Hepatocellular carcinoma: genes and variants

Genes linked to Hepatocellular carcinoma

• CTNNB1: Catenin beta-1

  It links cadherins to the cytoskeleton at adherens junctions and, when stabilized by Wnt signaling, enters the nucleus to regulate transcription. Activating somatic variants drive many cancers, while germline loss-of-function variants cause CTNNB1 neurodevelopmental disorder.

  3 disease-causing and 0 uncertain variants in CTNNB1 are linked to Hepatocellular carcinoma.

• MET: Hepatocyte growth factor receptor

  Hepatocyte-growth-factor signaling through this pathway promotes cell survival, proliferation, motility, and invasive growth during development and tissue repair. Exon 14 skipping, amplification, activating mutations, or fusions can drive cancer and create actionable therapeutic dependencies.

  1 disease-causing and 33 uncertain variants in MET are linked to Hepatocellular 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.

  1 disease-causing and 2 uncertain variants in TP53 are linked to Hepatocellular carcinoma.

• 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.

  1 disease-causing and 0 uncertain variants in TERT are linked to Hepatocellular carcinoma.

• APC: Adenomatous polyposis coli protein

  A tumor-suppressor protein that promotes the removal of beta-catenin and helps keep Wnt signaling under control. It also organizes microtubules and actin in the cell, and inherited APC disruption is strongly associated with familial adenomatous polyposis and colorectal tumor risk.

  0 disease-causing and 13 uncertain variants in APC are linked to Hepatocellular carcinoma.

• 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 disease-causing and 5 uncertain variants in PIK3CA are linked to Hepatocellular carcinoma.

• 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 Hepatocellular carcinoma.

• ARID2: AT-rich interactive domain-containing protein 2

  It contributes DNA targeting and regulatory specificity to PBAF chromatin-remodeling complexes. Somatic loss-of-function alterations occur in melanoma, liver cancer, and other tumors, while germline variants can cause a Coffin-Siris-spectrum neurodevelopmental disorder.

  0 disease-causing and 0 uncertain variants in ARID2 are linked to Hepatocellular carcinoma.

• 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 0 uncertain variants in BRAF are linked to Hepatocellular carcinoma.

• 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 Hepatocellular carcinoma.

• 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 Hepatocellular carcinoma.

• CTLA4: Cytotoxic T-lymphocyte protein 4

  It restrains T-cell activation by competing with CD28 for CD80 and CD86 and by delivering inhibitory signals after immune activation. Haploinsufficiency causes immune dysregulation with autoimmunity and lymphoproliferation, while therapeutic blockade enhances antitumor immunity.

  0 disease-causing and 0 uncertain variants in CTLA4 are linked to Hepatocellular carcinoma.

• FLT3: Receptor-type tyrosine-protein kinase FLT3

  Its signaling supports survival and expansion of early hematopoietic progenitors. Internal tandem duplications and kinase-domain mutations produce constitutive activity in acute myeloid leukemia and are important prognostic markers and therapeutic targets.

  0 disease-causing and 0 uncertain variants in FLT3 are linked to Hepatocellular carcinoma.

• KIT: Mast/stem cell growth factor receptor Kit

  Stem-cell-factor signaling through this pathway supports hematopoietic progenitors, mast cells, melanocytes, and germ cells. Activating variants drive gastrointestinal stromal tumors, systemic mastocytosis, and other malignancies, whereas loss-of-function variants can cause piebaldism.

  0 disease-causing and 0 uncertain variants in KIT are linked to Hepatocellular carcinoma.

• 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 disease-causing and 0 uncertain variants in NFE2L2 are linked to Hepatocellular carcinoma.

• PDGFRB: Platelet-derived growth factor receptor beta

  Its signaling supports pericytes, vascular smooth-muscle cells, and other mesenchymal lineages during growth and tissue repair. Oncogenic fusions drive myeloid neoplasms, while germline activating or loss-of-function variants can cause developmental and vascular disorders.

  0 disease-causing and 0 uncertain variants in PDGFRB are linked to Hepatocellular carcinoma.

• 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 Hepatocellular carcinoma.

• RET: Proto-oncogene tyrosine-protein kinase receptor Ret

  Its activation by GDNF-family ligands guides development of the enteric nervous system, kidney, and other tissues. Activating variants cause multiple endocrine neoplasia type 2 and can drive cancer, whereas loss-of-function variants are an important cause of Hirschsprung disease.

