ERBB4 (HER4) somatic mutation / amplification
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BIO-ERBB4 |
|---|---|
| Type | Biomarker |
| Aliases | ERBB4 / HER4 mutationСоматична мутація / ампліфікація ERBB4 (HER4) |
| Status | reviewed 2026-05-04 | pending_clinical_signoff |
| Diseases | None declared |
| Sources | SRC-ESMO-NSCLC-METASTATIC-2024 SRC-NCCN-NSCLC-2025 |
Biomarker Facts
| Biomarker type | gene_mutation |
|---|---|
| Mutation details | {"exon": "multiple; kinase domain (E872K, E317K) and extracellular domain; fusions (ERBB4-NRG1 pathway)", "functional_impact": "gain-of-function (ERBB4 homodimerization or heterodimerization with EGFR/HER2/HER3 → PI3K/AKT, MAPK)", "gene": "ERBB4", "variant_type": "activating missense; amplification; fusion (rare)"} |
| Measurement | MethodTumor NGS panel (DNA); FISH for amplification; RNA-seq for fusions |
| Actionability lookup | {"gene": "ERBB4", "variant": "activating_mutation"} |
| Related biomarkers | BIO-EGFR BIO-ERBB2 BIO-ERBB3 BIO-NRG1 |
Notes
ERBB4 (HER4) is the fourth member of the ERBB/HER receptor tyrosine kinase family. Somatic mutations occur in ~2–3% of NSCLC (mixed histologies). Afatinib (pan-HER inhibitor) and neratinib have preclinical/early clinical activity against ERBB4-mutant tumors, but no prospective Phase III trial has demonstrated benefit in ERBB4-selected patients. Afatinib is FDA-approved for EGFR-mutant NSCLC and ERBB2-mutant NSCLC (exon 20) — ERBB4 mutation alone does not qualify for these approvals. NRG1 fusions (NRG1 is the primary ERBB4 ligand) are a distinct actionable alteration that activates ERBB3/ERBB4 signaling; afatinib and zenocutuzumab (bispecific anti-HER2/HER3) have shown activity in NRG1-fusion lung cancer. ERBB4 mutation per se is not currently an approved companion diagnostic target.
Used By
Actionability
BMA-ERBB4-NSCLC- ERBB4 (HER4) somatic activating mutations are identified in ~2–3% of NSCLC (mixed histolo...