFT 0.01
- P30S (p.Pro30Ser), rs1033508134, gnomAD 2-15940674-C-T, CADD 19.00, SIFT 0.02
- P30H (p.Pro30His), gnomAD 2-15940675-C-A, CADD 19.20, SIFT 0.06
- P30P (p.Pro30Pro), gnomAD 2-15940676-C-T, CADD 17.90
- p.Pro33dup, gnomAD 2-15940678-G-GCCC, CADD 15.50
- D31E (p.Asp31Glu), gnomAD rs1339230115, REVEL 0.19, MetaLR 0.05
- D31G (p.Asp31Gly), gnomAD rs1275764497, REVEL 0.36, MetaLR 0.14
- D31H (p.Asp31His), Ensembl rs2103323544, Likely pathogenic
- D31N (p.Asp31Asn), NCI-TCGA Cosmic COSV5525, Ensembl rs2103323544, REVEL 0.26, MetaLR 0.15, Conflicting interpretations, Inborn genetic diseases; Feingold syndrome type 1
- D31V (p.Asp31Val), gnomAD rs1275764497
- D31Y (p.Asp31Tyr), gnomAD 2-15942155-G-T, REVEL 0.35, MetaLR 0.14
- D31D (p.Asp31Asp), rs1339230115, gnomAD 2-15942157-C-T, CADD 14.00
- E32D (p.Glu32Asp), TOPMed rs1033952007, gnomAD rs1033952007
- E32G (p.Glu32Gly), Ensembl rs1572216932
- E32K (p.Glu32Lys), gnomAD rs1218586780, REVEL 0.38, MetaLR 0.14
- E32Q (p.Glu32Gln), gnomAD rs1218586780
- E32E (p.Glu32Glu), rs1033952007, gnomAD 2-15942160-A-G, CADD 13.50
- D33A (p.Asp33Ala), Ensembl rs1558533634, REVEL 0.29, MetaLR 0.12
- D33E (p.Asp33Glu), Ensembl rs2103323592
- D33G (p.Asp33Gly), Ensembl rs1558533634, REVEL 0.32, MetaLR 0.12
- D33H (p.Asp33His), TOPMed rs1481041288
- D33N (p.Asp33Asn), TOPMed rs1481041288, REVEL 0.22, MetaLR 0.06
- D33V (p.Asp33Val), Ensembl rs1558533634
- D33D (p.Asp33Asp), gnomAD 2-15942163-T-C, CADD 12.30
- D34A (p.Asp34Ala), TOPMed rs1662701850
- D34E (p.Asp34Glu), NCI-TCGA TCGA novel, Ensembl rs2103323617, Variant assessed as somatic; moderate impact.
- D34G (p.Asp34Gly), TOPMed rs1662701850
- D34V (p.Asp34Val), TOPMed rs1662701850
- D34D (p.Asp34Asp), rs2103323617, gnomAD 2-15942166-C-T, CADD 14.40
- F35L (p.Phe35Leu), ExAC rs766296336, TOPMed rs766296336, gnomAD rs766296336, REVEL 0.27, MetaLR 0.16
- F35Y (p.Phe35Tyr), gnomAD 2-15942168-T-A, REVEL 0.36, MetaLR 0.23
- F35C (p.Phe35Cys), gnomAD 2-15942168-T-G, REVEL 0.40, MetaLR 0.29
- Y36* (p.Tyr36Ter), TOPMed rs1208455293, gnomAD rs1208455293
- Y36C (p.Tyr36Cys), Ensembl rs1572216960
- Y36F (p.Tyr36Phe), Ensembl rs1572216960
- Y36H (p.Tyr36His), Ensembl rs2103323641, REVEL 0.22, MetaLR 0.22
- Y36S (p.Tyr36Ser), Ensembl rs1572216960
- Y36Y (p.Tyr36Tyr), rs1208455293, gnomAD 2-15942172-C-T, CADD 13.00
- F37I (p.Phe37Ile), TOPMed rs1255684004, gnomAD rs1255684004, REVEL 0.10, MetaLR 0.05, Uncertain significance, not provided
Public MYCN analysis runs
- MYCN analysis run — MYCN (1,371 variants) — completed 2026-08-19