  0 disease-causing and 0 uncertain variants in RET are linked to Hepatocellular carcinoma.

• TSC2: Tuberin

  Together with TSC1, it inactivates RHEB and restrains mTORC1 when growth conditions are unfavorable. Loss-of-function variants cause tuberous sclerosis complex with hamartomas and tumors affecting the brain, kidneys, skin, heart, lungs, and other organs.

  0 disease-causing and 0 uncertain variants in TSC2 are linked to Hepatocellular carcinoma.

Weakly linked (only a few uncertain records): AQP7, CASP8, F13B, GNAI1 and HLA-DPA1.

Known disease-causing variants in Hepatocellular carcinoma

Same protein, different disease

• Pilomatrixoma is also caused by CTNNB1 variants; they fall mostly in different places as the Hepatocellular carcinoma variants (8 disease-causing).
• Severe intellectual disability-progressive spastic diplegia syndrome is also caused by CTNNB1 variants; they fall mostly in different places as the Hepatocellular carcinoma variants (5 disease-causing).
• Medulloblastoma is also caused by CTNNB1 variants; they fall mostly in different places as the Hepatocellular carcinoma variants (4 disease-causing).
• Renal cell carcinoma is also caused by MET variants; they fall mostly in different places as the Hepatocellular carcinoma variants (4 disease-causing).
• Dyskeratosis congenita is also caused by TERT variants; they fall mostly in different places as the Hepatocellular carcinoma variants (23 disease-causing).
• Idiopathic pulmonary fibrosis is also caused by TERT variants; they fall mostly in different places as the Hepatocellular carcinoma variants (13 disease-causing).
• Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 is also caused by TERT variants; they fall mostly in different places as the Hepatocellular carcinoma variants (13 disease-causing).
• Li-Fraumeni syndrome is also caused by TP53 variants; they fall mostly in different places as the Hepatocellular carcinoma variants (188 disease-causing).
• Adrenocortical carcinoma, hereditary is also caused by TP53 variants; they fall mostly in different places as the Hepatocellular carcinoma variants (23 disease-causing).
• Acute myeloid leukemia is also caused by TP53 variants; they fall mostly in different places as the Hepatocellular carcinoma variants (6 disease-causing).
• Familial cancer of breast is also caused by TP53 variants; they fall mostly in different places as the Hepatocellular carcinoma variants (5 disease-causing).
• Glioma susceptibility 1 is also caused by TP53 variants; they fall mostly in different places as the Hepatocellular carcinoma variants (5 disease-causing).

Diseases related to Hepatocellular carcinoma

• Colorectal cancer, also linked to APC, ARID1A, BRAF, CTNNB1 and 6 more
• Non-small cell lung carcinoma, also linked to BRAF, CD274, CDKN2A, CTLA4 and 5 more
• Renal cell carcinoma, also linked to BRAF, CTLA4, FLT3, KIT and 3 more
• Ovarian cancer, also linked to APC, CTNNB1, KIT, PIK3CA and 2 more
• Lung adenocarcinoma, also linked to ARID1A, BRAF, CDKN2A, RB1 and 2 more
• Acute myeloid leukemia, also linked to FLT3, KIT, PDGFRB, TERT and 1 more
• Gastrointestinal stromal tumor, also linked to FLT3, KIT, PDGFRB and RET
• Lung cancer, also linked to BRAF, CD274, NFE2L2 and PIK3CA
• Melanoma, also linked to ARID2, BRAF, CDKN2A and CTLA4
• Gastric cancer, also linked to APC, PIK3CA and TP53
• Malignant tumor of urinary bladder, also linked to CTNNB1, PIK3CA and RB1
• Melanoma, cutaneous malignant, susceptibility to, 8, also linked to BRAF, CDKN2A and TERT

Frequently asked questions

Which genes are linked to Hepatocellular carcinoma?

In CATVariant, Hepatocellular carcinoma is linked to 19 analyzed proteins: CTNNB1 (Catenin beta-1), MET (Hepatocyte growth factor receptor), TP53 (Cellular tumor antigen p53), TERT (Telomerase reverse transcriptase), APC (Adenomatous polyposis coli protein), PIK3CA (Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform) and 13 more.

How many genetic variants are linked to Hepatocellular carcinoma?

73 variants: 6 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 54 are of uncertain significance or have conflicting reports.

Which uncertain variants in Hepatocellular carcinoma 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.

Download every variant as CSV · Browse all diseases · Methods · About the Center