Head and neck squamous cell carcinoma: genes and variants
Explore variant evidence for Head and neck squamous cell carcinoma across 16 analyzed proteins (TP53, PTEN, CASP8, CD274, CDKN2A and 11 more). Linked ClinVar records include 2 pathogenic or likely pathogenic variants, 2 variants of uncertain significance and 5 with conflicting classifications.
Coverage includes proteins already analyzed in CATVariant, not every gene involved in this condition. Database links are associations, not an assessment of clinical gene–disease validity. Computable evidence prioritizes variants for expert review and does not reclassify them. Source labels are pooled across this disease family.
Data updated 2026-10-10. Automated aggregation, not a clinical review date.
Download variant evidence (CSV)
Genes linked to Head and neck squamous cell carcinoma
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.
2 ClinVar pathogenic / likely pathogenic and 6 uncertain variants in TP53 have source records linked to Head and neck squamous cell carcinoma. Association strength is not clinical gene validity.
PTEN: Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
A lipid and protein phosphatase that removes phosphate groups from signaling molecules, especially PIP3. By opposing the PI3K-AKT pathway, it limits cell growth and survival signals, and PTEN variants are associated with Cowden syndrome and multiple cancers.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in PTEN have source records linked to Head and neck squamous cell carcinoma. Association strength is not clinical gene validity.
CASP8: Caspase-8
It initiates death-receptor-mediated apoptosis but also regulates lymphocyte activation and inflammatory signaling. Biallelic loss-of-function variants can cause immunodeficiency with defective apoptosis and lymphocyte homeostasis, while somatic pathway alterations can promote cancer-cell survival.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in CASP8 have source records linked to Head and neck squamous cell carcinoma. Association strength is not clinical gene validity.
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 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in CD274 have source records linked to Head and neck squamous cell carcinoma. Association strength is not clinical gene validity.
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 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in CDKN2A have source records linked to Head and neck squamous cell carcinoma. Association strength is not clinical gene validity.
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 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in EGFR have source records linked to Head and neck squamous cell carcinoma. Association strength is not clinical gene validity.
EP300: Histone acetyltransferase p300
It acetylates histones and transcription factors and acts as a central coactivator for developmental and stress-responsive transcription. Germline loss-of-function variants cause Rubinstein-Taybi syndrome type 2, while acquired alterations occur in several cancers.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in EP300 have source records linked to Head and neck squamous cell carcinoma. Association strength is not clinical gene validity.
FAT1: Protocadherin Fat 1
A large cell-surface cadherin involved in cell polarity, cell-cell contact, and directed cell migration. These functions help organize developing and renewing tissues.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in FAT1 have source records linked to Head and neck squamous cell carcinoma. Association strength is not clinical gene validity.
HRAS: GTPase HRas
Its GTP-bound state activates RAF-MEK-ERK and other pathways downstream of growth-factor receptors. Somatic activating variants drive several cancers, while germline activating variants cause Costello syndrome.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in HRAS have source records linked to Head and neck squamous cell carcinoma. Association strength is not clinical gene validity.
KMT2D: Histone-lysine N-methyltransferase 2D
It deposits enhancer-associated H3K4 methylation and coordinates developmental gene expression through chromatin regulatory complexes. Heterozygous loss-of-function variants are a major cause of Kabuki syndrome, and somatic mutations are common in several lymphomas and solid tumors.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in KMT2D have source records linked to Head and neck squamous cell carcinoma. Association strength is not clinical gene validity.
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.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in NFE2L2 have source records linked to Head and neck squamous cell carcinoma. Association strength is not clinical gene validity.
NOTCH1: Neurogenic locus notch homolog protein 1
Ligand-dependent cleavage releases an intracellular domain that directly controls transcriptional programs governing cell fate and differentiation. Pathogenic variants can cause congenital aortic-valve disease and left-sided heart defects, while activating or inactivating somatic changes contribute to several cancers.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in NOTCH1 have source records linked to Head and neck squamous cell carcinoma. Association strength is not clinical gene validity.
