Lung cancer: genes and variants

Genes linked to Lung cancer

• PRKN: E3 ubiquitin-protein ligase parkin

  Its parkin ubiquitin-ligase activity marks damaged mitochondrial proteins after PINK1 activation and helps eliminate dysfunctional mitochondria through mitophagy. Biallelic loss-of-function variants are a major cause of autosomal recessive juvenile or early-onset Parkinson disease.

  4 disease-causing and 7 uncertain variants in PRKN are linked to Lung cancer.

• 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.

  1 disease-causing and 6 uncertain variants in BRAF are linked to Lung cancer.

• KRAS: GTPase KRas

  A small GTPase that acts as a molecular switch in the RAS-MAPK signaling pathway. By cycling between GDP- and GTP-bound states, it relays growth and survival signals, and activating KRAS variants are common drivers of cancer.

  1 disease-causing and 1 uncertain variants in KRAS are linked to Lung cancer.

• PIK3CA: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform

  Its p110-alpha catalytic activity generates PIP3 and activates AKT-dependent growth, survival, and metabolic signaling downstream of many receptors. Activating variants are frequent cancer drivers and, when present mosaically during development, can cause PIK3CA-related overgrowth spectrum.

  1 disease-causing and 1 uncertain variants in PIK3CA are linked to Lung cancer.

• ALK: ALK tyrosine kinase receptor

  Its kinase signaling influences neural development and cell growth, but constitutive activation can become strongly oncogenic. ALK fusions, activating mutations, or amplification drive anaplastic large-cell lymphoma, subsets of lung cancer, and neuroblastoma and can be targeted with ALK inhibitors.

  1 disease-causing and 0 uncertain variants in ALK are linked to Lung cancer.

• ERBB2: Receptor tyrosine-protein kinase erbB-2

  ERBB2, also called HER2, is a cell-surface receptor tyrosine kinase that works with other ERBB receptors to transmit growth signals. It helps organize signaling and cytoskeletal responses, and abnormal ERBB2 activity is a major feature of several cancers.

  0 disease-causing and 25 uncertain variants in ERBB2 are linked to Lung cancer.

• CD274: Programmed cell death 1 ligand 1

  By engaging PD-1, it suppresses activated T cells by engaging PD-1 and thereby limits immune-mediated tissue damage. Many cancers exploit high PD-L1 expression to evade immune attack, making the PD-1/PD-L1 axis a central target of immune-checkpoint therapy.

  0 disease-causing and 0 uncertain variants in CD274 are linked to Lung cancer.

• EGFR: Epidermal growth factor receptor

  A cell-surface receptor tyrosine kinase that responds to epidermal-growth-factor family ligands. Ligand binding activates phosphorylation cascades that regulate cell growth, survival, and differentiation, which is why EGFR changes are important in cancer biology.

  0 disease-causing and 0 uncertain variants in EGFR are linked to Lung cancer.

• PDCD1: Programmed cell death protein 1

  PDCD1 is an inhibitory receptor on activated T cells that binds PD-L1 and PD-L2. Its signaling helps maintain immune tolerance by restraining T-cell activation, making the protein important in autoimmunity and cancer immunotherapy.

  0 disease-causing and 0 uncertain variants in PDCD1 are linked to Lung cancer.

• NFE2L2: Nuclear factor erythroid 2-related factor 2

  It activates antioxidant, detoxification, and metabolic genes when released from KEAP1-mediated degradation. Somatic activating variants can lock cancer cells into a persistent stress-resistant state and promote therapy resistance.

  1 disease-causing and 0 uncertain variants in NFE2L2 are linked to Lung cancer.

