Lung adenocarcinoma: genes and variants

Genes linked to Lung adenocarcinoma

• 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.

  3 disease-causing and 0 uncertain variants in BRAF are linked to Lung adenocarcinoma.

• 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.

  3 disease-causing and 0 uncertain variants in ERBB2 are linked to Lung adenocarcinoma.

• ROS1: Proto-oncogene tyrosine-protein kinase ROS

  Its normal physiologic signaling remains incompletely defined, but chromosomal rearrangement can place its kinase domain under constitutive control. ROS1 fusion kinases are actionable oncogenic drivers in non-small-cell lung cancer and several other tumors.

  2 disease-causing and 2 uncertain variants in ROS1 are linked to Lung adenocarcinoma.

• TP53: Cellular tumor antigen p53

  It coordinates transcriptional responses to DNA damage and other cellular stresses, promoting cell-cycle arrest, senescence, DNA repair, or apoptosis when appropriate. Loss of this tumor-suppressive control is one of the most common events in cancer, while germline pathogenic variants cause Li-Fraumeni syndrome.

  0 disease-causing and 3 uncertain variants in TP53 are linked to Lung adenocarcinoma.

• ARID1A: AT-rich interactive domain-containing protein 1A

  It helps BAF chromatin-remodeling complexes open or reposition nucleosomes at regulatory regions and thereby control lineage-specific transcription. Somatic loss is frequent in several cancers, while germline haploinsufficiency can cause Coffin-Siris syndrome.

  0 disease-causing and 0 uncertain variants in ARID1A are linked to Lung adenocarcinoma.

• 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.

  0 disease-causing and 0 uncertain variants in CDKN2A are linked to Lung adenocarcinoma.

• 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 adenocarcinoma.

• KEAP1: Kelch-like ECH-associated protein 1

  It continuously targets NRF2 for degradation under basal conditions but releases this brake when reactive electrophiles or oxidative stress modify KEAP1. Somatic loss-of-function variants can lock tumors into a persistent antioxidant state that promotes survival and treatment resistance.

  0 disease-causing and 0 uncertain variants in KEAP1 are linked to Lung adenocarcinoma.

• 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.

  0 disease-causing and 0 uncertain variants in KRAS are linked to Lung adenocarcinoma.

• RB1: Retinoblastoma-associated protein

  It restrains E2F-dependent transcription and prevents inappropriate G1-to-S cell-cycle progression until proliferative signals are appropriate. Loss of function is a fundamental cancer-driving event, while germline pathogenic variants cause hereditary retinoblastoma and increase risk of additional tumors.

  0 disease-causing and 0 uncertain variants in RB1 are linked to Lung adenocarcinoma.

• RBM10: RNA-binding protein 10

  It regulates alternative pre-mRNA splicing and influences expression of proteins controlling cell growth, apoptosis, and differentiation. Loss-of-function variants cause TARP syndrome, while somatic inactivation is recurrent in lung adenocarcinoma and other cancers.

  0 disease-causing and 0 uncertain variants in RBM10 are linked to Lung adenocarcinoma.

• SMARCA4: SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4

  Its ATPase activity drives nucleosome remodeling in BAF-family complexes and thereby controls access to regulatory DNA. Germline pathogenic variants cause Coffin-Siris syndrome or rhabdoid-tumor predisposition, while somatic loss defines several aggressive cancers.

  0 disease-causing and 0 uncertain variants in SMARCA4 are linked to Lung adenocarcinoma.

• 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.

  0 disease-causing and 0 uncertain variants in STK11 are linked to Lung adenocarcinoma.

• 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 0 uncertain variants in TERT are linked to Lung adenocarcinoma.

• U2AF1: Splicing factor U2AF 35 kDa subunit

  It recognizes the AG dinucleotide at 3-prime splice sites during early spliceosome assembly. Recurrent S34 and Q157 hotspot mutations alter splice-site selection and are important drivers of myelodysplastic syndromes, AML, and some solid tumors.

  0 disease-causing and 0 uncertain variants in U2AF1 are linked to Lung adenocarcinoma.

• CDK12: Cyclin-dependent kinase 12

  It promotes transcription of long DNA-repair and genome-maintenance genes through RNA-polymerase-II phosphorylation. Loss-of-function alterations occur in prostate, ovarian, and other cancers and can create a characteristic pattern of genomic instability.

  1 disease-causing and 0 uncertain variants in CDK12 are linked to Lung adenocarcinoma.

Weakly linked (only a few uncertain records): TLR4 and APC.

Known disease-causing variants in Lung adenocarcinoma

Which prediction tools work for Lung adenocarcinoma

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

• CATVariant: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• RASopathy is also caused by BRAF variants; they fall mostly in different places as the Lung adenocarcinoma variants (36 disease-causing).
• Cardio-facio-cutaneous syndrome is also caused by BRAF variants; they fall mostly in different places as the Lung adenocarcinoma variants (26 disease-causing).
• Cardiofaciocutaneous syndrome is also caused by BRAF variants; they fall mostly in different places as the Lung adenocarcinoma variants (17 disease-causing).
• Noonan syndrome is also caused by BRAF variants; they fall mostly in different places as the Lung adenocarcinoma variants (11 disease-causing).
• Noonan syndrome and Noonan-related syndrome is also caused by BRAF variants; they fall partly in the same places as the Lung adenocarcinoma variants (10 disease-causing).
• Malignant tumor of urinary bladder is also caused by ERBB2 variants; they fall mostly in different places as the Lung adenocarcinoma variants (6 disease-causing).

Diseases related to Lung adenocarcinoma

• Non-small cell lung carcinoma, also linked to BRAF, CDKN2A, EGFR, ERBB2 and 7 more
• Colorectal cancer, also linked to ARID1A, BRAF, EGFR, ERBB2 and 2 more
• Hepatocellular carcinoma, also linked to ARID1A, BRAF, CDKN2A, RB1 and 2 more
• Acute myeloid leukemia, also linked to KRAS, TERT, TP53 and U2AF1
• Melanoma, cutaneous malignant, susceptibility to, 8, also linked to BRAF, CDKN2A, STK11 and TERT
• Lung cancer, also linked to BRAF, EGFR, ERBB2 and KRAS
• Gastric cancer, also linked to ERBB2, KRAS and TP53
• Malignant tumor of urinary bladder, also linked to ERBB2, KRAS and RB1
• Hereditary breast ovarian cancer syndrome, also linked to CDK12, KRAS and TP53
• Familial pancreatic carcinoma, also linked to KRAS, STK11 and TP53
• Lung carcinoma, also linked to BRAF, EGFR and TERT
• RASopathy, also linked to BRAF and KRAS

Frequently asked questions

Which genes are linked to Lung adenocarcinoma?

In CATVariant, Lung adenocarcinoma is linked to 16 analyzed proteins: BRAF (Serine/threonine-protein kinase B-raf), ERBB2 (Receptor tyrosine-protein kinase erbB-2), ROS1 (Proto-oncogene tyrosine-protein kinase ROS), TP53 (Cellular tumor antigen p53), ARID1A (AT-rich interactive domain-containing protein 1A), CDKN2A (Tumor suppressor ARF) and 10 more.

How many genetic variants are linked to Lung adenocarcinoma?

17 variants: 9 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 8 are of uncertain significance or have conflicting reports.

Which uncertain variants in Lung adenocarcinoma 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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