NSD1: Histone-lysine N-methyltransferase, H3 lysine-36 specific
It regulates developmental transcription through chromatin modification, including H3K36 methylation. Haploinsufficiency causes Sotos syndrome with childhood overgrowth, characteristic facial features, and developmental delay, while somatic rearrangements occur in some leukemias.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in NSD1 have source records linked to Head and neck squamous cell carcinoma. Association strength is not clinical gene validity.
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 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in PDCD1 have source records linked to Head and neck squamous cell carcinoma. Association strength is not clinical gene validity.
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.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in PIK3CA have source records linked to Head and neck squamous cell carcinoma. Association strength is not clinical gene validity.
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 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in SMARCA4 have source records linked to Head and neck squamous cell carcinoma. Association strength is not clinical gene validity.
Weakly linked (only a few uncertain records): KEAP1.
ClinVar pathogenic and likely pathogenic variants linked to Head and neck squamous cell carcinoma
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| TP53 G266E | 266 | DNA binding | Pathogenic / likely pathogenic (★★) |
| TP53 H193R | 193 | DNA binding | Pathogenic / likely pathogenic (★★) |
Same protein, different disease
- Li-Fraumeni syndrome also has ClinVar records linked to TP53 variants; they fall mostly in different places as the Head and neck squamous cell carcinoma variants (188 pathogenic / likely pathogenic).
- Adrenocortical carcinoma, hereditary also has ClinVar records linked to TP53 variants; they fall mostly in different places as the Head and neck squamous cell carcinoma variants (23 pathogenic / likely pathogenic).
- Acute myeloid leukemia also has ClinVar records linked to TP53 variants; they fall mostly in different places as the Head and neck squamous cell carcinoma variants (6 pathogenic / likely pathogenic).
- Hereditary breast cancer also has ClinVar records linked to TP53 variants; they fall mostly in different places as the Head and neck squamous cell carcinoma variants (5 pathogenic / likely pathogenic).
- Glioma susceptibility 1 also has ClinVar records linked to TP53 variants; they fall mostly in different places as the Head and neck squamous cell carcinoma variants (5 pathogenic / likely pathogenic).
Diseases related to Head and neck squamous cell carcinoma
- Urinary bladder cancer, also linked to CDKN2A, EGFR, EP300, HRAS and 3 more
- Non-small cell lung carcinoma, also linked to CD274, CDKN2A, EGFR, PDCD1 and 2 more
- Colorectal cancer, also linked to EGFR, EP300, NFE2L2, PIK3CA and 1 more
- Lung cancer, also linked to CD274, EGFR, NFE2L2, PDCD1 and 1 more
- Hepatocellular carcinoma, also linked to CD274, CDKN2A, NFE2L2, PIK3CA and 1 more
- Lung adenocarcinoma, also linked to CDKN2A, EGFR, SMARCA4 and TP53
- Hereditary breast cancer, also linked to PIK3CA, PTEN and TP53
- Gastric cancer, also linked to PDCD1, PIK3CA and TP53
- Esophageal cancer, also linked to CDKN2A, PDCD1 and TP53
- Melanoma, also linked to CDKN2A, PDCD1 and PTEN
- Noonan syndrome, also linked to HRAS and PIK3CA
- Cowden disease, also linked to PIK3CA and PTEN
Frequently asked questions
Which genes have records linked to Head and neck squamous cell carcinoma?
This view contains 16 analyzed proteins: TP53, PTEN, CASP8, CD274, CDKN2A and 11 more. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.
What do the clinical classifications mean?
Linked records include 2 pathogenic or likely pathogenic variants, 2 variants of uncertain significance and 5 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.
Does the evidence score change a VUS classification?
No. 0 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.
Can I download the variant evidence?
Download the CSV for all 10 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses 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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