Known disease-causing variants in Lung cancer

Which prediction tools work for Lung cancer

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

• CATVariant: 88 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 83 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Autosomal recessive juvenile Parkinson disease 2 is also caused by PRKN variants; they fall mostly in different places as the Lung cancer variants (15 disease-causing).
• RASopathy is also caused by BRAF variants; they fall mostly in different places as the Lung cancer variants (36 disease-causing).
• Cardio-facio-cutaneous syndrome is also caused by BRAF variants; they fall mostly in different places as the Lung cancer variants (26 disease-causing).
• Cardiofaciocutaneous syndrome is also caused by BRAF variants; they fall mostly in different places as the Lung cancer variants (17 disease-causing).
• Noonan syndrome is also caused by BRAF variants; they fall mostly in different places as the Lung cancer variants (11 disease-causing).
• Noonan syndrome and Noonan-related syndrome is also caused by BRAF variants; they fall mostly in different places as the Lung cancer variants (10 disease-causing).
• RASopathy is also caused by KRAS variants; they fall mostly in different places as the Lung cancer variants (23 disease-causing).
• Noonan syndrome is also caused by KRAS variants; they fall mostly in different places as the Lung cancer variants (16 disease-causing).
• Cardiofaciocutaneous syndrome is also caused by KRAS variants; they fall mostly in different places as the Lung cancer variants (9 disease-causing).
• Autoimmune lymphoproliferative syndrome is also caused by KRAS variants; they fall partly in the same places as the Lung cancer variants (5 disease-causing).
• Non-small cell lung carcinoma is also caused by KRAS variants; they fall mostly in different places as the Lung cancer variants (5 disease-causing).
• PIK3CA related overgrowth syndrome is also caused by PIK3CA variants; they fall mostly in different places as the Lung cancer variants (30 disease-causing).
• Cowden syndrome is also caused by PIK3CA variants; they fall mostly in different places as the Lung cancer variants (23 disease-causing).
• Megalencephaly-capillary malformation-polymicrogyria syndrome is also caused by PIK3CA variants; they fall mostly in different places as the Lung cancer variants (22 disease-causing).
• Ovarian neoplasm is also caused by PIK3CA variants; they fall mostly in different places as the Lung cancer variants (5 disease-causing).
• PIK3CA constitutional syndrome is also caused by PIK3CA variants; they fall mostly in different places as the Lung cancer variants (4 disease-causing).
• Immunodeficiency, developmental delay, and hypohomocysteinemia is also caused by NFE2L2 variants; they fall partly in the same places as the Lung cancer variants (3 disease-causing).

Diseases related to Lung cancer

• Non-small cell lung carcinoma, also linked to ALK, BRAF, CD274, EGFR and 4 more
• Colorectal cancer, also linked to BRAF, EGFR, ERBB2, KRAS and 2 more
• Ovarian cancer, also linked to ALK, ERBB2, PIK3CA and PRKN
• Gastric cancer, also linked to ERBB2, KRAS, PDCD1 and PIK3CA
• Lung adenocarcinoma, also linked to BRAF, EGFR, ERBB2 and KRAS
• Hepatocellular carcinoma, also linked to BRAF, CD274, NFE2L2 and PIK3CA
• Noonan syndrome, also linked to BRAF, KRAS and PIK3CA
• Malignant tumor of urinary bladder, also linked to ERBB2, KRAS and PIK3CA
• Ovarian neoplasm, also linked to ERBB2, PIK3CA and PRKN
• RASopathy, also linked to BRAF and KRAS
• Noonan syndrome and Noonan-related syndrome, also linked to BRAF and KRAS
• Cardiofaciocutaneous syndrome, also linked to BRAF and KRAS

Frequently asked questions

Which genes are linked to Lung cancer?

In CATVariant, Lung cancer is linked to 10 analyzed proteins: PRKN (E3 ubiquitin-protein ligase parkin), BRAF (Serine/threonine-protein kinase B-raf), KRAS (GTPase KRas), PIK3CA (Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform), ALK (ALK tyrosine kinase receptor), ERBB2 (Receptor tyrosine-protein kinase erbB-2) and 4 more.

How many genetic variants are linked to Lung cancer?

60 variants: 9 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 40 are of uncertain significance or have conflicting reports.

Which uncertain variants in Lung cancer look disease-causing?

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

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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