Melanoma, cutaneous malignant, susceptibility to, 8: genes and variants

Genes linked to Melanoma, cutaneous malignant, susceptibility to, 8

• CDKN2A: Tumor suppressor ARF

  The ARF product of CDKN2A is a tumor-suppressor protein that binds MDM2 and helps preserve p53 activity. By promoting cell-cycle arrest and apoptosis, it provides an important barrier to uncontrolled cell growth from within the nucleolus.

  6 disease-causing and 9 uncertain variants in CDKN2A are linked to Melanoma, cutaneous malignant, susceptibility to, 8.

• STK11: Serine/threonine-protein kinase STK11

  It activates AMPK-family kinases to coordinate cellular energy sensing, polarity, and growth restraint. Germline loss-of-function variants cause Peutz-Jeghers syndrome and its associated cancer predisposition, while somatic loss is common in lung and other cancers.

  4 disease-causing and 88 uncertain variants in STK11 are linked to Melanoma, cutaneous malignant, susceptibility to, 8.

• MITF: Microphthalmia-associated transcription factor

  2 disease-causing and 227 uncertain variants in MITF are linked to Melanoma, cutaneous malignant, susceptibility to, 8.

• CDK4: Cyclin-dependent kinase 4

  Together with D-type cyclins, it phosphorylates RB-family proteins and commits cells to progress from G1 toward DNA replication. Amplification or pathway activation is common in cancer, while rare activating germline variants predispose to familial melanoma.

  0 disease-causing and 17 uncertain variants in CDK4 are linked to Melanoma, cutaneous malignant, susceptibility to, 8.

• TERT: Telomerase reverse transcriptase

  It extends telomeric DNA using an internal RNA template and helps counter progressive chromosome-end shortening in stem and proliferative cells. Loss-of-function variants cause telomere-biology disorders, while promoter activation and increased activity support unlimited proliferation in many cancers.

  0 disease-causing and 14 uncertain variants in TERT are linked to Melanoma, cutaneous malignant, susceptibility to, 8.

• BRAF: Serine/threonine-protein kinase B-raf

  It relays activated RAS signals through MEK and ERK to control proliferation, differentiation, and survival. Activating variants, especially V600E, drive melanoma and several other cancers and create sensitivity to pathway-directed therapies.

  0 disease-causing and 19 uncertain variants in BRAF are linked to Melanoma, cutaneous malignant, susceptibility to, 8.

Known disease-causing variants in Melanoma, cutaneous malignant, susceptibility to, 8

Which prediction tools work for Melanoma, cutaneous malignant, susceptibility to, 8

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• PolyPhen-2: 90 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 79 out of 100

Same protein, different disease

• Familial melanoma is also caused by CDKN2A variants; they fall mostly in different places as the Melanoma, cutaneous malignant, susceptibility to, 8 variants (15 disease-causing).
• Melanoma-pancreatic cancer syndrome is also caused by CDKN2A variants; they fall partly in the same places as the Melanoma, cutaneous malignant, susceptibility to, 8 variants (11 disease-causing).
• Melanoma and neural system tumor syndrome is also caused by CDKN2A variants; they fall partly in the same places as the Melanoma, cutaneous malignant, susceptibility to, 8 variants (5 disease-causing).
• Peutz-Jeghers syndrome is also caused by STK11 variants; they fall mostly in different places as the Melanoma, cutaneous malignant, susceptibility to, 8 variants (24 disease-causing).
• Waardenburg syndrome is also caused by MITF variants; they fall mostly in different places as the Melanoma, cutaneous malignant, susceptibility to, 8 variants (10 disease-causing).

Diseases related to Melanoma, cutaneous malignant, susceptibility to, 8

• Lung adenocarcinoma, also linked to BRAF, CDKN2A, STK11 and TERT
• Familial melanoma, also linked to CDK4, CDKN2A and TERT
• Non-small cell lung carcinoma, also linked to BRAF, CDKN2A and STK11
• Hepatocellular carcinoma, also linked to BRAF, CDKN2A and TERT
• Melanoma, also linked to BRAF, CDKN2A and MITF
• Alzheimer disease, also linked to CDK4 and CDKN2A
• Lung carcinoma, also linked to BRAF and TERT
• Parkinson disease, also linked to CDK4 and CDKN2A
• Hypertrophic cardiomyopathy, also linked to BRAF
• RASopathy, also linked to BRAF
• Noonan syndrome, also linked to BRAF
• Noonan syndrome and Noonan-related syndrome, also linked to BRAF

Frequently asked questions

Which genes are linked to Melanoma, cutaneous malignant, susceptibility to, 8?

In CATVariant, Melanoma, cutaneous malignant, susceptibility to, 8 is linked to 6 analyzed proteins: CDKN2A (Tumor suppressor ARF), STK11 (Serine/threonine-protein kinase STK11), MITF (Microphthalmia-associated transcription factor), CDK4 (Cyclin-dependent kinase 4), TERT (Telomerase reverse transcriptase) and BRAF (Serine/threonine-protein kinase B-raf).

How many genetic variants are linked to Melanoma, cutaneous malignant, susceptibility to, 8?

412 variants: 12 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 374 are of uncertain significance or have conflicting reports.

Which uncertain variants in Melanoma, cutaneous malignant, susceptibility to, 8 look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

Which variant effect predictor works best for Melanoma, cutaneous malignant, susceptibility to, 8?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.79, based on 9 disease-causing and 96 harmless variants).

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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